Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease.

Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory bowel disease (IBD). Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon. In addition, catechins can also regulate the infiltration and proliferation of immune related-cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce the inflammatory relations and provide benefits to IBD. Perhaps catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions. Furthermore, catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways. Finally, catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve the IBD. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium. This paper elaborates the currently known possible molecular mechanisms of catechins in favor of IBD.

Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity.

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

Gut microbiota and female health.

The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.

Use of curcumin and its nanopreparations in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn's disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.

VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis.

VSL#3 probiotics can be effective on induction and maintenance of the remission of clinical ulcerative colitis. However, the mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on dextran sulfate sodium (DSS)-induced colitis in rats. Acute colitis was induced by administration of DSS 3.5 % for 7 days in rats. Rats in two groups were treated with either 15 mg VSL#3 or placebo via gastric tube once daily after induction of colitis; rats in other two groups were treated with either the wortmannin (1 mg/kg) via intraperitoneal injection or the wortmannin + VSL#3 after induction of colitis. Anti-inflammatory activity was assessed by myeloperoxidase (MPO) activity. Expression of inflammatory related mediators (iNOS, COX-2, NF-κB, Akt, and p-Akt) and cytokines (TNF-α, IL-6, and IL-10) in colonic tissue were assessed. TNF-α, IL-6, and IL-10 serum levels were also measured. Our results demonstrated that VSL#3 and wortmannin have anti-inflammatory properties by the reduced disease activity index and MPO activity. In addition, administration of VSL#3 and wortmannin for 7 days resulted in a decrease of iNOS, COX-2, NF-κB, TNF-α, IL-6, and p-Akt and an increase of IL-10 expression in colonic tissue. At the same time, administration of VSL#3 and wortmannin resulted in a decrease of TNF-α and IL-6 and an increase of IL-10 serum levels. VSL#3 probiotics therapy exerts the anti-inflammatory activity in rat model of DSS-induced colitis by inhibiting PI3K/Akt and NF-κB pathway.

Green tea consumption and risk of esophageal cancer: a meta-analysis of published epidemiological studies.

We performed a meta-analysis to analyze the association of various levels of green tea consumption with risk of esophageal cancer. We searched MEDLINE, EMBASE, and the Cochrane Library for studies of green tea consumption and esophageal cancer and identified 12 observational studies. For esophageal cancer, the pooled relative risk (RR) was 1.09 [95% confidence interval (CI), 0.76-1.55] for greatest vs. non/least green tea consumption; however, there was significant heterogeneity across studies (P = 0.00, I(2) = 75.5%). Compared with subjects who drank no/least green tea, the pooled RR was 1.14 (95% CI = 0.97-1.35) for moderate drinkers, 0.94 (95% CI = 0.77-1.13) for those who drank little, and 0.97 (95% CI = 0.77-1.22) for all subjects who had ever drunk green tea. Subgroup analysis showed that the RR was 0.46 (95% CI = 0.29-0.73) for female subjects. The results of the present meta-analysis are that any association between green tea and risk of esophageal cancer remains unclear. Subgroup analyses indicated that greater consumption of green tea might reduce the risk of esophageal cancer in female subjects. However, the results are based on limited research. Further research is needed to confirm the results and clarify the likely biological mechanisms.

Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis.

BACKGROUND: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case-control and cohort studies to investigate the association between coffee consumption and liver cancer. METHODS: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case-control studies and seven cohort studies. RESULTS: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42-0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40-0.63) for case-control studies and 0.48 (95% CI: 0.38-0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25-0.56) in males and 0.60 (95% CI: 0.33-1.10) in females. The OR was 0.45 (95% CI: 0.36-0.56) in Asian studies and 0.57 (95% CI: 0.44-0.75) in European studies. The OR was 0.39 (95% CI: 0.28-0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46-0.66) after adjustment for a history of liver disease. CONCLUSIONS: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.

Heat-killed VSL#3 ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in rats.

To determine the effects of heat-killed VSL#3 (B. breve, B. longum and B. infantis; L. plantarum, L. bulgaricus, L. casei and L. acidophilus; S. salivarius subsp. thermophilus) therapy in the dextran sulfate sodium (DSS)-induced acute experimental colitis in rats. Acute experimental colitis was induced in rats by 5% DSS and freely drink for seven days. Beginning on Day 8, rats underwent gavage once daily for seven days with heat-killed probiotic VSL#3 (0.6 g/kg/day), colonic damage was evaluated histologically and biochemically seven days after gavage. Expression of inflammatory related mediators (STAT3, P-STAT3) and cytokines (IL-6, IL-23, TGFß) in colonic tissue were detected. The results revealed that heat-killed and live VSL#3 have identical anti-inflammatory properties by the assessed DAI (disease activity index), colon length, histological tissue and MPO activity. Heat-killed and live VSL#3 results in reduced IL-6, IL-23, TGFß, STAT3 and P-STAT3 expression in colonic tissue. Heat-killed and live VSL#3 have showed the similar anti-inflammatory activity by inhibiting IL-6/STAT3 pathway in the DSS-induced acute experimental colitis in rats.

Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.

Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.

Potential therapeutic targets for nonalcoholic fatty liver disease: Glucagon-like peptide 1.

Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to liver mortality and morbidity. Hepatocellular injury in nonalcoholic steatohepatitis (NASH) is caused by an increase in metabolic substrates (glucose, fructose, and fatty acids), leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury. The pathogenesis of this disease is largely associated with obesity, type 2 diabetes, and increasing age. To date, there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis. Since one of the pathogenic drivers of NASH is insulin re-sistance, therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH. Currently, the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is a safe, well-studied therapeutic for NAFLD/ NASH patients. Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis. However, improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD. Given the complex pathophysiology of NASH, combining therapies with complementary mechanisms may be beneficial. Researchers have conducted trials of semaglutide in combination with antifibrotic drugs. However, the results have not fully met expectations, and it cannot be ruled out that the reason is the short trial time. We should continue to pay increasing attention to GLP-1RAs.

Therapeutic drug monitoring in inflammatory bowel disease treatments.

Recently, biological drugs have played a leading role in the treatment of inflammatory bowel disease, and therapeutic drug monitoring (TDM) may be useful in maximizing their effectiveness. TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate. We believe that concentration thresholds should be individualized based on patients' disease severity, extent and phenotype, and therapeutic purposes should also be considered, with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission. Proactive and reactive TDM can help optimize treatment, especially in patients receiving anti-tumour necrosis factor, and guide dose adjustment or drug conversion with lower cost. TDM is a promising approach to achieve precision medicine and targeted medicine in the future.

Corrigendum to "Probiotic mixture VSL#3: An overview of basic and clinical studies in chronic diseases".

[This corrects the article on p. 1361 in vol. 8, PMID: 32368530.].

Nicotinamide Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice through Its Anti-Inflammatory Properties and Modulates the Gut Microbiota.

Vitamin B (nicotinamide (NAM)), one of the most important nutritional components for humans, exerts anti-inflammatory activity. This study was aimed at investigating the effect of NAM on the gut microbiota and short-chain fatty acids (SCFAs) in mice with chronic colitis. Colitis was induced in C57BL/6 male mice by administration of 1.5% dextran sulfate sodium (DSS), and the mice were intraperitoneally injected with normal saline (NS) or NAM. NAM treatment ameliorated weight loss and changes in colon length, disease activity index (DAI) score, and histologic scores. Moreover, enzyme-linked immunosorbent assay (ELISA) analysis of LPL cells revealed that the level of interleukin- (IL-) 6, IL-12p70, IL-1ß, tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, IL-21, and IL-17A was increased, while IL-10 was reduced, in the chronic colitis group compared to the control group, but the levels of all these factors were restored after NAM treatment. Then, 16S rRNA sequencing of the large intestinal content was performed, and analysis of alpha diversity and beta diversity showed that the richness of the gut microbiota was decreased in the DSS group compared to the control group and restored after NAM treatment. In addition, NAM modulated specific bacteria, including Odoribacter, Flexispira, and Bifidobacterium, in the NAM+chronic colitis group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that NAM treatment restored disruptions in the functions of the gut microbiota (replication and repair, cell motility) in mice with DSS-induced colitis. Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Our results suggest that NAM treatment could alleviate DSS-induced chronic colitis in mice by inhibiting inflammation and regulating the composition and function of gut microbiota.

Primary localized gastric amyloidosis: A scoping review of the literature from clinical presentations to prognosis.

Localized gastric amyloidosis (LGA) is a rare disease characterized by abnormal extracellular deposition of amyloid protein restricted to the stomach and it is confirmed by positive results of Congo red staining. Over decades, only a few cases have been reported and studies or research focusing on it are few. Although LGA has a low incidence, patients may suffer a lot from it and require proper diagnosis and management. However, the pathology of LGA remains unknown and no overall review of LGA from its presentations to its prognosis has been published. Patients with LGA are often asymptomatic or manifest atypical symptoms, making it difficult to differentiate from other gastrointestinal diseases. Here, we report the case of a 70-year-old woman with LGA and provide an overview of case reports of LGA available to us. Based on that, we conclude current concepts of clinical manifestations, diagnosis, treatment, and prognosis of LGA, aiming at providing a detailed diagnostic procedure for clinicians and promoting the guidelines of LGA. In addition, a few advanced technologies applied in amyloidosis are also discussed in this review, aiming at providing clinicians with a reference of diagnostic process. With this review, we hope to raise awareness of LGA among the public and clinicians.

Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review.

Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.

A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer.

