Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p<0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Aristotle vs. Ringelmann was a discussion between two distinct research teams from the ETH Zürich who argued whether the productivity of Open Source software projects scales sublinear or superlinear with regard to its team size. This discussion evolved around two publications, which apparently used similar techniques by sampling projects on GitHub and running regression analyses to answer the question about superlinearity. Despite the similarity in their research methods, one team around Ingo Scholtes reached the conclusion that projects scale sublinear, while the other team around Didier Sornette ascertained a superlinear relationship between team size and productivity. In subsequent publications, the two authors argue that the opposite conclusions may be attributed to differences in project populations, since 81.7% of Sornette’s projects have less than 50 contributors. Scholtes, on the other hand, sampled specifically projects with more than 50 contributors. This publication compares the research from both authors by replicating their findings, thus allowing for an evaluation of how much project sampling actually accounted for the differences between Scholtes’ and Sornette’s results. Thereby, the discovery was made that sampling bias only partially explains the discrepancies between the two authors. Further analysis led to the detection of instrumentation biases that drove the regression coefficients in opposite directions. These findings were then consolidated into a quantitative analysis, indicating that instrumentation biases contributed more to the differences between Scholtes’ and Sornette’s work than the selection bias suggested by both authors.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Celiac disease (CD) is a permanent intolerance to dietary protein, gluten, from wheat rye and barley. It occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and innate immune activation are responsible for breaking oral tolerance to gliadin, the gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several evidences show that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD, through the modulation of intestinal permeability and the regulation of the immune system. Here we show that gliadin induces a chronic ER stress condition in the small intestine of a CD mouse model and that the co-administration of probiotics efficiently attenuates both UPR and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, rebalancing the gut microbiota composition by probiotics administration might rep-resent a new strategy to treat CD affected patients.

Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of human gut bacteria microbiota on the gut resistome and the relationship between gut background microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was used to systematically review studies that characterised gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher ARG abundance compared to older infants and adults. Studies that reported correlation revealed positive correlations between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. Overproduction of pro-inflammatory cytokines, including TNF-α and IL-1b, can lead to several diseases eg.,, cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fibres and phenolic acids that have inverse association with the risk of inflammation. The dietary fibres and phenolic acids composition of whole grains is very distinct over different grains. Whole grains (cereals and pseudo-cereals) are rich in both dietary fibres e.g., arabinoxylan, β-glucan and phenolic acids e.g., hydroxycinnamic acids, hydroxybenzoic acids, which are predominantly present in the bran layer. Although the biological mechanisms underlying widely reported association between whole grains consumption and a lower risk diseases are not fully understood. The modulatory effects of whole grains on inflammation also likely to be influenced by several mechanisms, including the effect of dietary fibres and phenolic acids, while some of these effects are direct, others involve gut microbiota, which transform important bioactive substances into more useful metabolites that moderate inflammatory signaling pathway. Thus, the aim of this review is two folded: first is to discuss the types of dietary fibres and phenolic acids commonly found in cereals and pseudo-cereals, and their health benefits observed in animal and human studies. Second, we review existing literature on the linkage between consumption of whole grains and markers of subclinical inflammation, the role of dietary fibres, phenolic acids, and gut microbiota on the anti-inflammatory activity of whole grains intake. Altogether, scientific data on the ant-inflammatory properties of whole grains are encouraging, further researches are needed to cover the gap between the emerging sciences of whole grains dietary fibres, phenolic acids and inflammation.

(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.

Reactive oxygen species (ROS) are a major risk factor for the development of oxidation and inflammation. Ryegrass (pasture), a natural dietary fiber source, acts as an antioxidant with well-known anti-inflammatory properties. The current study aimed to examine the alkaline phosphatase (ALP)-dependent Kelch-like-ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway that facilitates the anti-oxidative and anti-inflammatory properties of pasture and its protective effects on ileal permeability, systemic inflammation, nutrient absorption, liver dysfunction, growth performance, intestinal organ development, and metabolic syndrome in commercial diet-challenged geese. The lipopolysaccharides (LPS), ALP, ROS, and tight junction proteins were determined from the ileum tissues, and the antioxidant enzymes, immunoglobulins, and metabolic syndrome were determined from liver tissues via Enzyme-linked immunosorbent assay (ELISA) kits. While the Nrf2 and LPS/ROS/Keap1-induced inflammatory cytokines were determined by the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. The intestinal morphology was examined by Hematoxylin and Eosin (H&E) staining to determine nutrient absorption in ileal tissues. Pasture-dependent ALP activity significantly ameliorated commercial diet-induced LPS and ROS-facilitated ileal barrier dysfunction and systemic inflammation. The pasture supplementation induced nutrient absorption by influencing intestinal organ development. Our biochemical assays showed that the activation of Nrf2 significantly increased antioxidant enzymes and immunoglobulins, and decreased Keap1 and malondialdehyde (MDA) concentrations in the liver tissues after pasture supplementation. The correlation analysis of ALP, LPS, ROS, and Keap1-Nrf2 pathway-dependent antioxidant enzymes with other host markers showed that pasture supplementation induced intestinal barrier function via reducing LPS/ROS-induced intestinal permeability and systemic inflammation in the ileum and liver tissues. Pasture intake might attenuate LPS/ROS-induced gut permeability, systemic inflammation, and metabolic syndrome and augment gut barrier functions, nutrient absorption, immunity, and growth performance, possibly by its Keap1-Nrf2 pathway-dependent antioxidant properties.

