Silybum marianum L. is a well-known medicinal herb, primarily used in liver protection. Light strongly affects several physiological processes along with secondary metabolites biosynthesis in plants. Herein, S. marianum was exploited for in vitro potential under different light regimes in the presence of melatonin. The optimum callogenic response occurred in combination of 1.0 mg/L α-naphthalene acetic acid and 0.5 mg/L 6-Benzylaminopurine under photoperiod. Continuous light associated with melatonin treatment increased total flavonoid content (TFC), total phenolic content (TPC) and antioxidant potential, followed by photoperiod and dark treatments. The increased level of melatonin has a synergistic effect on biomass accumulation under continuous light and photoperiod, while adverse effect was observed under dark condition. More detailed phytochemical analysis showed maximum total silymarin content (11.92 mg/g DW) when placed under continuous light + 1.0 mg/L melatonin. Individually, the level of silybins (A and B), silydianin, isolsilychristin and silychristin was found highest under continuous light. Anti-inflammatory activities were also studied and highest percent inhibition was recorded against 15-LOX for cultures cultivated under continuous light (42.33%). The current study helps to better understand the influence of melatonin and different light regimes on silymarin production as well as antioxidant and anti-inflammatory activities in S. marianum callus extracts.

Background: Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluate its anti-inflammatory potential. Methods: HEVe was obtained by maceration and phytochemicallly analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulted from croton oil-induced dermatitis in mice. Cell viability assay was conducted to determine non-cytotoxic concentrations of HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production.Results: Phytochemical analysis of HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. Oral treatment of acute peritonitis with HEVe reduced total leukocytes, neutrophils, TNF-α and IL-1β, and elevated IL-10 levels. The application of HEgVe reduced local edema. The HEVe on RAW 264.7 cells exhibited no cytotoxicity and cells with HEVe reduced TNF-α, IL-1β, and NO levels, and increased IL-13 levels. Conclusions: HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, which is likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance.

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILD) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for improvement of lung function in patients with fibrotic ILD. Methods: This registry-based study included 142 patients with fibrotic ILD as defined by presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 progressed. Multivariate analyses found prognostic significance for age <60 years (OR 5.4; 95%CI 1.9-15.4; p=0.002), lactate dehydrogenase (LDH) >250U/L (OR 2.5; 95%CI 1.1-5.8; p=0.043) and blood monocyte count <0.8G/L (OR 3.5; 95%CI 1.1-11.3; p=0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age <60 years (OR 8.5 (95%CI 2.1-33.4; p=0.002) as the only significant variable. Conclusion: Younger age, higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Ischemic heart disease is the leading cause of mortality worldwide. There is evidence of the participation of Aβ in thrombosis and clinical manifestations of acute coronary syndromes. In this study, we investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in acute coronary syndrome. This is a single-center, cross-sectional, observational, and correlation study that included 65 patients within the first 12 hours after symptom onset (chest pain, shoulder pain, or chest discomfort) with ST-elevation and non-ST elevation myocardial infarction who were admitted in the Coronary Care Unit, biochemical parameters of Aβ peptides levels were evaluated. Our results show that NSTEMI patients had a higher prevalence of hypertension, diabetes, smoking, and prior myocardial infarction when compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI, but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) in both groups. In this analysis, NSTEMI patients had higher prevalence of cardiovascular risk factors. Considering the toxic properties of Aβ-42 in coronary endothelial cells and cardiomyocytes, this peptide may be useful in risk stratification scores in patients with NSTEMI.

The onset and progression of human inflammatory joint diseases are strongly controlled by the activation of resident synovium/infrapatellar fat pad (IFP) pro-inflammatory and pain-transmitting signaling. We recently reported that intra-articularly injected IFP-derived Mesenchymal Stem/Stromal Cells (IFP-MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P (SP) via neutral endopeptidase CD10 (neprilysin). Our hypothesis is that IFP-MSC robust immunomodulatory therapeutic ef-fects are largely exerted via their CD10-bound exosomal secretome (IFP-MSC EXOs) by attenuating synoviocyte pro-inflammatory activation and articular cartilage degradation. Herein, IFP-MSC EXOs were isolated from CD10High- and CD10Low-expressing IFP-MSC cultures and their exosomal miRNA cargo was assessed using multiplex methods. Functionally, we interrogated the effect of CD10High and CD10Low EXOs on stimulated by inflammatory/fibrotic cues synoviocytes monocultures and cocultures with IFP-MSC de-rived chondropellets. Finally, CD10High EXOs were tested in vivo for their therapeutic capacity in an animal model of acute synovitis/fat pad fibrosis. Our results showed that CD10High and CD10Low EXOs possess distinct miRNA profiles. Reactome analysis of miRNAs highly present in exosomes showed their involvement in the regulation of six gene groups, particularly the immune system. Stimulated synoviocytes exposed to IFP-MSC EXOs demonstrated significantly reduced proliferation and altered inflammation-related molecular profiles compared to control stimulated synoviocytes. Importantly, CD10High EXOs treatment of stimulated chondropellets/synoviocytes cocultures indicated a significant chondroprotective effects. Therapeutically, CD10High EXOs treatment resulted in robust chondroprotective effects by retaining articular cartilage structure/composition and PRG4 (lubricin)-expressing cartilage cells in the animal model of acute synovitis/IFP fibrosis. Our study suggests that CD10High EXOs possess immuno-modulatory miRNA attributes with strong chondroprotective/anabolic effects for articular cartilage in vivo. The results could serve as a foundation for EXOs-based therapeutics for the resolution of detrimental aspects of immune-mediated inflammatory joint changes associated with conditions such as osteoarthritis (OA).

The use of selective pro resolving mediators including the monohydroxylates are promising substances for the management of different acute and chronic diseases.In the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre-eclampsia are still serious complications during pregnancy.The use of enriched marine oil nutritional’s may contribute to an attenuation of these diseases as the containing selective pro resolving mediators exhibit pro resolutive actions that can positively modulate inflammatory diseases and those leading to serious obstetrical complications.

Microglia are the resident immune cells of the central nervous system. Upon stimulus presentation microglia polarize from a resting to an activated state. Microglial translocator protein 18 kDa (TSPO) is considered as a marker of inflammation. Here, we characterized the role of TSPO by investigating the impact of TSPO deficiency on human microglia. We used TSPO knockout (TSPO-/-) variants of the human C20 microglia cell line. We found a significant reduction in the TSPO-associated protein VDAC1 in TSPO-/- compared to control cells. Moreover, we assessed the impact of TSPO deficiency on calcium levels and the mitochondrial membrane potential. Cytosolic and mitochondrial calcium concentrations were increased in TSPO-/- cell lines, whereas the mitochondrial membrane potential tended to be lower. Assessment of the mitochondrial DNA copy number via RT-PCR revealed a decreased amount of mtDNA in the TSPO-/- cells when compared to controls. Moreover, metabolic profiles of C20 cells were strongly dependent on the glycolytic pathway. However, TSPO depletion did not affect the cellular metabolic profile. Measurement of the mRNA expression levels of the pro-inflammatory mediators revealed an attenuated response to proinflammatory stimuli in TSPO-depleted cells, implying a role of the TSPO protein in the process of microglial polarization.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism of action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis,and antiviral mechanism of action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanism of actions as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.

Abstract: Sustainable use of Native American heritage places is viewed in this analysis as serving to preserve their traditional purposes and sustain the cultural landscapes that give them heritage meaning. The research is about the potential impacts of heritage tourism to selected Native American places at Arches National Park, Canyonlands National Park, and Hovenweep National Monument. The impacts of tourists to a heritage place must be understood as having both potential effects on the place itself and on an integrated cultural landscape. Impacts to one place potentially change other places- functions in a Native American landscape and the integrity of the landscape itself. The analysis is based on 696 interviews with representatives from nine tribes and pueblos, who in addition to defining the cultural meaning of places, officially made 349 heritage management recommendations. The U.S. National Park Service interprets Natives American resources and then brings millions of tourists to these through museums, brochures, outdoor displays, and ranger-guided tours. Native American ethnographic study participants argued that tourist education and regulation can increase the sustainability of Native American places in a park and can help protect related places beyond the park.

