Curcumin, as the main active component of Turmeric (Curcuma Longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

Aim: To study the relationship between the location of chest pain (topography) and site of coronary artery involvement in patients of Acute coronary syndrome (ACS) undergoing percutaneous transluminal coronary angioplasty (PTCA). Materials and Method: This observational study analyzed 589 angina topographic sites in 411 consecutive patients hospitalized for Acute Coronary syndrome (ACS) who underwent PTCA at a tertiary care center between January 2017 and December 2019. All parameters including the characteristics and site of the anginal pain, Electrocardiogram (ECG), and Coronary angiography (CAG) findings were recorded and analyzed for their topographical correlation with site of culprit vessel involvement. Result: Out of 411 patients, 337 were Males (82.0%) and 74 (18.0%) were females with 589 topographic sites of angina. The mean age of the study subject was 57.03± 11.28 years. In both ST elevation Myocardial Infarction (STEMI) and Non-ST-elevation Myocardial Infarction (NSTEMI), the Left anterior descending (LAD) was the most affected vessel in 201(63.4%) and 49(53.3%) respectively. The correlation coefficient for LAD occlusion was 0.298 (p=0.001) for the Retrosternal site. The Left Circumflex (LCX) artery showed a positive correlation of 0.647 (p= 0.001) for Jaw with Neck pain and of 0.585 (p=0.001) for Backache with Shoulder pain. The Right Coronary Artery (RCA) showed a positive correlation of 0.713 (p=0.001) for Retrosternal plus Jaw and Neck pain and of 0.719 (p=0.001) for Retrosternal plus Backache. Conclusion: The study reveals a significant correlation between chest pain topography and site of coronary artery involvement. It provides a basis for future research to develop tools that help healthcare professionals quickly identify culprit artery in ACS.

Fibrosis is a prevalent and detrimental condition associated with various diseases with a high impact on global morbidity and mortality rates. Despite its diverse causes and affected organs, common underlying mechanisms drive the development and progression of the disease. These mechanisms include an exaggerated inflammatory response, excessive activation of fibroblasts, and abnormal tissue remodeling following severe or repetitive tissue injury. Although significant advancements have been achieved to enhance our understanding of fibrosis, there is still a gap between identifying potential antifibrotic targets and successfully translating them into effective clinical interventions. Novel approaches that target specific cellular and molecular processes involved in fibrosis hold promise for reducing the pathological consequences of the disease. Understanding the pathogenesis and clinical implications of fibrotic diseases is crucial for developing effective therapeutic strategies and improving patient outcomes. In this review, we introduce the concept of fibrosis, discuss the mechanisms by which it arises, and explore existing and emerging therapeutic approaches in development.

Introduction Cochlear implants are a modern approach for the treatment of multiple cases of profound sensorineural hearing loss. Factors such as the ethiology of hearing loss and the potential for achieving good postoperative outcomes are considered in cochlear implantation. Additionally, surgical strategies, protocols, the experience of the surgeon and audiologist, and the presence of postoperative issues and risks that may require revision surgery should also be taken into account. The surgeon specialized in cochlear implantation must inform the patient and his relatives not only about the surgical technique but also about possible complications. The literature shows different rates of complications evaluated both in adults and in children. An evaluation of adverse events in order to prevent complications can be made if the definition of medical complications and mistakes is strictly approached based on the CLAVIEN-DINDO classification system. The rate of complications can be compared with existing literature. Studies demonstrate the need for preoperative vaccination for pneumococcus, which can prevent complications, especially in patients with inner ear malformations who present an increased postoperative risk Relevant Sections This review is structured around the collection of specialized literature from PubMed, organized into subchapters related to intraoperative complications such as Gusher syndrome, foreign body reaction, endocochlear inflammation phenomena, issues related to electrode positioning and associated complications, vestibular phenomena related to cochlear implantation, as well as late complications related to the surgical wound and cochlear implant extrusion. The important sections in this review are: Inner Ear Malformations and Gusher Syndrome: Intraoperative Complication Risks, Electrode Insertion and Positioning Issues, Intracochlear Inflammation, Foreign Body Reaction, and Intracochlear Fibrosis: Phenomena That Can Occur with Cochlear Implantation, Vestibular Disorders, Tardive Postoperative Complications: Wound Injuries and Cochlear Implant Extrusion and Otitis Media and Cholesteatoma as Complications of Cochlear Implantation Conclusions: Postoperative complications, although considered quite rare. The surgical limits and long-term evolution of cochlear implants cannot be concretely established, despite the fact that this intervention is considered safe in the medium and long term. Future directions Given that cochlear implants represent the most modern surgical technique for auditory rehabilitation in adults and children, with massive implications for quality of life, there is a tendency to extend surgical indications in the future, and especially to inform doctors in related specialties about the benefits of this medical device. Surgeons must be knowledgeable about cochlear implantation methods, as well as the methods for managing complications that can arise immediately postoperatively, as well as in the medium and long term.

Background: Inflammatory Bowel disease (IBD) is one of the worldwide health issues with increasing incidence. Recent data point out that those patients can have a defective immune system, rendering response to vaccinations suboptimal. Since 1990, Hepatitis B Virus (HBV) vaccination has been introduced among the compulsory childhood vaccinations in Oman. Given the questionable immunogenicity of vaccinations in IBD patients, we designed this study to quantify the immune response to scheduled HBV vaccine in IBD patients and compare it with that in a matching control cohort of healthy blood donors at Sultan Qaboos University Hospital (SQUH). Methods: This is a retrospective case-control study that was conducted between the 1st of July 2023 and the 31st of May 2024 at SQUH. Using the hospital information System (HIS), a total of 252 participants were enrolled in our study and divided into two groups. Group (1) included 126 IBD patients and group (2) included 126 healthy controls. Baseline demographics, medical comorbidities and viral serologies before and after vaccination were collected. The primary outcome of the study was to compare the long term immune response to HBV vaccine between the two groups. The secondary outcomes included identifying possible risk factors for suboptimal vaccine response. Results: One hundred and twenty-six participants were included in each group. Durable protective immune response to HBV vaccine was attained in 29 patients (23%) of the IBD group compared to 109 participants (86.5%) of the control group. There was a statistically significant association (p = 0.0156) between prednisolone treatment and low immune response to HBV vaccine. Moreover, esomeprazole usage exhibited a statistically significant association (p < 0.0001) with suboptimal response to HBV vaccine. Meanwhile, there was no statistically significant correlation between low immunogenicity to HBV vaccine and age, sex, type of IBD, comorbidities, and BMI. Conclusions: IBD patients are less immunogenic to HBV vaccination compared to healthy controls. Factors like esomeprazole and/or corticosteroid therapy might be associated with poor immune response. These findings highlight the importance of reassessing the immunogenicity of HBV vaccination and probably other protective vaccinations in all IBD patients as part of their standard of care.

