Garlic (Allium sativum L.) is a species of the onion family, Alliaceae that has been widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (Aged garlic extract) on proinflammatory genes relevant to COVID-19. To this aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 Spike protein (S-protein) or with the COVID-19 BNT162b2 vaccine in the absence or in the presence of AGE. The results obtained demonstrated that AGE is a potent inhibitor of the S-protein in-duced expression of the IL-1beta, IL-6 and IL-8 genes. Bio-plex analysis demonstrate that AGE reduced release of IL-6 and IL-8, that were highly induced by S-protein. No inhibition of cells growth, toxicity and proapoptotic effects were found in AGE-treated cells. The effects of one of the major AGE constituents (S-allyl cysteine, SAC) were studied on the same experimental model systems. SAC was able to inhibit the S-protein induced expression of IL-1beta, IL-6 and IL-8 genes and extracellular release of IL-6 and IL-8, con-firming that S-allyl cysteine is one of the constituents of AGE that are responsible for inhibiting S-protein induced pro-inflammatory genes. Docking experiments suggest that a possible mechanism of action of SAC is an interference with the activity of Toll-like receptors (TLRs), particularly TLR4, thereby inhibiting NF-B and NF-B regulated genes, such as IL-1beta, IL-6 and IL-8 genes. These results suggest that both AGE and SAC deserve further experimental efforts to verify their effects on pro-inflammatory genes in SARS-CoV-2 infected cells.

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

Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Our previous studies demonstrated that quercetin (Q) could be ingested and metabolized by macrophages and exerted prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effects on lipopolysaccharide (LPS)-treated macrophages ex vivo. To further clarify its possible anti-inflammatory mechanism, Q was selected to treat mouse peritoneal macrophages that obtained from female BALB/c mice exposed to LPS i.p. for 12 h. Relative gene expression of pro-/anti-inflammatory (TNF-α/IL-10) cytokines and components of inflammation-related intracellular signaling pathways (TLR2, TLR4, NF-κB, JAK2 and STAT3) was analyzed using two-step reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR). STAT3 protein phosphorylation was determined using an in-cell ELISA method. As a result, Q and its metabolite quercetin-3-O-β-D-glucuronide (Q3G) decreased TNF-α gene expression amounts and ratios of pro-/anti-inflammatory (TNF-α/IL-10) cytokine gene expressions, but increased IL-10 gene expression amounts in activated inflammatory macrophages, supporting a substantial anti-inflammatory potential of Q and Q3G treatments. However, Q3G had lower effects than those of Q. Importantly, Q inhibited TLR2 gene expression and phosphorylation of STAT3 protein in the inflamed cells. Our results are the first report to suggest that Q inhibits LPS-induced inflammation ex vivo through suppressing TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. Q has potential to further apply for treating inflammation-associated diseases.

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.

Objectives: The term "inflammageing” describes the process of inflammation-induced aging that leads living cells to a state of permanent cell cycle arrest due to chronic antigenic irritation. This in vitro study aimed to shed light on the mechanisms of “inflammageing” on human oral cells. Methods: Primary cultures of human gingival fibroblasts (hGFs) were exposed to variable pro-inflammatory stimuli, including lipopolysaccharide (LPS), Tumor Necrosis Factor-alpha (TNFa), and gingival crevicular fluid (GCF) collected from active periodontal pockets of systemically healthy patients. Inflammageing was studied through two experimental models, employing either late-passage (“aged”) cells (p.10) that were exposed to the pro-inflammatory stimuli or early-passage (“young”) cells (p.1) continuously exposed during a period of several passages (up to p.10) to the above-mentioned stimuli. Cells were evaluated for the expression of beta-galactosidase activity (histochemical staining), senescence-associated genes (qPCR analysis), and biomarkers related to a Senescence Associated Secretory Phenotype (SASP), through proteome profile analysis and bioinformatics. Results: A significant increase (p<0.05) of beta-galactosidase-positive cells was observed after exposure to each pro-inflammatory stimulus. The senescence-associated gene expression included upregulation for CCND1 and downregulation for SUSD6, and STAG1, a profile typical for cellular senescence. Overall, pro-inflammatory priming of late-passage cells caused more pronounced effects in terms of senescence, than long-term exposure of early-passage cells to these stimuli. Proteomic analysis showed induction of SASP, evidenced by upregulation of several pro-inflammatory proteins (IL-6, IL-10, IL-16, IP-10, MCP-1, MCP-2, M-CSF, MIP-1a, MIP-1b, TNFb, sTNF-RI, sTNF-RII, TIMP-2) implicated in cellular aging and immune responses. The least potent impact on the induction of SASP was provoked by LPS and the most pronounced by GCF. Conclusion: This study demonstrates that long-term exposure of hGFs to various pro-inflammatory signals induced or accelerated cellular senescence with the most pronounced impact noted for the late-passage cells. The outcome of this analyses provides insights into oral chronic inflammation, as a potential confounder of age-related diseases.

Objective. To evaluate serum neuronal and inflammatory biomarkers in asphyctic newborns treated with hypothermia alone or hypothermia plus melatonin, and whether biomarkers correlate with neurodevelopmental outcomes. Design. This is a pilot multicentre, randomised, controlled, double blind clinical trial. Neuronal glial fibrillary acidic protein (GFAP), granulocyte-macrophage colony-stimulating factor (GM-CSF), and inflammatory cytokines (interleukin (IL)-1, IL-2, IL-7 and IL-13) were measured in serum samples at hospital admission (T0), 24 hours (T1), 72 hours (T2) and 7-10 days of age (T3). Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales, Gross Motor Function Classification System (GMFCS) and the Tardieu scale) were performed at 6 and 18 months. Setting: Level 3 neonatal intensive care unit. Patients and interventions: 25 newborns were recruited. The treated patients received a daily dose of intravenous melatonin, 5 mg per kg body weight, for 3 days. Results. After adjusting the data for severity, in the group treated with melatonin, there is a decrease in plasma levels of GM-CSF, IL-2 and IL-13 at T1 compared to placebo, as well as, at T2, in GM-CSF concentrations, as well as IL-7 and IL-13 at T3. Evolutionarily, we found a significant decrease in GM-CSF concentrations in the treatment group compared to placebo, with no differences for the rest of the biomarkers. It is noteworthy that the sustained decrease in GM-CSF and inflammatory cytokines IL-2, IL-7 and IL-13 correlated with better neurodevelopmental outcomes at 6 and 18 months. Conclusions. In neonates with hypoxic-ischemic encephalopathy, the addition of iv melatonin to hypothermia therapy affects the plasma concentration of biomarkers in the first week of life, with a high correlation with long-term neurological prognosis.

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 is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the 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). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.

Some biologically active compounds isolated from sea cucumbers stimulate the body’s immune response through activating immune cells. Immune function is closed related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether daily administration of holothurian wall hydrolysates (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then oral administration of HWH (80 or 240 mg/kg), levamisole hydrochloride (LH, 40 mg/kg, positive control) respectively once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT-PCR) for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the productions of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such as Lactobacillus, Lachnospiraceae, Christensenellaceae, and Bifidobacterium, while suppressed the populations of Ruminococcus, Staphylococcus, and Streptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH, and supports the potential as new prebiotics, immunomodulatory agents, and medical additive for intestinal repair.

Pro-inflammatory cytokines play a role in the failure of β-cells in type 1 and type 2 diabetes. While existing data from ‘omics’ experiments allow for some understanding of the molecular mechanisms behind cytokine-induced dysfunction in β-cells, no report thus far has provided information on the direct imaging of the β-cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy of Insulinoma 1E (INS-1E) cells to investigate the structural properties of two subcellular membranous compartments involved in the production, maturation and secretion of insulin-containing granules, the Endoplasmic Reticulum (ER) and the Golgi Apparatus (GA). Our findings reveal that exposure of INS-1E cells to IL-1β and IFN-γ for 24 hours leads to significant structural alterations of both compartments. In more detail, both ER and GA fragment and give rise to vesicle-like structures with markedly reduced characteristic area and perimeter and increased circularity with respect to the original structures. These findings complement the molecular data collected thus far on these compartments and their role in β-cell dysfunction using and lay the ground for future optical-microscopy-based ex-vivo and in-vivo investigations.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 from mouse bone marrow derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed secretion of IL-1β and IL-6 with less effect on TNFα. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. Also, LPS produced an increase in itaconate and citrate and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of GSH and intermediates in its biosynthesis while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of UDP-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by inhibition of pro-inflammatory cytokines and by metabolic reprogramming of LPS activity in macrophages.