Abstract: Letter migrations between words in reading aloud (e.g., reading "cane love" as "lane love" or "lane cove") are known to result from a deficit in the visual-orthographic analysis and characterize attentional dyslexia. In spontaneous speech, individuals with impairment in the phonological output buffer may show migrations of phonemes between words. The purpose of this study was to examine whether migrations between words in reading aloud can also result from a deficit in the phonological output buffer, to explore the characteristics of migrations resulting from orthographic input and from phonological output deficits, and to examine methods to distinguish these two sources. Using tasks of reading aloud of 92-182 word pairs, we identified 18 adults and adolescents with developmental dyslexia who made between-word letter migrations in reading aloud, significantly more than age-matched controls (372 adults and 26 7th-graders). To distinguish between orthographic-input and phonological-output sources for these migrations, we administered a test assessing orthographic-input without spoken-output (written-semantic-decision on 140 migratable word pairs) and a test of repetition of 36 auditorily-presented migratable word pairs, assessing spoken output without orthographic-input (and word span tests). These tests indicated that the migrations of ten of the participants with dyslexia resulted from an orthographic-input deficit, and for the other eight participants, migrations resulted from a phonological-output deficit. We identified several differences between the two types of between-word errors: first, whereas the individuals with attentional dyslexia made omissions of a letter that appeared in the same position in the two words, the phonological output buffer group did not make such omissions. In addition, the groups differed in the origin of migration: orthographic input migrations involve letters that are orthographically adjacent, whereas phonological output migrations involve phonemes that have just been spoken or that are prepared together in the phonological buffer for production. This was manifested in that migrations from the line below and from two lines above occurred only in the orthographic input deficit group, and migrations occurred from a word vertically close to the target in the orthographic input group but from a word that has just been spoken (placed diagonally to the target) in the phonological output group. This study thus indicates that between-word migrations in reading-aloud can result not only from attentional dyslexia, but also from a phonological output buffer deficit, and offers ways to distinguish between the two.

Ocean big data is the scientific practice of using big data technology in the marine field. Data from satellites, manned spacecraft, space stations, airship, unmanned aerial vehicles, shore-based radar and observation stations, exploration platforms, buoys, underwater gliders, submersibles, and submarine observation networks are seamlessly combined into the ocean’s big data. Increasing numbers of scholars have tried to fully analyze the ocean’s big data. To explore the key research technology knowledge graphs related to ocean big data, articles between 1990 and 2020 were collected from the “Web of Science”. By comparing bibliometric software and using the visualization software Cite-Space, the pivotal literature related to ocean big data, as well as countries, institutions, categories, and keywords, were visualized and recognized. Journal co-citation analysis networks can help determine the national distribution of core journals. Co-citation analysis networks for documents show authors who are influential at key technical levels. Key co-occurrence analysis network keywords can determine research hot spots and research frontiers. The three supporting elements of marine big data research are shown in the co-citation network. These elements are author, institution, and country. By examining the co-occurrence of keywords, the key technology research directions for future marine big data were determined.

Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.

Shiga toxigenic E. coli (STEC) are an important cause of foodborne disease globally with many outbreaks linked to the consumption of contaminated foods such as leafy greens. Existing methods for STEC detection and isolation are time-consuming. Rapid methods may assist in preventing contaminated products from reaching consumers. This proof-of-concept study aimed to determine if a metabolomics approach could be used to detect STEC contamination in spinach. Using untargeted metabolic profiling, the bacterial pellets and supernatants arising from bacterial and inoculated spinach enrichments were investigated for the presence of unique metabolites that enabled categorization of three E. coli risk groups. A total of 109 and 471 metabolite features were identified in bacterial and inoculated spinach enrichments, respectively. Supervised OPLS-DA analysis demonstrated clear dis-crimination between bacterial enrichments containing different risk groups. Further analysis of the spinach enrichments determined that pathogen risk groups 1 and 2 could be easily discriminated from the other groups, though some clustering of risk groups 1 and 2 was observed, likely representing their genomic similarity. Biomarker discovery identified metabolites that were significantly associated with risk groups and may be appropriate targets for potential biosensor development. This study has confirmed that metabolomics can be used to identify the presence of pathogenic E. coli likely to be implicated in human disease.

Nanofiber (NF) products exhibit outstanding performances in the materials science, textile, and medical fields, which cannot be realized using conventional technologies. However, the safety of such products is debated because of the potential risk of nanomaterials and lack of standardized guidelines for safely evaluating NF products. The global safety evaluations of nanomaterials focused on evaluating the cytotoxicity of zero-dimensional materials including nanoparticles and nanotubes based on OECD criteria. The NFs are one-dimensional materials with nanometer diameters and considerable lengths. Many fibers are applied in a densely woven web-like form, and therefore, assessing cellular penetration and fiber toxicity using the same methods is inappropriate. This study verifies the safety of polyurethane (PU) and polyvinylidene fluoride (PVDF) polymers, which are currently applied in filters and masks. To this end, polymer NFs were collected from each product, and the NFs were compared with reference samples considering their physical properties using FT-IR and Raman spectroscopy. For the safety evaluation, DMSO stocks of varying concentrations of PVDF and PU NFs (at 0.5, 1, 5, and 10 μg/mL) were prepared, and the cytotoxicity and inhibitory effects on nitric oxide production and protein expression obtained via Western blot were identified.

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

Myelodysplastic syndromes (MDS) are diseases that occur when blood-producing cells in the bone marrow are damaged; such damage can affect one or more types of blood cells. Common types of MDS are refractory anemia with ring sideroblasts and refractory anemia with excess blasts (MDS-RS and MDS-EB, respectively). This work analyzed the proteomics of the medullary plasma of 10 patients with MDS-RS and MDS-EB compared to healthy control people. Overexpressed proteins that may be potential candidates for biological markers for the evaluation, study, and diagnosis of these diseases have been identified. These samples were subjected to immunodepleting, concentrated, and digested for further analysis by mass spectrometry. The ratios between selected groups and healthy people were calculated. Seven overexpressed proteins in both syndromes were identified as potential biomarker candidates: vitronectin (VTN), (2) fibrinogen (FGA), (3) pregnancy zone protein (PZP), (4) kininogen (KNG1), (5) immunoglobulin lambda chain (IGLL1), (6) complement factor C4b, and (7) hemopexin (HPX). A modified affinity chromatographic column with lectin frutalin (FTL) was used for non-depleted samples. Immunoglobulin M (IgM) was expressed in the samples from both syndromes. Surprisingly, IgM from patients with syndromes was over retained on the frutalin (FTL) column when compared with the control group. We further hypothesized that over retention of this protein by the FTL is due to the presence of α-galactosidic residues in the IgM of MDS-RS and MDS-EB patients. Differential recognition of proteins on non-depleted samples from the use of FTL appears to be a powerful tool for proteomic analysis.

Dioscorea praehensilis Berth is one of the wild yam species resistance to many yam disease (yam anthracnose disease and yam mosaic virus) grow in Ghana especially in the cocoa grown regions of the country. It is a crucial crop that has been known to contribute to poverty reduction and food gap. Genetic diversity in this yam species has been discovered to be eroding and neglected. In this study we evaluated the genetic diversity among 43 D. praehensilis collected from Ghana using simple sequence repeat (SSR). Using 11 SSR marker, a total of 99 number of alleles were generated with an average of 8.48 alleles per locus. The mean gene diversity was 0.81, mean polymorphism information content was 0.82 while mean Shannon information index was 1.94. Principal coordinate analysis (PCoA) revealed a contribution of 40.16% of the first three coordinate axes and grouped the 43 morphotypes into 2 groups while hierarchical cluster through UPGMA revealed the presence of 3 main clusters. Molecular variance (AMOVA) alongside the Fst revealed low genetic diversity and differentiation among accessions and population. Result of this study assess the genetic diversity and will facilitate the use D. praehensilis as sources of resistance gene into yam breeding program.

Dermatological consultations are a significant aspect of daily operations at small animal clinics, with atopic dermatitis (CAD) affecting almost 15% of the canine population. The ECS role in the skin reveals its direct action on homeostasis and deregulation, contributing to dermatopathies. It also details its presence in specialized skin cells, revealing a delicate and complex therapeutic potential. Due to the difficulties and the growing scientific evidence of the therapeutic benefits of cannabis, this work aimed to evaluate the anti-inflammatory effect of cannabis oil in treating CAD. Thus, canines diagnosed with CAD were divided into two groups: the group treated using full spectrum high cannabidiol (CBD) [cannabis oil orally] and the control group (olive oil). The evaluation methods for the effectiveness of the therapy were based on the measurement RNAm of interleukins 6, 10, and 31 and oxidative stress in the blood. Despite the theoretical basis, no significant results were obtained between the groups in this work. Thus, it is concluded that oral administration of full spectrum high CBD cannabis oil 2,5 mg/kg twice a day is not efficient in reducing IL and oxidative stress compared to placebo; nevertheless, it still presents a promising approach in the multi-target treatment of CAD.

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials for preparing a final product, However, the plant material waste still contain substances with an opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new non-wasting extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified total 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, total 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed a significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied with a formalin oedema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. The composite gels of polyethylene oxide and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

The aim of our present study was to investigate the effects of Gln supplementation on liver inflammatory responses and protein synthesis and degradation in muscle of LPS-challenged broilers. A total of 120 1d-old male broilers (Arbor Acres Plus) were randomly arranged in a 2 × 2 factorial design with five replicates per treatment and six broilers per replicate, containing two main factors: immune challenge (injected with LPS in a dose of 0 or 500 µg/kg of body weight) and dietary treatments (supplemented with 1.22% alanine or 1% Gln). After feeding with alanine or Gln diet for 15 days, broilers were respectively administrated with LPS or saline injection at 16 and 21 d. The results showed that Gln supplementation significantly reversed the adverse effects of LPS administration on growth performance, as evidenced as the increased ADFI and ADG, as well as the lowered F/G. Furthermore, Gln supplementation alleviated the increased mRNA expression of interleukin-6, interleukin-1β and tumor necrosis factor-α in liver induced by LPS. Moreover, the increased activities of aspartate aminotransferase, combined with the decreased expression of glutaminase in muscle, were observed by Gln addition. In addition, in comparison with saline treatment, LPS challenge altered signaling molecules mRNA expressions associated with protein synthesis and degradation. However, Gln supplementation reversed the negative effects on protein synthesis and degradation in muscle of LPS-challenged broilers. Taken together, Gln supplementation had benefit effects on improving growth performance, alleviating inflammatory responses, promoting protein synthesis and inhibiting protein degradation of LPS-challenged broilers.