HIV-1 Nef is a multifunctional protein with well-known lethal properties. HIV infects various cells from the brain compartment and expressed nef is responsible for developing neuropathogenic potential. HIV-infected glial cells express nefvirotoxinand stimulate the cascade of various pathways to activate uninfected cells to release neurotoxic elements damaging cells themselves. A lot of genetic variabilities of this protein have been reported from patients with HIV-associated neurocognitive disorders. To determine the neurotoxic potential of subtype-specific nef plasmids and nef plasmids of clinical samples with and without HAND were transfected in normal human astrocytes (NHA) and monocyte-derived macrophages (MDM) using nef-pCMV-HA plasmid constructs. Supernatants from subtype-specific Nef plasmids indicated the upregulation of proinflammatory cytokines. The induced expression might be due to the nef genetic variability or variations in the transfection efficiency and expression levels of nef.The mRNA expression of IL-6, IP-10, and TNF-α indicated upregulation of 5.0-fold in NHA and 3-fold in MDM with respect to empty vector control transfection. Further, the kynurenine metabolites were also assessed from culture supernatants of NHA and MDM indicating the upregulation of IDO and KYNU in NHA by 3.0-fold and 3.2-fold in MDM.The expression levels of nef and cytokines at the translational level were confirmed by western blotting and bio-plex Pro cytokine estimation assay respectively along with controls expressing green fluorescent protein (GFP).The oxidative stress was also found to be elevated as compared to control cells as determined by the estimation of nitric oxide from the culture supernatant to confirm the neurotoxic potential of HIV nef plasmids. The downregulation in the levels of cytokines, as well as kynurenine metabolites, was observed in culture supernatants after blocking the expression of nef using HIV nef siRNA. Phylogenetic analysis of Nef sequences indicated subtype C predominance except one sequence showing the partial sequence of HIV-1 subtype B sequence forming BC recombinantThe upregulation in the cytokine and pathway-specific metabolites might be linked with the neurotoxic potential of HIV-1 Nef leading to neuropathogenesis. In conclusion, the variation in the transfection efficiency, nef expression levels, and the genetic variability of Nef might be responsible for upregulating the expression levels of cytokines and kynurenine metabolites in astrocytes and MDM.

Recovery between physical efforts is essential for optimal performance in sports. Dietary supplements like cannabidiol (CBD) have been proposed to facilitate recovery and performance optimization. This systematic review aimed to: a) systematize the scientific evidence on CBD for recovery, b) associate CBD's biomedical properties with those required for optimal fatigue recovery, and c) recommend a future research agenda. Searches across databases identified 70 relevant studies from 1990-2022, including 38.6% preclinical, 31.4% clinical trials, and 30.0% reviews/meta-analyses across various populations like mice, rats, epileptics, and athletes. CBD demonstrated potentially beneficial properties for athlete recovery such as anti-inflammatory, neuroprotective, anxiolytic, and analgesic effects with doses ranging from 5-600mg administered orally, intravenously, and via other routes. However, rigorous confirmatory research specifically in athlete populations is lacking. While CBD appears promising for facilitating recovery and performance optimization, further randomized placebo-controlled trials are needed to test the acute and chronic effects of different CBD dosing regimens in athletes. Future research should focus on elucidating CBD's physiological mechanisms of action as they relate to post-exercise recovery, as well as its comparative effectiveness versus conventional medications and therapies. Advancing our understanding of CBD's role in athlete recovery could provide new therapeutic strategies to optimize recovery and performance.

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE) and shock that leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that has not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD; 5 on MV, 3 on ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association to PE. The main findings were reduced stroke volume, global ejection fraction (GEF) and preload parameters associated to increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction and increased permeability PE. Lung water correlated positively with heart rate (HR, r=0.20) and negatively with mean arterial pressure (r=-0.27) and GEF (r=-0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r=0.31) and negatively with cardiac index (r=-0.49), end-diastolic volume (r=-0.48) and GEF (r=-0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggests that in HCPS patients, increased permeability leads to PE, hypovolemia and circulatory impairment.

This study aimed to evaluate the physico-chemical properties, biocompatibility and bioabsorption of 3 different new membranes for bone guided regeneration (PLGA associated with hydroxyapatite and beta-TCP) with three thicknesses (200, 500 and 700 µm) implanted in mice subcutaneously. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the quantification of Carbon, Hidrogen and Nitrogen were used to characterize the physico-chemical properties. One hundred Balb-C mice were divided into 5 experimental groups: Group 1 - Sham (without implantation); Group 2 - 200 μm; Group 3 - 500 μm; Group 4 - 700 μm; and Group 5 - Pratix®. Each group was subdivided into four experimental periods (7, 30, 60 and 90 days). Samples were collected and processed for histological and histomorphometrical evaluation. The membranes showed no moderate or severe tissue reactions in the experimental periods studied. The 500 μm membrane did not show tissue reaction for any experimental periods studied. The 200 μm membrane membranes began to exhibit fragmentation after 30- day, while the 500 and 700 µm membranes started the fragmentation at 90-day. All membranes studied were biocompatible, and the 500µm membrane showed the best results being a promissory membrane for bone guided regeneration.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

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.

The aim of this study was to examine pathologic complete response (pCR) and overall survival (OS) of patients diagnosed with non-metastatic inflammatory breast cancer (IBC). A total of N=8,550 cases undergoing surgery were identified between 2004-2013, using the National Cancer Database (NCDB). Patients were grouped into 4 biologic subtypes (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). The median age at diagnosis was 56 years. On average, women were followed for 3.7 years [interquartile range=3.0]. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p<.0001). Compared with non-pCR (54%), patients experiencing pCR had superior 5-year survival (77%) (p<.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p<.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p<.0001). In this large multicentric analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. In the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, inducing antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS by autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Crigler-Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in two forms: CNS type 1 (CNS1), the more severe form with a complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients re-sponding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risks of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interven-tions.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems. The gut microbiota plays a crucial role in in metabolism regulation and immune responses through its interaction with the external environment. This article explores the intricate interplay between intestinal flora and the pathogenesis of PCOS, focusing on the pivotal role of microbial metabolites, specifically short-chain fatty acids (SCFAs). SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria alongside a notable overgrowth of opportunistic microorganisms. An overproduction of acetic acid (AA) and valeric acid (VA) in fecal samples suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (BMI), insulin resistance (IR), and chronic inflammation. This finding points to the potential therapeutic value of maintaining optimal AA levels in the blood. Although serum SCFA levels showed non-significant changes following metformin treatment, the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. This treatment also led to an increase in beneficial gut bacteria and a reduction in opportunistic pathogens, suggesting a restoration of gut microbial balance. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