Mild TBI (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite their high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI was previously provided. Thus, this study aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. Thus, it was shown that the increase of IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of the early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that the inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG in-duction of obesity upon systemic and muscular parameters of Wistar rats. Animals were exposed to MSG subcutaneously (4 mg.g-1 b.w.) or saline (1.25 mg.g-1 b.w.) daily from PND01 to PND05 (n = 24). After, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, and increased adiposity, induction hyperinsulinemia, and a pro-inflammatory scenario. In adulthood were found, peripheral insulin resistance, reduced muscle mass, oxidative capacity, neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty in restoring the muscle profile are related to the metabolic damages established early.

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

In this brief communication, we propose the concept that capillary regression may represent a primary pathogenic process underlying COVID-19 infection, particularly in the serious and life-threatening manifestations of the disease. We suggest that the marked elevations of pro-inflammatory mediators that are observed in these seriously ill patients may directly induce capillary regression and endothelial cell (EC) loss. Recent autopsy studies are demonstrating EC loss leading to widespread microthrombi and associated tissue damage. Recent work has indicated that interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNFα), and thrombin, individually and in combination, can potently cause capillary tube regression in experimental models in vitro and in vivo. Other pro-inflammatory mediators including interferon gamma (IFNγ), interleukin-4 (IL-4), and interleukin-13 (IL-13) were also shown to be pro-regressive and could be relevant mediators in COVID-19 patients. Interestingly, combinations of pharmacologic agents were identified that reduced capillary regression and protected capillary tube networks against these pro-inflammatory mediators. Such an approach might be an important therapeutic option going forward to treat key disease states where capillary regression plays a major underlying pathogenic role. Finally, if capillary regression is occurring in response to these pro-inflammatory mediators during COVID-19 infection, we suggest that combinations of blocking agents directed to these key pro-regressive mediators might be necessary to appropriately treat patients.

The human innate immune response to the pore-forming toxin of Vibrio cholerae VCC, is currently under study. Here, in vitro studies on a human macrophage cell line (THP-1), helped explore the activated pathways involved on the onset the innate immune response towards the cytotoxin. The secreted monomeric 65 KDa form interacts with mature macrophages in pg/ml concentrations, determined by dose response experiments after treatments under 1 h. Non vacuolating concentrations (pg/ml) were applied to the cells; immunoblots revealed activation of MAPKs: early overexpression of p38 and ERK. Cell lysis by release of lactate dehydrogenase (LDH) was not apparent in the first hour, nonetheless it was positive after 24 h. Finally, to discern whether the VCC stimulates transcriptional activators via MAPKs pathway, NF-κB and AP-1 were studied by real time quantitation. Increased expression of p50 (NF-κB), cJun and cFos (AP-1) was observed. Given that NF-κB is the transcription factor initiating inflammation of innate immune response and in turn, AP-1 is responsible for cell surviving response, results from this study lead us to conclude that VCC in vitro treatments, induce a pro-inflammatory and a surviving response, in less than one hour on activated macrophages.

(1) The present study investigated the effect of orally administered Limosilactobacillus fermentum HY7302 (HY7302) on the relationship between ocular tissue and the microbiome in the corneal injured dry eye mice model. (2) 0.1% benzalkonium chloride (BAC) was applied to the ocular surface for 14 days to induce corneal injury in male Balb/c mice. During the BAC treatment period, HY7302 (1 × 108 CFU/kg/day or 1 × 109 CFU/kg/day) or omega-3 positive control (200 mg/kg/day) were administered orally (n = 8/group). To examine signaling pathways affected by HY7302 treatment, the in vitro effects of HY7302 on tight junctions and the inflammatory response were investigated in a mouse colon epithelial cell line, CMT-93. (3) BAC exposure decreased tear production, induced ocular inflammation and corneal epithelial detachment, and altered gut microbiota. However, oral administration of HY7302 restored tear secretion and decreased corneal epithelial detachment in BAC-treated corneal injury mice. Further, HY7302 alleviated corneal inflammation via modulation of matrix metalloproteinase-9 (MMP-9) expression and alterations in gut microbiota composition. (4) These findings suggest that the gut–eye axis interaction between gut microbiota and eye tissue affects disease severity in corneal injury, and that alteration of the microbiota by HY7302 could improve eye health by regulating the inflammatory response.

Casein hydrolysate improves arterial stiffness, as estimated by brachial ankle pulse wave velocity (baPWV), in untreated hypertensive subjects. Facial pigmentation is a useful biomarker for arterial stiffness. This trial evaluated whether casein hydrolysate improves facial pigmentation in association with changes in arterial stiffness. A randomized, double-blind, placebo-controlled trial was conducted in 80 non-hypertensive Japanese participants randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation and baPWV were measured at baseline and at the end of the intervention. Other biochemical atherosclerosis-related parameters were also measured, including advanced glycation end products (AGEs). Changes in facial pigmentation showed a significant difference between the groups. Change in baPWV was significantly better in the active than in the placebo group. In contrast, no significant association was seen between changes in facial pigmentation and those in baPWV. Among other atherosclerosis-related factors, changes in advanced glycation products (AGEs) were significantly decreased in the active compared to the placebo group. Further, changes in facial pigmentation were positively correlated with those in AGEs. Changes in AGEs were independently associated with changes in facial pigmentation. Casein hydrolysate improves facial pigmentation in non-hypertensive participants. Casein hydrolysate may have beneficial effects on glycation stress.

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

: Rasmussen’s encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherectomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Further-more, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expres-sion of cell cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest potential involvement of cell cycle regulators in the progression of RE.

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.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in AD’s brain. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, expressed Iba1 and showed reduced viability, consistent with a neurotoxic effect of HPU. Rats received daily i.p. HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Thr205, Ser199 and Ser396 sites was seen in hippocampal homogenates of treated rats, with no alterations in total tau or GSK-3b levels. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.

ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in EndMT with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

This study grounded in the Affective Events Theory, explores how post-pandemic urban residents' nostalgic tourism influences environmental behaviors in rural areas. The article constructs a model of pro-environmental behavior in rural settings with nostalgic tourism as the antecedent variable, environmental responsibility and awe as mediators, ecological concern as a moderating variable, and pro-environmental behavior as the outcome variable. Analyzing 535 valid survey responses from urban residents and utilizing Partial Least Squares Structural Equation Modeling (PLS-SEM) to test research hypotheses reveals that nostalgic tourism significantly impacts environmental responsibility and awe. Environmental responsibility mediates between nostalgic tourism and pro-environmental behavior, forming a serial mediation chain with awe psychology, and its mediating effect is significant. However, awe psychology forms a serial mediation chain between nostalgic tourism and pro-environmental behavior, and its mediating effect is insignificant. Notably, environmental concern does not moderate the relationship between environmental responsibility and pro-environmental behavior, indicating no support for this hypothesis. The positive role of nostalgic tourism in pro-environmental behavior at rural tourism destinations enriches theoretical research on the nexus between nostalgia and environmental behavior, providing insights into the sustainable development of rural environments and the operation of rural tourism.

Background: Pro-golfers are increasingly trained scientifically, but swing technique characteristics have not yet been conclusively determined for golf performance. We investigated the relationship between the player's thorax, pelvis and club based on a wireless biofeedback system. We also determined whether thoracic and pelvic changes during different swing phases have different effects on ball striking. Methods: Eight male professionals performed 10 successful full-swing shots using a 5-iron and applied the K-vest wireless biofeedback system for analysis. Results: Peak angular velocities between the pelvis, torso, and clubs were all significantly different (p&lt;0.05) in the men's professional players. All players deviated more from the PGA players range metrics during the preparation stance. Excessive lateral pelvic bending angle, over-rotation, and hyperextension of the trunk were prevalent at the top of the backswing. Conclusions: Most players have an irrational sequence of pelvic, trunk and club rotation times, which is not conducive to improving club head speed and distance. Excessive pelvic rotation in the closed direction at the apex of the backswing is not conducive to maximizing the X-factor. At the moment of striking the ball, maintain a moderate forward trunk lean and full trunk rotation to avoid sports injuries.