Obesity and chronic inflammation are well-known risk factors for cancer. Interleukin-33 (IL-33) functions in inflammatory diseases, particularly those related to obesity and cancer. However, the correlation and molecular mechanisms linking IL-33, obesity, and cancer remain unclear. IL-33 is a nuclear cytokine released as an alarm signal when cells are damaged or stressed. It is expressed in epithelial, endothelial, and fibroblast-like cells during normal conditions and in-flammation. When IL-33 is present, immune cells expressing the IL-1RL1/ST2 receptor are alerted in response to tissue damage or cell injury. Research on IL-33 and its correlation with obesity has revealed improvements in inflammatory and metabolic changes associated with obesity. IL-33 can have both pro-tumorigenic and antitumorigenic effects, depending on the cellular content, in-flammatory environment, expression levels, and bioactivity of IL-33. This review will discuss the various functions of IL-33 in obesity-driven inflammation and cancers and how they intersect.

Background/Aim: microRNAs (miRNAs) are key regulators of both physiological and pathophysiological mechanisms in diabetes and gastrointestinal (GI) dysmotility. Our previous studies have demonstrated the therapeutic potential of miR-10a-5p mimic and miR-10b-5p mimic (miR-10a/b mimics) in rescuing diabetes and GI dysmotility in murine models of diabetes. In this study, we elucidated the safety profile of a long-term treatment with miR-10a/b mimics in diabetic mice. Methods: Male C57BL6 mice were fed a high-fat, high-sucrose diet (HFHSD) to induce diabetes and treated by five subcutaneous injections of miR-10a/b mimics for a 5-month period. We examined the long-term effect of the miRNA mimics on diabetes and GI dysmotility, including an assessment of cancer risk as well as liver and colon inflammation using cancer and inflammatory biomarkers. Results: HFHSD-induced diabetic mice subcutaneously injected with miR-10a/b mimics monthly for 5 months exhibited a marked reduction in fasting blood glucose levels with restoration of insulin and significant weight loss, improved glucose and insulin intolerance, and restored GI transit time. In addition, the miR-10a/b mimic treated diabetic mice showed no indication of risk for cancer development and inflammation induction in the liver, colon, and blood for the 5 months post injections. Conclusion: This longitudinal study demonstrates that miR-10a/b mimics, when subcutaneously administered in diabetic mice, effectively alleviate diabetes and GI dysmotility for 5 months with no discernible risk for cancer or inflammation in the liver and colon. The sustained efficacy and favorable safety profiles position miR-10a/b mimics as promising candidates in miRNA-based therapeutics for diabetes and GI dysmotility.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

Ostreococcus tauri is a simple unicellular green alga representing an ecologically important group of phytoplankton in oceans worldwide. Modern molecular techniques must be developed in order to understand the mechanisms that permit adaptation of microalgae to their environment. We present for the first time in O. tauri a detailed characterization of individual genomic integration events of foreign DNA of plasmid origin after PEG-mediated transformation. Vector integration appears to be random, occurring mainly at a single locus, and thus confirming the utility of this technique for insertional mutagenesis. While the mechanism of double-stranded DNA repair in the O. tauri model remains to be elucidated, we clearly demonstrate by genome resequencing that the integration of the vector leads to frequent structural variations (deletions/insertions and duplications) and some chromosomal rearrangements in the genome at the insertion loci, and often within the vector sequence itself. From these observations, we speculate that a non-homologous end joining-like mechanism is required during random insertion events, as described in plants and other freshwater algal models. PEG-mediated transformation is therefore a promising molecular biology tool, not only for functional genomic studies, but also for biotechnological research in ecologically important marine algae.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

Looking for effective synthetic methods for 1H-pyrazolo[3,4-b]quinolines preparation, we came across a procedure where in a three component reaction catalyzed by L-proline, 4-aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines are formed. These compounds can be easily oxidized to a fully aromatic system, which gave hope for a synthetic method that could replace e.g. Friedländer condensation, often used for this purpose, although severely limited by the availability of suitable substrates. However, after careful repetition of the procedures described in the publication, it turned out that the compounds described therein do not form at all. The actual compounds turned out to be 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles). 4-Aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines were prepared by another method and used as standards to compare the products formed in the original procedure.