The real long-term influences of in utero drug exposure in pregnant women on childhood development have yet to be fully determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining therapeutic drug levels in maternal blood. Most antibody therapies used in patients with Inflammatory Bowel Disease (IBD) are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here we propose an up to date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the blood cord, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the second and third trimesters, leading to increasing maternal IFX concentrations. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance regarding the safety profile of anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable but very low and therefore it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. It is currently not recommended in patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact for making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the blood cord, the infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data currently available.

Glucocorticoid administration is a common clinical practice in attempt to decrease inflammation associated with, and improve resectability of, canine mast cell tumors (MCTs). However, the impact of neoadjuvant glucocorticoids on histological features and proliferation indices of canine MCTs is unknown. The objective of this study was to evaluate changes in tumor grade, mitotic count, Ki67, AgNOR, and AgNORxKi67 scores following short-course, anti-inflammatory neoadjuvant prednisone in canine patients with MCTs. This was a prospective, single-arm pilot study. Client-owned dogs with treatment-naïve, cytologically-confirmed MCTs were enrolled. Patients underwent an initial incisional biopsy followed by a 10-14 day course of anti-inflammatory prednisone, and surgical resection. All histological samples were randomized, masked, and evaluated by a single pathologist. Unstained paired pre- and post-treatment samples were submitted to a commercial laboratory for Ki67 and AgNOR immunohistochemical analysis. There were 11 dogs enrolled with 11 tumors. There were no statistical differences between the pre- and post-treatment histological parameters of mitotic index, Ki67, AgNOR, or Ki67xAgNOR. There were no clinically-significant alterations between pre-treatment and post-treatment in the assignment of tumor grades. A short-course of anti-inflammatory prednisone does not appear to alter the histological parameters that affect grade-determination, nor significantly alter the proliferation indices in canine MCTs.

Silybum marianum (L.) Gaertn is a rich source of antioxidants and anti-inflammatory flavonolignans with great potential for use in pharmaceutical and cosmetic products. Its biotechnological production using in vitro culture system has been proposed. Chitosan is a well-known elicitor that strongly affects both secondary metabolites and biomass production by plants. The effect of chitosan on S. marianum cell suspension is not known yet. In the present study, suspension cultures of S marianum were exploited for their in vitro potency to produce bioactive flavonolignans in the presence of chitosan. Established cell suspension culture was maintained on the same hormonal media supplemented with 0.5 mg/L BAP (6-benzylaminopurine) and 1.0 mg/L NAA (α-naphthalene acetic acid) under photoperiod 16/8 h (light/dark) and exposed to various treatments of chitosan (ranging from 0.5 to 50.0 mg/L). The highest biomass production was observed for cell suspension treated with 5.0 mg/L chitosan, resulting in 123.3 g/L fresh weight (FW) and 17.7 g/L dry weight (DW) productions. Chitosan treatment resulted in an overall increase in the accumulation of flavonoids, phenolic compounds and silymarin. High accumulation levels of silybin B, silydianin and silybin A were recorded by HPLC analysis. The corresponding extracts displayed interesting antioxidant and anti-inflammatory capacities. In particular, high ABTS antioxidant activity (741.5 μM Trolox C equivalent antioxidant capacity) was recorded in extracts obtained in presence of 0.5 mg/L of chitosan. On the opposite, highest inhibitions of cyclooxygenase 2 (COX-2, 30.5 %), secretory phospholipase A2 (sPLA2, 33.9 %) and 15-lipoxygenase (15-LOX-2, 31.6 %) enzymes involved in inflammation process were measured in extracts obtained in presence of 5.0 mg/L of chitosan. Taken together, these results highlight the high potential of the chitosan elicitation of the S. marianum cell suspension for enhanced production of antioxidant and anti-inflammatory silymarin-rich extracts.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL receptor deficient mice. CETP expression did not change lipid-stained lesion areas but decreased macrophage content (CD68), neutrophil accumulation (LY6G) and aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone marrow-derived cells reduces inflammatory features of atherosclerosis. These novel mechanistic observations may help explain the failure of CETP inhibitors to reduce atherosclerotic events in humans.

(1) Background: Inflammatory bowel diseases (IBD) involve complex interactions between genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The current study aimed to identify novel mucosal metabolic pathways that are altered during chronic colitis and to determine microbial contributions to such changes. (2) Methods: The chronic Dextran sulfate sodium (DSS) colitis was induced for five weeks in 7-9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. (3) Results: Our novel findings demonstrated increases in several host- and mi-crobe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. (4) Conclusions: These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.

The lethal combination involving TB and HIV, known as 'syndemic’ diseases synergistically act upon one another to magnify the disease burden. Individuals on ART are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic markers still remain a grey area of investigation. Here, we reviewed the latest research developments in IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Ovine footrot is a complex multifactorial infectious disease, causing lameness in sheep with major welfare and economic consequences. Dichelobacter nodosus is the main causative bacterium, however, footrot is a polymicrobial disease with Fusobacterium necrophorum, Mycoplasma fermentans and Porphyromonas asaccharolytica also associated. There is limited understanding of the host response involved. Proinflammatory mediators interleukin (IL)-1β and C-X-C Motif Chemokine Ligand 8 (CXCL8) have been shown to play a role in the early response to D. nodosus in dermal fibroblasts and interdigital skin explant models. To further understand the response of ovine skin to bacterial stimulation, and to build the understanding of the role of the cytokines and chemokines identified in transcriptomic data, primary ovine interdigital fibroblasts and keratinocytes were isolated, cultured and stimulated with lipopolysaccharide (LPS), D. nodosus or F. necrophorum in the presence and absence of M. fermentans, whilst measuring mRNA expression and protein release of CXCL8 and, IL-1β. Stimulation with LPS, D. nodosus or F. necrophorum resulted in increased transcript levels of IL-1β and CXCL8 in M. fermentans free cells, however, only an increase in CXCL8 protein release was observed. No IL-1β protein release was detected despite increases in IL-1β mRNA, suggesting the signal for intracellular pre-IL-1β processing may be lacking when culturing primary cells in isolation. Keratinocytes and fibroblasts naturally infected with M. fermentans showed little response to LPS, a range of D. nodosus preparations or heat-inactivated F. necrophorum. Primary single cell culture models complement ex vivo organ culture models to study different aspects of the host response to D. nodosus. Ovine keratinocytes and fibroblasts infected with M. fermentans had a reduced response to experimental bacterial stimulation. However, in the case of footrot where Mycoplasma spp. are associated with diseased feet, this natural infection gives important insights into the impact of multiple pathogens on the host response.

Flowers have always accompanied people thanks to their manifold aesthetic properties. Some species have also become a component of human diet. Recent years have seen an increased interest in edible flowers and, consequently, research has been undertaken to determine their chemical composition. Dyes abundantly contained in flowers, whose role is to attract pollinating animals, are recognized substances with health promoting properties. Anthocyanins are a group of dyes that is very common in petals and other parts of flowers. Studies carried out in the twentieth and twenty-first century have found very strong antioxidant and anti-inflammatory properties of anthocyanins. Therefore, flowers used by humans for centuries to decorate their surroundings may become an easily available source of nutrients and health-promoting substances. This paper discusses the health-promoting properties of anthocyanins and collects literature on anthocyanin content in edible flowers commonly grown on balconies, terraces and roofs.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

Torenia Concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent a manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286) and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor) and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (a NOS inhibitor). Collectively, our findings suggest that TCEE confers protection from endothelial dysfunction by activating the Akt/CaMKII/AMPK/eNOS/NO signaling pathway.

The clinical relationship between diabetes and inflammation is well-established. Various branches of science independently have confirmed that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with Type 2 diabetes mellitus (T2DM). Under diabetic condition, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress and tissue damage are believed to have a role in the development of diabetes. Although the exact mechanism underlying the oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in onset and progression of vascular disease, kidney disease, hepatic injury, pancreas damage and, therefore holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications therapy fails to achieve the normal range for glycated hemoglobin target, signifying treatment resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical in vivo and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision of the future diabetes clinical trials.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural origin (Tussilago farfara)has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. Neuropathic pain was induced in mice by PSNL surgery performed on day 1 and ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose dependent manner. ECN significantly reversed the severity of neuropathic pain by improving distress symptoms and survival rate. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, anti-neuropathic potential of ECN might be due to inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles.Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment.Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls.Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment.Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS is a new drug target to treat FEP.

