Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5–200 mg/kg with an intervention time of 7–28 days were relatively effective. Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC.

Liver diseases, including NAFLD and cirrhosis, are significant health issues. This study used Mendelian Randomization (MR) to identify causal links between gut microbiota, lipidomes, immunophenotypes, inflammatory factors, and liver diseases, while also evaluating the therapeutic potential of Lactobacillus salivarius in NAFLD murine models. Summary statistics from GWAS for gut microbiota traits, lipidome components, immune cell counts, inflammatory cytokines, and liver disease traits were analyzed. MR analysis identified causal relationships, with sensitivity analyses confirming the results. Notable findings included 53 gut microbiota taxa, 28 lipidome components, 92 immune cell types, and 8 cytokines linked to liver diseases. Key taxa like Megamonas funiformis increased liver disease risk, while phosphatidylcholines (PCs) were protective. Immune markers such as CD33 on CD33dim HLA-DR- correlated with higher risk, while CD3 on CD39 + resting Tregs and LIF/LIF-R were protective. In vivo, Lactobacillus salivarius treatment significantly improved metabolic and hepatic parameters. The study emphasizes the causal role of gut microbiota and related factors in liver diseases and highlights Lactobacillus salivarius as a promising therapeutic option for NAFLD.

Preventing postoperative bleb scar formation is an effective way of improving glaucoma filtration surgery (GFS) outcome. Use of more effective antifibrotic drugs with fewer adverse effects may be a good way to address the problem. In the present study, we use a primary cell model, consisting of Tenon's fibroblasts obtained from patients with glaucoma, which were stimulated with TGF-β1 to induce the fibrotic phenotype. We explored the effects of niclosamide on TGF-β1-induced fibrosis in these cells and examined its underlying mechanism of action. A transcriptome sequencing assay was used to explore possible signaling pathways involved. Niclosamide inhibited cell proliferation and migration, and decreased the levels of alpha-smooth muscle actin, type I and type III collagen in human Tenon's fibroblasts induced by TGF-β1. Niclosamide also induced apoptosis and counteracted TGF-β1-induced cytoskeletal changes and extracellular matrix accumulation. Moreover, niclosamide decreased TGF-β1-induced phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) protein expression in human Tenon's fibroblasts. The results indicate that niclosamide inhibits TGF-β1-induced fibrosis in human Tenon's fibroblasts by blocking the MAPK-ERK1/2 signaling pathway. Thus, niclosamide is a potentially promising antifibrotic drug that could improve glaucoma filtration surgery success rate.

Excessive extracellular matrix (ECM) deposition leads to renal fibrosis, a typical hallmark of chronic kidney disease. Liquiritin is a flavonoid extracted from the rhizome part of Glycyrrhiza glabra and has anti-fibrotic and nephroprotective effects. However, its role and underlying mechanism in renal fibrosis remain unknown. Human renal proximal tubular epithelial cells (HRPTEpiCs) were stimulated with 10 ng/mL TGF-β1 to induce renal fibrosis models in vitro. The morphology of HRPTEpiCs was observed under a light microscope. CCK-8 was utilized to test cell viability. Immunofluorescence staining was conducted to measure α-SMA expression in HRPTEpiCs. RT-qPCR was used to assess relative mRNA expression. The protein levels of ECM markers, epithelial mesenchymal transition (EMT) markers, and MAPK signaling-related molecules in HRPTEpiCs were tested using western blotting. TGF-β1-treated HRPTEpiCs showed a fibroblast-like morphology, and the morphology of HRPTEpiCs was restored by liquiritin. Liquiritin suppressed TGF-β1-stimulated ECM deposition and EMT process in HRPTEpiCs. Additionally, liquiritin repressed TGF-β1-induced MAPK signaling activation in HRPTEpiCs. Liquiritin mitigates TGF-β1-triggered EMT process and ECM deposition in HRPTEpiCs by inactivating MAPK signaling, thus preventing renal fibrosis.

