How autophagy, a potential therapeutic target, regulates intestinal inflammation.

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.

Preclinical evidence for quercetin against inflammatory bowel disease: a meta-analysis and systematic review.

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-1ß (IL-1ß), 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.

Berberine for gastric cancer prevention and treatment: Multi-step actions on the Correa's cascade underlie its therapeutic effects.

Gastric carcinoma (GC) is a complex multifactorial disease occurring as sequential events commonly referred to as the Correa's cascade, a stepwise progression from non-active or chronic active gastritis, to gastric precancerous lesions, and finally, adenocarcinoma. Therefore, the identification of novel agents with multi-step actions on the Correa's cascade and those functioning as multiple phenotypic regulators are the future direction for drug discovery. Recently, berberine (BBR) has gained traction owing to its pharmacological properties, including anti-inflammatory, anti-cancer, anti-ulcer, antibacterial, and immunopotentiation activities. In this article, we investigated and summarized the multi-step actions of BBR on Correa's cascade and its underlying regulatory mechanism in gastric carcinogenesis for the first time, along with a discussion on the strength of BBR to prevent and treat GC. BBR was found to suppress H. pylori infection, control mucosal inflammation, and promote ulcer healing. In the gastric precancerous lesion phase, BBR could reverse mucosal atrophy and prevent lesions in intestinal metaplasia and dysplasia by regulating inflammatory cytokines, promoting cell apoptosis, regulating macrophage polarization, and regulating autophagy. Additionally, the therapeutic action of BBR on GC was partly realized through the inhibition of cell proliferation, migration, and angiogenesis; induction of apoptosis and autophagy, and enhancement of chemotherapeutic drug sensitivity. BBR exerted multi-step actions on the Correa's cascade, thereby halting and even reversing gastric carcinogenesis in some cases. Thus, BBR could be used to prevent and treat GC. In conclusion, the therapeutic strategy underlying BBR's multi-step action in the trilogy of Correa's cascade may include "prevention of gastric mucosal inflammation (Phase 1); reversal of gastric precancerous lesions (Phase 2), and rescue of GC (Phase 3)". The NF-κB, PI3K/Akt, and MAPK signaling pathways may be the key signaling transduction pathways underlying the treatment of gastric carcinogenesis using BBR. The advantage of BBR over conventional drugs is its multifaceted and long-term effects. This review is expected to provide preclinical evidence for using BBR to prevent gastric carcinogenesis and treat gastric cancer.

Pharmacological effects of berberine on models of ulcerative colitis: A meta-analysis and systematic review of animal studies.

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-1ß (IL-1ß), 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.

Limiting potential COVID-19 contagion in squatting public toilets.

BACKGROUND: Since the outbreak of the SARS-CoV-2 virus in December 2019, the COVID-19 pandemic continues to threaten global stability. Transmission of SARS-CoV-2 is mostly by respiratory droplets and direct contact but viral RNA fragments have also been detected in the faecal waste of patients with COVID-19. Cleanliness and effective sanitation of public toilets is a concern, as flushing the toilet is potentially an aerosol generating procedure. When the toilets are of the squatting type and without a cover, there exists a risk of viral contamination through the splashing of toilet water and aerosol generation. OBJECTIVE: This study aims to determine whether the cleanliness of public toilets was a concern to the general population during the COVID-19 pandemic, and whether a squatting toilet was preferred to a seated design. METHODS: A questionnaire was designed and posted on "WeChat" contact groups of the investigators. RESULTS: The survey showed that 91% of participants preferred squatting toilets, but that 72% were apprehensive of personal contamination when using public toilets. Over 63% of the respondents had encountered an incidence of water splash and would prefer public toilets to be covered during flushing and 83% of these respondents preferred a foot-controlled device. CONCLUSION: This survey suggests that consideration should be given to the installation of a simple foot-controlled device to cover public squatting toilets to help restrict potential COVID-19 contamination and to meet hygienic expectations of the public.