The etiology of autism spectrum disorder (ASD) has not yet been completely elucidated. Through time, multiple attempts have been made to uncover the causes of ASD. Different theories have been proposed, such as that it is caused by “Gods Wrath,” alterations in the gut–brain axis with an emphasis on gut dysbiosis, post vaccine complications, and genetic or even autoimmune causes. In this review we present data covering over 170 000 participants at age ranging from 2 to 14 years focusing on human cell changes rather than using animal models found in previous studies. The male/female ratio was 4:1. Data collection occurred in many countries covering ethnically diversified subjects. Moreover, we aimed to show how the progress in genetic techniques influences the explanation of medical White Papers in ASD area.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes I attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of interleukins-10 , 19 and 22 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a control group were enrolled. The demographic data, serum levels of IL-10, IL-19, and IL-22, and biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). Both male and female T2DM subjects in Group A showed significant decreases in IL-10 levels as compared to controls; however, there were insignificant changes in IL-10 levels in Groups C and D. T2DM patients in groups C and D, in both males and females, depicted very significant (p 0.001) increases in IL-19 levels as compared to controls and group A. Patient groups A to D displayed a progressive elevation of Il-22 levels irrespective of gender, although significant alterations were seen only in groups B to D, with p 0.05 for group B and p 0.01 for groups C and D respectively, as compared to healthy controls. Conclusions. IL-10 showed a strong relationship with T2DM in males with varying degrees of obesity, but females depicted relatively higher IL-10 levels in obese and highly obese groups, pointing to a protective phenomenon. IL-19 levels showed significant increases in all four groups, irrespective of gender. IL-22 appears to be unrelated to T2DM per se but shows an association with varying degrees of obesity.

The gut microbiome is important in the homeostasis of gut health and has pivotal roles in digestion, immune regulation, and metabolic processes. The gut microbiome has been implicated in range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We have yet to identify a single microbe that causes either ulcerative colitis or pouchitis, however, perturbations in the gut microbiome are associated with disease states. Importantly, we can manipulate the gut microbiome using dietary interventions, medications, and faecal microbiota transplantation. This review will summarise our knowledge of gut microbiome therapies in ulcerative colitis and pouchitis.

Antiphospholipid syndrome (APS) otherwise known as Hughes syndrome is a systemic autoimmune disease typically linked with characteristic features like thrombosis and pregnancy morbidity with the presence of antiphospholipid antibodies (aPLs). Although anticoagulation is the current flagship treatment for APS, there are reports indicating a considerable failure following this regimen in a significant number of obstetric APS and thrombotic APS cases. Antiphospholipid antibodies (aPLs) bind anionic phospholipids or protein-phospholipid complexes within the cell membrane. Here, we gave a general overview of the biology of APS and the human gut microbiome, our current understanding of the gut bacteria-immune axis in autoimmunity focus on the potential link to APS, highlighting the implicated microorganisms in this context, and proposing recommendations on future therapeutic development.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Osmotic demyelination syndrome (ODS) is an acute demyelinating disorder characterized by the loss of myelin in the center of the basis pons which is defined as central pontine myelinolysis (CPM) and demyelination process in locations outside the pons which is defined as extrapontine myelinolysis (EPM). ODS including CPM and EPM is mainly caused by the rapid correction of hyponatremia. However, there are several reports of ODS in medical condition such as malnutrition, alcoholism, liver transplantation, malignancy, sepsis, electrolyte imbalance including hypernatremia, hypokalemia, hypophosphatemia, and chronic illness. Rarely, ODS was reported in patients with hyperammonemia or hyperbilirubinemia without sodium fluctuations. The symptoms usually correspond to the lesion site and EPM precedes CPM. Because ODS may be irreversible, prevention is more important. Here, we report a case of ODS secondary to the hyperammonemia and hyperbilirubinemia, as it can have unfavorable prognosis.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family - E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be dif-ferent. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that E. radiata EAq was effective against all three strains, while E. cinerea EAq was only effective against E. coli. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a pro-tein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 75% at a concentration of 250 g/ml, significantly higher than the placebo. Ellagic acid, a pri-mary phytochemical found in the extracts, demonstrated noteworthy toxic and pharmacokinetic characteristics and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in sili-co. The study suggests that the extracts and their primary phytochemicals could enhance the effi-cacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As phar-maceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

Heel pain in the “funnel-shaped” space between the calcaneus, talus, and talocalcaneonavicular and subtalar joints may be representative of Sinus Tarsi syndrome. The pain is often characterized by a burning, numbness, or tingling sensation that can stem from strains and tears on the ligaments in that area. Injury treatment typically includes balance training, muscle exercises, bracing, foot orthosis, and non-steroidal anti-inflammatory drugs (NSAIDs). This study presents Wharton Jelly (WJ) tissue allografts as an alternative intervention for patients who fail standard-care treatments. WJ targets tissue defects, unlike other therapies, which aim to reduce swelling and symptomatic pain. This study includes five female patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. After an average of 80 days, the cohort had an overall 85.29% improvement in pain. The study's limitations include a small cohort size and a non-blinded design. Given the significant improvement in pain, WJ tissue allograft, combined with other techniques, presents an optimal patient care plan for tissue defects associated with Sinus Tarsi syndrome when standard-of-care treatments fail. These results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Prototypical functions of the chemokine receptor CCR6 include immune regulation by manoeuvring cell chemotaxis and selective delimiting of the pro-inflammatory TH17 and regulatory Treg subsets during chronic or acute systemic inflammation. Inhibition of CCR6 is proposed to attenuate disease symptoms and promote recuperation of multiple inflammatory and autoimmune disorders. Prescription medicines with pharmacodynamics involving the inhibition of the chemokine axis CCR6-CCL20 is very limited. Developing such therapeutics is still at an early experimental stage which has mostly utilized pre-clinical models and neutralizing mono or polyclonal antibodies against either partner, CCR6 or CCL20. Other methods have been constitutive use of small molecules as peptide inhibitors or small interfering ribonucleic acid (siRNA) to interfere with transcription at the nuclear level. We in our review aim at introducing the wide array of potential CCR6-CCL20 inhibitors that have been tried to date in the research field with accent on attendant immune-modulator capacity and which are immensely promising compounds as forerunners of future curatives. 16 different tractable inhibitors of the CCR6-CCL20 duo have been identified to possess high medicinal potential to the drug developers worldwide to treat autoimmune and inflammatory diseases. A multitude of antibody preparations are already available in the current pharmaceutical market as patented treatment for diseases in which the CCR6-CCL20 axis is operative, yet must be used only as supplements with existing routinely prescribed medication as they collectively produce adverse side effects. Novel inhibitors are needed to evaluate this invaluable therapeutic target which holds much promise in the research and development of complaisant remedies for inflammatory diseases.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