We investigated the efficacy of a Rumex crispus and Cordyceps sinensis mixture made using the Beopje (Korea traditional processing method to remove anti-nutrients and enhance phytochemicals) method to regulate immune cell responses toward nitric oxide (NO) production, pro-inflammatory cytokines, and inflammation related genes in mice splenocytes. The six experimental groups were as follows: control (control), Rc-Cs (Rumex crispus (Rc) and Cordyceps sinensis (Cs) mixture, 6:4), TMC (Taemyeongcheong, commercial healthy drink containing Rc-Cs), LPS (lipopolysaccharide), LPS+Rc-Cs, and LPS+TMC. The Rc-Cs mixture reduced nitric oxide (NO) production in LPS-induced splenocytes. Moreover, Rc-Cs enhanced production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6 compared to the control (no treatment). However, Rc-Cs inhibited production of pro-inflammatory cytokines in LPS-induced splenocytes. In addition, LPS+Rc-Cs also significantly suppressed mRNA expression of IL-1β and IL-6 compared to LPS treatment. Interestingly, Rc-Cs did not increase mRNA levels of iNOS and COX-2, which are inflammation related genes compared to the control, while LPS+Rc-Cs reduced mRNA levels of iNOS and COX-2 compared LPS alone (p < 0.05). TMC showed a similar pattern compared to Rc-Cs. Therefore, Rc-Cs treatment in splenocytes enhanced NO production and pro-inflammatory cytokines compared to the control, whereas Rc-Cs treatment in LPS-induced splenocytes reduced NO production, pro-inflammatory cytokines, and inflammation related genes. Thus, Rc-Cs regulated immune cells responses by increasing pro-inflammatory cytokines in splenocytes and reducing toxin (LPS)-induced inflammation. These results indicate that a Rumex crispus and Cordyceps sinensis mixture (Rc-Cs) and TMC containing Rc-Cs promote immune cells responses and anti-inflammatory activities.

This study aims to determine the protective effects of red seaweed Eucheuma cottonii (EC) ethanol extract on acute colitis disease in mice. Male BALB/c mice used for acute colitis disease model by induced 2.5% (w/v) of dextran sulfate sodium (DSS) for 7 days for all groups, except control group. The DSS-induced mice then treated by three different doses of EC extracts (0.35, 0.70, 1.75 g/kg body weight), curcumin (as a positive control, 0.10 g/kg), and a group was orally only by water. In 8^th day, the mice sacrificed and collected the blood, then measured the body weight, colon weight, and colon length. Disease activity index (DAI), pro-inflammatory such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, as well as IL-10 as anti-inflammatory were measured. The results showed that after treatment for 7 days, EC extract protected the weight loss and decreased the colon weight per length ratio. In addition, EC extract also decreased the pro-inflammatory cytokines expression in serum and increased the IL-10. Moreover, EC extract protected the colonic tissue damage. According to this results, the EC ethanol extract might be can used for the treatment of colitis disease.

Social responsibility is imperative for its important function in the growth of societies and organizations. However, the research on corporate social responsibility (OSR) has predominantly focused on the actions of organizations. Not much has been discussed regarding the employee's behaviours in promoting the development of social responsibility within organizations. CI is known for its significant role in the organization's various outcomes, Although a conceptualization and some empirical support have been provided for its relationship with the behaviour of employees, However, the effect of CI on employee socially responsible behaviours has not yet been investigated. In this article, following OC and OI theories, we improve the research model which can describe mechanisms underpinning through which CI, OI and POS support actions for employees' social responsibility. Data was collected from members of service professionals in Saudi Arabia and examined using Structural Equation Modeling- Partial Least Squares. The findings indicated that CI actions and activities develop the skills that motivate employees to support social responsibility inside and outside the organization. Moreover, our research paper explained the mechanism under which CI activities reshape employees' socially responsible manners. The current study is among the first to look at how to modify the socially responsible behaviour of employees across organizations, which can be a starting point for transforming those employees into a sustainable society.

BackgroundIt is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals plays a role. MethodsWe used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. ResultsThe prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ=0.55; P<0.001], K. pneumoniae [ρ=0.58; P<0.001]; A. baumanii [ρ=0.54; P=0.004]; P. aeruginosa [ρ=0.48; P=0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. ConclusionsReducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various gram negative bacterial species.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis severity was evaluated using histology and colonoscopy. Mice were mono-inoculated with C. albicans, C. tropicalis or co-challenged with both species. Mice were administered 3% DSS to induce acute colitis. Biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) assay. Abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. Co-challenged mice showed decreased colitis severity compared to mono-inoculated mice. The XTT assay demonstrated a marked decrease of C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface leading to a reduction in biofilm formation.

The severe respiratory distress syndrome (SRDS) has been a significant clinical issue in modern respiratory medicine. Its role in COVID-19 pandemic is not well defined. Outside-the-hospital SRDS is usually community-acquired septic pneumonia; however, in-hospitals incidences are complicated by co-infections. While SRDS is genetically selected in European and African origins, these are not clear in Middle East, particularly in COVID-19 backgrounds. There is a severe paucity in high quality data on correlations between COVID-19, ARDS, co-infectome, and patient demographics. We have conducted a comprehensive investigation on 298 patients for associations of SRDS, coinfections, and patient demographics on COVID-19 patients’ outcomes. Of these, 9.4% (n=28) had SRDS, and the rest (90.6%) had not. 54% of those with SRDS died while 84% survived; SRDS fatality was highly significant (Chi-square test P-value = 0.00000246). Irrespective of gender, the age of patients was significantly associated with SRDS (72.9 +/-8.9) compared to those without it (56.2 +/-15.1). However, there was no significant difference neither in the age of admitted patients before COVID-19 (58.5 +/-15.3) and during COVID-19 (57.2 +/-15.5) nor in the gender and COVID-19 fatality (Fisher Exact test 2-sided 1.000, 1-sided .546) ruling out that SRDS age-specificity were selected by virus susceptibility. A 100% of SRDS patients without bacterial co-infections survived while only 25% of those with co- infectome did not; this association was highly significant (P value= 0.00041). Co-infections alone without underlying SRDS was also associated with high fatality among patients (P value= 0.00000000076). Almost all COVID-19 patients without co-infectome (99.2%) survived while 28% of those with bacterial co-infection died. The major bacterial pathogens that potentially predisposed to SRDS, were Acinetobacter baumannii, and Escherichia coli either alone or in a mixed infection with Klebsiella pneumoniae were predominant species identified during SRDS attack. Thus, Gram-negative co-infectome potentially induced fatal SRDS aggravating COVID-19 outcome. These findings have significant clinical implications in specific differential diagnosis of SRDS syndromes for subsequent empiric therapy and patient management strategies. Future vertical investigation for similar mechanisms of cytokine-induced SRDS by Gram negative pathogens is imperative since hypervirulent strains are rapidly circulating in the region. The study is limited by a single center study confined to Ha’il hospitals; large scale investigation in major national hospitals would gain more insights.

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceded safe levels at 64 sites. We assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in Escherichia coli. Methods Spearman’s regression was used to assess the country-level association between the national prevalence of fluoroquinolone resistance in E. coli and the median ciprofloxacin concentration in the countries rivers. Results The prevalence of fluoroquinolone resistance in E. coli was positively correlated with the concentration of ciprofloxacin in rivers (ρ=0.36; P=0.011; N=48). Conclusions Steps to reducing the concentrations of fluoroquinolones in rivers may help prevent the emergence of resistance in E. coli and other bacterial species.

The USDA-FSIS considers mechanically-tenderized beef as ‘non-intact’ and a food safety concern because of the potential for translocation of surface E. coli O157:H7 into the interior of the meat that may be cooked ‘rare or medium-rare’ and consumed. We evaluated 14 potential spray interventions on E. coli O157:H7-inoculated lean beef wafers (~10⁶ CFU/cm² , n=80) passing through a spray system (18 sec dwell time, ~40 PSI) integrated into the front end of a Ross TC-700MC tenderizer. Inoculated and processed beef wafers were stomached with D/E neutralizing broth and plated immediately, or were held in refrigerated storage for 1-, 7-, or 14 days prior to microbial plating. Seven antimicrobials that showed better performance in preliminary screening on beef wafers were selected for further testing on beef subprimals in conjunction with blade tenderization. Boneless top sirloin beef subprimals were inoculated at ~2 x 10⁴ CFU/cm² with a four-strain cocktail of Escherichia coli O157:H7 and passed once, lean side up, through an integrated spray system and blade tenderizer. Core samples obtained from each subprimal were examined for the presence/absence of E. coli O157:H7. Absence of E coli O157:H7 translocated into core samples correlated with the ability of the antimicrobials to reduce bacterial levels on the surface of beef prior to blade tenderization.