Background and objectives: The fact that the results of troponin and Nt-proBNP interfere from biotin caused some commercial firms to update their measurement methods. In particular, the clinical incompatibility of cardiac test results may affect the risk of morbidity and mortality. The aim of this study is to investigate the interference effects of 7 different contrast agents on cardiac markers (Troponin-I, Nt-proBNP, Mass CK-MB, CK, AST, LDH) and coagulation tests (PT, APTT). Materials and Methods: Seven different contrast medias were added into control materials by using interference protocol. Concentration of PT, APTT, CK, AST, LDH, Mass CK-MB, Troponin-I, Nt-proBNP were measured by Sysmex CS-2100, Abbott c16000, Siemens Centaur XP and AFİAS-6 analyzer. The amount of deviations from target values were calculated. Results: 7 different contrast medias caused negative interference in troponin levels between 57.43% and 62.87%. It was found that different contrast medias produced false negativity in the pro-BNP test ranging from 6.11% to 96.01%. Enzymes and coagulation tests have been less affected. Conclusions: Different contrast medias may cause false negative cTnI and pro-BNP. Therefore, the contrast medias which causes the least interference should be preferred. The results of samples taken in the first hour of contrast imaging should be interpreted with care.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications, formed by reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied in respect of glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in dramatic suppression of primary seed metabolism, although secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Inflammasomes are multiprotein complexes that activate inflammatory responses by inducing pyroptosis and secretion of pro-inflammatory cytokines. Along with many previous studies on inflammatory responses and diseases induced by canonical inflammasomes, an increasing number of studies have demonstrated that non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 inflammasomes, are emerging key players in inflammatory responses and various diseases. Flavonoids are natural bioactive compounds found in plants, fruits, vegetables, and teas and have pharmacological properties in a wide range of human diseases. Many studies have successfully demonstrated that flavonoids play an anti-inflammatory role and ameliorate many inflammatory diseases by inhibiting canonical inflammasomes. Others have demonstrated the anti-inflammatory roles of flavonoids in inflammatory responses and various diseases, with a new mechanism by which flavonoids inhibit non-canonical inflammasomes. This review discusses recent studies that have investigated the anti-inflammatory roles and pharmacological properties of flavonoids in inflammatory responses and diseases induced by non-canonical inflammasomes and further provides insight into developing flavonoid-based therapeutics as potential nutraceuticals against human inflammatory diseases.

The current study aimed to assess the components of the intervention program “Aquatic”, targeted at the reduction of bottled water use in adolescence. The Comprehensive Action Determination Model was chosen as a theory of change for the development and evaluation of pro-environmental behavior intervention. We examined the impact of five experimental intervention factors (water bottles, promo video, prompts, goal setting, and feedback) on eight intervention program outcomes: Perceived behavioral control, Social norm, Habit, Awareness of need, Awareness of consequence, Personal norm, Intention, and Behavior. The study sample consisted of 419 adolescents (52.8% girls, Mage = 15.21, SDage = .64) from Lithuania. A factorial experimental study design was used, and a Latent change modeling approach was applied for the evaluation of individual and combined effects of intervention components. Promo video, Prompts, and Goal setting had a positive effect on Awareness of consequence, Social norm, and Awareness of need, respectively. Receiving a Water bottle in combination with the Promo video had a positive effect on Perceived behavioral control and in combination with Prompts as well as Goals – on Awareness of need. Water bottles, Promo-video, Prompts, and Goals, but not Feedback, had value in the promotion of targeted pro-environmental outcomes.

Ligand and structure based virtual screening approaches were applied to clinical stage drugs as well as those approved for human use in an attempt to repurpose drugs for potential use against COVID-19. This approach involved ligand-based shape similarity searches, structure-based docking and pharmacophore searches with the help of pharmacophore queries derived from available ligands and receptor structures. Several compounds appeared as hits in pharmacophore and shape similarity searches and those docking to the SARS-CoV-2 viral 3CL protease were then ranked on the basis of docking scores.

Activation of the NLRP3 inflammasome plays a crucial role in innate immune response. During cell division, the NLRP3 inflammasome activation must be strictly controlled. Here, we discovered the anaphase promoting complex subunit 10 (Anapc10, APC10), a substrate recognition protein of the anaphase promoting complex/cyclosome (APC/C), is a critical mediator of the NLRP3 inflammasome activation. APC10 protein interacts with NLRP3, and co-localizes with NLRP3 protein in the cytoplasm. During interphase, APC10 interacts with NLRP3 to promote the NLRP3 inflammasome activation. During mitosis, APC10 disassociates from the NLRP3 inflammasome to inhibit the inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch of the NLRP3 inflammasome activation during cell cycle.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

This study aims to examine how Green Human Resource Management (GHRM) practices influence the development of an environmentally sustainable culture that encourages employees to exhibit pro-environmental behaviours in public and private hospitals in Egypt. A total of 491 healthcare employees were surveyed and the data was analysed using Partial Least Squares Structural Equation Modelling (PLS-SEM). The research identified significant positive correlations between GHRM practices, a pro-environmental psychological climate, environmental knowledge, and employees' environmentally favourable behaviours. The results emphasised the significance of tailored GHRM strategies for different sectors and showed how psychological climate and knowledge mediate the conversion of human resource management (HRM) practices into sustainable behaviours. The study extends the literature by highlighting the relevance of GHRM practices within a healthcare setting in a developing country and indicates that the success of environmental practices is closely linked to their visibility and integration into routine operations. The focus of future studies should be on the long-term effects of GHRM practices, the impact of individual differences, and comparative studies across different sectors and countries to obtain a deeper understanding of how organisational sustainability is influenced by GHRM practices.

This is a review on social laser theory completed with its new developments and applications. An important methodological step towards similarity with quantum physics is the invention and consistent operation with infons. These are excitations of the quantum social-information field carrying social energy and coarse grained content of communications (their color and quasi-color). We study in more detail interactions of infons with social atoms, the processes of absorption and emission (spontaneous and stimulated). We also analyze the dynamics of iterations of the cascades of infons in the social resonators. The latter are based on social networks coupled to laser's gain medium composed of social atoms. Consideration of the pro-war and pro-peace beams leads to the general discussion on the competing beams of social radiation and the conditions for their creation and coexistence. The role of social networks in lasing is illustrated by the protests during the COVID-19 pandemic. It is highlighted that a human gain medium can approach the state of population inversion with supply of infons of one sort (quasi-color), but the stimulated emission can be induced by injection into the gain medium of infons of a different quasi-color. We call this behavior of social atoms memorylessness. This theoretical property is illustrated with the examples from the modern social-political life.

Abstract: Background The incidence of Heart failure is increasing across the world. Over one million people in the UK have heart failure and around 200,000 new diagnoses are made every year (Conrad et al, 2018).Estimates suggest that, further 385,000 people with heart failure who are currently undetected, undiagnosed and, consequently, are missing out on life-preserving treatments. Most of the heart failure cases are of elderly population. The prevalence of heart failure slowly increases with age until about 65 years of age, and then more rapidly. In United Kingdom, the prevalence of heart failure in elderly population is estimated to be about [NICE, 2018a] 1 in 35 people who are aged between 65 – 74 years of age and 1 in 15 people who are aged 75 – 84 years of age. The average age at first diagnosis is 76 years of age [NICE, 2018a]. As per the statistics, heart failure accounts for 2% of bed occupancy in entire NHS as well as accounts for 5% of all NHS emergency admissions. Hospitalization for decompensated heart failure (DHF) carries a poor prognosis, with frequent readmissions. As per the updated NICE guidelines, B-type natriuretic peptide (BNP) is used in the diagnostic criteria and management of heart failure. BNP is secreted by overloaded left ventricle as a response to fluid overload. This study is to evaluate the prognostic value of BNP in elderly population with decompensated heart failure. Methods We conducted a retrospective observational cohort study of 88 elderly patients who were admitted with decompensated heart failure between September 2023 to April 2024 in Lagan valley hospital – Lisburn and Ulster Hospital – Dundonald, Northern Ireland. Suspected heart failure admissions were randomly selected as snapshots of each month. Among these admissions, 88 Heart failure cases were identified based on echocardiogram findings and NT- pro BNP levels performed on initial admission. The same cohort was followed up for 12 weeks period for specific end points. The end points that were considered were readmissions with heart failure or deaths. Furthermore, Heart failure follow ups were also assessed during post discharge as well. A fraction of patients had repeat BNP checked during the follow up and their clinical features were correlated. All cases were categorized in to two main cohorts as HFrEF cohort and HFpEF cohort. Patients with left ventricular ejection fraction ≥50% were categorized as HFpEF, while those with <40% as were categorized as HFrEF. Each cohort was subdivided to further 3 sub categories depending on the BNP values. Prognostic values and all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups. ROC curve was carried out to establish the cutoff level of BNP and the mortality analysis was done utilizing Kaplan Meier curves. Results In this cohort study, two major heart failure cohorts were analyzed for specific end points under six main sub-cohorts. The data analysis shows that mortality rate is 29.1% when NT Pro BNP values is more than 2000. The heart failure readmission rate is 45.6% when NT Pro BNP value is more than 2000. 66.6% re-admission rate was demonstrated with rising NT-Pro BNP values during heart failure follow up. This was much lower with patients who had declining NT- Pro -BNP values during heart failure follow u which was 33.3% Satisfactory statistical power of the study, which demonstrated that NT- Pro BNP can be used as prognostic marker for mortality in elderly patients with heart failure irrespective of their ejection fraction. Conclusions NT Pro BNP can be used as a prognostic biomarker for elderly patients with heart failure. Satisfactory statistical evidence was shown on this study to prove that higher BNP values on admission predicts higher mortality rate. Significant evidence was demonstrated in this study to show that there are higher re-admission rates with higher NT pro BNP levels specially in elderly population. Furthermore, the study demonstrated that, there is higher mortality and morbidity rate with rising NT Pro BNP levels during heart failure follow up. In conclusion, all these three parameters shows that NT Pro- BNP levels can be used as a prognostic bio marker for elderly patients with heart failure, irrespective of their ejection fraction status. Furthermore, we would like to indicate that monitoring NT Pro BNP levels in all heart failure cases could be beneficial to prevent mortality and morbidity. Furthermore, it would be an aid to optimize heart failure medications prior to have an episode of decompensation of heart failure as well.