Inflammation and insulin resistance are recognized as central features in the pathology of psoriasis, profoundly affecting the lives of those affected by this condition. The relationship between lifestyle choices and psoriasis is well-documented, highlighting the potential benefits of dietary modifications and physical activity in managing the condition during exacerbations. Furthermore, growing evidence emphasizes the significant impact of nutritional interventions on various skin disorders, particularly those characterized by inflammation and insulin dysregulation. Notably, the role of dietary fats is of particular interest, with their influence on inflammation and insulin resistance in psoriasis garnering increasing attention. Moreover, the association between excessive adiposity and heightened psoriatic severity underscores the importance of weight management strategies in disease management. This review explores the intricate relationship between specific dietary fats and inflammation in psoriasis, offering a comprehensive analysis of their implications for disease progression and management.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Background: The Advanced Lung Cancer Inflammation Index (ALI) is a novel, comprehensive index that integrates inflammation and nutritional status, incorporating parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). Unlike traditional inflammation biomarkers, this study aims to evaluate the prognosis of IPF patients by considering both inflammation and nutritional status. Method: A total of 102 patients with IPF were included in the study. Clinical data were obtained from the patients’ medical records. NLR and ALI score were calculated based on data collected at the initiation of antifibrotic treatment using the following formula: Neut/Lym and albumin × BMI / NLR. Results: IPF subject subgroups in terms of ALI based on gender–age–physiology (GAP) stages (1,2,3), FVC (median split, <70% vs ≥70%), DLCO (<51% vs ≥51%), 6-Minute Walk Test (6MWT) (<350 vs ≥350) and CCI (≤1 vs >1). ALI showed significant difference depending on the categories of GAP stage, FVC, DLCO, and 6MWT but these differences were not observed based on the charlson comorbidity index (CCI) categories (sırasıyla p=0.000, p=0.000, p=0.000, p=0.001, p=0.233). Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the sensitivity and specificity of ALI, albumin, NLR, and BMI in determining the mortality risk in IPF patients. ALI demonstrated a sensitivity of 63.6% and a specificity of 98.9% at a threshold of 11.2 (AUC = 0.945, 95% CI 0.892–0.998, p < 0.000). Conclusion: We determined that ALI levels are significantly associated with disease severity and mortality in patients with IPF.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

The gut microbiome is a collection of microorganisms and parasites that reside in the gastrointestinal tract. There are many factors that can affect the composition of this community, such as age, sex, medications, and environmental triggers. The relationship between the human host and the gut microbiota is very important for both the survival and development of the organism. The disruption of this relationship can lead to the development of various inflammatory diseases. CBD and THC are used to treat muscle spasticity associated with multiple sclerosis. It is now clear these compounds also benefit patients with neuroinflammation. A study that investigated the role of gut microbiota in treating the inflammation and paralysis in a mouse model demonstrated that treatment with CBD and THC produced significant decrease in the inflammation levels. They also exhibited a significant increase in the number of anti-inflammatory cytokines. The presence of certain cannabinoids can suppress neuroinflammation and prevent microbial dysbiosis. Several studies have revealed the role of the gut microbiota in the development and maintenance of skeletal integrity and bone mineral density. The gut is a major source of nutrients, including vitamins B and K. It can also influence the development and maintenance of bone matrix. The presence of the gut microbiota can influence the actions of certain T regulatory cells, which can lead to the development of bone formation and proliferation. In addition, its metabolites can prevent bone loss. The gut microbiota can help maintain the bone's equilibrium and prevent the development of metabolic diseases, such as osteoporosis. In this review, the dual functions gut microbiota plays in the regulation of gut-bone axis and gut-brain axis and the impact of CBD on these roles are discussed in detail.

Inflammation is the body’s response to infection, injury, or other stimuli. Acute inflammation is a crucial component of the immune system’s defense, aimed at eliminating infected or damaged cells and halting disease progression. A subtle interaction between pro- and anti-inflammatory processes determines its progression to inflammation resolution or to chronic inflammation. In this study, we propose a generic model of inflammation through a system of reaction-diffusion equations involving various inflammatory and anti-inflammatory cells and cytokines. We investigate the formation of patterns, determined by the emergence of Turing structures, through linear stability analysis and numerical simulations. These theoretical findings are further supported by observations of similar patterns in skin diseases.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

Background: Monocyte-derived dendritic cells (mo-DCs) play a vital role in the innate immune response by activating Th17 cells, which in turn release the pro-inflammatory cytokine IL-17. We hypothesised that following repetitive mechanical strain, tenocytes activate monocyte-derived dendritic cells, which in turn, drive the pathogenesis of tendinopathy. Aim: The aim of the study was to determine if monocyte-derived dendritic cells are upregulated in a human tendinopathy model. Method: Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from 7 patients undergoing arthroscopic shoulder surgery. Healthy control samples of subscapularis tendon were collected from 5 patients undergoing arthroscopic stabilization surgery. Tendon biopsy samples were evaluated immunohistochemically by quantifying the presence of monocyte-derived dendritic cells (CD11C and CD206). Results: Tendinopathic tendon samples exhibited significantly greater (2-3-fold) monocyte-derived dendritic cell expression when compared with healthy control tissue (P &lt; .05). Conclusion: This study provides evidence for a monocyte-derived dendritic cell upregulation in early-stage human tendinopathy.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

The tumor necrosis factor receptor associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-B activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1 secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we show that intraarticular injection of TRAF1 deficient macrophages into knee joints of wildtype (WT) mice subjected to the collagen antibody induced arthritis (CAIA) model of RA significantly exacerbated joint inflammation, immune cell infiltration and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

Chronic inflammation may have a detrimental impact on human health as it tends to result in cancer. In addition, it is often linked to different steps that participate in tumorigenesis, including cellular transformation, survival, promotion, invasion, proliferation, angiogenesis, and metastasis. Hence, inflammation predisposes cancer development and plays a vital role in promoting all tumorigenesis stages. Inflammation is caused by many factors, such as bacterial and viral infections, tobacco smoking, autoimmune diseases, obesity, asbestos exposure, and many others, increasing cancer risk. Moreover, cancer can be enhanced by mutations that proceed to cancer progression. Consequently, it leads to immunosuppression and provides a favorable background for tumor development. Although many studies address the question of relationships between inflammation and cancer development, little attention is paid to the link between inflammation and blood cancer. Therefore, the current study reviews the role of inflammation in cancer development, particularly in blood cancer. A meta-analysis research approach meets the research objective and answers the research question. The review results indicate that chronic inflammation directly relates to the development of many cancer types, blood cancer in particular.