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation in the intestines, with the primary types including ulcerative colitis and Crohn's disease. The link between autophagy, a catabolic mechanism in which cells clear protein aggregates and damaged organelles, and intestinal health has been widely studied. Experimental animal studies and human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation and other aspects. However, few articles have summarized and discussed the pathways by which autophagy improves or exacerbates IBD. Here, we review how autophagy alleviates IBD through the specific genes (e.g., ATG16L1, IRGM, NOD2 and LRRK2), crosstalk of multiple phenotypes with autophagy (e.g., Interaction of autophagy with endoplasmic reticulum stress, intestinal antimicrobial defense and apoptosis) and autophagy-associated signaling pathways. Moreover, we briefly discuss the role of autophagy in colorectal cancer and current status of autophagy-based drug research for IBD. It should be emphasized that autophagy has cell-specific and environment-specific effects on the gut. One of the problems of IBD research is to understand how autophagy plays a role in intestinal tract under specific environmental factors. A better understanding of the mechanism of autophagy in the occurrence and progression of IBD will provide references for the development of therapeutic drugs and disease management for IBD in the future.

Early weaning is an effective method for improving the utilization rate of sows in intensive pig farms. However, weaning stress induces diarrhea and intestinal damage in piglets. Berberine (BBR) is known for its anti-diarrhea properties and ellagic acid (EA) is known for its antioxidant properties, however, whether their combination improves diarrhea and intestinal damage in piglets has not been studied, and the mechanism remains unclear. To explore the combined effects in this experiment, a total of 63 weaned piglets (Landrace × Yorkshire) were divided into three groups at 21 days. Piglets in the Ctrl group were treated with a basal diet and 2 mL saline orally, while those in the BE group were treated with a basal diet supplemented with 10 mg/kg (BW) BBR, 10 mg/kg (BW) EA, and 2 mL saline orally. Piglets in the FBE group were treated with a basal diet and 2 mL fecal microbiota suspension from the BE group orally, respectively, for 14 days. Compared with the Ctrl group, dietary supplementation with BE improved growth performance by increasing the average daily gain and average daily food intake and reducing the fecal score in weaned piglets. Dietary supplementation with BE also improved intestinal morphology and cell apoptosis by increasing the ratio of villus height to crypt depth and decreasing the average optical density of apoptotic cells; meanwhile, improvements also involved attenuating oxidative stress and intestinal barrier dysfunction by increasing the total antioxidant capacity, glutathione, and catalase, and upregulating the mRNA expressions of Occludin, Claudin-1, and ZO-1. Interestingly, the oral administration of a fecal microbiota suspension to piglets fed BE had similar effects to those of the BE group. According to 16S rDNA sequencing analysis, dietary supplementation with BE altered the composition of the microbiota, including firmicutes, bacteroidetes, lactobacillus, phascolarctobacterium, and parabacteroides, and increased the metabolites of propionate and butyrate. In addition, Spearman analysis revealed that improvements in growth performance and intestinal damage were significantly correlated with differential bacteria and short-chain fatty acids (SCFAs). In brief, dietary supplementation with BE improved the growth performance and intestinal damage by altering the gut microbiota composition and SCFAs in weaned piglets.

Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.

