BACKGROUND Oxymatrine (OMT) has the potential to regulate intestinal microbiota and hepatic metabolites. AIM To explore the underlying mechanisms by which OMT exerts its effects on metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS An MASLD rat model induced by a high-fat, high-sucrose diet was treated with OMT. Assessments included serum/Liver biochemical parameters, histopathology (hematoxylin eosin and oil red O staining), intestinal permeability, 16S rRNA gut microbiota sequencing, and hepatic metabolomics. Correlation analysis linked changes in microbiota to metabolic shifts. To test the hypothesis that gut microbiota mediates the efficacy of OMT, we conducted fecal microbiota transplantation experiments. RESULTS OMT effectively alleviated MASLD in rats by improving serum lipid profiles (P < 0.05), reducing hepatic steatosis (P < 0.05) and inflammatory cytokine levels (P < 0.05), and enhancing intestinal barrier function. It substantially restored gut microbiota diversity, increasing beneficial genera such as Lactobacillus, modulating hepatic metabolites such as luteolin (P < 0.001), and lowering adrenic acid (P < 0.001), which are linked to lipid and inflammatory pathways. Correlation analysis indicated a strong association between changes in specific microbiota and metabolic improvement. Fecal microbiota transplantation experiments indicated that transferring OMT-modulated microbiota recapitulated the therapeutic effects in recipients, suggesting that the gut microbiota contributed substantially to the efficacy of OMT. CONCLUSION This study indicated that OMT alleviated MASLD in rats by regulating intestinal microbiota and hepatic metabolites, highlighting its promise as a therapeutic agent.

The incidence of drug-induced liver injury (DILI) is on the rise, and discontinuation of suspected causative drugs is the core therapeutic principle. However, some patients may progress to moderate-to-severe liver injury, liver failure, or chronicity; thus, pharmacotherapy maybe considered a potentially valuable supportive treatment option in appropriate clinical contexts. At present, there is no unified consensus on the therapeutic indications and drug selection for DILI worldwide, and irrational practices such as prophylactic medication, indication-free medication and polypharmacy exist in China. This review proposes formulating therapeutic indications based on the severity, type of liver injury and Hy's Law, identifying TBIL≥2 × ULN, cholestatic and mixed liver injury, acute liver failure (ALF), and high risk of ALF as indications for pharmacotherapy. For drug selection, N-acetylcysteine (NAC) is recommended by all domestic and international guidelines, Glucocorticoid (GC) may be used in selected cases, and hepatoprotective drugs such as magnesium isoglycyrrhizinate (MgIG) and bicyclol are widely prescribed in China. Pharmacotherapeutic regimens can be tailored according to the type and severity of liver injury.

In cholestatic drug-induced liver injury, serum liver function tests typically demonstrate concurrent elevations in alkaline phosphatase and γ-glutamyltransferase, with or without increases in alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Isolated elevation of alkaline phosphatase is rare. Herein, we report a case of drug-induced liver injury characterized by isolated alkaline phosphatase elevation for clinicians. Following treatment with ursodeoxycholic acid, the patient achieved complete recovery. Clinicians should recognize that drug-induced liver injury may also present as an isolated elevation of alkaline phosphatase.

This study aims to assess the diagnostic value of drug withdrawal for drug-induced liver injury (DILI). Seventeen cases of suspected DILI were retrospectively analyzed at the time of initial diagnosis. Pertinent patient demographics such as gender, age, suspected causative drugs, initial serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and additional clinical parameters were documented. Subsequently, the suspected drugs were discontinued without the administration of liver-protective interventions, and the hepatic function of the patients was reassessed weekly. Based on the criteria of whether serum ALT/AST levels decreased by more than 50% from their respective baseline values after 1 week, patients were categorized into either the rapid decline group or the non-rapid decline group. This observation period was extended for 4 weeks, succeeded by a subsequent follow-up period of 4 weeks. Most patients recovered liver function within 3 weeks after drug withdrawal. The rapid decline group (12/12) recovered fully, compared to 4/5 in the non-rapid group. Liver enzyme levels (ALT/AST) differed significantly between groups over 4 weeks, with the rapid group showing a larger initial AST drop. All other factors like age and gender were similar. The time to disease recurrence was also comparable. A high DILI probability was confirmed in 16 of the 17 suspected cases, indicating a 94.11% diagnostic accuracy for DILI. In conclusion, this retrospective analysis underscores the potential of drug withdrawal as an effective management strategy for suspected DILI. The findings reveal that the cessation of suspected causative drugs, without the administration of liver-protective treatment, leads to recovery in hepatic function, as evidenced by the normalization of serum ALT and AST levels, contributing to the diagnosis of DILI.