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

This study aimed to determine the impact of a novel formulation of a supplement composed of the natural ingredients: bromelain, quercetin, and Lentinula edodes, on the gut microbiota of healthy adult dogs. Adult healthy female dogs were administered either a placebo (CTR, n = 15) or the supplement (TRT, n=15) over 28 days. Stool samples were collected for 16S rRNA sequencing before supplement administration (T0), at completion of supplement administration (T28), and one week after the end of supplement administration (T35) to characterize changes in the gut microbial communities. QIIME was used to determine both alpha- and beta-diversity and ANCOM-BC was used to identify differences in taxonomic abundances before and after supplementation. We found a significant decrease in overall diversity in CTR group, but no significant differences in overall diversity in the TRT group over time. Furthermore, we found differences in the abundance of several taxa in both CTR and TRT groups but differences in abundance of beneficial bacteria were more pronounced in TRT group. Specifically, we found increases in the abundance of sequences belonging to the genera Bifidobacterium, Lactobacillus, and Pediococcus at T28 in the TRT group with significant increases in Bifidobacterium and Lactobacillus persisting at T35 when compared to T0. Importantly, members of these genera are known to be pro anti-inflammatory and associated with a healthy gut microbiota in dogs. The results of our study show the potential of our supplement to selectively enhance specific beneficial bacterial taxa, offering a targeted approach to modulating the gut microbiome without causing disruptions to the overall equilibrium.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

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

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

The yak (Poephagus grunniens) has evolved unique adaptations to survive the harsh environment of the Tibetan Plateau, while their gut microorganisms play a crucial role in maintaining the health of the animal. Gut microbes spread through the animal population not only by horizontal transmission but also vertically, which enhances microbial stability and inheritance between generations of the population. Homogenization of gut microbes in different animal species occurs in the same habitat enhancing interspecies coexistence. Using the yak as a model animal, this paper reviews the adaptive strategies under extreme environments and how the gut microbes of the yak circulate throughout the Tibetan Plateau system, which not only affects other plateau animals such as plateau pikas, but can also have a profound impact on the health of people. By examining the relationships between yaks and their gut microbes, this review provides new perspectives in understanding the adaptations of plateau animals and the stability of the ecosystem.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with in-gested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant to help evaluate potential effects of ingested jet fuel. Results of the in vivo study provided evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), indi-cations of abnormal estrous cycles, and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while the alternative jet fuel derived from the camelina plant was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid re-ceptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action.

Thimerosal (TmHg) has been used in thimerosal-containing vaccines (TCV) and various med-icines, although to our knowledge, there are no studies evaluating its effects on microglia. Microglia are a crucial glial component that have important functions in inflammatory diseases, particularly in the Central Nervous System (CNS). They are also considered a key player in neurotoxicity. Furthermore, microglia are responsible for the activation of immune responses and plays an essential role for the maintenance of brain homeostasis. Microglial response is important for the maintenance of CNS immune regulation. Moreover, microglia cells partici-pate in the removal of cellular debris and pathogens, playing an important role as neuroprotectants in several CNS diseases, including neurodegeneration. The objective of this study was to evaluate the effects of TmHg and its metabolite ethylmercury (EtHg) on microglial cells. Our novel findings demonstrated that microglia are more sensitive to TmHg than to EtHg with EC50 1.4 ± 0.4 μM and 2.3± 0.9 μM for 24h, respectively. The mercury compounds also induced the transcription of pro-inflammatory markers s such as IL-1β; iNOS, and to a lesser extent TNF-α expression. Likewise, the increase in Beclin-1 expression - a protein associated to autophagy - and the number of senescent cells indicate that microglia are activated by TmHg and EtHg. The effects of thimerosal may have different consequences depending on the health status and susceptibility of the populations.

Cholera is a diarrheal disease prevalent in populations without access to clean water. Cholera is caused by Vibrio cholerae, which colonizes the upper small intestine in humans once ingested. A growing number of studies suggests the gut microbiome composition modulates animal behavior. Zebrafish are an established cholera model that can maintain a complex, mature gut microbiome during infection. Larval zebrafish, which have immature gut microbiomes, provide the advantage of high-throughput analyses for established behavioral models. We identified the effects of V. cholerae O1 El Tor C6706 colonization at 5 days post-fertilization (dpf) on larval zebrafish behavior by tracking startle responses at 10 dpf. We also characterized the larval gut microbiome using 16S rRNA sequencing. V. cholerae-infected or uninfected control groups were exposed to either an alternating light/dark stimuli or a single-tap stimulus, and average distance and velocity were tracked. While there was no significant difference in the light/dark trial, we report a significant decrease in distance moved for C6706-colonized larvae during the single-tap trial. This suggests that early V. cholerae colonization of the larval gut microbiome has a dampening effect on sensorimotor function, supporting the idea of a link between the gut microbiome and behavior.