Dissemination of resistant pathogens via food supply chains is a notable public health danger from farm to fork. The proposed work analysed the distribution of E. coli among various sources of animal-based food supply chain. Overall, 500 samples were heaped up from livestock, poultry sectors, environment, fisheries, and dairy. Standard microbiological procedures were used to isolate and identify E. coli. Further, isolates were confirmed by using MALDI-TOF and virulence associated genes (VAGs). The phenotypic resistance pattern of the isolates was determined by molecular identification of antibiotic resistance genes (ARGs) through PCR using specific primers. Shiga toxin producing E. coli (STEC) were subjected to PCR based O typing using specific primers against different O types. Overall results revealed that 154 (30.5%) samples were confirmed as E. coli, in which77 (50%) isolates were MDR E. coli. Among these, total 52 (67.53%) isolates showed array of VAGs in which 21 (40.38%) were confirmed as STEC based on stx1 and stx2. Furthermore, 12/52 (23.07%) isolates were detected as Non-O157 STEC co-harboring mcr-1 and blaNMD-1. Overall, O26 STEC was found to be the most prevalent among different non-O157 types. Herein, results proposed that detection of such STEC MDR E. coli causing serious public health consequences in developing countries.

Background: The present work aimed to estimate the economic impact of PTSD following COVID-19 in a population of patients affected by systemic autoimmune disease (SAD) using a cost-of-illness approach and accounting for the perspective of society. Methods: Considering data collected from SAD patients enrolled in a specialized outpatient clinic in the Tuscany region, Italy, generalized-linear-models and LASSO logistic regression were used to evaluate the impact of PTSD on costs and its relevance as possible predictors of being a high-cost patient, respectively. Results: Considering 301 SAD patients, 161 (51.2%) of whom diagnosed with PTSD, the overall costs were 3,670 [890;40,529] Euro per patient/year among patients with PTSD and 2,736.7 [283;21,078] Euro per patient/year among those without PTSD (P-value<0.001), with differences mainly attributable to significantly greater direct non-healthcare and indirect costs. PTSD was estimated to increase overall costs (β=0.296 (0.140), P-value=0.035), direct non-healthcare (β =1.193 (0.392), P-value =0.002) and indirect costs (β =3.741 (1.136), P-value =0.001). PTSD diagnosis was also significantly associated with the likelihood of being a high-cost patient. Conclusions: Findings from the present study offer a novel perspective on the economic impact of COVID-19 and provide valuable data for policymakers to better understand demand for healthcare services and associated costs.

Abstract: In recent years, low frequency (LF) electroencephalogram (EEG) signals have been decoded to obtain kinematic trajectories with the aim of achieving closed loop natural control. However, decoded trajectories suffer variability and low correlation against the measured movement. This paper suggests that if EEG features of motor intents are directly associated with fixed points along a given range of motion, then the natural kinematic parameters can be quantified. A novel classification method is proposed to evaluate this hypothesis along with equations for obtaining the movement parameters (velocity, acceleration). Furthermore, this implies that the force of an end-effector and work done in moving the end-effector may be computed, leading to natural control of EEG-based robotic arms and neuroprostheses. Finally, expectations are that combining the proposed method with existing classification methods will increase the accuracy and scalability of brain-computer interface (BCI) applications.

Abstract: We have filled a 24 mm diameter glass sphere with a transparent polymer-gel that is radio-fluorogenic, i.e. it becomes (permanently) fluorescent when irradiated, with an intensity proportional to the local dose deposited. The gel consists of >99.9% tertiary-butyl acrylate (TBA) pre-polymerized to ~15% conversion, and ~100 ppm maleimido-pyrene (MPy). Its dimensions and physical properties are close to those of the vitreous body of the human eye. We have irradiated the gel with a 3 mm diameter, 200 kVp X-ray beam with a dose rate of ~1 Gy/min. A 3D (video) view of the beam within the gel has been constructed from tomographic images obtained by scanning the sample through a thin sheet of UV light. To minimize optical artifacts, the cell was immersed in a square tank containing a refractive-index-matching medium. The 20%-80% penumbra of the beam was determined to be ~0.4 mm. The research was a preparatory investigation of the possibility of using the method to monitor the millimetre diameter proton pencil beams used in ocular radiotherapy.

In plants, phase change from the juvenile stage to maturity is a tightly controlled process at the physiological and genetic level, which is controlled by evolutionary highly conserved microRNAs. These phase changes are more pronounced in woody plant species, but the majority of molecular genetic studies on the regulation of this transition has been done in annual model or crop species. This process is of particular significance for the in vitro propagation of woody plant species, as individuals or tissues that have undergone the transition to vegetative maturity are recalcitrant to propagation. Development of effective methodologies for silver birch vegetative propagation are required to increase the efficiency of breeding programs. Conserved miRNAs that were differentially expressed between juvenile and mature silver birch tissues were identified using high-throughput sequencing of small RNA libraries. These differentially expressed miRNAs could potentially be utilized to develop markers indicating the juvenility or maturity of silver birch explants and in vitro cultures. In addition, the obtained results will provide an insight into the molecular mechanisms regulating vegetative phase change in silver birch and other perennial woody plant species.

DNA-methylation clocks inform not only about chronological but also biological age, which brings a high resolution and precise understanding of age-related pathology and physiology. Attempts based on transcriptomic and epigenetic approaches arise as integrative biomarkers linking the quantification of stress response with a given fitness trait and may help to identify biological age markers, also considered welfare indicators. In gilthead sea bream, targeted gene expression and DNA-methylation analyses in white skeletal muscle proved sirt1 as a reliable marker of age-mediated changes of energy metabolism. To complete the list of welfare auditing biomarkers, wide-analyses of gene expression and DNA-methylation in one- and three-year old fish were combined. After discriminant analysis, 668 differentially expressed transcripts were matched with those containing differentially methylated (DM) regions (14,366), and 172 were overlapping. Through enrichment analyses and selection, two sets of genes were retained: 33 showing an opposite trend for DNA-methylation and expression, and 57 down-regulated and hypo-methylated. The first set displayed apparently a more reproducible and reliable pattern and 10 multifunctional genes with DM CpG in regulatory regions (sirt1, smad1, ramp1, psmd2 – up-regulated; col5a1, calcrl, bmp1, thrb, spred2, atp1a2 – down-regulated) were deemed candidate biological age markers for an improved welfare auditing in gilthead sea bream.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, SHBG, androstenedione) and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration's tool for RCTs and the Newcastle–Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and 95% confidence interval (95%CI) of circulating inflammatory markers, androgens and LH between baseline and post-weight loss values. Eleven studies (n=323) were eligible for the systematic review, of which nine (n=286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n=286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n=140), TNF- α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n=162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n=147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n=197) after weight loss compared to baseline levels among PCOS women. Meta-analysis of five studies (n=173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD -0.43, 95%Cl, -0.65, -0.21). These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined.

The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbic flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbic flora, and the role of autophagy in intestinal epithelial cells and provides the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “anti-inflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The confluence of the maternal and fetal circulations occurs at the placenta, which is the first or-gan to develop. Placental pathology can provide an accurate diagnosis of inflammation inside the amniotic sac. The pathological alterations of preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospec-tive study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department in our institution so that grading and staging of any evident inflammatory response could be evaluated and associated with baby gender. Eighty-four full-term placentas were col-lected after delivery. Placentas that were considered normal and were not sent to the histo-pathology department were taken. Morphological examination of fresh placenta was conducted. Full thicknesses of placenta samples were taken from central and marginal regions of placental disc. Fetal and maternal inflammatory responses syndrome were assessed. Villitis of unknown etiology (VUE) and chronic deciduitis also were evaluated in the placenta. Immunohistochemis-try (IHC) was also performed to evaluate patterns of inflammation in the placenta using an-ti-CD8 and anti-CD68 antibodies. The correlation between the silent pathologies and clinical complications or involvement of developing fetal inflammatory response syndrome was meas-ured. In this study, seventeen (20%) maternal inflammatory samples and ten (12%) fetal inflam-matory samples showed inflammatory responses. The frequency of chronic deciduitis and villi-tis of unknown etiology was more remarkable among Saudi pregnant women than the previ-ously reported findings in the literature of placental pathology. The prevalence of fetal and ma-ternal inflammatory response was greater in the placentas of mothers of males than in placentas of female mothers. Grading placental inflammation usually predict the degree of maternal an-ti-fetal cellular rejection. Fetal inflammatory response syndrome usually goes unnoticed in Sau-di Arabia. There are differences in the inflammatory response in the placenta based on the sex of the newborn. Increasing the number of placental samples that must be sent for microscopic in-spection may be preferable due to their significance in identifying the causes of chronic disor-ders.

Background: Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&NS) pathways. Methods: We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI).Findings: Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA- patients. SA+ patients showed significantly (p<0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA- patients, those with SA+ showed significant (p<0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p<0.001) levels of inflammation and neurotoxicity as compared with controls. Conclusions: Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.