HMGB1 is a key late inflammatory mediator upregulated during air pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays significant roles in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 level may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense for air pollution-induced oxidative stress lung damage. Here, a standardized bioflavonoid antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis induced by oxidative stress and endotoxemia. Murine hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized in vivo. Effect of the bioflavonoid composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed macrophages in vitro. Hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, western blot analysis for protein and HMGB1 as well as bacterial counts in the lung and airways have been performed. Statistically significant decrease in mortality (50%), reduced proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage, increased bacterial clearance of airways and lungs; reduced airway total protein, and extracellular HMGB1 were observed in vivo. A statistically significant 75.9% reduction in the level of HMGB1 and increased phagocytosis activity were also observed in vitro. The compilation of data in this report strongly suggest that the bioflavonoid composition could be indicated for oxidative stress induced lung damage protection possibly through attenuation of extracellular HMGB1.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fe-cal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospec-tively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seven-ty-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen me-tabolites were no longer different from healthy controls.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

The Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), established in 2019, aims to foster research in Canada and contribute to finding the causes and possible treatments for myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS), thereby reducing the impact of ME/CFS on the health of Canadians. The main objectives of this paper are to suggest standards for ME/CFS research for the collection of data from participants (Recommended Data Elements) and to consider other factors, such as design, language, cultural issues, equity, and diversity. Consensus of the relevant contents of this research guideline was reached during the ICanCME working group meetings and were based on existing guidelines. Members of the working group contributed to guideline development based on their respective expertise. The proposed research guidelines could improve research quality and advance knowledge in the field of ME/CFS, and ultimately benefit ME/CFS patients.

Objective To observe the effect of roxadustat on blood pressure and micro-inflammatory response in patients with hemodialysis anemia, and to provide a viable technique for the treatment of hemodialysis anemia patients. Methods A total of 100 hemodialysis anemia patients admitted to the Nephrology Department of our hospital from July 2020 to July 2021 were enrolled and randomly divided into an observation group (roxadustat) and a control group (human recombinant erythropoietin (rhEPO). The clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure were recorded and compared. Results There was no significant difference in baseline data and serum indicators (P>0.05). The study group demonstrated superior performance to the control group in terms of clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure (all P<0.05). Conclusion Compared with rhEPO treatment, roxadustat exhibits a promising outcome in treating anemia and has slight impact on blood pressure of patients.

The purpose of this paper is to evaluate the possible application of a therapeutic carnivore diet regimen in the treatment of chronic inflammatory bowel disease (IBD). Based on current research and anecdotal reports, we hypothesized that the diet might potentially exhibit both anti-inflammatory and microbiome-modulating properties salutary to the IBD patient population. Our hypothesis demands comprehensive clinical validation. Therefore, in this paper, we review theories on ketogenic and carnivore diets, discussing their immunomodulatory effects and propose an experimental study to test the feasibility, safety, and clinical efficacy of the carnivore diet for IBD treatment.

. Sealants and adhesives are used in the repair and preservation of damaged solid organs. This study examines the matrix metalloproteinases (MMP) activity in the healing of liver injuries treated with two biological adhesives (Tachosil® and GelitaSpon®) as well as that of a new elastic cyanoacrylate (Adhflex®). Methods. We induced in 90 male rats hepatic lesions using a Stiefel biopsy punch in the liver. Wound healing was assessed 2, 6, and 18 days after injury by quantifying MMP1, 2, 8, 9, and 13 tissue levels. The histopathological repair was evaluated by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and CD31, CD68 immunohistochemical marker. The three sealants used contributed to the complete healing of hepatic lesions. Both histopathology and MMP findings point to the fact that degradation with Adhflex® is slower and causes a strong inflammatory reaction at the onset of healing. Results. All the MMPs measured showed higher values early in the healing process in animals treated with Adhflex® and Tachosil, expression for MMP2 and MMP9 being significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant greater values of MMP8 and MPP13 than the Adhflex group. Animals treated with Adhflex® showed a sustained overexpression in all MMPs even at the latest wound healing stages. Conclusion. Notably, the overexpression of the MMPs did not negatively influence the histological healing process of liver injuries. Since all hepatic trauma injuries should be treated as emergencies, any easy-to-use and rapid sealant, like Adhflex®, could be considered an adequate treatment option.

Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Klippel-Feil disease is a condition characterized by a defect in the spine, consisting in the fusion or non-separation of two or more vertebrae of the cervical tract. It usually affects 1 every 50.000 newborns, and the pathogenesis remains unknown to date, although the role of certain genes deputed in segmentation processes is being studied. A single case of gene Myosin Heavy Chain 3 (MYH3) mutation is described by researchers. Affected patients are often characterized by a relatively short neck and, therefore, poor mobility, a low hairline and obesity and may have other health problems of different nature. The frequent presence of comorbidities worsens the quality of life of these young patients. The following case describes the synergistic effect of Incobotulinum toxin type A and physiotherapy in a small patient with MYH3 mutation-related Klippel-Feil Syndrome (KFS) complicated by bilateral paraplegia, to improve the spasticity condition of the lower limbs. To assess improvements over time, the patient underwent rating scales to determine spasticity (Modified Ashworth Scale: MAS), the neck’s range of motion (ROM), and muscle tone by using MyotonProÒ. Specifically, measurements were taken on the day of the first medical examination (T0), the month after the injection and the startup of therapeutic exercise (T1), at three months (T2), and then once a month for a total of 6 months (T3, T4 and T5). This therapeutic approach led to entirely satisfactory results with the child’s well-being, prolonged until the sixth month and with a total absence of any side effects.

Caudal regression syndrome (CRS) is a congenital abnormality characterized by an incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of the inferior limbs (flaccid paraplegia) and neurogenic bladder and bowel. Given the effects of growth hormone (GH) on the proliferation, differentiation and migration of neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and every 6 months later. Six months after commencing the treatment GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved any muscle over the knees and controlled his sphincters. Three years later he walked with the help of canes, there was plantar flexion and GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal territories, below the level of the incomplete spinal cord in CRS. Most likely, GH acts on ependymal SC NSCs, as the hormone does in the neurogenic niches in the brain.

Goldenhar Syndrome (GS), also known as oculoauriculovertebral spectrum (OVAS), is a rare congenital condition characterized by impaired development of structures such as ears, eyes, nose, palate, lip, mandible, maxilla, and teeth. The etiopathogenesis is multifactorial and dependent on genetic and environmental factors, yet the syndrome has many unknowns. We report a case of a 31-year-old male diagnosed clinically with GS as an infant with an absent left ear, hearing loss, absent left lung lobe, reduced growth of left upper limb, decreased size of left face, absent left kidney, and a missing left thumb, who was seen in the genetic clinic for prenatal genetic counseling. A microarray comparative genome hybridization (aCGH) was performed for copy number abnormalities and targeted NGS panels were performed for hereditary hearing loss and limb/digital malformations. aCGH revealed a 471kb loss at 16p12.2 and a mosaic 7.3Mb gain at 19p12q12. Metaphase FISH confirmed the orientation of 19p12q12 gain as small supernumerary ring chromosome 19. NGS revealed multiple variants (MYH14 c.4001C&gt;T, PDE1C c.8C&gt;T, ADGRV1 c.15502A&gt;G, CDH23 c.8772C&gt;A, MYO3A c.484G&gt;A, ADAMTS10 c.506G&gt;A, CHUK c.1294C&gt;T, CSPP1 c.1972A&gt;G, and TCTN2 c.160G&gt;A). Due to the heterogeneous clinical manifestation and genetic heterogeneity of GS, a comprehensive genetic testing strategy is needed for timely diagnosis and better patient care.