The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after Lacrimal Gland (LG) ablation. The LG of Wistar rats were submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n=7-10/group). The eye wipe test, slit-lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 03 groups have shown corneal neovascularization. Histology revealed changes in LG, and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2 and RUNX-1 at M1 and M2 in G1 and RUNX-3 mRNA at M1 in G1, and in G2 at M2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1β mRNA in the Trigeminal Ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation or grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Type-1 Diabetes Mellitus (T1D) onset and development is closely linked with imbalance of gut microbiome, while supplementation with probiotics may result in positive alterations in gut microbiome composition. In the present study, the effect of a dietary intervention including free or immobilized cells of the presumptive probiotic Pediococcus acidilactici ORE5 on Corinthian currants, a food with beneficial impact in the condition of diabetes, was investigated. Male Wistar rats were studied which were divided into 4 groups: healthy animals, which received the free (H_FP) or the immobilized cells (H_IPC), and diabetic animals, which received the free (D_FP) or the immobilized cells (D_IPC), for 4 weeks (109 cfu/day, in all groups). At the end of the dietary intervention, D_IPC group exerted lower concentration of the inflammatory cytokine IL-1b compared to D_FP. Consumption of immobilized on Corinthian currants P. acidilactici ORE5 cells by diabetic animals led to increased loads of fecal lactobacilli and lower levels of Enterobacteriaceae, coliforms, and E. coli, while Actinobacteria phylum, Akkermansia, and Bifidobacterium genera abundances were increased, and fecal lactic acid was elevated. Overall, the results of the present research demonstrated that functional ingredients can ameliorate gut dysbiosis present in T1D and could be used to design dietary patterns aiming at T1D management. However, well-designed clinical trials are necessary, in order to confirm the beneficial effects in humans.

Diet plays a pivotal role in the overall health of an individual. Not only does it help carry out and regulate certain physiological functions, but it also can determine the composition of the gut microbiome. While the relative number of microorganisms that make up the gut microbiome vary between individuals and can be dependent on different environmental factors, there is evidence to suggest that composition of the microbiome can correlate with overall health or disease. When the GI microbiome is disturbed or suddenly changes it results in microbiome dysbiosis, a condition that correlates with the presence of certain diseases. Diseases linked to microbiome dysbiosis range from metabolic disorders, inflammatory bowel diseases to disorders of the brain. Many of these diseases are linked to the connection between the brain and the gut, known as the brain-gut axis. This bidirectional communication is important to maintain normal intestinal function, but is also responsible for the GI response to emotions as well as the emotional response to GI disturbances. By exploiting the interaction between microbiome health and nutrition, diet can be used to alleviate disease symptoms, protect against the development of certain conditions, and better maintain overall health. This review will examine the effects of nutrition on the microbiome, diseases linked to disruption of the normal microbiome, and the way that altering the diet can mitigate symptoms or prevent disease.

This study investigated the development of novel probiotic formulations specifically designed for rainbow trout aquaculture. The project evaluated the effects of two formulations containing potential probiotic strains isolated from rainbow trout itself. These effects were assessed on various parameters including growth performance, immune response, liver enzyme activity, gene expression related to immunity, and the composition of the bacterial gut microbiota in rainbow trout (Oncorhynchus mykiss). In a completely randomized experimental design, a total of 450 rainbow trout were randomly divided into 70-liter fiberglass tank. The study included six treatments of three replicates (n=18 tanks). Six dietary treatments were included (A) and (B) containing three strains of Pediococcus sp P15, Lactococcus lactis ml3, Weissella cibaria ml6 at two dosages (300 and 500 mg/kg), treatments (C) and (D) containing five strains of P. sp P15, L. lactis ml3, W. cibaria ml6, Enterococcus faecium E10 and Lactobacillus curvatus 13A at two dosages (300 and 500 mg/kg), a commercial probiotic (E) at 300 mg/kg, and a control group (F) without probiotics. Treatments of (A), (B) and (E) resulted in the highest final weights in compared to control group. Fish fed treatments (A) and (B) had the lowest FCR than other groups. Treatments (A) and (D) showed a significant increase in immunoglobulin M (IgM) concentration compared to other groups. The expression of tumor necrosis factor (TNF) was significantly lower in group (A) than the control. In contrast, the expression of interleukin 6 (IL6) and immunoglobulin T (IgT) was increased 4.4-fold and 41-fold, respectively, in group (A) compared to control group. Among the probiotic fed treatments, group (A) showed a significant higher number of lactic acid bacteria compared to other groups during the experiment. This study highlights the significant role of treatment (A) containing three strains of P. sp P15, L. lactis ml3, and W. cibaria ml6 at a dosage of 300 mg/kg as a potential probiotic product for the rainbow trout industry.