Global biodiversity loss and climate change highlight the importance of environmental knowledge and behavior in the population at large. Americans gain environmental knowledge almost exclusively from sources outside of formal schooling, and increasingly, the internet and social networking sites (SNS) are the preferred sources of that specific, just-in-time learning. The North Carolina Native Plant Forum is a regionally specific Facebook group focused on environmental education with over 80,000 members. This case study used 14 forum member interviews and analysis of the Facebook site itself to explore the Native Plant Forum and its users through the lens of the Technologies for Pro-Environmental Actions Model (TPAM). These data revealed a process of information seeking, sharing experiences, obsession, and pro-environmental intentions leading to the planting of native plant species that host and support pollinators and wildlife. Users of the forum expressed how much they learned from the Facebook group and particularly valued the photographs shared daily by other forum members of their native planting projects. The ability of social networking sites to support and incentivize pro-environmental knowledge and behaviors is a critical area of research for adapting environmental education to a new information age and for combating multiple overlapping environmental crises.

Macrophages are the key effector cells of innate immunity which show two polarized states: M1, classically activated and M2, alternatively activated. Tumor-associated macrophages (TAMs) which usually show M2 polarization, are immunosuppressive cells that enhance tumor metastasis and invasion. Also, enrichment of TAMs is known to be closely associated with poor prognosis of cancer patients. Therefore, TAMs are considered to be promising targets for immunotherapy. Importantly, tumor-derived exosomes emerged as a crucial player in immune regulation which can remodel the tumor microenvironment towards immunosuppressive state. Of note, few studies have shown that exosomes could induce polarization of macrophages towards M2 type in tumor condition, while others showed activation of M1 or mixed phenotype. Considering the role of TAMs in cancer, there is an urgent need to decipher the exosome-mediated cross-talk between tumor cells and macrophages.For this, we used murine model of Dalton’s lymphoma (DL), wherein, firstly, we evaluated increased exosome burden by assessing exosome level in serum as well as in various tissues of tumor-bearing host. Next, proteomic profiling of lymphoma-derived exosomes was done which revealed the presence of immunomodulatory proteins. Of note, these proteins were known to alter the macrophage polarization. In order to assess the effect of these exosomes on macrophages, we performed in vitro study using RAW264.7 cells. In vitro study revealed that frequent uptake of exosomes mediated a morphological change in macrophages which reduced their phagocytic activity. In parallel, exosomes increased reactive oxygen species (ROS) level and inhibited LPS-induced nitric oxide (NO) level in macrophages. Also, exosomes upregulated the expression of arginase-1 (an M2 marker) in macrophages but decreased the LPS-induced nitric oxide synthase 2 (NOS2) (an M1 marker) expression. Moreover, we observed a pro-tumoral cytokine profile in macrophages incubated with exosomes. Our study suggests that exosome load increases in lymphoma-bearing hosts systemically. Importantly, lymphoma-derived exosomes mediate the activation of macrophages towards pro-tumoral M2 type. Our results give an insight into the exosome-mediated tumor and immune cell cross-talk which could serve as an important prospect for targeting in cancer immunotherapy.

We conduct a thematic analysis of a U.S. adult sample’s self-reported motives and perception of environmental activists’ motives to engage in pro-environmental behavior via a qualitative online survey. We identified themes using a two-stage coding procedure, whereby the research team first helped to code all content into one or more of 17 inductive content categories, then the lead investigator examined themes in each of the categories and created 5 themes based on both inductive and theoretical (e.g., moral foundations theory) considerations: a) harm and care, b) purity, c) waste and efficiency, d) spreading awareness, and e) self-interest (mostly non-financial). Endorsement of themes were qualitatively similar across individuals’ own self-described motives and perceptions of environmental activists’ motives.

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, a characteristic multi-follicular morphology of the ovary, an elevated ratio of LH/FSH, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. Inflammatory processes consist of the acute inflammatory response and resolution processes initiated concomitantly. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. SPM biosynthesis starts from the essential polyunsaturated fatty acids DHA, DPA, or EPA via certain hydroxylated intermediates (18-HEPE, 17-HDHA, 14-HDHA). The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Blood samples were taken (20 ml), separated into plasma and serum, and analyzed by HPLC/MS-QQQ. Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Ratio [(sum of pro-inflammatory molecules)/sum of SPMs]. Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

In recent decades, reports of deforestation, mass extinctions, biodiversity loss, and emergencies like floods and droughts have clearly highlighted the impact of human activities on these outcomes. This underscores the need for significant lifestyle changes to mitigate this impact. Pro-environmental behavior (PEB) change involves adopting actions that protect the environment and reducing environmentally harmful activities. While qualitative research may provide unique insights into PEB barriers that are challenging to capture through quantitative methods, reports of qualitative studies are scattered across different literatures with little integration. With the present review, we bring together insights from qualitative studies on PEB barriers and examine whether those studies reveal barriers compatible with existing barrier frameworks from environmental psychology. We identified 38 qualitative studies on barriers to PEB change. Our analysis revealed that most of the barriers to individual pro-environmental action identified in qualitative studies align with environmental psychology frameworks. These barriers were experienced not only by individuals in their role as consumer or citizen, but also by community-level actors (e.g., seeking to implement pro-environmental policies) and industrial decision-makers (e.g., aiming to reduce the ecological footprint of their business activities). Our findings underscore the multifaceted nature of barriers to PEB change and emphasize the importance of addressing structural and institutional factors alongside individual-level interventions.

Objectives This study aimed to evaluate the eicosanoid and pro-resolutive parameters in Post Covid Syndrome (PCS) patients during 12 weeks of a supplementation with a marine oil enriched in SPMs. Patient and methods The study was conducted in 53 adult patients with a PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: Polyunsaturated fatty acids: EPA, DHA, ARA, DPA, Specialized Pro-resolving mediators (SPMs) 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different amounts of intake were evaluated: daily use of 500mg, 1500mg, and 3000mg were compared to a control group without use of the product. Results In the serum from PCS patients, an increase of 17-HDHA, 18-HEPE, 14-HDHA could be observed. Also, a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected. Both differences were significant (p < 0.05). There were no differences between the three treatment groups. Fatigue and dyspnoea showed a trend to improve after supplementation in all groups. Conclusions A clear enrichment in serum of the three monohydroxylated SPMs could be observed also at a dosage of 500 mg per day. In the same way, a clear improvement in fatigue and dyspnoea was observed with this dosage. Clinical Trial Registry: ISRCTN13270662.

The steep decline in the price of wind and solar photovoltaics provides a possibility to decarbonize electricity deeply and affordably. This study uses HOMER Pro energy modeling tool to model an optimized grid-connected renewable energy system for a community in southern Alberta, Canada. The study's goal is to identify the best renewable energy technology combinations that can provide electricity at the lowest levelized cost of energy (LCOE) and has lesser greenhouse gas emission as compared to the electricity produced by traditional fossil fuel. Gleichen, is a small town in southern Alberta and is near to numerous commercial wind and solar projects given the region’s high quality renewable resources. “Tri-brid” systems consisting of wind turbines, solar photovoltaics, and battery energy storage systems (BESS) are considered and compared based on electricity prices, net present cost, and greenhouse gas emissions savings. This tri-brid system is connected to the grid to sell excess electricity generated or buying electricity when there is less or no availability of solar and wind. The tri-brid energy system has an estimated LCOE of 0.0705 CAD/kWh which is competitive with the price of electricity generated by natural gas and coal which is 0.127 CAD/kWh.