Selenium (Se) is an essential trace chemical element that is widely distributed worldwide. Se exerts its immunomodulatory and nutritional activities in the human body in the form of selenoproteins. Se has increasingly appeared as a potential trace element associated with many human diseases, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that Se and selenoproteins exert their immunomodulatory effects on HCC by regulating the molecules of oxidative stress, inflammation, immune response, cell proliferation and growth, angiogenesis, signaling pathways, apoptosis, and other processes in vitro cell studies and in vivo animal studies. Se concentrations are generally low in tissues of patients with HCC, such as blood, serum, scalp hair, and toenail. However, Se concentrations were higher in HCC patient tissues after Se supplementation than before supplementation. This review summarizes the significant relationship between Se and HCC, and details the role of Se as a novel immunomodulatory or immunotherapeutic approach against HCC.

Beta-carotene and its protective effect on gastric cancer.

Beta-carotene is an important natural pigment that is very beneficial to human health. It is widely found in vegetables and fruits. The three main functions are antioxidant effects, cell gap junction-related functions and immune-related functions. Because of its diverse functions, beta-carotene is believed to prevent and treat many chronic diseases. Gastric cancer is one of the most important diseases it can treat. Gastric cancer is a type of cancer with a high incidence. Its etiology varies, and the pathogenesis is complex. Gastric cancer seriously affects human health. The role of beta-carotene, a natural nutrient, in gastric cancer has been explored by many researchers, including molecular mechanisms and epidemiological studies. Molecular studies have mainly focused on oxidative stress, cell cycle, signal transduction pathways and immune-related mechanisms of beta-carotene in gastric cancer. Many epidemiological surveys and cohort studies of patients with gastric cancer have been conducted, and the results of these epidemiological studies vary due to the use of different research methods and analysis of different regions. This paper will summarize the results of these studies, mainly in terms of molecular mechanisms and epidemiological research results, which will provide a systematic basis for future studies of the treatment and prognosis of gastric cancer. This paper will help researchers identify new research directions.

Distinctive gut microbial dysbiosis between chronic alcoholic fatty liver disease and metabolic-associated fatty liver disease in mice.

The gut microbiota, which may affect normal physiological and biochemical functions, has an important role in the development of human liver diseases. The aim of the present study was to investigate differences in the gut microbiota between chronic alcoholic fatty liver disease (AFLD) and metabolic-associated fatty liver disease (MAFLD). AFLD was induced by chronic alcohol administration and MAFLD was induced by a Western-style diet in C57BL/6 mice. After 8 weeks, the levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß and IL-10 were assessed and H&E staining of mouse liver tissue was performed. High-throughput sequencing of 16S ribosomal DNA from the intestinal contents was used to analyze the different effects of AFLD and MAFLD on the gut microbiota. Differences in the gut microbiota composition were assessed by the t-test. The results revealed increases in LPS, ALT, AST, TG, IL-1ß and TNF-α in the AFLD group. Compared with those in the MAFLD control group, the MAFLD group exhibited increased plasma ALT, TG, TC, IL-6, IL-1ß and TNF-α levels and decreased plasma IL-10 levels. In addition, the α- and ß-diversities revealed that the AFLD and MAFLD groups exhibited obvious changes in the gut structure (with an increase in abundance in the AFLD group and a decrease in abundance in the MAFLD group). In comparison to the AFLD control group, Enterococcaceae were the most abundant bacteria at the family level and Enterococcus and Streptococcus were the most abundant bacteria at the genus level in the AFLD group. However, in the MAFLD group, Lachnospiraceae was the most abundant at the family level, with increases in Erysipelatoclostridium, Gordonibacter and Streptococcus at the genus level and a decrease in the genus Bifidobacterium. In conclusion, the present study confirmed that the AFLD and MAFLD groups harbored differences in the gut microbiota. The marked differences in the gut microbiota at the family and genus levels may contribute to the development process of FLD.

Eosinophilic pancreatitis: a review of the pathophysiology, diagnosis, and treatment.

Eosinophilic pancreatitis (EP) is an extremely rare disease caused by purely eosinophilic infiltration of the pancreas. EP is prone to being misdiagnosed as pancreatic cancer, causing unnecessary economic and physical harm to the patient. We report three cases of EP that were cured by steroids without relapse from 2017 to now. The clinical data of the three patients, including clinical manifestations, serological manifestations, imaging (ultrasound, computed tomography, and MRI), pathological diagnosis and treatment, and telephone follow-up of all patients, were retrospectively analysed. In addition, a literature search was conducted on the Web of Science and PubMed databases using key terms related to EP, considering case reports with no restrictions on the date of publication or language. In conclusion, we analysed 19 cases and determined the diagnostic criteria for EP. The diagnostic algorithm for EP can be used to diagnose EP easily. We hope that our standards and algorithm can reduce the rate of misdiagnosis and contribute to clinical diagnosis and treatment. In addition, we expect to evaluate more EP cases to test our diagnostic criteria and design a systematic diagnostic flow chart.