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.

The Kalanchoe genus is composed of more than 100 species that usually thrive in tropical environments, which have been used in folkloric medicine to treat various illnesses, including dermatological conditions. With this, the present study assesses the pharmacognostical and pharmacological properties of different species of the Kalanchoe genus as elements for a potential treatment for dermatological-related conditions, from findings of existing literature and studies. It was analyzed that the Kalanchoe pinnata plant, or one of the most common species of Kalanchoe, have been observed to have distinct morphological and microscopic characteristics. Further, it was discovered that different species of Kalanchoe have anti-inflammatory, antioxidant, antibacterial, and wound healing properties, which enable the plant to be used for dermatological products that are available to the market. With this, it is recommended that further studies be conducted in other understudied species of Kalanchoe regarding their pharmacological properties, as well as the use of other structures of the Kalanchoe plant for treatment of various dermatological conditions.

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation associated conditions (FXPAC), also caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, is linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa, epidemiology, clinical features and challenges faced, such as discrimination against affected persons, limited awareness and research, poor access to resources and genetic services and treatment. It further provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of these disorders. This review will improve understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC in the region.

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.

(1) Background: Colon cancer is one of the leading causes of cancer morbidity and mortality globally. It is a multi-step process that involves genetic and epigenetic modifications leading to histological and morphological changes. Several complementary therapeutic options have been analyzed, shedding light on plant-based medication as a potential treatment for colon cancer. Flavonoids such as quercetin are known to have anti-cancer and anti-inflammatory properties. This in vitro study examines quercetin's anti-inflammatory, anti-apoptotic, anti-angiogenesis effects and antioxidant properties in colon cancer cells. (2) Methods: The antioxidant capacity of quercetin-treated cells was investigated using biochemical assays, and angiogenesis and cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). The epigenetic modulation and differential expression of aging, apoptotic, and proliferation genes, and Histone deacetylases (HDACs) were also investigated. (3) Results: In this study, the quercetin-treated group significantly reduced the antioxidant enzymes, cytokines, and VEGF levels, altering the expression of epigenetic factors. Quercetin also induced significant senescence in colon cancer cells. Moreover, a considerable increase was observed in the apoptotic and hTERT genes. In contrast, a decrease in p53, proliferation genes, and HDACs was observed, providing a basis for the clinical use of quercetin in cancer treatment. (4) Conclusion: In vitro studies showed that quercetin treatment efficiently induces senescence and apoptosis in colon cancer cells. We also found that quercetin effectively modulated the expression of p53, Wnt1, CTNNB1, and HDACs, indicating that it could be used to treat colon cancer.

This study examines the matrix metalloproteinase (MMP) activity in the healing of liver injuries treated with biological adhesives Tachosil^® and GelitaSpon^® and the elastic cyanoacrylate Adhflex^®. Hepatic lesions were induced in male rats using a Stiefel biopsy punch. Healing was assessed 2, 6, and 18 days after injury by quantifying tissue levels of MMP1, 2, 8, 9, and 13. Histopathological repair was evaluated using hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and immunohistochemical markers CD31 and CD68. The sealants contributed to complete healing. Histopathology and MMP findings indicate that Adhflex^® has slower degradation and a strong inflammatory reaction at the onset of healing. Early on, all MMPs showed higher levels in Adhflex^® and Tachosil^®-treated animals, and MMP2 and MMP9 expressions were significantly higher in the Adhflex-treated group at 18 days post-injury (T3). The Adhflex^® group had significantly higher MMP8 and MPP13 levels than other treated groups and showed a sustained overexpression of all MMPs, even in the latest healing stages. Notably, the overexpression did not negatively influence the histological healing process. All hepatic trauma injuries should be treated as emergencies, and any easy-to-use and rapid sealant like Adhflex^® could be considered as an option for treating liver trauma.

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.

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signalling pathways and transcription programs. Forkhead Box G1 (FOXG1) is one of the master regulators that plays fundamental roles in forebrain development, from the timing of neurogenesis to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as increased yield of information from high throughput omics opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems to highlight prospects of research and possible clinical interventions.

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.

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.

The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in-depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

Cherries have been largely investigated due to their high content in phenolics in order to fully ex-plore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of Saco cherry, using RAW 264.7 mac-rophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric ade-nocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygen-ase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the sweet cherries incorporation in new pharmaceutical products, smart foods and nutraceuticals.

This study evaluated the effects of high-temperature and high-pressure treatment on the antioxidant and anti-inflammatory activities of carrot extracts. The total polyphenol and flavonoid content of heated carrot extract increased as the heating temperature increased, with 403.93 mg GAE/100 g and 53.14 mg CE/100 g at 150°C. DPPH and ABTs radical scavenging activity (IC50) of heated carrot extract also increased as the heating temperature increased, with 4.65 mg/mL and 7.31 mg/mL, respectively, at 150°C. The reducing power increased with the heating temperature. Heated carrot extract did not exhibit any temperature- or concentration-dependent cytotoxicity. Nitric oxide (NO) generation was suppressed as the heating temperature and NO production increased. The heated carrot extract showed a decrease in the production of dose-dependent TNF-α, IL-1β, and IL-6 compared to the control group. The above results show that heated carrot extract had effective antioxidant and anti-inflammatory activities.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

Objective: To develop and validate the short version of the JAEN Scale for use in women with Fibromyalgia Syndrome (FMS) to make the balance disorder measurement process more efficient. Methods: A Cross-sectional observational validation study was conducted. Fifty-six women with FMS and 44 healthy control were included. Certain items of the original tool were selected with the aim of 1) Improving internal consistency by reducing item redundancy 2) Obtaining a diagnostic capacity with an Area Under the ROC Curve (AUC) greater than 0.70 for discriminating FMS patients and fallers. The internal consistency, factorial validity, concurrent validity and diagnostic capacity of the new tool were analyzed. Results: Factorial analysis showed a two-factor structure that explained 72% of variance. Cronbach alpha coefficients of 0.904 were obtained for the total score of the JAEN-10 items. Concurrent validity analysis showed strong correlations of the JAEN-10 with other instruments that measured quality of life, postural balance or disability related to dizziness. The score of the JAEN-10 items showed an AUC of 0.858 with a sensitivity of 64.29 and a specificity of 95.45 for discriminating between FMS and healthy controls, and an AUC of 0.835 with a sensitivity of 90.48 and a specificity of 67.24 for discriminating between fallers and non-fallers.; Conclusions: The 10-item JAEN scale is a valid instrument for discriminating between subjects with or without FMS and between fallers and non-fallers. Its psychometric properties are good and similar to those of the original 20-item scale. Moreover, it is quicker to complete, which may be relevant in subjects with a tendency to experience fatigue.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.