Statins are the first choice for lowering low-density lipoprotein cholesterol (LDL-C) and preventing atherosclerotic cardiovascular disease (ASCVD). However, statins can also upregulate proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn might limits the cholesterol-lowering effect of statins through the degradation of LDL receptors (LDLR). Di’ao Xinxuekang (DXXK) capsule, as a well-known traditional Chinese herbal medicine for the prevention and treatment of coronary heart disease, can alleviate lipid disorders and ameliorate atherosclerosis in atherosclerosis model mice and downregulate the expression of PCSK9. In this study, we further explored whether DXXK has a synergistic effect with atorvastatin (ATO) and its underlying molecular mechanism. The results showed that both ATO monotherapy (1.3 mg/kg) and ATO combined with DXXK therapy significantly lowered serum lipid levels and reduced the formation of atherosclerotic plaques and the liver lipid accumulation. Moreover, compared with ATO monotherapy, the addition of DXXK (160 mg/kg) to the combination therapy further lowered LDL-C by 15.55% and further reduced the atherosclerotic plaque area by 25.98%. In addition, the expression of SREBP2, PCSK9 and IDOL showed a significant increase in the model group, and the expression of LDLR was significantly reduced; however, there were no significant differences between the ATO (1.3 mg/kg) and the model groups. When ATO was combined with DXXK, the expression of LDLR was significantly increased and was higher than that of the model group and the expression of SREBP2 and PCSK9 in the liver was also significantly inhibited. Moreover, it can be seen that the expression of SREBP2 and PCSK9 in the combination treatment group was significantly lower than that in the ATO monotherapy group (1.3 mg/kg). Besides, the expression of IDOL mRNA in each treatment group was not significantly different from that of the model group. Our study suggests that DXXK might have a synergistic effect on the LDL-C lowering and antiatherosclerosis effects of ATO through the SREBP2/PCSK9 pathway. This indicates that a combination of DXXK and ATO may be a new treatment for atherosclerosis.

Coptis Chinensis Franch is widely used in the treatment of diabetes, and berberine is the primary bioactive component in it. Evidence from previous studies has shown that berberine supplementation is effective for treating diabetic nephropathy (DN) in animal models. In this systematic review and meta-analysis, we evaluated the effects and potential mechanisms of action of berberine in animal models of DN. Relevant studies were searched from the English language databases PubMed, Web of Science, and Embase starting from the establishment of the database till June 2022. Twenty-five studies were included, and the risk of bias tool from SYRCLE was used to assess the methodological quality. Statistical analysis was conducted using STATA 15.1. Fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (SCR), and the kidney index (KI) were the primary outcomes to be analyzed. The overall results showed that berberine improves the indicators of renal function, such as BUN, SCR, proteinuria, and KI. Meanwhile, berberine also improved inflammatory indicators, such as IL-6 and TNF-α, and oxidative stress indicators, such as the superoxide dismutase activity and malondialdehyde content. Additionally, berberine lowered the levels of known risk factors, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL). These beneficial effects of berberine in DN may be related to its anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. However, to assess the anti-diabetic nephropathy effects and safety of berberine in a more accurate manner, additional large-scale, long-term, and high-quality preclinical trials are needed to confirm these findings before clinical application.

Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease, the occurrence of which has been increasing worldwide. Research in recent years has found that the level of lysozyme in the feces and blood of UC patients is abnormally elevated, and the bacterial product after the action of lysozyme can be used as an agonist to recognize different cell pattern receptors, thus regulating the process of intestinal inflammation. Berberine (BBR), as a clinical anti-diarrhea and anti-inflammatory drug, has been used in China for hundreds of years. In this study, results showed that BBR can significantly inhibit the expression and secretion of lysozyme in mice. Therefore, we try to investigate the mechanism behind it and elucidate the new anti-inflammatory mechanism of BBR. In vitro, lipopolysaccharide (LPS) was used to establish an inflammatory cell model, and transcriptomic was used to analyze the differentially expressed genes (DEGs) between the LPS group and the LPS + BBR treatment group. In vivo, dextran sulfate sodium salt (DSS) was used to establish a UC mice model, and histologic section and immunofluorescence trails were used to estimate the effect of BBR on UC mice and the expression of lysozyme in Paneth cells. Research results showed that BBR can inhibit the expression and secretion of lysozyme by promoting autophagy via the AMPK/MTOR/ULK1 pathway, and BBR promotes the maturation and expression of lysosomes. Accordingly, we conclude that inhibiting the expression and secretion of intestinal lysozyme is a new anti-inflammatory mechanism of BBR.