Though melatonin is known to improve ultraviolet B (UVB)-induced oxidative damage and inflammatory conditions via blockade of nuclear factor (NF)-κB, interleukin (IL)-6, there is no report on anti-wrinkle effect of melatonin to date. Hence in the present study, anti-wrinkle mechanism of melatonin was elucidated in UVB treated HaCaT keratinocytes and hairless mice. Herein melatonin protected against a radical initiator tert-Butyl hydroperoxide (t-BOOH) induced reactive oxygen species (ROS) production, matrix metalloprotease 1 (MMP-1) and cytotoxicity in HaCaT keratinocytes. Also, melatonin suppressed the expression of sonic hedgehog (SHH) and GLI for hedgehog signaling, p-NF-kB, cyclooxygenase (COX-2), p-ERK for inflammatory responses in UVB treated HaCaT keratinocytes. Furthermore, melatonin protected skin from wrinkle formation, transdermal water loss in hairless mice irradiated by UVB for 8 weeks. Notably, melatonin prevented against epidermal thickness and dermal collagen degradation in UVB irradiated hairless mice by Hematoxylin & Eosin and Masson’s trichrome staining. Taken together, these findings suggest that melatonin reduces wrinkle formation via inhibition of ROS/SHH and inflammatory proteins such as NF-kB/COX-2/ERK/MMP1.

In (Venetz et al., 2019), authors rebuilt the essential genome of Caulobacter crescentus through the process of chemical synthesis rewriting and studied the genetic information content at the level of its essential genes. Then, they reduced the native Caulobacter crescentus native Caulobacter NA1000 genome sequence real genome ( 4042929 bp ) to the 785,701-bp reduced synthetic genome. Here we demonstrate the existence of a palindromic-like mirror structure that exists in real genomes and disappears totally in the synthetic genome. This biomathematic meta-organization is based on characteristic proportions of Fibonacci numbers between DNA single strand nucleotides proportions TC / AG on the one hand and TG / AC on the other hand. In both cases, we suggest that this meta-structure enhances the three-dimensional cohesion of the two DNA strands of the genome. We then generalize this study to the different synthetic genomes and synthetic cells published by the Craig Venter Institute on Mycoplasma Mycoides JCVI-syn1.0 (in 2010), JCVI-syn3.0 (in 2016) and JCVI-syn3A (in 2019). Finally, in the discussion section, we extend this study to synthetic genomes of E-Coli and Yeast chromosome XII.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

It is well known that the strong-evidence foodborne outbreaks of human campylobacteriosis are associated with the consumption of raw or incompletely thermally processed poultry meat, whereas broilers act as the main reservoir for Campylobacter species. Campylobacter jejuni and Campylobacter coli are the two main species of campylobacters detected in chicken meat, while they account for almost 90% of the reported cases of campylobacteriosis in humans. Over 80% of these cases are attributed to C. jejuni and about 10% of them are due to C. coli. Therefore, until recently the dominance of C. jejuni against all other Campylobacter spp. isolated from chicken meat samples was well established and unquestionable. Lately, however, C. coli has been increasingly recovered from chicken meat to such an extent that it is now evident that it often comprises the dominant species among the identified campylobacters in the meat samples. This work attempts for the first time a detailed review in the literature to deepen into this noteworthy epidemiological swift in the prevalence of C. jejuni and C. coli, along with the distribution of Campylobacter spp. in chicken meat. Factors such as the sampling method followed for screening campylobacters in broiler carcasses (e.g., swabs or carcass rinsates, skinned or skinless meat excised samples) and part of the animal carcass from which the sample is obtained (e.g., neck, breast, leg), seasonality of sampling (summer vs. winter) and environmental conditions (e.g., rainfall, relative humidity) at the farm level, the isolation procedure (enumeration or detection) and pathogen identification (biochemical or molecular), the enrichment and plating isolation media (e.g., Bolton vs. Preston broth, charcoal-based vs. chromogenic agars), as well as the biofilm-forming ability of different campylobacters, highlight the multivariate dimension of the phenomenon and are thoroughly discussed in the present review.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

In traditional oriental medicine, carrots (Daucus carota L.) are considered effective medicinal herbs; however, the use of D. carota leaves (DGL) as therapeutic agents has not been explored in depth. Therefore, we aimed to demonstrate the value of DGL, generally treated as waste while developing plants for wide industrial availability. Six flavone glycosides were isolated and identified from DGL, and their constituents were identified and quantitated using an NMR and HPLC/UV method, which was optimized and validated. The structure of chrysoeriol-7-rutinoside from DGL was elucidated for the first time. The method exhibited adequate relative standard deviation (&lt;1.89%) and recovery (94.89–105.97%). The deglycosylation of DGL flavone glycosides by Viscozyme L and Pectinex was assessed. Upon converting the reaction contents to percentages, the luteolin, apigenin, and chrysoeriol groups showed values of 85.8, 33.1, and 88.7%, respectively. The enzyme-treated DGL had a higher inhibitory effect on TNF-α and IL-2 expression than that of the carrot roots or carrot leaves without enzyme treatments. These results highlight the importance of carrot leaves and could be used as baseline standardization data for commercial development.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.

Background: The Balaruc-les-Bains’ thermal mud was found to be colonized predominantly by microorganisms, with cyanobacteria constituting the primary organism in the microbial biofilm observed on the mud surface. The success of cyanobacteria in colonizing this specific ecological niche can be explained in part by their taxa-specific adaptation capacities, and also the diversity of bioactive natural products that they synthesize. This array of components has physiological and ecological properties that may be exploited for various applications.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels <50 nmol/L) rate was higher (73% vs 22%) in the obesity than in the normal-weight group. All cardiometabolic factors were altered in the obesity compared with the normal-weight group. After the 3-month weight-loss program, 25(OH)D levels was >50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D <50 nmol/L) at baseline showed a significant correlation between the change in PTH and CRP (p=0.02) in the supplemented obesity group, while the increase in 25(OH)D only tended to be correlated with CRP decrease. Vitamin D supplementation could reduce VD insufficiency in adolescent with obesity, but does not have any additional effect on cardiometabolic factors when combined with a weight-loss program.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

Background and Aims Insulin resistance is pivotal in the pathogenesis of Metabolic Syndrome (MetS), which predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (Ty-G index), a validated measure of insulin resistance also predicts MetS, T2DM, severity of albuminuria and ASCVD. There is scantly data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Patients and Methods Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver operating Characteristic (ROC) curve analysis revealed that TyG index was an excellent predictor of MetS with an area under the curve of 0.87 and it correlated with both hepatic and adipose tissue insulin ressitance .Both serum FFA levels and non-HDL-cholesterol increased significantly over tertiles of TyG index. Based on TyG index tertiles and or correlations, C reactive protein, endotoxin, chemerin , interleukin-6 levels and monocyte toll-like receptor (TLR)- 4 and TLR-2 and their cellular signaling were significantly associated with TyG index . Conclusion: Increased non-HDL-C and most importantly a pro-inflammatory state evidenced by both circulating and cellular biomarkers could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD.

OBJECTIVE: To investigate the value of serum inflammatory factor levels in acute ischemic stroke patients after revascularization therapy in assessing acute prognosis. METHODS: 94 patients with acute ischemic stroke who underwent revascularization therapy admitted to our hospital from January 01, 2022 to January 01, 2024 were studied. The main evaluation index was modified Rankin Scale score (mRS) after 3 months, and patients with mRS score >2 were categorized into the poor prognosis group, and the rest were the good prognosis group. As well as the treatment of revascularization in all patients was used as a division into a thrombus extraction group and an intravenous thrombolysis group. Logistic regression analysis was applied to explore the independent risk factors for the prognosis of patients treated with recanalization for acute ischemic stroke. RESULTS: Two groups with good (59 cases) and poor (35 cases) prognosis were divided according to the mRS score. There were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The NIHSS score, hospitalization days, previous cardiac history, hospitalization days, LDL, fasting glucose, IL-6, and TNF-a at the time of admission were lower than those in the poor prognosis group, and the difference was statistically significant. In the patients in the embolization group, there were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The pre-hospital NHISS score, IL-6, and TNF-a of patients in the good prognosis group were lower than those in the poor prognosis group, and the difference was statistically significant. CONCLUSION: IL-6 and TNF-α may be used as predictors of prognosis after revascularization therapy for acute ischemic stroke, and this conclusion also applies to patients in the embolization group.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Inflammatory Bowel Disease (IBD) is a chronic and progressive inflammatory disorder affecting the gastrointestinal tract (GT) caused by a wide range of genetic, microbial, and environmental factors. IBD is characterized by chronic inflammation, decreased gut microbial diversity and dysbiosis, with a lower amount of beneficial bacteria and a concomitant increase of pathogenic species. It is well known that dysbiosis is closely related to the induction of inflammation and oxidative stress, this last caused by an imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity that leads to cellular ROS accumulation. ROS are responsible for the intestinal epithelium oxidative damage and the increased intestinal permeability found in IBD patients and their reduction could represent a potential therapeutic strategy to limit the IBD progression and alleviate its symptom. Recent evidence highlighted that dietary polyphenols, natural antioxidants, are able to maintain redox equilibrium in the GT preventing gut dysbiosis, intestinal epithelium damage and radical inflammatory responses. Here, we suggest that the relatively new foodomics approaches, together with new technologies for promoting the antioxidative properties of dietary polyphenols, including novel delivery systems, chemical modifications and combination strategies, may provide critical insight to determine the clinical value of polyphenols for IBD therapy and a comprehensive perspective for implementing natural antioxidants as potential IBD candidate treatment.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

Substantial studies have focused on early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aβ), is hallmark of AD, can be observed in vivo via positron emission tomography imaging using amyloid tracer or cerebrospinal fluid assessment, but costly expensive. The current study aims to identify and compared predictability in magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aβ status in AD cohort using machine learning (ML) approaches. The predictability in candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aβ positivity. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. A feature selection model could distinguish abnormal levels of Aβ with the predictability of 0.85, indicating the same performance with MRI-based models. The result has first to identified the predictability in MRI markers using ML approaches, and secondary to demonstrate the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost-efficient method for detecting cerebral Aβ status compared to MRI markers.