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.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Backround: Thoracic trauma causes life-threatening organ injuries, ranging from simple abrasions to contusions of intrathoracic organs. In this study, we aimed to investigate the effects of bosentan on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Methods: Thirty-seven animals male Sprague-Dawley rats were divided into 5 groups. All 4 groups, except for the control group, were performed to PC. In the first group, C: control group (n=6) consisted of unprocessed and untreated. The second group, PC3 (n=8) underwent of 3 days PC performed. The third group, PC-B3 (n=8) received 100 mg/kg bosentan was given orally once a day for 3 days. The fourth group, PC7 group (n=7) underwent of 7 days PC performed, and the fifth group PC-B7 (n=8) received 100 mg/kg bosentan was given orally once a day for 7 days. While ET-1, NF-B, TNF-, and HIF-1 was measured by ELISA method, TAC and PAB by spectrophotometric in lung tissue samples. Results: ET-1, NF-B, TNF-, HIF-1, and PAB levels were higher, while TAC activities were lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-- levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05) while NF-B, HIF-1, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan treatment causes decreased ET-1, NF-B, TNF-, HIF-1, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: We found that the use of bosentan decreased the severity of oxidative stress in the lung and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, oxidative stress in some diseases that may be accompanied by ischemia.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

The pathogen Cryptococcus neoformans is a major cause of fungal meningitis in humans. As with other melanotic microorganisms associated with human diseases, the cell wall-associated melanin of C. neoformans is a major virulence factor that contributes to its ability to evade host immune responses. The levels of melanin substrate and the regulation of melanin formation could be influenced by the microbiota-gut-brain axis. Moreover, recent studies show that C. neoformans infection causes dysbiosis in the human gut microbiome. In this review, we discuss the potential association between cryptococcal meningitis and the gut microbiome. Additionally, we emphasize the promising prospects of targeting the gut microbiome as a means of diagnosing and treating this debilitating disease.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium brevis BBr60 group or a placebo group. Both groups received diet guidance and took either BBr60 (1×1010 CFU/day) or a placebo for 12 weeks. Re-searchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pre-treatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulating BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Maternal obesity and gestational diabetes mellitus (GDM) are the most common metabolic conditions with have unfavourable impact on maternal and fetal health. Key biosubtrats such as apelin, vascular endothelial growth factor (VEGF), leptin, and DNA methylation play crucial roles in these pathologic conditions. Apelin is a peptide involved in regulating glucose metabolism and cardiovascular functions. This molecule also interacts with the apelin receptor to enhance glucose uptake, suggesting potential therapeutic implications for managing GDM and obesity. Leptin, a hormone predominantly produced by adipose tissue, regulates appetite and energy balance. In obesity, leptin levels are often high, but a resistance to its effects develops, disrupting normal metabolic processes. Similarly, in GDM, elevated leptin may impair glucose metabolism and contribute to insulin resistance. VEGF is critical for angiogenesis, the formation of new blood vessels, and is often found in increased concentrations in obese individuals and those with GDM. This elevation may contribute to abnormal placental function and vascular complications, exacerbating both conditions. DNA methylation, an epigenetic modification, plays a crucial role in gene expression regulation. In both GDM and obesity, altered DNA methylation patterns have been observed, affecting genes involved in metabolism, inflammation, and insulin sensitivity. These epigenetic changes may predispose individuals to metabolic disorders. In our study we investigated placental apelin, leptin, VEGF, and DNA methylation interconnection in the pathophysiology of GDM and obesity during gestation. They have similar or different influencing on metabolic regulation, vascular function, and gene expression in GDM and obesity? Sonogpahic examinatios supported the metabolic analyses for that understanding their roles may lead to better management and therapeutic strategies for these conditions.

It is estimated that pancreatic cancer will be the 2^nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

The microbioma is presently one of the hottest areas of scientific and medical research and exerts a marked influence on the host during homeostasis and disease. Fermented foods arise in the human relationship to the microbial environment. Further to the traditionally recognized effects of fermented foods and beverages on the digestive health and well-being there is now strong evidence on their general health benefits, namely the significance on the gut microbiota and brain functionality. We highlight the possibilities in this field, how little is still known, and call for a convergence of interdisciplinary research fields of One Health microbe-nutrition with fermented foods and gut-brain research. A consequence of civilisation, changes in present-day society in diets with more sugar, fat and salt, habits and lifestyle, contributes to the likelihood of an inflammatory microbiome, particularly the global epidemics of obesity and mental health. Although two recent papers claim that probiotics perturb rather than aid in microbiota recovery back to baseline after antibiotic administration in humans, consuming fermented foods has shown to reduce inflammation so improve gut health and the proper function of the body’s immune system.

Schizophrenia is a complex mental disorder influenced by genetic and environmental factors, including diet. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Nutritional deficiencies, such as lack of omega-3 fatty acids, vitamin D, and B vitamins, during prenatal and postnatal periods can nega-tively impact neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia show imbalances in antioxidant enzymes such as: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced levels of antioxidants (vitamin E, vitamin C), leading to increased oxidative stress markers such as malondialdehyde (MDA). Cytokine-mediated inflammation, microglial activation, and gut dysbiosis are associated with schizophrenia onset and symptom severity. There is no clear and universally accepted diet for the treatment of schizophrenia, which is considered the most popular. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the general health of patients, including the mediterranean diet, ketogenic diet, gluten-free diet and DASH diet. A healthy diet rich in anti-inflammatory and antioxidant nutrients can help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D and B vitamins are par-ticularly important for brain development and function. In this review we will focus on the influence of diet on schizophrenia. Additional research is needed to develop per-sonalized dietary recommendations for patients with schizophrenia.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