Background While observational studies have suggested a potential link between metabolic syndrome (MetS) and an increased risk of colon polyps, the causal nature of this association remains uncertain. This study used a two-sample Mendelian randomization (MR) approach to evaluate the relationship between MetS and colon polyps. Methods A two-sample MR analysis was performed using data on MetS, its indicators, and colon polyps obtained from publicly available genome-wide association studies in the Integrative Epidemiology Unit (IEU) and MAGIC databases. Outliers were removed using Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), followed by MR calculations and false discovery rate (FDR) correction. The primary analysis was conducted with the inverse variance-weighted (IVW) method. Results The IVW results indicated no association between hypertension, hyperlipidemia, or diabetes and the risk of colon polyps. High-density lipoprotein cholesterol (HDL-C) (P=0.005), 2-hour glucose (P=0.004), glycated hemoglobin A1c (P=0.004), and the ratio of omega-6 to omega-3 fatty acids (P<0.001) were negatively associated with colon polyps. Conversely, body mass index (BMI) (P<0.001), body fat percentage (P=0.002), waist-to-hip ratio adjusted for BMI (P=0.001), total cholesterol (TC) (P=0.002), triglycerides (TG) (P<0.001), and both omega-3 (P<0.001) and omega-6 fatty acid levels (P=0.02) were positively associated with colon polyps. The relationships between these metabolic indicators and colon polyps remained significant after FDR correction. Conclusion Obesity-related traits, TC, and TG may increase the risk of colon polyps, while HDL-C may have a protective effect.

ETHNOPHARMACOLOGICAL RELEVANCE:Non-alcoholic fatty liver diseases (NAFLD), including nonalcoholic steatohepatitis (NASH) and cirrhosis, are strongly associated with insulin resistance and glucose intolerance. Gan-tang-yi decoction (GTYD), as a famous classical prescription effectively reduced the elevated level of blood glucose, and improved insulin resistance in cirrhotic patients. However, its specific chemical compositions and molecular mechanisms are still unclear. AIM OF THE STUDY:The current study aimed to investigate the active ingredients of GTYD and molecular mechanisms underlying the effect of GTYD against insulin resistance of NASH and cirrhosis. MATERIALS AND METHODS:Active ingredients of GTYD were evaluated by UPLC-Q-TOF/MS in both positive and negative ion modes. The TCMSP database and SwissTarget Prediction database were utilized to identify the major active components and possible targets of GTYD. The diabetes-related targets were screened in the databases of GenCLiP 3, OMIM, and GeneCards. The intersection of these databases was utilized to identify possible GTYD targets for insulin resistance. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network and hub target proteins were obtained from the STRING database. The hub targets were validated by RT-qPCR analysis. Furthermore, an insulin-resistant rat model of NASH and cirrhosis was created by subcutaneously injecting CCl4 combined with high fat and high sucrose diet to verify the therapeutic effects and the molecular mechanisms of GTYD in vivo. RESULTS:A total of 91 compounds were identified from GTYD by UPLC/Q-TOF-MS/MS. After removing duplicates, there were 230 targets associated with both disease and medicines. Targets of GTYD involve many biological processes, such as the positive regulation of cellular metabolic and cellular lipid metabolic processes. KEGG enrichment showed that PI3K/Akt and AGE/RAGE pathways played a prominent role in the treatment. RT-qPCR from the GTYD-treated rats revealed that TNF-α, IL-6, VEGFA, STAT3, IL-1B, and MAPK3 mRNA levels in the insulin resistance of NASH and cirrhosis rats were down-regulated. Up-regulated IRS2/PI3K/Akt and down-regulated AGE/RAGE and MAPK/NF-κB signal pathways were closely related to the therapeutic effect of GTYD against insulin resistance of NASH and cirrhosis rats by biology methods. CONCLUSIONS:GTYD functions as a hepato-protective formula in the insulin resistance of NASH and cirrhosis and exerts its effects via IRS2/PI3K/Akt and AGEs/RAGE signaling pathways.