Genetic diversity is inevitable in making any crop improvement program successful. DNA fingerprinting technology to assess the genetic relationship among the selected genotypes for identification and cataloging of different species and cultivars of roses is a promising tool for Rosa genomes. The inter-simple sequence repeats markers (ISSRs) were used to investigate the genetic diversity among twenty-one diverse Rosa genotypes belonging to two different species, Rosa hybrida and R. damascena, and three distinct groups of rose varieties, namely Hybrid Tea, Floribunda, and Damask roses. Twenty-four ISSR primers yielded a total of 280 scorable amplified fragments from 250-1800 bp in length, from which 244 were polymorphic, resulting in an average of 86.4% polymorphism. UPGMA cluster analysis based on Jaccard’s pairwise similarity coefficient values ranged from 0.264 to 0.818, clearly distinguished different species and genotypes, grouping them into three distinct clusters. The results confirmed a high degree of variation in the rose germplasm studied highlighting the potential of improvement in roses for the ornamental and perfume industry.

Background: Persistent up regulation of NF-κB leads to chronic inflammation and subsequent microglial activation and takes neurons towards death by activating death receptor domains and the p53 pathway. Thus, inhibition of NF-κB may lead to more effective treatment for Parkinson’s disease. Therefore, we have used mangiferin, specific inhibitor of NF-κB in this study. Method: The study utilized male Wistar rats weighing 200-250 gm (n=8 in each group). Stereotactic surgery of rats was done to induce 6-OHDA lesioning in rats. On day 42, rats were subjected to behavioural studies to evaluate effect of mangiferin and their brains were taken out after euthanasia to perform biochemical and molecular studies. Results: Mangiferin significantly increases locomotor parameters in 6-OHDA lesioned rats. It also decreases activity of Cyclooxygenase enzyme which then leads to decrease concentration of inflammatory cytokines. Microglial inflammation was also substantially reduced by reducing MPO concentration. Oxidative stress burden was also reduced after treatment with mangiferin as indicated by increase in Total Antioxidant Capacity, SOD and Catalase and reduction in concentration of MDA. Treatment with mangiferin also reduces burden of oxidative stress by increasing the activity of NRF2/ARE pathway. Activity of Caspase 3 and 9 was also significantly reduced after treatment with mangiferin. Significant decrease in activity of both Cox1 and Cox 2 was also observed. Maximum improvement in all parameters was observed in rats treated with grouping of mangiferin 45mg.kg-1 and levodopa 10mg.kg-1. Treatment with levodopa alone has no significant effect on biochemical and molecular parameters though it significantly improves behavioural parameters. Conclusion and Implications: Results of this study suggest that mangiferin has protective effect in hemi-parkinsonian rats by inhibiting NF-κB. Current treatment of Parkinson’s disease does not target the underlying problem of the disease. Therefore, combination therapy of mangiferin and levodopa can be helpful in better management of Parkison’s.

Helicobacter pylori, a gram-negative bacteria usually found in stomach and first part of small intestine, is known to cause infections and ulcers and may have association with cancer. Normally, the treatment options include combinations of antibiotics with proton pump inhibitors and antiinflammatory drugs. However, all of them have high systemic exposure, and hence, unfavourable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is very limited. We have attempted to develop a predominantly gut-restricted formulations of antibiotic + adjuvant combinations as a basis for potentially more safe and efficacious treatment of gastrointestinal tract infections. We have considered E. coli (as a model of H. pylori) and Lactobacilli to study the antibacterial activity of nanogel with combined drugs (classical antibiotics and individual components of essential oils). It has been shown that levofloxacin (LF) in combination with zephirol demonstrates synergy effect against E. coli (cell viability has decreased by about 50%) and weakens the effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant is also shown to be effective. Using FTIR and UV spectroscopy, it has been proved that chitosan nanogels with the drug are well adsorbed on the mucosal model, thereby increasing the bioavailability of drugs. Using ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which is potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. Thus, chitosan nanogels loaded with a combination of drugs can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract, and applicable to difficult-to-treat bacteria.

Over the past few decades, aircraft Ground Handling Operations (GHO) have been investigated by numerous researchers. Some aspects of GHO have been more focused on than others due to their importance in the GH processes. For instance, GHO performance has been tackled from different perspectives while workers and vehicles allocation suffer from the lack of research in the area. This paper is a literary review of the research that has been conducted in different areas of GHO. It sheds light on GHO performance, resource allocation and scheduling, operations scheduling, vehicle routing, and workers and vehicles allocation.

The genus Vigna is penta-tropical having more than 200 species with many desirable economically important traits. The aim of study was to validate the in-silico polymorphism of whole genome sequence developed mungbean specific SSR markers and their transferability among the different Vigna species. The present study utilized a set of 200 SSR markers developed from whole genome sequence of mungbean and validated using a diversity panel of 25 accessions which belongs to 13 Vigna species. Out of 200 SSR markers, 130 markers (65%) were polymorphic across the various Vigna species and the number of alleles amplified varied between 7 to24. The SSR markers showed more than 90 percent transferability across the different Vigna species accessions. Based on allelic data, the 25 Vigna accessions grouped into three clusters based upon the unweighted pair group method with arithmetic mean (UPGMA) phylogenetic tree. The principal co-ordinates analysis (PCA) biplot graph and UPGMA based neighbor joining clustering diagram showed similar pattern of Vigna accessions distribution. The population structure assessment has grouped the cultivated and wild species accessions into two sub-population. The estimated marker parameters such as polymorphic information content (0.09 – 0.84), marker index (0.091 – 3.342) and effective multiplex ratio (1.0 – 4.0) suggested their adequacy in several genetic studies such as parental selection, hybrid testing, genetic mapping and marker aided breeding programmes for genetic enhancement of species belonging to the Vigna genus.

The alarming rise of antibiotic resistance has made it imperative to find novel antimicrobial medications. This study reports the design and synthesis of new molecules based on benzofuran-pyrazole scaffolds hybridized with various N/O heterocycles using the molecular hybridization process. The newly synthesized candidates were confirmed using micro-analytical and spectral analyses, and their antimicrobial characteristics were assessed against different bacterial and fungal isolates in comparison with novobiocin and clotrimazole as antibacterial and antifungal standards, respectively. In addition, the new compounds were further evaluated as in vitro antioxidants and anti-inflammatory congeners. The most promising broad spectrum antimicrobial compounds 9, 10 with values ranging from 2.50-20.60 μg/mL were further examined as E. coli DNA gyrase B enzyme suppressors using novobiocin as a reference drug. In silico computational studies revealed that compound 9 produced a good fit in the active site of E. coli DNA gyrase B in comparison to novobiocin. Additionally, the drug similarity and ADMET parameters of compound 9 were examined in conjunction with the antibiotic ciprofloxacin, making it a potential candidate for further development as a promising antimicrobial agent.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Background: Despite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field. Methods: In this study, type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression, and histopathological changes in the mice kidney and liver. Results: The obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (p< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (p< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines and adhesion molecules such as TNF-α, IL-6, and NF-κB levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group. Conclusion: In conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways. Keywords: Diabetes, Dimethyl fumarate, Alloxan, Anti-inflammatory responses, Hepato-renal-protective effects.

