Biosynthesis, structure and biological function of cholesterol glucoside in Helicobacter pylori: A review.

Helicobacter pylori (H pylori) is a common pathogen, and about 50% of the world population have been infected with it, so the infection of H pylori has been an urgent public health problem worldwide. H pylori has evolved a variety of strategies to help itself colonize, adapt to the environment and proliferate. Cholesterol glucoside (CG), a characteristic substance in H pylori, is related to the membrane stability, morphology, inflammation induction and immune evasion of H pylori. Therefore, CG may be a new target to weaken the infection effect of H pylori. The biosynthesis process, structure and biological function of CG specific to H pylori, as well as anti-CG drugs are discussed and analyzed in this review, in order to explore whether the inhibition of CG synthesis can be an effective strategy to eradicate H pylori.

Prognostic impact of gamma-glutamyl transpeptidase to platelets ratio on hepatocellular carcinoma patients who have undergone surgery: a meta-analysis and systematic review.

Gamma-glutamyl transpeptidase to platelet ratio (GPR) is an inflammatory index and has been used as a prognostic index for a variety of tumors. However, the association between GPR and hepatocellular carcinoma (HCC) still remained controversial. Therefore, we performed a meta-analysis to determine the prognostic impact of GPR on HCC patients. PubMed, Embase, Cochrane Library, Web of Science, the Chinese National Knowledge Infrastructure, Wanfang Database, Chinese VIP Database, the US Clinical Trials Registry, and the Chinese Clinical Trials Registry were searched from inception to December 2022. A hazard ratio (HR) with a 95% confidence interval (CI) was used to evaluate the association between preoperative GPR and the prognosis of HCC patients. Ten cohort studies including 4706 HCC patients were identified. This meta-analysis showed that higher GPRs were closely related to worse overall survival (HR: 1.79; 95% CI: 1.35-2.39; P < 0.001; I2 = 82.7%), recurrence-free survival (HR: 1.30; 95% CI: 1.16-1.46; P < 0.001; I2 = 0%), and disease-free survival (HR: 1.84; 95% CI: 1.58-2.15; P < 0.001; I2 = 25.4%) in patients with HCC. This meta-analysis suggests that preoperative GPR appears to be significantly associated with the prognosis of HCC patients who have undergone surgery and may be an effective prognostic marker. Trial registration: PROSPERO: CRD42021296219.

Inflammasome and pyroptosis in autoimmune liver diseases.

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

Regulation of autophagy by non-coding RNAs in gastric cancer.

Autophagy is a conserved cellular self-digesting process that degrades obsoleting proteins and cellular components and plays a crucial role in the tumorigenesis, metastasis, and drug resistance of various tumors such as gastric cancer (GC). As a hotspot in molecular biology, non-coding RNAs (ncRNAs) are involved in the regulation of multiple biological processes, such as autophagy. Increasing evidence indicate that various ncRNAs exert double roles in the initiation and progression of GC, either serve as oncogenes or tumor suppressors. Recent studies have shown that some ncRNAs could modulate autophagy activity in GC cells, which would affect the malignant transformation and drug resistance. Whether the function of ncRNAs in GC is dependent on autophagy is undefined. Therefore, identifying the underlying moleculr targets of ncRNAs in autophagy pathways and the role of ncRNA-regulated autophagy in GC could develop new treatment interventions for this disease. This review summarizes the autophagy process and its role in GC, and the regulatory mechanisms of ncRNAs, as well as focuses on the dual role of ncRNAs-mediated autophagy in GC, for the development of potential therapeutic strategies in GC patients.

Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis.

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS). Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software. Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: -1.77; 95%CI: -1.96 to -1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: -15.75; 95%CI: -26.89 to -4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: -9.72; 95%CI:-12.26 to -7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: -7.07; 95%CI: -9.96 to -4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: -5.45; 95%CI: -6.82 to -4.08; p < 0.001), and clinical symptom scores (WMD: -5.37; 95%CI: -6.13 to -4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20-0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87-2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14-0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33-1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high. Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319680], identifier [CRD42022319680].

