Selenium Yeast Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice by Reducing Proinflammatory Cytokines and Regulating the Gut Microbiota and Their Metabolites.

Background: Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice. Methods: Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated. Results: Selenium yeast lowered IL-1ß, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P<0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P<0.05), and butyric acid (P<0.05). Conclusion: Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.

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.

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.

Alanyl-Glutamine (Ala-Gln) Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by Regulating the Gut Microbiota, PI3K-Akt/NF-κB/STAT3 Signaling, and Associated Pulmonary Injury.

The aim of this study was to investigate the protective effect of alanyl-glutamine (Ala-Gln) on acute colitis complicated by pulmonary injury induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The results showed that Ala-Gln intervention alleviated weight loss, the disease activity index (DAI), colon shortening, and pathological injury and regulated the absolute number of CD4+T-cell subsets in mesenteric lymph nodes (MLNs). In addition, Ala-Gln intervention significantly ameliorated the composition of the gut microbiota in mice with DSS- induced acute colitis, significantly decreasing the relative abundance of Desulfovibrionaceae and increasing the abundances of Gastranaerophilales, Clostridia-vadinBB60, and Alistipes. Moreover, Ala-Gln treatment significantly inhibited the activation of the PI3K-Akt/NF-κB/STAT3 inflammatory signaling pathways in the colon of mice with DSS-induced acute colitis. Notably, Ala-Gln intervention also alleviated the pulmonary injury as well as the imbalance in levels of CD4+T-cell subsets in pulmonary tissue in mice with DSS-induced acute colitis. In conclusion, Ala-Gln alleviates DSS-induced acute colitis by regulating the gut microflora and PI3K-Akt/NF-κB/STAT3 signaling pathways, as well as by alleviating accompanying pulmonary injury.

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.

Methotrexate showed efficacy both in Crohn's disease and ulcerative colitis, predictors of surgery were identified in patients initially treated with methotrexate monotherapy.

Objective: This study aimed to evaluate methotrexate efficacy in patients with Crohn's disease (CD) and ulcerative colitis (UC), and identify predictors of surgery for patients who were initially treated with methotrexate monotherapy. Design: We performed a retrospective analysis of 34,860 patients with inflammatory bowel disease (IBD) in the IBD Bioresource (United Kingdom) prior to 9 November 2021. Logistic regression was used to identify factors associated with methotrexate efficacy. The data were randomly stratified into training and testing sets (7:3). Nomograms were developed based on Cox regression analysis outcomes. The predictive accuracy and discriminative ability were determined using the concordance index (C-index) and calibration curves. Results: Overall, 1,042 patients (CD: 791, UC: 251) were included. Independent factors associated with effective methotrexate monotherapy were younger age at diagnosis, latest therapy period, exclusive upper gastrointestinal tract disease (for CD), and longer duration between diagnosis and methotrexate initiation (for UC). For CD, predictors in the nomogram were gender, treatment era, tolerance, lesion site, perianal involvement, disease behaviour, and biologics requirements (C-index: 0.711 and 0.732 for training and validation cohorts, respectively). For UC, the factors were age at diagnosis and sex (C-index: 0.784 and 0.690 for training and validation cohorts, respectively). Calibration curves demonstrated good agreement between predictions and actual observations.

Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review).

Bile acids (BAs) are the major components of bile and products of cholesterol metabolism. Cholesterol is catalyzed by a variety of enzymes in the liver to form primary BAs, which are excreted into the intestine with bile, and secondary BAs are formed under the modification of the gut microbiota. Most of the BAs return to the liver via the portal vein, completing the process of enterohepatic circulation. BAs have an important role in the development of hepatocellular carcinoma (HCC), which may participate in the progression of HCC by recognizing receptors such as farnesoid X receptor (FXR) and mediating multiple downstream pathways. Certain BAs, such as ursodeoxycholic acid and obeticholic acid, were indicated to be able to delay liver injury and HCC progression. In the present review, the structure and function of BAs were introduced and the metabolism of BAs and the process of enterohepatic circulation were outlined. Furthermore, the mechanisms by which BAs participate in the development of HCC were summarized and possible strategies for targeting BAs and key sites of their metabolic processes to treat HCC were suggested.

Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in elderly individuals. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in elderly MPM patients. METHODS: From the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥ 65) and the adult group (< 65). We compared the clinical-pathological characteristics and treatment methods of the elderly group (N = 665) and the adult group (N = 827). At the same time, we analysed specific selected clinicopathological parameters and prognostic factors for elderly MPM patients. RESULTS: Compared with the adult group, the elderly group had higher percentages of male patients (P = 0.017) and white patients (P = 0.043) and lower proportions of insured patients (P < 0.001) married patients (P < 0.001), patients with peritoneal tumours (P = 0.006) and patients who underwent surgery (P < 0.001) and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). Elderly patients had a shorter median survival time than adult patients (6 months vs. 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR 3.913, P < 0.001), poorly differentiated (HR 3.900, P < 0.001), distant metastasis (HR 1.735, P = 0.001), no cancer-directed surgery (HR 1.733, P < 0.001), and no chemotherapy (HR 1.532, P < 0.001) were independently associated with poorer prognosis in elderly MPM patients. CONCLUSION: Compared with adult patients, elderly MPM patients had a higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.

Allicin in Digestive System Cancer: From Biological Effects to Clinical Treatment.

Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori, enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites.

Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy.

The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.

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.

Selenium-Enriched Lactobacillus acidophilus Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice by Regulating Inflammatory Cytokines and Intestinal Microbiota.

Aim: To evaluate the effect of Selenium-enriched Lactobacillus acidophilus (Se-enriched L. acidophilus) on dextran sulfate sodium (DSS)-induced colitis in mice. Methods: Mice were randomly divided into four groups: a control group, a control + Se-enriched L. acidophilus group, a chronic colitis group, and a chronic colitis + Se-enriched L. acidophilus group (n = 10 each group). The mice were sacrificed on the 26th day. The disease activity index, survival rates, and histological injury score were determined. Cytokines produced by lamina propria lymphocytes (LPLs), the selenium (Se) concentrations in serum and colon tissue and the mouse intestinal microbiota were evaluated. Results: Se-enriched L. acidophilus can improve histological injury and the disease activity index in mice with chronic colitis and reduce IL-1ß, IL-6, IL-12p70, TNF-α, IL-23, IFN-γ, IL-17A, and IL-21 (P < 0.05) and increase IL-10 (P < 0.05) expression levels. Moreover, Se-enriched L. acidophilus can increase the ß diversity of intestinal microbiota in mice with chronic colitis, significantly reduce the relative abundance of Lactobacillus and Romboutsia (P < 0.05), and significantly increase the relative abundance of Parasutterella (P < 0.05). Conclusions: Se-enriched L. acidophilus can improve DSS-induced chronic colitis by regulating inflammatory cytokines and intestinal microbiota.

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.

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.].

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.

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.

FOXO4 ameliorates alcohol-induced chronic liver injury via inhibiting NF-κB and modulating gut microbiota in C57BL/6J mice.

BACKGROUND: Intestinal mucosa barrier function and gut-liver axis are impaired by ethanol in chronic alcoholic liver disease (ALD). However, the possible mechanism is not clear. This study aimed to investigate the effects of Forkhead Box O4 (FOXO4) on alcohol-induced chronic liver injury and its molecular mechanism(s). METHODS: Male C57BL/6J mice were injected with or without FOXO4-WT, FOXO4-TB or NF-κB vectors, and fed with Lieber-DeCarli liquid diets containing 36% ethanol for eight weeks to induce chronic ALD. Thereafter, blood, liver, colon and fecal samples were collected. Biochemical parameters, endotoxin and inflammatory cytokines in the blood and antioxidant enzymes in the liver were tested by commercial kits. Histopathological changes in the liver were evaluated by HE staining. In addition, the mRNA and protein expression of FOXO4, NF-κB, ZO-1 and Occluding in the colon were measured by quantitative real-time PCR and Western blot, respectively. Furthermore, gut microbiota composition in the fecal samples was investigated with 16S rDNA sequencing. RESULTS: FOXO4 significantly ameliorated liver histopathological damage. Moreover, FOXO4 reduced the serum endotoxin, biochemical parameters (ALT, AST, ALP and TG), antioxidant enzymes (ROS and MDA), inflammatory cytokines (IL-6, IL-1ß, and TNF-α), but restored the levels of GSH, SOD and IL-10. Furthermore, FOXO4 significantly inhibited the expression of NF-κB, p-NF-κB p65, p-IKKα and p-IKKß, and up-regulated the expression of ZO-1 and Occludin. Additionally, FOXO4 modulated the gut microbiota composition and certain bacteria including Odoribacter, Parasutterella and Psychrobacter. CONCLUSION: These findings suggest that FOXO4 protects against alcohol-induced chronic liver injury via inhibiting NF-κB and modulating gut microbiota in C57BL/6J mice.