Berberine (BBR) is the main active constituent of the Rhizoma coptidis (Huanglian) and has multiple biological activities. Although current evidence suggests that the BBR has a multi-target effect in ulcerative colitis (UC), its action and mechanism are unclear. The purpose of this meta-analysis was to assess the pharmacological effects and potential mechanisms of BBR in UC models. Studies were searched from four databases (PubMed, Embase, Web of Science, and Cochrane Library) until March 2022. Standardized mean difference (SMD) and 95% confidence intervals (CI) were used for the adjudication of outcomes. Stata 15.0 software was used for statistical analysis. Twenty-eight publications and 29 studies involving 508 animals were included in the meta-analysis. The results showed that BBR reduced disease activity index (DAI) scores, alleviated UC-induced colon length (CL) loss, prevented weight loss, and reduced histological colitis score (HCS). Mechanistically, BBR was found to reduce myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, reduce levels of pro-inflammatory factors interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and mRNA expression of interleukin 17, increase levels of anti-inflammatory factor interleukin 10 (IL-10), and to increase levels of tight junction protein zonula occludens-1 (ZO-1) and occludin, which may involve antioxidant, anti-apoptotic, neuromodulation, anti-fibrotic, anti-inflammatory, barrier protection, and flora regulation aspects. However, additional attention should be paid to these outcomes due to the heterogeneity and methodological quality of the studies.

Background Yuanzhi powder (YZP) has been extensively investigated as a natural prescription with therapeutic benefits for Alzheimer's disease (AD). However, its active compounds and underlying immune mechanism for treating AD are still unclear. This study aimed to investigate the immune mechanism of YZP against AD through high-performance liquid chromatography (HPLC)-based network pharmacology and gene chip technology. Methods Active components of YZP were obtained from HPLC and public databases. Subsequently, GSE5281, GSE28146, GSE29378, and GSE97760 from the Gene Expression Omnibus (GEO) database were downloaded to extract AD difference genes (DEGs). The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways, which implicate the targets of YZP for AD, were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT. Results 83 YZP active compounds and 641 DEGs associated with AD, including quercetin, berberine, 3,6′-disinapoylsucrose, coptisine, and palmatine, were evaluated. We showed that FOS, CCL2, and GJA1 were the core targets and that the gap junction is an essential signaling pathway in YZP for AD. Furthermore, the AD group had a higher infiltration level of naïve B cells and resting CD4 memory T cells, as determined by the CIBERSORT. Notably, the immune cells-targets network demonstrates that GJA1 and GRM1 are intimately related to naïve B cells and plasma cells. Conclusions YZP may help treat AD by targeting proteins with key active compounds to regulate naïve B cells and plasma cells. Our results demonstrate a new immune mechanism for treating AD with YZP.

BACKGROUND:Inflammatory bowel disease (IBD) is a chronic, potentially cancerous disease with limited treatment options. Quercetin may be a novel treatment for IBD. However, its efficacy and safety are unknown. Our goal was to conduct a systematic evaluation to summarize the preclinical effects of quercetin, which may help guide future studies. METHODS:The literature was drawn from three English databases (PubMed, Embase, and Web of Science), and the quality of the included literature was assessed using the SYRCLE list (10 items). The meta-analysis was performed using STATA 15.1 software. RESULTS:A total of 11 animal studies with 199 animals were involved. The current meta-analysis showed that quercetin could reduce histological score (HS), Disease Activity Index (DAI), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide(NO), malondialdehyde (MDA), myeloperoxidase (MPO) activity and increase colon length (CL), weight change degree (WCD), interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase (SOD) activity and catalase (CAT) activity, which may involve anti-inflammatory, anti-oxidative stress, cytoprotective, barrier protection, flora regulation. CONCLUSIONS:In conclusion, preclinical evidence suggests that quercetin is an ideal agent for IBD treatment. However, the validity of the findings may be compromised by the low methodological quality and the small number of studies included. There may be some discrepancies between the results of the current analysis and the real situation. More rigorous experimental designs and more comprehensive studies are needed to test the protection of quercetin against IBD.