Secondary prevention after SCA (acute coronary syndrome) is of paramount importance to reduce the incidence of MACE and improve prognosis in follow-up. The control of avoidable risk factors, lifestyle modifications, but especially careful control of cholesterolemia (with a target of LDL-C

The Kounis syndrome (KS) is an acute coronary syndrome triggered by allergic or hypersensitiv-ity reactions. Incidence rates vary, with studies reporting 19.4 per 100.000 among all admissions and 3.4% among allergy patients. This review explores the expanding understanding of KS, en-compassing various manifestations, and focusing on both clinical data and forensic findings useful in performing the diagnosis. The pathophysiology of this syndrome involves a complex in-terplay between allergic reactions and the cardiovascular system. Mast cell activation, histamine release, leukotrienes, cytokines, and platelet activation can contribute to the coronary events. A classification system with three types (Allergic Angina, Allergic Myocardial Infarction, Allergic Stent Thrombosis) aids in categorizing presentations. The diagnosis of KS relies on clinical presentation, laboratory findings and imaging. Post mortem assessment of KS is based on the in-tegration of circumstantial data, autopsy and histological findings. Biochemical and immuno-histochemical analyses also contribute to post-mortem diagnosis. In conclusion, a combined, multidisciplinary approach, should be gained to ease diagnostic pro-cess which is crucial for forensic practitioners in confirming KS occurrence.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception, in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Ephedra alata Decne. (Ephedraceae) is a medicinal species commonly used to treat cancers, respiratory diseases, fever, and hypertension. The present study aimed to establish a phytochemical profile, evaluate the antioxidant potential and estimate the anti-inflammatory activities of .. Aqueous and methanolic extracts of E. alata aerial parts were phytochemically investigated using standard methods. DPPH, phosphomolybdenum total antioxidant capacity and reducing power assays were used to evaluate the antioxidant activity. Antioxidant activity was determined using total antioxidant capacity, the scavenging activity of the stable DPPH free radical and ferric reducing antioxidant power assays. The anti-inflammatory activity was determined using egg albumin membrane denaturation and human red blood cells membrane stabilizing assays. The anti-inflammatory potential of E. alata extracts was evaluated using human red blood cells membrane stabilization, egg albumin and BSA albumin denaturation assays. Quinones, anthraquinones, steroids, phytosteroids, phenols, terpenoids, flavonoids, saponins, glycosides, Cardiac glycosides, reducing sugars and anthocyanins were present in the E. alata’s aqueous extract, in addition to coumarins and proteins in the methanolic extract. The highest total phenolic and flavonoid content was recorded in the aqueous extract with 8.66 ±0.09 mg GA/g and 248.04 ±1.47 mg Q/g, respectively. On the other hand, E. alata methanolic extract had the highest tannin content of 62.12 ±0.10 mg C/g. The best radical scavenging activity (IC50 = 4.63±0.00 mg/ml) and total antioxidant capacity were exhibited by the E. alata aqueous (7.35±0.12 mg/ml AAE), whereas the methanolic extract possessed the highest reducing power activity (1.81±0.00 mg AAE/ml). Regarding the anti-inflammatory activities, E. alata methanolic extract exerted the highest HRBC stabilization of 34.72 ±0.08% whereas the aqueous extract exhibited the highest bovine serum and Egg albumin denaturation inhibition of 99.22 ±0.02% and 73.31 ±0.90, respectively. Taken together, our results suggest that E. alata aerial parts aqueous and methanolic extracts can be utilized as future antioxidants and anti-inflammatory ethnomedicines owing to their rich bioactive molecules content.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Lynch syndrome (LS) is an autosomal dominant genetic condition caused by mutations in the DNA mismatch repair (MMR) genes in the germline. Colorectal cancer and/or LS-associated cancer are more likely in people who carry pathogenic mutations in these genes. Cancers of the endometrium, small intestine, stomach, pancreas, and biliary tract, ovarian, brain, upper urinary tract, and skin are among the cancer types linked to LS. The criteria for a clinical diagnosis of LS, as well as the processes for genetic testing to identify carriers of pathogenetic mutations in MMR genes, have been known for a long time. The precise description of the pathogenicity associated with MMR genetic variants is critical in the mutation detection analysis, especially in order to enroll mutation carriers in endoscopic surveillance programs that are more suited to them. As a result, this may aid in the improvement of LS-related cancer prevention efforts. In this review, we discuss recent advances in the molecular genetics of LS.

The influence of the addition of 2.5, 5, 7.5, and 10.0% of dried Enoki and Maitake mushrooms on the content of bioactive compounds and some pro-health properties of pasta was studied. The qualitative and quantitative analysis of phenolic compounds performed using the LC-MS/MS technique indicated the highest amount of phenolic compounds in pasta supplemented with Maitake. However, all pasta enriched with Enoki mushrooms contained statistically significant-ly higher content of α-glucans in comparison to the control. In samples subjected to gastrointes-tinal digestion, the antioxidant, and potential anti-inflammatory activities were significantly higher than ethanolic and PBS extracts of samples. The ethanolic extracts from pasta fortified with dried Enoki and Maitake mushrooms had higher antioxidant activity (in some of the anti-radical and reducing power assays ) as well as a higher ability to inhibit lipoxygenase (E2.5 and E5 samples) compared to the control sample. Also some in vitro digested samples of pasta en-riched with dried Enoki and Maitake mushrooms showed higher chelating power (E10, M7.5 and M10); reducing power (E5, E7.5, and M10) and lipoxygenase inhibition (E7.5, E10 and M10) than the control. In conclusion, Enoki and Maitake mushrooms can be used for fortification of semo-lina pasta, conferring healthier characteristics of the product.

Background: Migraine is the commonest complex neurological disorder affecting over a billion people worldwide. Neuroinflammation has long been considered to play an important role in the pathophysiology of migraine. The main aim of this single-centre, proof of concept, retrospective study was to determine the possible clinical utility of systemic immune-inflammatory response in migraine with and without aura in a hospitalized cohort. We measured the role of universally available serial white blood cell counts to calculate the serial systemic immune-inflammatory indices (SSIIi) and the potential association between aura and SSIIi changes in a cohort of migraine patients admitted to tertiary care center in Melbourne Australia.Main body: We retrospectively assessed patients' medical records presenting to Western Health with migraine over an 18 month period. Patients were classified as either having migraine with aura (MA) or without aura (MO) based on ICHD-3 criteria. Baseline demographics and brain imaging findings in each group were evaluated. Patients with two sets of white blood cell counts during the admission were included in the analysis. SSIIi were calculated as, neutrophil counts x platelet counts / lymphocyte counts. Correlation between SSIIi and MA and MO were assessed using SPSS27.Conclusion: SSIIi were elevated in MA and MO followed by a downward trend in both groups, with MA being statistically significant. This proof-of-concept study suggests the potential role of systemic inflammation in pathobiology of migraine. SSIIi appear to show clinical utility. Further comprehensive ,controlled , multicenter studies are required to clarify the exact role of systemic inflammatory response and the clinical utility of SSIIi in a subset of migraine in the Emergency department setting.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