Aims: This systematic review aims to evaluate the influence of Environmental Enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. Methods: A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. Key-findings: A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. Findings: This systematic review highlights the significant impact of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

The demand for industries to enhance sustainability is rising in response to climate change worries. A pervasive and intensifying worldwide environmental problem, plastic pollution has a particularly severe impact on climate change. The production of significant volumes of plastic garbage occurs mostly in Asian regions. So, it's commonplace to talk about pro-environmental conduct nowadays. Indonesia and Taiwan are chosen as case studies of developed and developing regions, respectively. The cultural differences between the two areas do, however, exist in terms of environmental values, and this further influences consumer behavior. In order to understand how environmental education has influenced pro-environmental behavior, this study examines how environmental attitude, knowledge, motivation, and intention have changed as a result of environmental education. By sending electronic questionnaires to a sample of 235 respondents (110 Indonesian and 125 Taiwanese), gathered between March 11 and April 30, 2023, we employ quantitative approaches and data-gathering procedures. The CB-Structural Equation Modelling with AMOS analytical tool is used to examine the data. We are able to draw important conclusions from the study of differences between Indonesian and Taiwanese and make suggestions for more research as well as theoretical and managerial ramifications.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

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

Edcraft, a recycling and upcycling event for Malaysian secondary school students, particularly in the Klang Valley area in 2020. The event's goal was to look into gamified solutions to encourage recycling and upcycling among the students’ age group. Lectures, talks, practical exercises and games were used to teach students about climate change and environmental preservation. According to a post-event survey, the percentage of participants who recycle has climbed significantly: 76% now recycle, compared to only 24% previously. The study discovered that gamification-based activities could effectively facilitate recycling and upcycling behaviours. Such solutions can be applied to encourage behavioural changes in different contexts. By interviewing 15 Edcraft students in a focus group study setting, researchers could better understand the motivations. Themes such as 'social connections are vital', 'convenience and rewards are significant motivators', 'gamified activities help attract and engage teens' and 'environmental knowledge is crucial to prolonging recycling' emerged from the thematic analysis. This manuscript proposes gamified activities to induce a behavioural change in upcycling, and the findings yield helpful insights to fuel pro-environmental behaviours.

Under some employment circumstances, individuals in some organizations are willing to engage in unethical behaviors that benefit one’s own supervisors who have a great power to decide the levels of evaluation and compensation for each individual. In this study two hypotheses were examined. First, based on social identification theory, we hypothesized that individuals’ feeling a sense of oneness with one’s own supervisors promote unethical pro-supervisor behaviors (UPSB). Second, based on a person-situation interactionist model, we hypothesized that this positive relationship is strengthen if the individual perceives lower levels of one’s own employability. Data were collected from 185 individuals of various types of organizations in South Korea. A time-lagged field study supported our hypotheses. In particular, supervisor identification was positively related to UPSB. Further, for individuals with a weaker employability perception, supervisor identification was positively related to UPSB.

Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf^-/-Mri^-/-Trp53^+/- and Xlf^-/-Paxx^-/-Trp53^+/- mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.

According to Hofstede’s theory of cultural dimensions, cultures differ in cultural values and norms; values and norms that may influence differences in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Further, because men and women have been socialized within particular cultures, gender differences may exist in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Trendsetters have characteristics that are interrelated with creative traits and behaviors, perhaps inclining them to endorse pro-environmental behaviors. However, the interrelationships among these variables remain unexplored. Thus, the purpose of this study was to examine these three variables among college students in South Korea and the United States, specifically looking at cultural and gender differences. Participants were 225 Korean college students and 221 U.S. college students. Questionnaires included demographic items and scales measuring trendsetting, creative traits and behaviors, and pro-environmental behaviors. Data analyses included descriptive statistics, Cronbach’s alpha reliability, MANOVA, ANOVA and SNK posthoc test. Results show that U.S. (vs Korean) students indicated greater trendsetting and creative traits and behaviors but not greater pro-environmental behaviors. Fashion trendsetting groups in both Korea and the U.S. differed in creative traits and behaviors and pro-environmental behaviors. Among Korean trendsetting groups, reluctant adopters scored lowest on creative traits and behaviors and pro-environmental behaviors. Among U.S. trendsetting groups, trendsetters scored highest on creative traits and behaviors and pro-environmental behaviors; reluctant adopters scored lowest on pro-environmental behaviors. Theoretical and practical implications are provided for researchers and marketers.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Microorganisms such as bacteria, viruses and fungi are frequently the cause of infections. Antimicrobial agents, such as antibiotics, antivirals, and antifungals, are used to target and eliminate these infectious agents. Treating infections is crucial to prevent them from spreading, causing complications, or becoming chronic. On the other hand, inflammation is a natural response of the immune system to injury, infection, or irritation. While acute inflammation is a natural and protective process, chronic inflammation can contribute to various health issues, including autoimmune diseases, allergies, and chronic conditions like arthritis. Although herbal remedies have been used for centuries and can be effective in certain situations, it is crucial to use them with caution. Not all herbal remedies are supported by scientific evidence, and their safety and efficacy can vary. Thus, we conducted this review to determine the potential health benefits of agarwood as an antimicrobial and anti-inflammatory agent. Original articles were searched in three databases (PubMed, Scopus and Google Scholar) from the year 2013 to 2023 using the Medical subject heading (MeSH) terms “antimicrobial” and/or “anti-inflammatory”, crossed with the term “agarwood”. Synonyms and relevant search terms were also searched.  The most studied agarwood for antimicrobial and anti-inflammatory agents is Aquilaria sinensis. Some studies have shown its potential application as a biopesticide for mosquito control and as a potent inhibitor for fungi, including Lasiodiplodia theobromae, Fusarium oxysporum, and Candida albicans. Moreover, it is capable of inhibiting Bacillus subtilis and Staphylococcus aureus activities. In conclusion, agarwood and its isolates are worthy of further biomedical investigation and could be developed as potential candidates for the treatment or prevention of various microbial and inflammatory diseases. This review reveals that despite the absence of clinical trials, agarwood exhibits antimicrobial and anti-inflammatory properties.

Due to the host immunological disease brought on by infection is sepsis, multiple organ dysfunction syndrome (MODS), which has a high morbidity and mortality rate, could be the result. With advances in pathogen detection technologies, breakthroughs in anti-infection drugs, and the creation of organ function support, the clinical diagnosis and treatment of sepsis have advanced significantly. Pathogen-induced abnormal immunological responses, which can range from excessive inflammation to immunosuppression, are recognized to play a significant role in the high death rate. Unfortunately, no medications that are specifically intended to treat sepsis have been licensed. In order to offer a theoretical foundation for the management of sepsis, we will now discuss current advancements in research on immunological responses in sepsis. The prognosis of sepsis patients may be improved by developing and optimizing a dynamic immune system treatment plan based on anti-infection therapy, fluid replacement, support for organ function, and timely application of immunomodulatory therapies

The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMRspectroscopy and spectroscopy methods were used to characterize the structural properties of newly synthesized derivatives. In order to observe the attributes of drug-like candidates of these derivatives, the number of their molecular properties was estimated. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Findings suggested that Compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8and G10 showed lower binding affinity than Indomethacin when docking performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities were performed for synthesized compounds. Compounds 10 and 11 exhibited significant COX-1 and COX- enzyme inhibitory action with IC50 values of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. The highest analgesic action was exhibited by derivative G11and the compound G10 showed the highest anti-inflammatory response.

Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of polyacetylene-rich vegetables with reduced risk of inflammation and cancer. Polyacetylene supplementation can influence cell growth, gene expression, and immunological responses, and reduce tumour number in rat and mouse models. Cancer chemoprevention by dietary polyacetylenes involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, UPR pathway, growth factor signalling, cell cycle progression, and apoptosis. This review summarises the published research on falcarinol-type polyacetylene compounds and their mechanisms of action regarding cancer chemoprevention and treatment, and also identifies some gaps in our current understanding of the health benefits of these polyacetylenes.

Pulmonary fibrosis causes scar tissue formation that disrupts the functioning of the lungs. Uncaria gambir (Hunter) Roxb (hereafter gambir)—a plant native to West Sumatra in Indonesia—contains flavonoid (+)-catechin and has strong antioxidant activity, and it can be used to combat pulmonary fibrosis. This random in vivo experimental study analyzed the antifibrotic effect of gambir on the lungs of rats with bleomycin-induced fibrosis. The subjects were 10 groups of 10-week-old male rats weighing around 200–250 g. All groups were terminated at the end of the seventh week or on day 50. The lungs were cleaned, and tissues were taken to analyze inflammatory cell counts and TGF-β1 levels using bronchoalveolar lavage (BAL) with ELISA; type I collagen and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels using immunohistochemistry (IHC); and activation of NF-κB using ELISA and Western blot assays. The most severe histopathological characteristic based on the modified Ashcroft score was in the bleomycin group (BG), whereas the mildest was in the 262 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G262). The results showed a significant difference in the BAL inflammatory cell count (p = 0.017; p &lt; 0.05). AF G262 differed most from the other antifibrotic groups in terms of the number of inflammatory cells (0.63), TGF-β1 levels (3.80), and NF-κB levels (0.48), followed by the 131 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G131), which also differed most from other antifibrotic groups in terms of NF-κB (0.48), TIMP-1 (11.74), and collagen I (14.50) levels. Western blot analysis showed that the fibropreventive and antifibrotic groups had a specific band size of p65, whereas no specific band binding existed in the control group. This study concluded that the administration of AF G262 could improve fibrosis by lysing the extracellular matrix (ECM) in rat lungs.