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

Background: Platelets are increasingly recognised for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. Methods: This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasising recent publications. Results: Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Conclusion: Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

Arrhythmogenic cardiomyopathy is a primary genetic disease caused by mutations of the desmosome genes. Ever since the introduction of new imaging criteria, like cardiovascular magnetic resonance, the diagnosis of arrhythmogenic cardiomyopathy is more challenging as left ventricular or biventricular variants may cause resemblance with other cardiomyopathies or myocarditis. Not only this, but they may also share an acute phase that might determine even more confusion and misdiagnosis which can influence prognosis and outcome. In this case report we present a 31-year-old patient with multiple clinical pictures: acute chest pain, new onset of heart failure and arrhythmia symptoms which determined a dynamic change in clinical diagnosis and management, ultimately taking into consideration arrhythmogenic cardiomyopathy. Through the article we try to emerge and explain common pathophysiological pathways shared by arrhythmogenic cardiomyopathy and other clinical entities with a special focus on inflammation. The final question remains: “If there is more than one heart disorder that eventually will lead to the same clinical picture, one could not but wonder if arrhythmogenic cardiomyopathy is rather a syndrome than a specific condition?”

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in close vicinity as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

Gut microbiota is a complex and dynamic ecosystem that influences various aspects of human health. Unfortunately, there is a lack of literature highlighting the importance of gut microbiome especially in diabetes management. This paper performs bibliometric analysis to establish the rising interest of researchers in this area and the importance of gut microbiota in diabetes management. Subsequently, the study performs a narrative review to provide an overview of the gut microbiota consisting of bacteria, archaea, fungi, and viruses, and its diversity, composition, and variation among individuals. The paper further discusses the role of the gut microbiota in different diseases, including Clostridium difficile infection, behavioral disorders, cancer, obesity, diabetes, atherosclerosis, and inflammatory bowel disease, among others. It emphasizes the link between gut dysbiosis (imbalanced gut microbiota) and the development of chronic metabolic disorders. Additionally, the paper discusses the factor negatively impacting the gut microbiota. The paper concludes by explaining the mechanistic abnormalities that link dysbiosis to type 2 diabetes, including changes in short-chain fatty acid production, amino acid metabolism, bile acid regulation, and the production of specific bacterial products. Thus, the paper highlights the importance of understanding gut microbiota and related mechanisms for developing therapeutic interventions targeting the gut microbiota.

The mammalian gut ecosystem plays critical roles in multiple functions related to health and homeostasis. In many cases, disturbances in the gut ecosystem are associated with a large number of metabolic and chronic diseases and disorders such as diabetes, cancer, and obesity. A diverse community of microorganisms ranging from viruses to bacteria comprise the gut microbiota, which is often considered as an organ in itself. Recent studies have profiled the influence of lifestyles and dietary behavior by comparing the gut microbiome of populations with different cultural underpinnings. In this review, we provide an overview of the studies which report the influence on the gut microbial composition of dietary and lifestyle patterns in different contexts such as western industrialized countries and indigenous cultures (corresponding to different lifestyle gradients such as hunter-gatherers and pastoralists) and how this association may influence health and disease.

Nutrition is crucial for the management of patients affected by chronic kidney disease (CKD) to slow down disease progression and to correct symptoms. The mainstay of the nutritional approach to renal patients is protein restriction coupled with adequate energy supply to prevent malnutrition. However, other aspects of renal diets, including fiber content, can be beneficial. This paper summarizes the latest literature on the role of different types of dietary fiber in CKD, with special attention to intestinal microbiota and the potential protective role of renal diets. Fibers have been identified based on aqueous solubility, but other features, such as viscosity, fermentability, and bulking effect in the colon should be considered. A proper amount of fiber should be recommended not only in the general population but also in CKD patients, to achieve an adequate composition and metabolism of intestinal microbiota and to reduce the risks connected with obesity, diabetes, and dyslipidemia.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Gut microbiota plays a critical role in physiological regulation throughout life and is specifically modified to meet the demands of individual life stages and during pregnancy. Maternal gut microbiota is uniquely adapted to the pregnancy demands of the mother and the developing fetus. Both animal studies in pregnant germ-free rodents and human studies have supported a critical association between the composition of maternal microbiota during pregnancy and fetal development. Gut microbiota may also contribute to the development of the fetal gut-brain axis (GBA), which is increasingly recognized for its critical role in health and disease. Most studies consider birth as the time of GBA activation and focus on postnatal GBA development. This review focuses on GBA development during the prenatal period and the impact of maternal gut microbiota on fetal GBA development. It is hypothesized that adaptation of maternal gut microbiota to pregnancy is critical for the GBA prenatal development and maturation of GBA postnatally. Consequently, factors affecting maternal gut microbiota during pregnancy, such as maternal obesity, diet, stress and depression, infection, and medication, also affect fetal GBA development and are critical for GBA activity postnatally. Altered maternal gut microbiota during gestation has been shown to have long-term impact postnatally and multigenerational effects. Thus, understanding the impact of maternal gut microbiota during pregnancy on fetal GBA development is crucial for managing fetal, neonatal, and adult health, and should be included among public health priorities.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