This study investigates the synergistic impact of fermenting kale juice with Limosilactobacillus strains on its antioxidant and anti-inflammatory properties. Kale's rich nutrient profile, especially its flavonoids, offers potential health benefits. Probiotic lactic acid bacteria are employed in kale fermentation to enhance nutrient bioavailability and generate bioactive compounds. Kale juices fermented with L. reuteri EFEL6901 or L. fermentum EFEL6800 exhibited superior microbial growth. Free sugars and amino acids were converted to alcohols and organic acids, affecting the organoleptic and health-related properties of product. In addition, fermentation increased quercetin and kaempferol content, indicating improved availability. Furthermore, the fermented juice exhibited notable antioxidant activity and suppressed NO production, revealing anti-inflammatory potential. Gene expression analysis confirmed reduced pro-inflammatory markers and elevated anti-inflammatory cytokines. This research highlights the promising potential of fermented kale juice, enriched with Limosilactobacillus strains, as a functional food with combined antioxidant and anti-inflammatory benefits.

The chemopreventive effects of various mixed cereal grain (MCG) samples on azoxymethane (AOM, 10 mg/kg) and dextran sulfate sodium (DSS, 2% w/v)-induced colorectal cancer (CRC) in C57BL/6J mice were studied. The main MCG preparation consisted of fermented brown rice (FBR), glutinous brown rice, glutinous Sorghum bicolor, glutinous Panicum miliaceum, Coix lacryma-jobi and black soybean at an appropriate mixing ratio. Other MCG preparations contained rice coated with 5% Phellinus linteus and 5% Curcuma longa (MGR-PC), or 10% Phellinus linteus (MCG-P), or 10% Curcuma longa (MCG-C). Consumption of dietary MCG-PC by CRC mice significantly increased colon length, decreased the ratio of colon weight to length, and reduced the number of colon tumors. Similar effects, although to a lower extent, were observed in CRC mice fed with MCG-P, followed by those fed with MCG-C, MCG, FBR or white rice (WR). MCG-PC significantly suppressed colonic neoplasia, and decreased the levels of various cytokines (tumor necrosis factor: Tnf, interleukin 1 beta: Il1b, interleukin 6: Il6, and interferon gamma: Ifng) in serum and colon tissue of the CRC mice. In addition, MCG-PC increased the mRNA expressions of tumor protein p53(Tp53) and cyclin-dependent kinase inhibitor 1A(Cdkn1a), activated pro-apoptotic caspase 3(Casp3), and reduced expression of both mRNA and protein of inducible inducible nitric oxide synthase 2 (Nos2), prostaglandin-endoperoxide synthase 2 (Ptgs2), and cyclin D1(Ccnd1) in colon tissue. These findings suggest that than compared with other cereal grain preparations, MCG-PC had a greater activity against AOM/DSS-induced CRC by reducing intestinal inflammation, and modulating the expression of certain carcinogenesis related factors (Nos2, Ptgs2, Tp53, Cdkn1a, Ccnd1 and Casp3) in colon tissue of CRC mice.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Indigestible oli-gosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of gut microbiota. Their mechanism of action is mainly attributed to their carbon source as specific probiotics, producing related metabolites, and regulating the gut mi-crobial community. However, due to the selective utilization of oligosaccharides, some factors such as the types and structures of oligosaccharides have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides in microorganisms and elaborates how oligosaccharides affect the host's immune system, inflam-mation levels and energy metabolism by regulating microbial diversity and metabolic function, which in turn will affect the onset and progress of chronic diseases, especially diabetes, obesity, depression and intestinal inflammatory diseases, constipation. In this review, we re-examine the interaction mechanisms between gut microbiota and its associated metabolites and diseases, and explore new strategies for promoting human health and combating chronic diseases through di-etary interventions.

Background: After the outbreak of a novel coronavirus (i.e. SARS COV2) in China and its diffusion around the world, great attentions was reserved to the increased incidence of venous thromboembolism in these patients. A specific antiviral action of heparins toward SARS COV2 has been reported in vitro such as a well know action of heparins to prevent VTE in inpatients with infective disease has already been reported since several years. Yet, because fondaparinux represent the pharmacological antithrombotic active sequence of all heparins and because its clinical indication o prevent VTE in inpatients is similar to heprains, we realized a retrospective analysis in inpatients with SARS COV2 on the incidence of VTE during pharmacological prophylaxis with enoxaparin or fondaparinux. This retrospective analysis was named FONDENOXAVID. Methods: We conducted a retrospective cohort study that used patients with SARS COV2 during the Italian outbreak from February 18, 2020 to April 30, 2020. Our aim was to compare the clinical characteristics, prophylactic treatment and outcomes in inpatients positive to SARS COV2 at risk to develop venous thromboembolism, in particular venous thrombosis with or without pulmonary embolism, during in-hospital primary thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and eventually ad hoc functions. Results: There were not significative differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprpophylaxis for SARS COV2. The cumulative incidence of thrombotic events was not different in patients that used enoxaparin or fondaparinux as thromboprpophylaxis. No differences were found also in d-dimer and fibrinogen levels test at the admission and after 3 weeks as markers of prolonged inflammation due to SARS COV2. Discussion: The increased incidence of VTE in vivo has been reported in several studies although prophylaxis with low molecular weight heparin was conducted in some of them. The clinical indication to prevent VTE was similar for heparins and fondaparinux. In our results a non-inferiority to prevent VTE was recorded when inpatients with SARS COV2 were treated with prophylactic doses of enoxaparin or fondaparinux according to international guidelines. The incidence of VTE in this retrospective analysis showed that Fondaparinux at fixed doses of 2.5 mg daily was not inferior to enoxaparin (4000 UI daily). Our results testify that fondaparinux and enoxaparin showed the same efficacy to reduce the incidence of VTE in inpatients with SARS COV2.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

For decades, neurologic and other extra glandular manifestations have been described in Sjögren’s syndrome (SS). More recently, neuropathic, psychological and cognitive alterations are being considered part of the disease. The lacrimal glands (LG), the ocular surface (OS), salivary glands (SG) and the central nervous system (CNS) are integrated to modulate the autonomic functions and, not just those organs, but also the hippocampus, which is linked to the autonomic nervous system, and modulate behavior responses appears to be compromised in the SS. Recent studies confirm that the tryptophan/kynurenine pathway (TKP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating the indoleamine-pyrrole 2,3-dioxygenase (IDO) in SS. This pathway interferes on serotonergic and glutamatergic neurotransmission, mostly in the hippocampus, and other structures of the CNS. Although not demonstrated, it is plausible that this constant interference induces clinical signs of SS, and contributes to the discrepancy between symptoms and signs, towards manifestations of hyperalgesia and depression in patients with SS. Therapeutic strategies are being reexamined and new options designed and tested to regulate the involved steps of the TKP. In the future, the application of this concept may offer a clue to the mosaic of manifestations of SS.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