Growth hormone therapy (GHT) can improve growth velocity and final height but can also accelerated the process of bone growth, which is related to structural bone modelling, both in formation and resorption. The study evaluated the capacity of bone turnover markers to predict early growth response to one year GHT in short stature children born as small for gestational age (SGA). 25 prepubertal SGA children were included. We have estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type I), P3NP (N-terminal procollagen type III), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA, IRA and ELISA methods. A statistically significant increase in bone resorption markers (Ctx ) was found both at 6 and 12 months. P1NP bone markers increased at 6 months and after 12 months of therapy. The P3NP marker of collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months and similarly ALP. We have found a significant correlation between height (cm) and Ctx after 6 -12 months as well as P1NP / height (SD) after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We find a strong reaction of bone resorption and bone formation markers during growth hormone therapy that may determine their selection as prediction of GH treatment outcome in SGA children. However, the issue requires further research.

Xaa-Pro dipeptidase (XPD, EC 3.4.13.9; also known as prolidase) catalyzes the hydrolysis of iminopeptide bond in the trans Xaa-Pro dipeptides (Xaa represents any amino acid except proline), which makes it find wide applications in food, medical and environmental protection fields. In the present study, a novel Xaa-Pro dipeptidase from Aspergillus phoenicis ATCC 14332 (ApXPD) was molecularly and biochemically characterized. Reclassification based on phylogenetic analysis and version 12.5 MEROPS database showed that this enzyme was the only fungal XPD in the unassigned subfamily which shared the highest sequence similarity with Xanthomonas campestris prolidase but not with that from the more related fungal species A. niudulans. As compared with other prolidases, ApXPD also contained an N-terminal tail (residues 81-89) and an additional region (PAPARLREKL), and used a different arginine residue for dipeptide selectivity. After heterologous expression and partial purification, recombinant ApXPD was highly active and stable over the alkaline range from 8.5 to 10.0, with a maximum activity at pH 9.0 and more than 80% activity retained after 1-h incubation at pHs of 8.5-10.0 (55oC). It also had an apparent optimum temperature of 55oC and remained stable at 20-30oC. Moreover, this enzyme was a cobalt dependent prolidase that only cleaved dipeptides Lys-Pro, Gly-Pro and Ala-Pro rather than other dipeptides, tripeptides and tetrapeptides. All these distinct features make A. phoenicis ATCC 14332 XPD unique among currently known prolidases, thus defining a novel Xaa-Pro dipeptidase subfamily.

Over the past decade, significant developments have occurred in treatment strategies for ovarian cancer, yet targeted therapy with few side effects is still a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs, with a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial for understanding the pathophysiology of ovarian cancer since many isoforms are essential for the metabolism of xenobiotics and steroid hormones, which drive the disease's development. The purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with their polymorphisms' effect on chemotherapy metabolism. Finally, we provide our thoughts on opportunities to exploit metabolic CYP expression for novel therapeutic development to treat ovarian cancer.

Stories considered to be the most popular form of lore, which can facilitate the moral and ethical deliberation of sustainability to our children. It is evident that children response better with stories than any other form of communication. Once the stories end, the les-sons remain. The values tangled with the lesson transmits ahead as they grow. Stories has always become instrumental and the most conventional way of teaching values by using illustrations from our lives. The major aim of this paper is to explore the values that ex-pressed in Bengali child-lore through stories and tales; and develop a framework by using ‘scaffolding & mapping’ approach. This framework will attempt to analyse two com-monly recognized stories; scaffolding them with the generally acknowledged principles of sustainability management; and mapping with the major aspects of sustainability (social, economic and environmental) to investigate how stories can influence children on build-ing pro-sustainability attitude. This approach has been chosen, as recent research already points out the issues in implementing sustainability in education, but no one has yet found the way forward. The hypothesis that this theoretical article builds on is that an in-terdisciplinary approach and different pedagogical tools could help in building the bridge towards implementing sustainability in education as well as in society. This paper is part of the series of papers that are investigating how folk values into pri-mary education can support reviving the degrading sustainability in Bangladesh as well as help building pro-sustainability attitude for the future generation.

Gwadar is essential for Pakistan's financial stability. The third deep-water port in Pakistan, Gwadar, plays a significant part in trade between the Gulf countries, Africa, China, United Arab Emirates, and Cordillera Administrative Region. However, the load Shedding of 12-16 hours in Gwadar is the most concerning issue. Pakistan imports 70 MW of electricity from Iran. The wind and solar system are already installed but for a limited residential area. In Gwadar, there are enough renewable energy resources that can be utilized for electricity generation. In this context, a Techno and Economic Analysis is performed using the Hybrid Optimization Model for Multiple Energy Resources (HOMER) Pro. Two models are considered for this study. Model-1 includes PV/Wind Turbine/ and Battery while Model-2 consists of PV/Wind Turbine/Converter and Grid. The yearly energy generated by Model-1 and Model-2 is 57.37 GWh and 81.5 GWh, respectively. The levelized cost of electricity (LCOE) for Model-1 and Model-2 is respectively $0.401/kWh and $0.0347/kWh. It is shown that the simple payback of Model-1 is of 6.70 years, and the simple payback of Model-2 is 7.77 years. Due to the high LCOE of Model-1, its payback year is lesser than model-2. All of these facts indicate that Model 2 is the most optimal solution.

Although the positive relationship between religion and environmental behavior is well-argued, empirical research about the relationship between religion and public pro-environmental behavior is relatively lacking. This paper aims to explore the group differences in the influence of religion on public pro-environmental behavior and the mediating role of environmental risk perception in religion and public pro-environmental behavior. Using the Chinese General Social Survey data in 2013 for empirical analysis, this study’s results show that there are group differences in the impact of religion on public pro-environmental behavior. Women with religious beliefs are more willing to engage in public pro-environmental behavior than those without religious beliefs. Religious believers over the age of 45 are more willing to participate in public pro-environmental behavior than those without religious beliefs. Political participants with religious beliefs are more willing to practice public pro-environmental behavior than those without religious beliefs. In addition, we found that environmental risk perception can act as partial mediation in religious and public pro-environmental behavior. In other words, religious beliefs are deeply embedded in local political and social culture. In order to correctly understand the relationship between religion and public pro-environmental behavior, it is necessary to consider religion in a specific cultural background.

Responding to the substantial finance gap for achieving Sustainable Development Goal 6.1 and 6.2, the Water and Sanitation sector has mobilized to launch new blended finance vehicles with increasing frequency. The sustainability and scale-up of financial solutions is intended to support increased access to unserved, marginalized populations. However, without addressing foundational issues in the sector, any finance mechanism, whether public, private or blended, will be a short-term, band-aid solution and the sector will continue the cycle of dependency on external assistance. This paper presents the results of a collaborative effort of Water.org, IRC WASH and the World Bank Water Global Practice. Drawing from the latest research on effective public financial management and based on evidence from the countries where these organizations work, the paper demonstrates that sustainable success in mobilising finance at large scale is dependent on a reasonable level of performance across 10 foundational areas. The paper presents evidence on the 10 foundational areas and discusses why other aspects of finance and governance while necessary are not sufficient. Better coordination amongst all development partners and governments, including a collective commitment to and prioritization of working on these foundational issues, is a necessary first step.

This article investigates the impact of minimalism, collectivist culture, and environmental concern support on green purchase intention through the mediating role of pro-environmental behaviours. We found the following key insights based on our analysis of data from 385 participants in collectivist cultures at the emerging economy countries: (1) pro-environmental behaviours have a positive mediating relationship between minimalism and green purchase intention; (2) pro-environmental behaviours have a positive mediating relationship between collectivist culture and green purchase intention; and (3) pro-environmental behaviours have a positive mediating relationship between environmental concern and green purchase intention. Additionally, the findings show that people who embrace minimalism in collectivist cultures are more inclined to take part in activities that benefit the environment. Similarly, the findings will have an influence on policy-making and practical implementation in similar socioeconomic conditions. Implications relating to theory and practice are discussed.

