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Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease that includes ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis of IBD is not fully understood but is most reported associated with immune dysregulation, dysbacteriosis, genetic susceptibility, and environmental risk factors. Vitamin D is an essential nutrient for the human body, and it not only regulates bone metabolism but also the immune system, the intestinal microbiota and barrier. Vitamin D insufficiency is common in IBD patients, and the abnormal low levels of vitamin D are highly correlated with disease activity, treatment response, and risk of relapse of IBD. Accumulating evidence supports the protective role of vitamin D in IBD through regulating the adaptive and innate immunity, maintaining the intestinal barrier and balancing the gut microbiota. This report aims to provide a broad overview of the role vitamin D in the immune system, especially in the pathogenesis and treatment of IBD, and its possible role in predicting relapse.

Crohn’s disease (CD), a chronic inflammatory bowel disease, is witnessing a rising global incidence. Adalimumab (ADA), a biological agent, is widely used in its treatment. However, patients exhibit significant individual variability in responses to ADA therapy. This study focuses on developing and validating a machine learning – based predictive model to assess the clinical remission of CD patients at 12 and 48 weeks post – ADA treatment, while identifying the key influencing factors. A single – center retrospective study was conducted, involving patients from the Second Xiangya Hospital of Central South University between 2017 and 2024. Comprehensive data on demographics, lifestyle, disease characteristics, and laboratory indicators were collected and preprocessed. The dataset was partitioned into an 80% training set and a 20% test set. Six machine learning models, including Random Forest and Gradient Boosting Machine, were employed to construct the prediction model. Model performance was evaluated using metrics such as accuracy, sensitivity, and specificity. The SHAP analysis was performed to elucidate the key factors. The results indicated that the XGBoost model outperformed other models across multiple evaluation metrics. Fecal calprotectin (Fc), a marker of intestinal inflammation, showed that lower levels were associated with a tendency towards mucosal healing. C - reactive protein (CRP), on the other hand, reflected systemic inflammation. Both biomarkers significantly influenced the prediction outcomes at different time points. The developed model serves as a valuable tool for clinical stratification and personalized treatment planning. Future research should expand sample diversity through multi – center collaboration and integrate multi – omics data, such as gut microbiome and metabolomics, to further enhance the model’s ability to capture the molecular mechanisms underlying the disease.

Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis. Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up. The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including , and . The pathogenic bacteria , , and were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower to ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group. Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.

Abnormal immune regulation is a key feature of the complex pathogenic mechanism of ulcerative colitis (UC). In particular, macrophages and group 2 innate lymphoid cells (ILC2s) are important components of natural immunity that have been shown to play important roles in the pathogenesis of UC, as well as decreased E‐cadherin expression on the colonic mucosa. However, it remains unclear how these components interact with each other. In this study, we investigated the molecular mechanisms of UC mediated by macrophage‐derived exosomes. We showed for the first time that miR‐21a‐5p expression is increased in the peritoneal exosomes of mice with dextran sulphate sodium induced enteritis and that miR‐21a‐5p expression correlates negatively with E‐cadherin expression in enterocytes. Moreover, we confirmed that miR‐21a‐5p was mainly derived from M1 macrophages and demonstrated that KLRG1, a surface inhibitory receptor on ILC2s, participated in excessive ILC2 activation in UC by promoting GATA‐3. In conclusion, our results suggest molecular targets and provide a theoretical basis for elucidating the pathogenesis of UC and improving its treatment.

Background The relationship between Helicobacter pylori ( H. pylori ) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. Methods We established two H. pylori -infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. Results Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori . DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.” Conclusions Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Background Anti-inflammatory therapy is an effective strategy in the treatment of type 2 diabetes (T2D). Studies found that inflammatory responses in vivo were strongly associated with defects in the mucosal barrier function of the gut epithelium. While some microbial strains could help repair the intestinal mucosa and maintain the integrity of the intestinal barrier, the specific mechanisms remain to be fully elucidated. The present study investigated the effects of Parabacteroides distasonis ( P. distasonis ) on the intestinal barrier and the inflammation level in T2D rats and explored the specific mechanisms. Results By analyzing the intestinal barrier function, the inflammatory conditions, and the gut microbiome, we found that P. distasonis could attenuate insulin resistance by repairing the intestinal barrier and reducing inflammation caused by the disturbed gut microbiota. We quantitatively profiled the level of tryptophan and indole derivatives (IDs) in rats and fermentation broth of the strain, demonstrating that indoleacrylic acid (IA) was the most significant factor correlated with the microbial alterations among all types of endogenous metabolites. Finally, we used molecular and cell biological techniques to determine that the metabolic benefits of P. distasonis were mainly attributed to its ability to promote IA generation, active the aryl hydrocarbon receptor (AhR) signaling pathway, and increase the expression level of interleukin-22 (IL-22), thus enhancing the expression of intestinal barrier-related proteins. Conclusions Our study revealed the effects of P. distasonis in the treatment of T2D via intestinal barrier repairment and inflammation reduction and highlighted a host-microbial co-metabolite indoleacrylic acid that could active AhR to perform its physiological effects. Our study provided new therapeutic strategies for metabolic diseases by targeting the gut microbiota and tryptophan metabolism.