The performance of weaned piglets suffers from severe limitations resulting from diarrhoea. Therefore, this trial was performed to investigate the effects of Bacillus coagulans as an alternative to antibiotics on piglet growth performance and intestinal health. Ninety (initial BW = 7.70 ± 0.17 kg, weaning age of 26 days) healthy weaned piglets with similar BWs were selected and randomised into three treatment groups. Pigs in the negative control (NC) group were fed a basal diet, pigs in the positive control (PC) group were fed the basal diet plus antibiotics, and pigs in the test group (BC) were fed the basal diet plus Bacillus coagulans at 600 g/t; the trial lasted for 28 days. The results showed that the ratios of feed to gain (F:G) of both the BC and PC groups from 1 to 21 days were significantly lower (P < 0.05), and the average daily weight gain (ADG) of the BC group from 22 to 28 days was significantly higher (P < 0.05) than that of the NC group in terms of growth performance. The diarrhoea index was lowest in the PC group, followed by the BC group, and highest in the NC group. The BC group had a lower diarrhoea index at the later stage. We performed 16S rRNA sequencing to measure the intestinal bacteria and found that the BC group had a higher intestinal bacteria diversity than the NC and PC groups (P < 0.05). From days 1 to 21, the main differential species were Ruminococcaceae_UCG-014 and Faecalibacterium (P < 0.05); from days 22 to 28, the main differential species were Prevotella_9, unclassified_f__Lachnospiraceae, Anaerovibrio, and Ruminococcaceae_UCG-002 (P < 0.05). The correlation analysis between growth performance and species revealed specific gut microorganisms responsible for variation in F:G, ADG, and diarrhoea index, such as Prevotellaceae, Clostridium_sensu_stricto_1, Ruminococcaceae, Phascolarctobacterium, and Anaerovibrio. In conclusion, Bacillus coagulans changed the microbial composition in the faeces of weaned piglets, which had positive effects on growth performance and the diarrhoea index. Therefore, our study provided new insight into the future application of Bacillus coagulans as an additive.

Internal body temperature is the gold standard for the fever of pigs, however non-contact infrared imaging technology (IRT) can only measure the skin temperature of regions of interest (ROI). Therefore, using IRT to detect the internal body temperature should be based on a correlation model between the ROI temperature and the internal temperature. When heat exchange between the ROI and the surroundings makes the ROI temperature more correlated with the environment, merely depending on the ROI to predict the internal temperature is unreliable. To ensure a high prediction accuracy, this paper investigated the influence of air temperature and humidity on ROI temperature, then built a prediction model incorporating them. The animal test includes 18 swine. IRT was employed to collect the temperatures of the backside, eye, vulva, and ear root ROIs; meanwhile, the air temperature and humidity were recorded. Body temperature prediction models incorporating environmental factors and the ROI temperature were constructed based on Back Propagate Neural Net (BPNN), Random Forest (RF), and Support Vector Regression (SVR). All three models yielded better results regarding the maximum error, minimum error, and mean square error (MSE) when the environmental factors were considered. When environmental factors were incorporated, SVR produced the best outcome, with the maximum error at 0.478 °C, the minimum error at 0.124 °C, and the MSE at 0.159 °C. The result demonstrated the accuracy and applicability of SVR as a prediction model of pigs′ internal body temperature.

Normal intestinal microflora and microecology are essential for normal physiological functions in human body. Intestinal microflora imbalance is often observed in patients with alcoholic liver disease and manifests as abnormal number and constituent ratio of intestinal microflora, dysfunction of intestinal mucosal barrier, bacterial translocation, and intestinal endotoxemia, and it plays an important role in the development and progression of alcoholic liver disease. In addition, intestinal microflora also has influence on alcohol metabolism. Probiotics or fecal microbiota transplantation can regulate intestinal microflora and may play an active role in the treatment of alcoholic liver disease. Further studies are needed to discuss the standardized use of microecologics, dose selection, dosage form, and course of treatment during the prevention and treatment of alcoholic liver disease.