Obesity is associated with chronic low-grade inflammation. Polyunsaturated fatty ac-ids such as omega-3 (n-3), are essential in the pro-resolution of inflammation. An 8-week double-blind randomized clinical trial was conducted with a n-6:n-3, 5:1 ratio, along with daily 1.8 g of n-3 supplementation vs. placebo. A total of 40 subjects were included, 21 in omega 3 group and 19 in placebo group. The n-3 supplementation had a superior effect compared to placebo increasing levels of Resolvin D1 [129.3 (-90.1 - 193.5) vs. -16.8 (-237.8 - 92.5) pg/mL, p=0.041], IL-10 [1.4 (-0.7 - 4.6) vs. -2.0 (-5 - 0.05) pg/mL, p=0.001], and decreasing IL-6 [-0.67 (2.72 - -0.59) vs. 0.03 (-0.59 - 1.84) pg/mL p=0.015], and MCP-1 [-29.6 (-94.9 - 5.50) vs. 18.3 (-97.3 - 66.35) pg/mL, p=0.040]. In con-clusion, n-3 supplementation promoted resolution of inflammation by increasing sys-temic levels of Resolvin D1, IL-10, and decreasing IL-6 and MCP-1.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

This paper is a follow-up to a previous study that was conducted in a research forest and identified the optimal method for Diameter at Breast Height (DBH) estimation as a circular scanning and fitting ellipses to 4cm stem cross-sections at breast height. The aim of this study was to determine whether the identified method is applicable to natural boreal forests as well. The iPad Pro LiDAR scanner was used to acquire point clouds for 15 sites representing a range of natural boreal forest conditions in Ontario, Canada, and estimate DBH. The secondary objective was to determine if tested stand (Species composition, age, density, understory) or tree (Species, DBH) factors affected the accuracy of estimated DBH. Overall, estimated DBH values were within 1cm of actual DBH values for 78 of 133 measured trees (59%). An RMSE of 1.5cm (8.6%) was achieved. Stand age had a large effect (&gt;0.15) on the accuracy of estimated DBH values, while density, understory, and DBH had moderate effects (0.05-0.14). No trend was identified between accuracy and stand age. Accuracy improved as understory density decreased and as tree DBH increased. Inertial Measurement Unit (IMU) and positional accuracy errors with the iPad Pro scanner limit the feasibility of using this device for forest inventories.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have been attracted attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. This review explores the emerging role of omega-3 FAs and their specialized pro-resolving mediators (SPMs) in the context of macrophage polarization, with a focus on chronic liver diseases. Omega-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have promising effects in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. SPMs, such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties. These mediators modulate the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLD, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3 and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. However, the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment require further investigation. Understanding the intricate relationship among SPM and macrophage polarization holds unlimited potential for the development of novel therapeutic strategies for chronic liver diseases.

In Lubumbashi, the capital of Haut Katanga in the Democratic Republic of the Congo (DR Congo), diesel power plants are a common source of electricity. The need to utilise local renewable energy sources in DR Congo has increased due to the unreliability of the state grid and the rising cost of running Diesel generators. Solar photovoltaic (PV) panels and batteries, in particular, have recently seen significant price drops. Therefore, it is important for operators and suppliers to choose optimal generators together with a renewable energy system to lessen the energy deficit. Diesel generators are still widely used in DRC, but their efficiency pales in contrast to that of more recent power facilities. Consuming fossil fuels results in high expenses for upkeep and operation, in addition to severe environmental damage. This study assessed the feasibility of using local weather and technical data to evaluate the efficiency of a diesel power plant hybridized with a PV system. Hybrid Optimization Model for Electric Renewable (HOMER) simulations suggest that the hybrid system schedule is preferable due to its many economic and environmental advantages for the local community and its inhabitants. The promotion of such a hybrid system, then, may encourage the sustainable economic development of a stable source of electricity for the Congo Region.

Conservation of natural habitats in human-dominated landscapes is critical for halting biodiversity loss. Maintaining habitat quantity and connectivity requires landscape-level collective action, which results from environmental decisions made by individual land owners. We investigate how individual decision making in a rural collective translates into quantitative differences in landscape-level environmental outcomes. Behavioral science has become a critical domain of knowledge in conservation, but little attention has been paid to how multiple behavioral drivers determine the success of collective environmental action. We developed a social-ecological model for landscape-level conservation using a detailed data set of 600 land owners in New Zealand. With the model, we tested whether the effect of social influence networks on collective conservation action was altered by their interplay with land owners’ personal characteristics, connections to cross-scale actors and local environmental contexts. Interactions between multiple behavioral drivers determined the environmental outcomes of collective action in unexpected ways by modifying, muting or amplifying the effects of single drivers. Importantly, we detected a social-ecological mechanism for rapid change in the extent of protected habitats, which can explain highly successful or failed environmental outcomes of collective conservation. Further, when environmentally desirable and undesirable behaviors spread simultaneously through the social network, homophily and network cohesion hinder desirable environmental outcomes. This effect can be modified by other drivers such as social responses to local environmental change. Thus, understanding how the antagonistic and synergistic effects of behavioral drivers can be best utilized in conservation will benefit biodiversity and ensure benefits that humans obtain from biodiversity.

This study investigated the efficacy and safety of a propolis mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multi-centered randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. Results revealed that the PMEC group showed significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p&lt;0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to baseline. While clinical parameters trended towards improvement in both groups, inter-group differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Bangladeshi medicinal plants (BMP) have been used as traditional medicinal plants to treat chronic inflammatory diseases, but the antioxidant and anti-inflammatory effects of the bark of BMP are not yet known. The objective of this study was to determine antioxidant and anti-inflammatory activities using methanolic extracts of bark obtained from 15 medicinal spices of Bangladesh plants. The bark methanol extracts of BMP evaluated the total antioxidant activity and anti-inflammatory effect of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Among the 15 bark extracts of BMP, Albizia odoratissima (A. odoratissima), Engelhardia spicata (E. spicata), and Shorea robusta (S. robusta) showed the highest total phenolic contents and total antioxidant capacity by reducing free radicals scavenging activity. In particular, the three bark extracts significantly reduced the mRNA expression of LPS-induced inflammatory cytokines and inflammation-inducible enzymes in macrophages. Also, the mRNA expression of NADPH oxidase 2 was significantly suppressed by three bark extracts in LPS-induced RAW 264.7 macrophages. The results suggest that among the 15 bark extracts obtained from medicinal plant in Bangladesh, three bark extracts of A. odoratissima, E. spicata, and S. robusta exert total antioxidant capacity by reducing free radicals scavenging activity and inhibitory effects on LPS-stimulated inflammation in macrophages.

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.

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulated immune responses and chronic tissue inflammation. In the setting of inflammatory bowel disease (IBD), dipeptidyl peptidase 4 (DPP4) and gut microorganisms have been proved to interplay, potentially influenced by dietary factors. This rapid review aimed to study the DPP4-gut microbiome link in IBD. A literature search across five databases and two other sources identified seven relevant studies reporting data on DPP4 and gut microbiome, in patients with IBD-related IMIDs or in vitro or in vivo models: one cross-sectional, one in vitro, and five in vivo studies. The findings revealed a significant impact of DPP4 and its substrates, i.e. glucagon-like pep-tide-1/2 (GLP-1/2), on the composition of gut microbiome and on the development of dysbiosis. Increased DPP4 activity is associated with decreased GLP-1/2, increased pathogenic bacteria from Actinobacteria, Bacteroidetes, Deferribacteres, Firmicutes, Fusobacteriota, Proteobacteria, and Verrucomicrobia phyla, and decreased -diversity of beneficial gut microbes, including Clostridiaceae, Lachnospiraceae, and Ruminococcaceae families and short-chain fatty ac-id-producing bacteria like Odoribacter and Butryvibrio spp., with exacerbation of intestinal in-flammation. This overview revealed that understanding the DPP4-gut microbiome association is critical for the development of DPP4-targeted therapeutic strategies to guarantee gut microbiome balance and modulation of immune response in IBD.

Recent research has specifically targeted the decision-making process of eco-friendly individuals, emphasizing the significance of recycling and its impact on sustainability. Our study extends this inquiry by examining the correlation between recycling participation and pro-environmental behavior among consumers, integrating the concepts of self-efficacy, feelings of pride, and social pressure into our analysis. Utilizing Partial Least Squares-Structural Equation Modeling (PLS-SEM), we aimed to explore the intricate relationships that underpin these behaviors. Results suggest that self-efficacy and feelings of pride significantly influence individuals' recycling behaviors, highlighting the role of psychological and social factors in promoting environmental sustainability. Interestingly, it was concluded that social pressure did not have the expected moderating effect on increasing consumers' feelings of pride and self-efficacy toward recycling activities.This study not only sheds light on the underlying mechanisms that drive pro-environmental actions but also contributes to understanding sustainability promotion through recycling and offers insights for policymakers and environmental advocates to foster environmental responsibility and behavior change.

Inflammation is a conserved process that involve the activation of immune and non-immune cells aiming at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called “low-grade systemic chronic inflammation”, characterized by tissue and organ damages, metabolic changes and increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are well recognized anti-inflammatory and immunomodulatory agents able to influence many aspects of the inflammatory process. The aim of this article is to review the recent literature that relates to the modulation of human disease, such as rheumatoid arthritis, by n-3 PUFAs.

The study aimed to investigate the effect of climate change exposure on affect and pro-environmental behavioural intentions in a randomised controlled trial. An online survey was completed by 100 adult participants and included measures of affect and pro-environmental behavioural intentions pre- and post-exposure. Participants were randomly allocated to a group that saw a climate change video (n=55) or a group that saw a non-climate change video (n=45). The findings showed were that participants in the climate change group showed a significant increase in negative affect and pro-environmental behavioural intention scores post-video exposure compared to the non-climate change video group. This suggests that climate change video exposure negatively influences affect but also potentially increases the intention to act pro-environmentally. These findings have the potential to support policies and societal change, however further investigation into the type of contents, actual behaviour change, and impacts on diverse populations (e.g., minority groups) is needed that influences pro-environmental behaviours is required. Furthermore, to achieve a greater impact, future research should be conducted measuring actual pro-environmental behaviour change, including with those from diverse populations.