Tumor suppressing role of serum-derived exosomal microRNA-15a in osteosarcoma cells through the GATA binding protein 2/murine double minute 2 axis and the p53 signaling pathway.

Exosomes are emerging tools for transporting lipids, proteins, microRNAs (miRNAs), or other biomarkers for clinical purposes. They have produced widespread concern in managing human diseases, including osteosarcoma (OS). This study focuses on the function of serum-derived exosomal miR-15a in the growth of OS cells and the mechanism of action. Differentially expressed genes between OS and normal samples were screened using two datasets GSE70367 and GSE65071. miR-15a was poorly expressed, whereas GATA-binding protein 2 (GATA2) and murine double minute 2 (MDM2) were abundantly expressed in OS samples. miR-15a and its target mRNAs, including GATA2, were enriched in the p53 signaling pathway. miR-15a directly targets GATA2 mRNA to inhibit its expression, whereas GATA2 activates the transcription of MDM2, a negative regulator of p53. Overexpression of GATA2 and MDM2 promoted proliferation and cell cycle progression of MG-63 cells, whereas miR-15a blocked this axis and suppressed cell growth. miR-15a was identified as a major cargo of serum-derived exosomes, and exosomes conveying miR-15a were internalized by OS cells. This study demonstrated that miR-15a suppresses the GATA2/MDM2 axis to inhibit the proliferation and invasiveness of OS cells in vitro through the p53 signaling pathway.

Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis.

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.

[Effects of xinwei granule on STAT3 and p-STAT3 signal pathway in rats with precancerous lesion of gastric cancer].

OBJECTIVE: To study the effects of Xinwei Granule (XG) on signal transducers and activators of transcription (STATs) and tyrosine phosphorylation of signal transducers and activators of transcription 3 (p-STAT3) signal pathway in rats with precancerous lesions of gastric carcinoma (PLGC). METHODS: Totally 96 Wistar rats were randomly divided into the blank control group (abbreviated as the blank group, n = 16) and the model group (n = 80). The PLGC rat model was established by complex pathogenic factors, in which methyl-N'-nitro-N-nitrosoguanidine (MNNG) was mainly used. After successful modeling, 75 rats randomly selected were divided into the model group, the Vitacoenzyme group, the low dose XG group, the middle dose XG group, and the high dose XG group, 15 in each group. Fifteen rats were randomly selected from the blank group, and fed with ordinary standard forage and administered with 10 mL/kg 0.9% sodium chloride by gastrogavage. XG at 1.254 g/kg, 2.508 g/kg, and 5.016 g/kg was respectively administered to rats in the three XG groups by gastrogavage. Rats in the model group were administered with 10 mL/kg 0.9% sodium chloride by gastrogavage. Vitacoenzyme was administered to rats in the Vitacoenzyme group. Vitacoenzyme Tablet was pulverized to prepare 0.1 g/mL 0.9% sodium chloride suspension and administered by gastrogavage. All the medication was performed once daily and continued for 12 weeks. The general conditions (including rats' fur, activity, food and water, excrement, body weight, and survival), the pathological changes in the gastric mucosa, as well as the expressions of STAT3 and p-STAT3 were observed. RESULTS: Compared with the blank group,the expression levels of STAT3 and p-STAT3 increased in the model group (P < 0.05). The general conditions, such as the activity, food and water intake, and body weight were improved in each XG group. Compared with the model group, the expressions of STAT3 and p-STAT3 decreased in each XG group with statistical difference (P < 0.05). The occurrence of PLGC, i.e., intestinal metaplasia (IM) and dysplasia (DYS) significantly decreased with statistical difference (P < 0.05). Compared with the Vitacoenzyme group, the occurrence of IM and DYS significantly decreased in the middle and high dose XG groups, showing statistical difference (P < 0.05). The expressions of STAT3 and p-STAT3 decreased more significantly in the middle and high dose XG groups, showing statistical difference (P < 0.05). CONCLUSIONS: XG could obviously improve the pathological conditions of gastric mucosa in rats with PLGC. It could fight against the progress of PLGC by down-regulating the expressions of STAT3 mRNA and p-STAT3.