Non-alcoholic fatty liver disease (NAFLD) is a liver disease without approved treatment. Oxymatrine (OMT) has protective effects in various liver diseases. We aimed to investigate the roles and mechanisms of OMT in NAFLD. NAFLD models were established using high-fat and high-sucrose diet-fed rats and oleic acid (OA)-stimulated hepatocytes, respectively. Then, OMT was used to treat the NAFLD models, with metformin as a positive control. Liver damage, lipid accumulation and hepatic lipid profile of NAFLD rats were assessed. Peroxisome proliferator activated receptor alpha (PPARα), sirtuin 1 (Sirt1)/adenosine 5‘-monophosphate-activated protein kinase (AMPK) pathway- and fatty acid oxidation (acyl-CoA oxidase 1 and carnitine palmitoyltransferase 1A)-associated proteins were measured both in vivo and in vitro. Furthermore, hepatocytes were transfected with si-Sirt1 and oe-PPARα to verify the mechanisms of OMT in NAFLD. NAFLD rats supplemented with OMT displayed reduced liver damage and lipid accumulation. After OMT intervention, the liver lipid profile of NAFLD rats was changed greatly, most of the top differentially expressed lipid metabolites were triglyceride, moreover, diacylglycerol content was decreased in NAFLD rats. OMT activated the Sirt1/AMPK pathway and PPARα, and upregulated acyl-CoA oxidase 1 and carnitine palmitoyltransferase 1A expressions in NAFLD models. In vitro, OMT enhanced viability, and improved lipid accumulation in OA-stimulated hepatocytes. However, the protective functions of OMT in OA-exposed hepatocytes were offset by Sirt1 knockdown, while PPARα overexpression further counteracted the effects of Sirt1 knockdown. OMT could relieve NAFLD by promoting Sirt1/AMPK pathway- and PPARα-mediated hepatic fatty acid oxidation, indicating that OMT is a potential approach for NAFLD treatment.

The potential association between dietary inflammatory index (DII) and colorectal cancer (CRC) risk, as well as colorectal adenomas (CRA) risk, has been extensively studied, but the findings remain inconclusive. We conducted this systematic review and dose-response meta-analysis to investigate the relationship between the DII and CRC and CRA. We comprehensively searched the PubMed, Embase, Cochrane Library, and Web of Science databases for cohort and case-control studies reporting the relationship between DII and CRA, or between DII and CRC, as of 15 July 2025. The pooled odds ratios (ORs) and 95

Nonalcoholic Steatohepatitis (NASH) is a common liver disease with limited treatment options. Oxymatrine (OMT) has been reported to treat liver diseases effectively. This study aims to explore the mechanisms of OMT in NASH. Male Sprague-Dawley rats were fed a high-fat and high-sucrose diet and hepatocytes were stimulated with oleic acid (OA) to establish NASH models, then, NASH models were intervened with OMT. In vivo, liver injury and lipid accumulation extents were evaluated by serum and liver biochemical indexes, and histological analysis. In vitro, cell viability and lipid accumulation degrees were measured. Additionally, the relationships between perilipin 2 (Plin2) and liver X-activated receptor alpha (LXR alpha) as well as Plin2 and sterol regulatory element binding protein-1c (SREBP-1c), sirtuin 1 (Sirt1)/adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway-, liver X-activated receptor (LXR)/Plin2/SREBP-1c pathway- and lipid synthesis-related proteins were detected both in vivo and in vitro. Finally, Sirt1 was knocked down in hepatocytes. OMT not only reduced serum alanine aminotransferase activity and triglyceride content, liver triglyceride and free fatty acid levels in NASH rats, but also improved hepatic injury and lipid accumulation. In vitro, OMT enhanced viability, and downregulated lipid accumulation in OA-induced hepatocytes. Both in vivo and in vitro results revealed Plin2 directly interacted with LXR alpha and SREBP-1c, and OMT activated Sirt1/AMPK pathway but inhibited the expressions of LXR/Plin2/SREBP-1c pathway and lipid synthesis (acetyl-CoA carboxylase, fatty acid synthase, stearoylCoenzyme A desaturase 1) related proteins in NASH models. Importantly, Sirt1 knockdown reversed the protective effects of OMT in OA-stimulated hepatocytes. OMT may reduce hepatic lipid synthesis in NASH by activating the Sirt1/AMPK pathway and inhibiting the LXR/Plin2/SREBP-1c pathway, suggesting that OMT may be a promising strategy for treating NASH.