Although functional gastrointestinal disorder (FGID) is a common clinical condition, its risk factors remain unclear. We performed a Mendelian randomization study to explore the association between plasma lipids and the risk of FGID. Instrumental variables closely related to six plasma lipids were obtained from the corresponding genome-wide association studies, and summary-level data on FGID, including irritable bowel syndrome (IBS) and functional dyspepsia (FD), were extracted from the FinnGen study. The primary inverse variance weighted method and other supplementary analyses were used to evaluate the causal relationship between diverse plasma lipids and FGID. For each increase in the standard deviation of triglyceride levels, there was a 12.0% increase in the risk of IBS rather than that of FD. Low- and high-density lipoprotein cholesterol, total cholesterol, apolipoprotein A, and apolipoprotein B levels were not associated with the risk of IBS or FD. Through this study, we identified the causal role of triglycerides in the pathogenesis of IBS, which could benefit further basic and clinical research.

The clinical application of music therapy and research into its use and effectiveness are common in Western countries. The physiological role of this type of therapy is to stimulate the central nervous system through music, which may have a sedative, analgesic effect, and reduce negative emotions. Previous studies have confirmed that music can be effective for a range of psychological disorders, including post-stroke depression (PSD). There is, however, a lack of systematic evaluation of its effectiveness, and variability in sample size and in the quality of research has detracted from the persuasiveness of findings. Based on PRISMA 2020, articles on music therapy intervention in post-stroke depression were identified through the Web of Science, PubMed, EMBASE, CNKI, Weipu, and Wanfang databases. The retrieval time was taken from the establishment of the database to October 18, 2022. Two researchers conducted a stringent evaluation of the quality of the articles and extracted the data. They then used RevMan5.3 software for meta-analysis. Twenty articles were listed, involving 1625 patients. Meta-analysis results showed that music therapy could lower scores on the Hamilton Depression Rating Scale (HDRS/Ham-D), the National Institutes of Health stroke scale and self-rated depression scale for patients with PSD. Music therapy was also shown to improve the Barthel Index for Activities of Daily Living and treatment efficacy of PSD patients. However, music therapy did not reduce the incidence of adverse reactions in PSD patients. Music therapy has benefits in improving HDRS/Ham-D score and symptoms of PSD patients, and could be more widely applied. •Based on PRISMA 2020, articles on music therapy intervention in PSD were first identified through the Web of Science, PubMed, EMBASE, CNKI, Weipu, and Wanfang databases.•Music therapy could lower scores on the Hamilton Depression Rating Scale, the National Institutes of Health stroke scale and self-rated depression scale for patients with PSD. Music therapy was also shown to improve the Barthel Index for Activities of Daily Living and treatment efficacy of PSD patients.•Music therapy did not reduce the incidence of adverse reactions in PSD patients.

Current evidence shows an inter-country inconsistency in the effect of lesion size on the technical difficulty of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the specific correlation and quantify the ensuing risks. This retrospective study consisted of 405 ESD cases with gastric single lesion from April 2015 to April 2023. The correlation and risk prediction of lesion size with technical difficulty was explored to provide further clinical evidence. An additive generalized model and recursive algorithm were used to describe the non-linear association, and a linear two-piece regression was constructed to analyze the inflection point. Subgroup analysis and interaction were used to explore intergroup characteristics. Overall, difficult cases had larger lesion sizes, and the more significant the increase, the higher the risk of technical difficulty. In the full model, after adjusting for all covariates, each 1 mm, 3 mm, 5 mm, 7 mm, and one standard increase in lesion size increased the risk of technical difficulty by 8%, 26%, 42%, 72%, and 125%, respectively. There is a nonlinear positive correlation between lesion size and risk of technical difficulty, and the premeditated inflection point was 40 (mm) via two-piecewise linear regression and recursive algorithm. Subgroup analysis showed a stronger correlation between lesion size and difficult ESD in the upper site and submucosal fibrosis groups. Available evidence suggests that lesion size as a risk signal nonlinearly increases the technical difficulty of gastric ESD procedure, especially in cases of upper site and submucosal fibrosis, which deserves further investigation.

The deacetylation process regulated by histone deacetylases (HDACs) plays an important role in human health and diseases. HDAC6 belongs to the Class IIb of HDACs family, which mainly modifies non-histone proteins located in the cytoplasm. HDAC6 plays a key role in tumors, neurological diseases, and inflammatory diseases. Therefore, targeting HDAC6 has become a promising treatment strategy in recent years. ACY-1215 is the first orally available highly selective HDAC6 inhibitor, and its efficacy and therapeutic effects are being continuously verified. This review summarizes the research progress of ACY-1215 in cancer and other human diseases, as well as the underlying mechanism, in order to guide the future clinical trials of ACY-1215 and more in-depth mechanism researches.