Microbial composition across substrates in mangroves, particularly in the Middle East, remains unclear. This study characterized bacterial communities in sediment, water, Terebralia palustris snail guts, and plastic associated with Avicennia marina mangrove forests in two coastal lagoons in the Sea of Oman using 16S rDNA gene MiSeq sequencing. The genus Vibrio dominated all substrates except water, which featured unique genera Sunxiuqinia and Pseudomonas. There were significant differences in bacterial communities on different substrata, in particular plastic. Snail guts harbored the highest number of unique Operational Taxonomic Units (OTUs) in both lagoons. Plastic in the polluted Sawadi lagoon with low salinity harbored distinct genera like Vibrio, Aestuariibacter, Zunongwangia, and Jeotgalibacillus absent in Qurum lagoon with higher salinity and low pollution. Sawadi lagoon exhibited higher species diversity in sediment and plastic substrates, Qurum lagoon demonstrated lower overall species diversity. The PCA indicates that environmental factors like salinity, pH, and nutrient levels significantly influence bacterial community composition across substrates. Variations in organic matter and potential anthropogenic influences, particularly from plastics, further shape bacterial communities. This study highlights the complex microbial communities in mangrove ecosystems, emphasizing the importance of considering multiple substrates in mangrove microbial ecology studies.

Because data on the fungal gut community structure of African children are scarce, we aimed to describe by reanalysing rRNA ITS1 and ITS2metabarcoding data from a study designed to assess the influence of microbiota in malaria susceptibility in Malian children from the Dogon country. More specifically, we aimed to establish the core gut mycobiome and compare the gut fungal community structure of breastfed children, aged 0-2 years, with other age groups. Briefly, DNA was extracted from 296 children’s stool samples. Both rRNA ITS1 and ITS2 genomic barcodes were amplified and subjected to Illumina MiSeq sequencing. The ITS2 barcode generated 1,975,320 reads and 532 operational taxonomic units (OTUs), while the ITS1 barcode generated 647,816 reads and 532 OTUs. The alpha diversity was significantly higher by using the ITS1 compared to the ITS2 barcode (p

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-кB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-кB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-кB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-кB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-кB crosstalk.

The Ro60 autoantigen is an RNA-binding protein, and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates quality control and cellular dis-tribution of YRNAs, retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal TLRs and cytoplasmic RNA sensors, which typically sense patho-gen-associated molecular patterns (PAMPs) and mount the first line of defence against invading pathogens. However, recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for an-ti-drug antibody response among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mecha-nisms of autoimmune conditions.

Background: Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here we report studies that address this question. Methods: 14 weeks on high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Results: Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and prevent cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Conclusions: Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extra-cellular upstream signals involved in the regulation of anabolic and catabolic processes in cells, and plays a key regulatory role in cell growth and metabolism. Activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that the gut microbes and its complex metabolites can regulate host metabolic and immune responses through the mTOR pathway, and result in disorders of host phys-iological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases, and discuss the crosstalk between gut microbes and their metabolites and mTOR in the disorders in gastrointestinal tract, liver, heart and other organs. We also discuss the promising appli-cation of multiple potential drugs that can adjust the gut microbiota and mTOR signal pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

Worldwide, the demand for natural and synthetic sweeteners in the food industry as an alternative to refined sugar is increasing. This prompted more research to estimate its safety and effect on health. The gut microbiome is critical in metabolizing selected sweeteners, which might affect overall health. Recently, more studies evaluated the relationship between sweeteners and the gut microbiome. This review summarizes the current knowledge addressing the role played by the gut microbiome in metabolizing selected sweeteners. It also addresses the influence of the five selected sweeteners or their metabolites on GI cancer-related pathways. Overall, the observed positive effect of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, requires further investigation to understand the underlying mechanism. Furthermore, more research is needed to address the main challenges of studying the field, thus advancing it further.

Some management practices, such as maintaining birds under high group density, used in the poultry industry may cause birds stress, leading to injurious behaviors, such as injurious pecking, aggression, and cannibalism. In addition, some management practices used to prevent severe injuries in birds may cause pain. Beak trimming (BT), removal of 1/3 to 1/2 of a beak, is a routine husbandry procedure practiced in laying hens to prevent or reduce injurious behaviors. However, BT causes tissue damage, which may increase somatosensory sensitization of the damaged nerve tissues, resulting in pain (acute, chronic or both) in the treated birds because the beak is a complex, functional organ with an extensive nerve supply. BT has already been heavily regulated or prohibited in several European countries and, in time, this trend will impact the practice used in the United States poultry industry. With the growing public concern for poultry welfare there is a pressing need to identify and develop alternatives to BT. Probiotics defined “as a source of live (viable) naturally occurring microorganisms (direct-fed microbials)” have been used as dietary supplements or functional foods to target gut microbiota (microbiome) for prevention or therapeutic treatment of mental diseases including social stress-induced psychiatric disorders in humans and various experimental animals. In our studies, chickens were used as an animal model to assess if dietary supplementation of probiotic, Bacillus subtilis, reduces injurious behaviors following social challenge. Hens of Dekalb XL strain, an aggressive line, were used in the studies. Our results indicate that dietary supplementation of the Bacillus subtilis based probiotic reduces aggressive behaviors in chickens. These results suggest dietary probiotics could be a suitable strategy for increasing hosts’ health status and welfare conditions.