Objective To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. Methods A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. Results High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. Conclusion MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Background Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger’s and Begg’s tests. Results Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD=-30.17, 95% CI [-41.10, -19.23], P<0.001) and Shannon index (WMD=-0.11 95% CI [-0.18, -0.04], P=0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD=22.09, 95% CI [7.59, 36.00], P=0.003) and Shannon index (WMD=0.08, 95% CI [0.00, 0.15], P=0.037). Enterobacteriaceae (WMD=0.03 95% CI [0.00,0.05], P=0.047; WMD=0.02 95% CI [0.00,0.04], P=0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD=-0.00 95% CI [-0.01, -0.00], P=0.001; WMD=-0.00 95% CI [-0.00, -0.00], P=0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD=0.05 95% CI [0.03,0.07], P<0.001), Fusobacteria (WMD=0.02 95% CI [0.00,0.03], P=0.042), Streptococcaceae (WMD=0.03 95% CI [0.01,0.05], P=0.017), Prevotellaceae (WMD=0.02 95% CI [0.00,0.04], P=0.040), and Escherichia-Shigella (WMD=0.06 95% CI [0.01, 0.11], P=0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD=0.00 95% CI [0.00,0.01], P=0.032) and Streptococcus (WMD=0.00 95% CI [0.00,0.00], P=0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD=-0.07 95% CI [-0.12, -0.03], P=0.003), Bifidobacteria (WMD=-0.03 95% CI [-0.05, -0.01], P=0.016), and Klebsiella (WMD=-0.01 95% CI [-0.01, -0.00], P=0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD=-0.04 95% CI [-0.07, -0.02], P=0.002), Peptostreptococcaceae (WMD=-0.03 95% CI [-0.05, -0.00], P=0.021), Lachnospiraceae (WMD=-0.04 95% CI [-0.08,-0.00], P=0.037), Ruminococcaceae (WMD=-0.06 95% CI [-0.09,-0.03], P<0.001), Faecalibacterium (WMD=-0.01 95% CI [-0.02, -0.01], P=0.001), and Lachnoclostridium (WMD=-0.02 95% CI [-0.03, -0.00], P=0.040) was decreased in the CRC group, while Proteobacteria (WMD=0.04 95% CI [0.02,0.05], P<0.001) was increased. Conclusions The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.

功能性消化不良(functional dyspepsia,FD)是指位于上腹部的一个或一组症状,主要包括上腹部疼痛或烧灼感、餐后饱胀感、早饱感、食欲不振、嗳气、恶心和呕吐等,但不能用器质性、系统性或代谢性疾病等来解释[1].

BACKGROUND/AIM:High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was to investigate the influence of metformin (MET) and berberine (BER) on the intestinal microbiota of rats with NASH.MATERIALS AND METHODS:Forty specific pathogen-free male Sprague-Dawley rats were randomized into 4 groups. Model rats were fed high-fat diets to create NASH models. MET or BER rats were administrated MET or BER, respectively, at the onset of induction of NASH. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides were examined. Plasma endotoxin levels were measured using the turbidimetric endotoxin assay. The incidence of bacterial translocation describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. Hematoxylin and eosin and oil red O staining were used for histopathological analysis. High throughput 16S rRNA sequencing was carried out for analyzing the composition of intestinal microbiota.RESULTS:High-fat diets caused NASH after 16-week induction. Administration of MET and BER ameliorated NASH by attenuating hepatic steatosis and inflammation and decreasing the plasma levels of endotoxin. MET and BER restored the composition of the intestinal microbiota disrupted by NASH. Both MET and BER altered the abundance of Atopobiaceae, Brevibacterium, Christensenellaceae, Coriobacteriales, Papillibacter, Pygmaiobacter, and Rikenellaceae RC9 in rats with NASH. The screened intestinal microbiota may be responsible for the improvement in fat accumulation and glucose metabolism.CONCLUSION:MET and BER demonstrated beneficial effects on the intestinal microbiota, which was disturbed in NASH. This finding may explain the functional mechanism of MET and BER in NASH.

Abstract A polysaccharide LDOP‐A with a molecular weight of 9.9 kDa was isolated and purified from Dendrobium officinale leaves by membrane separation, cellulose column, and dextran gel column. The Smith degradable products, methylation products, and nuclear magnetic resonance analysis showed that LDOP‐A may be composed of →4)‐Glc‐(1→, →3,6)‐Man‐(1→, and →6)‐Glc‐(1→sugar residues. In vitro, simulated digestion assays showed that LDOP‐A could be partially digested in the stomach and small intestine, and produced a large amount of acetic acid and butyric acid during colonic fermentation. Further cell experiment results illustrated that LDOP‐A‐I (LDOP‐A digested by gastrointestinal tract) could induce glucagon‐like peptide‐1 (GLP‐1) secretion in NCI‐H716 cells without showing any cytotoxicity.