Cutaneous T-cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at a clinical and therapeutic level regarding the most well-known inflammatory mediators. An in-depth look has been given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression.From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major Interleukins known in inflammatory environments.Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL.In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

Aortic dissection is a clinicopathological entity caused by rupture of the intima leading to a high mortality if not treated. Over time, diagnostic and investigative methods, antihypertensive therapy, and early referrals have resulted in improving outcomes according to registry data. Some data has also emerged from recent studies suggesting a link between Human Cytomegalovirus (HCMV) infection and aortic dissection. Furthermore, the use of microRNAs have also become increasingly widespread in the literature. These have been noted to play a role in aortic dissections with elevated levels noted in studies as early as 2017. This review aims to provide a broad and holistic overview of the role of miRNAs, while studying the role of HCMV infection in the context of aortic dissections. The role of long non-coding RNAs, circular RNAs and microRNAs are explored to identify changes in expression during aortic dissections. The use of such biomarkers may one day be translated into clinical practice to allow early detection and prognostication of outcomes and drive preventative and therapeutic options in the future.

People with Down syndrome present cognitive difficulties that affect their reading skills. In this study we present results about the use of gestural interaction with Kinect sensor to improve the reading skills of students with Down syndrome. Following a case of study method for small samples with disabilities, measuring different variables related to reading skills in an experimental group and in a control group. We found improvements in the visual association, visual comprehension, sequential memory, and visual integration after this stimulation in the experimental group compared to the control group. Also, we found that the number of error and delay time of interaction decrease between sessions in the experimental group.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID. To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Pomegranate juice possesses therapeutic properties against metabolic syndrome. Microencapsulation of pomegranate juice (MPJ) may extend its shelf life; however, further research is necessary to ascertain its comparative efficacy with fresh juice. This work evaluated the effect of (MPJ) in an animal model with induced metabolic syndrome (MetS). Male Wistar rats were induced-MetS by administering 30% sucrose orally for 22 weeks. Once MetS was verified in the animals, 7 groups were formed as follows: control (Ctrl); MetS, MetS+Placebo; Ctrl+MPJ; MetS+MPJ1 600, MetS+MPJ2 1800, and MetS+MPJ3 2900 mg/kg. Systolic and diastolic blood pressure, glucose, triglycerides, and total HDL-c levels in the MetS+MPJ groups improved significantly (p &lt; 0.05) vs. the MetS group at the end of the study. Microencapsulation maintained the anti-metabolic syndrome properties of pomegranate juice and could be used to control metabolic syndrome.

Enteroaggregative Escherichia coli (EAEC) are highly heterogeneous in virulence; we wanted to understand the pathogenic potential of EAEC isolated various clinical and non-clinical sources in an animal model. We infected male BALB/c mice in six mice/group with 50 EAEC isolates, isolated from clinical and non-clinical sources. We studied colonization, weight loss, stool shedding, inflammatory markers and its relationship with 21 virulence genes and phylogroups, EAEC organ burden and histopathological changes. We detected significantly more inflammatory changes and fecal lactoferrin and calprotectin levels in mice infected with EAEC isolated from symptomatic cases. In clinical EAEC isolates, the presence of chromosomal genes {(aap (46%), aaiC (23.3%), and SPATEs (pet (13.3%), sat (20%), sigA and pic (6.6%)}, adhesive variants {(agg4A (53.3%), aggA (53.3%), aafA (36.6%), agg3A (40%)} of EAEC, and master regulator gene aggR (66.6%) were associated with higher levels of lactoferrin and calprotectin. Also, 70% (9/13) of EAEC isolated from acute diarrheal cases bearing chuA (70%) in our study were assigned to group B2 (4 isolates) and D (5 isolates). Real-time PCR analysis revealed that colonization by EAEC strains from different clinical and non-clinical sources occurs up to 10-15 days of life. Even from non-diarrhoeal stools and non-clinical sources, had the potential to cause prolonged colonization, weight loss, and inflammation in the intestine though the degree varied. Moreover, better understanding of EAEC pathogenic pathways is desperately needed in different clinical scenarios.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Sjogren syndrome (SS) is an autoimmune disease that involves salivary and lacrimal glands. There are rare articles describing hypohidrosis or anhidrosis in SS patients. Little is known about the histologic findings seen in patients with SS who do not report decreased sweating. We analyzed skin samples from 31 patients with SS who had undergone skin biopsies for reasons not related to SS. We assessed the number, distribution and pathologic changes within and around the eccrine ducts, glands and acrosyringia. The composition of the inflammatory infiltrate was additionally accessed utilizing immunohistochemical stains. Overall, in 60% of cases we observed some degree of inflammation. In virtually all cases the inflammatory infiltrate was located around the eccrine ducts at a distance from the non-SS pathology. It was mainly composed of CD3+ T cells with increasing number of B and plasma cells as periductal inflammation intensified. This study is the first histologic analysis of asymptomatic skin in patients with SS. It demonstrates the presence of skin involvement in the majority of SS patients. Our results emphasize the importance of systematic skin evaluation in this category of patients as well as counseling, early preventive measurements and timely treatment when indicated.

Given that metabolic syndrome, along with obesity as one of its key components, remains one of the leading yet insufficiently addressed public health issues, what contributes to the development and maintenance of the disorder must certainly attract the attention of professionals and scientists. Precisely because of this phenomenon, eating patterns associated with metabolic syndrome should be studied and attempts should be made to uncover patterns in occurrence. The aim of this study is to review the literature and consider the connection between metabolic syndrome and eating patterns such as emotional and compulsive eating, as well as through the lens of food addiction. Furthermore, we have attempted to uncover the role of psychiatry and psychotherapy in the treatment of metabolic syndrome and delve into the complexity of recognizing these patterns and emphasize the importance of a multidisciplinary approach in the treatment of metabolic syndrome.

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive proper-ties, especially given the beneficial properties of its fruits in this regard. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. Extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary de-pending on the organ, with the highest amount of polyphenols found in the leaves extract. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.88 mgTE/g for leaves to 65.25 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.93 mg TE/g) and the highest level was found for the barberry leaves (140.49 mgTE/g). The oxygen radical absorption capacity test (ORAC) showed the lowest value for the stem (167.70 mgTE/g) and the highest level for the leaves (267.81 mgTE/g). The range of percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of flavonoids, TPC, TFC, and the content of selected flavonoids. For the first time, phenolic acids, flavonoid agly-cones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. For the first time, the following phenol-ic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris: 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, flavonoid glycosides: eleuthero-side E, rutin, isoquercitin, luteoloside, nar-cissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones: catechin, luteolin, and eriodictyol were determined qualitatively and quantitatively for the first time as well.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.