In recent years, change in behaviour towards the environment has gained prominence as a policy tool to influence positive environmental value. Simultaneously, the role played by social identity in promoting pro-environmental action is gaining recognition. Within this work, the intersection between collective group identity and environmental behaviour has received very little attention. Group norms are considered a strong predictor of pro-environmental behaviour, yet the influence of social identity and collective action on environmental action has not been adequately investigated in a multi-ethnic setting. Within this context, this study examines the affective component of social identity influence on pro-environmental action. More succinctly, this study demonstrates how outgroups and in-groups’ relations and broader socio-cultural structures, values, interest, and norms impact environmental and sustainability transitions behaviours. Through interviews with participants across the four dominant social groups in South Africa, this study provides compelling evidence that country wide expressions of social identity and in-group dynamics shapes the individual behaviour regarding environmental and sustainability concerns and further strengthen the individual’s perspective for social environmental transformation. This study advances the need for a social-identity centred approach to foster pro-environmental and sustainability outcomes.

Metals are indispensable in the life of all organisms, in fact, their dysregulation causes various disorders caused by an interruption of their homeostasis. Nowadays different transition metals are incorporated into pharmaceutical products as diagnostic and therapeutic agents because of their electronic structure which gives them versatility in terms of tuning molecule properties, differently from organic molecules. Hence the interest in the study of metal-drug complexes from different points of view was born and many approaches were developed for the characterization, activation, delivery and molecular mechanisms clarification. The integration of these different approaches starting from chemoproteomics passing through nanoparticle systems to different activation strategies allows the understanding of the cellular responses of metallic drugs, which can be the basis for the design of new drugs and/or modification of drugs currently in use. This review aims to briefly summarize the recent advances in this area by describing the technological platforms and their possible applications to identify protein targets for discovering the mechanisms of action of metallodrugs, and to improve their efficiency in terms of administration.

This case study explores the impact of moderate-intensity exercise on a 35-year-old male novice runner diagnosed with Crohn's Disease (CD). Initially, his symptoms were managed with probiotics and rifaximin, but he experienced a resurgence after a COVID-19 infection, leading to treatment with budesonide. Despite initial hesitation, the patient resumed moderate-intensity running (60-80% VO2 max) after achieving remission. His bowel function, energy levels, and overall well-being improved significantly with exercise. This case suggests that structured physical activity can be beneficial for managing CD and maintaining remission, even amidst fluctuating symptoms and inflammatory markers. It supports the idea that moderate-intensity exercise, when carefully managed, does not inherently worsen the condition and can enhance quality of life. These findings advocate for personalized exercise programs as part of CD management, though further research is needed to establish comprehensive guidelines and evaluate the long-term effects of different exercise intensities on Crohn's Disease.

This literature review focusses on diagnostics of Equine Asthma (EA), possible influencing factors on diagnostic techniques and latest developments in diagnosing horses during EA remission or in case of subclinical disease. Routine EA diagnostics include clinical examination of the respiratory system including percussion and auscultation, clinical pathology including white blood cells and arterial blood gas analysis, bronchoscopy to evaluate the amount and viscosity of respiratory secretion, bronchoalveolar lavage and cytology of tracheal aspirates (TA) and bronchoalveolar lavage fluid (BALF). Grading of EA severity and inflammatory subtype is based on BALF cy-tology, while TA cytology helps to rule out previous bacterial infections. Different factors have an impact on the airways regarding structure of the epithelium, cytology and inflammatory markers possibly influencing the diagnosis of EA. Short-term exercise increases the total cell count and inflammatory mediators in BALF of men, asymptomatic horses and other species. Further factors involve cold or chlorinated air, long-term training effects and the co-incidence of further respir-atory disease, in particular exercise-induced pulmonary hemorrhage. As BALF cytology may be unremarkable during EA remission and low-grade disease, exercise and other factors stressing the bronchial epithelium may help to diagnose these patients.

Recent mental health research has highlighted inflammation's critical role in conditions like depression and bipolar disorder, examining correlations with markers such as calcium levels, thyroid function, and inflammatory markers. The study aims to compare unipolar and bipolar d depression samples in terms of socio-demographic and clinical features. Prospective enrollment of patients hospitalized at the University of Insubria Psychiatric Unit. Patients were administered psychometric questionnaires (Beck Depression Inventory-II, Mental Pain Questionnaire, Beck Anxiety Inventory, Clinical Global Impressions Severity scale, and Reasons for Living Inventory). Thirty-six patients (17 males, 19 females) were enrolled. A statistically significant association emerged between calcium levels and bipolar depression (Pearson Chi square=0.050) and between CRP and bipolar depression (Pearson Chi-square=0.017). Additionally, a statistically significant association was observed between the unipolar and bipolar depression subgroups and current substance abuse (p=0.0275) A statistically significant difference between the BRLF scores and UDD subgroup emerged (p=0.0126). The results of the pilot study revealed significant associations between calcium/CRP levels with depressive symptoms, particularly in bipolar depression. Further research on inflammatory markers is needed to refine diagnostic subtypes and therapeutic strategies.

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.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

Background: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids aetiological assessment. Methods: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of the myocarditis. Results: Of the 84 patients (median age 34 years, range 22–41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still’s disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. Conclusions: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

Since ancient times, various scientists and doctors have utilized different herbs to heal diseases. Due to the rise in drug resistance and the negative effects of chemosynthetic drugs, researchers and the general public around the world have become more interested in medicinal herbs and plant metabolites/extracts. This is due to its non-toxicity and several health benefits when used to treat diseases in clinical and medical settings. Ocimum basilicum is one such plant, possessing a wide range of bioactive phytochemicals including alkaloids, phenolics, flavonoids, tannins, saponins, reducing sugars, cardiac glycosides, steroids and glycosides, as well as complex pharmacological activities including anti-inflammatory, antifungal, antibacterial, antioxidant, wound healing and antiviral properties. The results of many studies on Ocimum basilicum plant extracts are collected and presented in this review. The plant extracts have an excellent potential to be used as medicinal raw materials and exhibit an extensive variety of therapeutic capacities, including antibacterial, antioxidant, wound healing, anti-inflammatory, antifungal, and antiviral properties.

Inflammation is natural protective response of the body tissue caused by various stimuli. Macrophages start and control the inflammatory response. Microalgae have high value of ingredients including carotenoids which are well known for anti-inflammatory properties and used for various products in functional food industries. A green microalgal, Tetraselmis species contains a various type of carotenoids such as lutein, violaxanthin, astaxanthin, fucoxanthin, α-carotene and β-carotene. Therefore, we studied whether carotenoids isolated from Tetraselmis sp. with different culture conditions in Raw 264.7 cells and zebrafish (Danio rerio) have an anti -inflammatory effect. Carotenoid extracts of natural seawater (NS) and magma seawater (MS) showed inhibitory activity of nitric oxide (NO) overproduction without toxicity. In addition, carotenoid extracts of NS and MS inhibited pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 1β and IL-6. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, which are inflammatory mediators also decreased by pretreatment of NS and MS. Carotenoid extracts of NS and MS pretreatment also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB). In conclusion, the carotenoid extract of Tetraselmis sp. has an anti -inflammatory effect and can be potential industrial ingredient.

Objective: To explore the inflammatory markers for the development of obliterative bronchiolitis (OB) after adenovirus infection in children. Methods: In this retrospective study, the medical data of 62 children with adenovirus pneumonia treated in our hospital between February 2020 and November 2021 were collected and assigned to an OB group (n = 30) or non-OB group (n = 32) according to the presence of OB. Clinical characteristics of patients included gender, age, prematurity, underlying disease, length of hospitalization, type of adenovirus infection, ventilator use, length of ventilator use, and laboratory index levels. Results: Children with OB were associated with higher serum ferritin levels versus those without (P < 0.05). There were no significant differences in the immunoglobulin E (IgE), interleukin-6 (IL-6), partial arterial pressure of oxygen (PaO₂), D-dimer, lactate dehydrogenase (LDH), and lymphocyte absolute values between the two groups of children (P > 0.05). Logistic multifactorial regression analysis revealed that the length of ventilator use and serum ferritin level were inflammatory markers for the development of OB in children with adenovirus pneumonia. Conclusion: The length of ventilator use and serum ferritin levels are inflammatory markers for the development of OB after adenovirus infection in children, and timely measurement of the above indicators in children is instrumental in predicting the prognosis of children.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

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.