BACKGROUNDMosapride significantly improves intestinal motility in liver cirrhosis, ultimately leading to the reduction in plasma endotoxin levels and bacterial translocation.OBJECTIVESTo investigate the effects of mosapride on intestinal microecology in cirrhotic rats and its potential mechanisms.MATERIAL AND METHODSForty-five healthy male Sprague-Dawley rats that were pathogen-free (weight 200-220 g) were randomly divided into a control group (n = 15), model group (n = 15) and mosapride group (n = 15). Then, the pathological changes in the liver and intestine were determined through tissue staining and using transmission electron microscope (TEM). Bacterial translocation was examined. High throughput 16S rRNA sequencing was performed to determine the changes of gut microbiota in each group.RESULTSCompared with the model group, mosapride treatment induced no attenuation in hepatic morphology and pathology changes. The TEM indicated no differences in intestinal structure in both groups. There was a significant decline in the rate of gut microbiota translocation in the mosapride group compared with the model group. There were intestinal microbiota changes in the mosapride group compared with that of the model group, including Bacteroidetes, Prevotellaceae, Alloprevotella, Ruminiclostridium, Negativicutes, Selenomonadales, Veillonellaceae, Anaerovibrio, Campylobacterales, Epsilonbacteraeota, Helicobacter, Oscillibacter, Verrucomicrobiales, Akkermansia, Intestinimonas, Eubacterium, Clostridiaceae, Clostridium, Bacteroides, Tyzzerella, Actinobacteria, and Bifidobacteriales. Among these bacteria, Alloprevotella showed a strong correlation with the other bacteria.CONCLUSIONSTaken together, we concluded that mosapride may reduce intestinal bacterial translocation through regulating the gut microbiota in rats with hepatic cirrhosis.

BACKGROUND The optimal duration of treatment for intestinal tuberculosis (TB), which remains a common disease worldwide, has not yet been established. The proposed randomized controlled study will aim to compare the efficacy of short-term six-month with nine-month anti-TB therapy for treating intestinal TB. METHODS This multicenter, open-label, double-blinded, randomized controlled trial conducted in the Affiliated Hangzhou Chest Hospital of Zhejiang University will include a total of 80 patients. Patients who meet the inclusion criteria will be randomly assigned to either the six-month (n=40) or nine-month (n=40) treatment group. The primary outcome will be complete response, which is defined as endoscopy displaying active lesion healing at the end of treatment. Participants will be scheduled for follow-up visits once a month in the first three months, then once every three months until the end of the treatment. The last follow-up will be one year after the treatment. Recurrence will be assessed one year after the end of treatment, which is defined as endoscopy displaying recurrent lesions after complete response. DISCUSSION In addition to the reports of tuberculous lymphadenitis and spinal TB, there are few appropriate randomized trials for the treatment of extrapulmonary TB with appropriate clinical endpoints. We believe that the proposed randomized controlled trial will provide further data on the efficacy of short-term six-month anti-TB therapy in intestinal TB patients. TRIAL REGISTRATION This trial will be registered on ClinicalTrial.gov.

Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¢ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3+ T cell proliferation and the proportion of interferon (IFN)-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide–conjugated PEGylated cationic liposomes–encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.

BACKGROUND:Currently, active ingredients of herbal extracts that can suppress lipid accumulation in the liver have been considered a potential treatment option for non-alcoholic fatty liver disease.METHODS:Steatosis rat model was created by high fat and high sucrose diet feeding and treated with oxymatrine (OMT). Serum biochemical parameters, liver histology and lipid profiles were examined. Hepatic differentially expressed proteins (DEPs) which were significantly changed by OMT treatment were identified by iTRAQ analysis. The expressions of representative DEPs, Sirt1 and AMPKα were evaluated by western blotting.RESULTS:OMT significantly reduced the body weight and liver weight of steatosis animals, decreased the serum levels of triglyceride and total cholesterol as well as the hepatic triglyceride and free fatty acid levels, and effectively alleviated fatty degeneration in the liver. A list of OMT-related DEPs have been screened and evaluated by bioinformatics analysis. OMT significantly decreased the expressions of L-FABP, Plin2, FASN and SCD1 and increased Sirt1 expression and AMPKα phosphorylation in the liver of rats with steatosis.CONCLUSION:The present study has confirmed the significant efficacy of OMT for improving steatosis and revealed hepatic proteomic changes and Sirt1/AMPK signaling activation by OMT treatment in rats with steatosis.

Following publication of the original article [1], the authors reported an error in affiliation 5.