Jatropha multifida L. is a plant belong to Euphorbiaceae family used in Benin pharmacopoeia because of its medicinal properties. The objective of this work is to appreciate the therapeutic power of this plant through the evaluation of some of its biological activities. After the preliminary phytochemistry, the polyphenols and flavonoids were quantified and identified by the LC-MS-ESI. The antimicrobial power of the extracts was investigated by agar medium diffusion. The antioxidant power of the extracts was evaluated by the reduction of the DPPH radical, the ABTS radical cation, the feric ion (FRAP) and the lipid peroxidation (LPO). Anti-inflammatory activity was assessed by inhibition of protein (albumin) denaturation. Indeed, different phenolic and flavonoid compounds namely, 2-Hydroxybenzoic acid, o-Coumaroylquinic acid, Apigenin-apiosyl-glucoside, Luteolin-galactoside, Luteolin-glucoside, Luteolin-rhamnoside, Quercetin-glucoside, Quercetin-arabinoside, Dicaffeoyquinic acid, Kaempferol-rhamnoside were identify. The J. mutifida extracts has a bactericidal effect with reference strains of wich CMBs vary from 22.67 mg/ml (S. aureus, S. enteridis, L. monocytogenes and C. albicans) to 47.61 mg/ml (E. coli) and with the meat isolated strains (S. equorum, S. saprophiticus, S. haemoliticus, S. cohnii and S. lentus). Ethanolic extract show the highest DPPH radical scavenging activity (IC₅₀ = 0.72±0.03 mg/ml) while methanolic extract showed the highest ferric ion reduction (46.23±1.10 µgEAA/g). Contrary to the FRAP method, the reducing power with ABTS method of water-ethanolic extract was greater (0.49±0.11 mol ET/g). The same extract show the highest albumin denaturation inhibition power (97.31±0.35%) at 1000µg/ml. J. multifida extracts are rich in bioactive compound with good biological activity

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Abstract: Systemic inflammatory response syndrome (SIRS) is a clinical diagnosis based on abnormalities in patients' vital signs and white blood cell count. Neutrophil-lymphocyte ratio (NLR) is used as an easily accessible parameter to assess the patient's inflammatory status and stress. There are some studies showing that NLR affected by the inflammatory response is a criterion to support the diagnosis of SIRS. In this study, it was aimed to compare the interrelation between SIRS (+) and SIRS (-) groups in patients with high positive feline coronavirus (FCoV) in the light of NLR. Based on the anamneses, physical examination findings, laboratory findings, enzyme immunoassay antibody test kit titer were included in the sick groups. These patients were further categorized based on the presence of SIRS symptoms, vital signs and laboratory findings. The NLR as diagnostic marker demonstrated to differ between high antibody titer FCoV positive and healthy cats. However the diagnostic significance of NLR remains questionable between the high antibody titer FCoV positive cats with SIRS (+) and SIRS (-). As a result of our study NLR can be used as a blood parameter like albumin/globulin ratio and elevated total bilirubin in cats with high FCoV antibody titer and high probability of developing FIP.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH&gt; 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p&lt;0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

High-frequency near-infrared diode laser provides high peak output, low heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1β-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1β and irradiated with high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. IL-1β treatment significantly increased the mRNA levels of IL-1β, IL-6, TNF-α, MMP-1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1β-induced expression of IL-1β, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1β-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser in OA.

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor of mesenchymal origin that most commonly presents in children. IMTs hold non-specific symptoms and radiological features, rendering diagnosis challenging. Presentation: We report a case of a 26-year-old man who was diagnosed at a different center with IMT of the right lower lobe. He underwent lobectomy with a positive gross margin, after which he was referred to our institution for further management, where we performed redo surgery with removal of residual tumor from the bronchial stump. The case presented here shows that interdisciplinary surgical planning is vital to ensure proper detection and successful tumor resection, while highlighting a unique case of recurrence necessitating a redo surgery.Conclusion: IMT is a rare entity in adults presenting with diverse, non-specific symptoms. IMT’s usually follow a favorable prognosis, but behavior may be unpredictable. While uncommon in adults, strong clinical suspicion is warranted. Complete surgical resection is the treatment of choice and follow up is crucial given the potential for recurrence.

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokine and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production by 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.

Human sepsis is one of the leading cause of death worldwide and is known to be a harmful damaging host inflammatory condition, primarily caused by endotoxin released by gram-negative bacteria. Despite antibiotics administration being widely used to treat disease, effective targeted therapeutic strategies for the sepsis are still lacking. Here, we demonstrate that CM1, a derivative of natural polyphenol chrysin, exerts anti-inflammatory activity by inducing the ubiquitin-editing protein TNFAIP3 and NAD-dependent deacetylase sirtuin 1 (SIRT1). We found that CM1 attenuated Toll-like receptor 4 (TLR4)-induced the generation of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signaling pathway. In addition, the treatment of macrophages with CM1 induced the expression of TNFAIP3 and SIRT1 in TLR4-stimulated primary macrophages, however the anti-inflammatory properties of CM1 was disappeared by siRNA silencing of TNFAPI3 or by the genetic and pharmacologic inhibition of SIRT1. Importantly, intravenously administration of CM1 resulted in the decreased susceptibility to endotoxin-induced sepsis, leading to inhibition of the generation of proinflammatory cytokines and neutrophils infiltration into lung than control mice. Collectively, these findings suggest that CM1 has the potential to be a treatment candidate for diverse inflammatory diseases including sepsis.

Geniposide is a major ingredient in the herb gardenia, and this study investigated effects of geniposide on lipopolysaccharide-stimulated macrophages (RAW 264.7). Griess reagent assay, Fluo-4 calcium assay, dihydrorhodamine 123 assay, multiplex cytokine assay, quantitative RT-PCR, and flow cytometry assay were done using RAW 264.7. Data showed that geniposide at concentrations of 10, 25, and 50 μM reduced significantly levels of nitric oxide, intracellular Ca2+, and hydrogen peroxide in lipopolysaccharide-stimulated RAW 264.7. Multiplex cytokine assay represented geniposide at concentrations of 10, 25, and 50 μM meaningfully suppressed levels of IL-6, G-CSF, MCP-1 and MIP-1α in RAW 264.7 provoked by lipopolysaccharide; additionally, geniposide at concentrations of 25 and 50 μM meaningfully suppressed levels of TNF-α, IP-10, GM-CSF, and MIP-1β. Flow cytometry assay represented that geniposide reduces significantly the level of phosphorylated P38 MAPK in RAW 264.7 provoked by lipopolysaccharide. Geniposide meaningfully suppressed lipopolysaccharide-induced transcription of inflammatory target genes such as Chop, Jak2, Fas, c-Jun, c-Fos, Stat3, Nos2, Ptgs2, Gadd34, Asc, Xbp1, Nlrp3, and Par-2. Taken together, geniposide exerts anti-inflammatory effects in lipopolysaccharide-stimulated macrophages via calcium-P38 MAPK pathway.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because the venom works so quickly, and antivenom cannot fix injuries that have already been triggered. This might be attributed to certain molecules amplifying the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, concurrent use of anti-inflammatories or other drugs associated with the antivenom remains uncommon. The aim of this study was to determine how various inflammatory mediators affected the leukocyte-endothelium interaction (LEI) following a B. jararaca bite. According to our findings, nitric oxide and cyclooxygenase pathway eicosanoids significantly contribute to alteration of LEI induced by B. jararaca venom. Conversely, lipoxygenase-mediated eicosanoids, histamine, or serotonin had minimal participation. Markedly, treatment with dexamethasone alongside antivenom mitigated alterations of LEI induced by the B. jararaca snake venom. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Zoon balanitis (ZB) is a mild and chronic inflammatory dermatosis that mostly affects uncircumcised men of middle and old age. The etiology of this disease remains unknown. Moreover, some authors have questioned the presence of this type of balanitis. Our study aimed to assess the expression of proinflammatory cytokines in ZB and demonstrate the presence of a characteristic expression pattern, different from that reported in the literature for penile lichen sclerosus(LS) and penile cancer. Skin biopsies from four foreskins affected by Zoon’s balanitis with surrounding morphologically unchanged skin and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision) were obtained. RNA was extracted from each biopsy, followed by quantitative assessment of the gene expression of interleukin 1-A(IL-1A), interleukin 1-B(IL-1B),interleukin 1 receptor antagonist(IL-1RN),interleukin 6(IL-6), transforming growth factor β1(TGF-β1), and interferon-gamma(INF-γ). The decreased level of IL-1A mRNA was observed in Zoon’s balanitis in both inflamed and healthy skin compared to control samples. There were no statistically significant differences in other investigated cytokines gene expression between Zoon’s balanitis and the control group. In conclusion, the expression of proinflammatory cytokines was not related to the course of zoon balanitis. Moreover, in the case of IL-1A, we observed the suppression of the immune response.

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

Many species of the Asteraceae family are used in traditional Mexican medicine for possessing healing properties. Ageratina pichinchensis (Asteraceae) is a plant used for the treatment of gastric ulcers, deep wounds and for its antifungal effects. The aim of this study was to establish a cell suspension culture of A. pichinchensis, quantify the anti-inflammatory constituents 2,3-dihydrobenzofuran and 3-epilupeol, to evaluate the anti-inflammatory potential of its extracts and perform a phytochemical analysis. Cell suspension cultures were established in MS culture medium supplemented with 30 g L-1 sucrose and 1.0 g L-1 α-naphthaleneacetic acid (NAA) plus 0.1 mg L-1 6-furfurylaminopurine (KIN). The ethyl acetate extracts of cell suspension cultures analyzed by GC revealed that the maximum production of compounds The anti-inflammatory activity of these extracts exhibited significant inhibition of NO production. Furthermore, the phytochemical study of EtOAc and MeOH extracts of the biomass on day 20 led to the identification of 17 known compounds. The structures of compounds were assigned by analysis of 1D and 2D NMR data and the remainder by GC-MS. This is the first report of the production of the (-)-Artemesinol, (-)-Artemesinol glucoside, Encecalin and 3,5-diprenyl-acetophenone compounds by a cell suspension cultures of A. pichinchensis.