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.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

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.

Elafibranor:A promising treatment for alcohol-associated liver disease?

We comment on an article by Koizumi et al.Elafibranor(EFN)is a dual pero-xisome proliferator-activated receptorα/δagonist.The experimental results from Koizumi et al demonstrated that EFN significantly increases intestinal barrier function and ameliorates liver fibrosis.These positive outcomes suggest that EFN could be a promising therapeutic option for alcohol-associated liver disease(ALD).However,this study has limitations that necessitate further research to evaluate the efficacy of EFN.Future studies should consider the use of more appropriate animal models and cell types,optimize the administration routes and dosages of the drug,and conduct an in-depth investigation into the underlying mechanisms of action to determine the therapeutic effects of EFN in humans.With sustained and in-depth research,EFN has the potential to emerge as a novel therapeutic agent for the treatment of ALD.

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 advan-cements 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 supple-mentation,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.

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.

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

Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted considerable attention for its combined effect.VSL#3 is the only probiotic considered as a kind of medical food;it mainly participates in the regulation of the intestinal barrier function,including improving tight junction protein function,balancing intestinal microbial composition,regulating immune-related cytokine expression and so on.The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans(including children).We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies,including digestive systemic diseases(gastrointestinal diseases and hepatic diseases),obesity and diabetes,allergic diseases,nervous systemic diseases,atherosclerosis,bone diseases,and female reproductive systemic diseases.

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer

Colorectal cancer(CRC),a multifactorial disease,is usually induced and developed through complex mechanisms,including impact of diet and lifestyle,genomic abnormalities,change of signaling pathways,inflammatory response,oxidation stress,dysbiosis,and so on.As natural polyphenolic phytochemicals that exist primarily in tea,tea polyphenols(TPs)have been shown to have many clinical applications,especially as anticancer agents.Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC.TPs can inhibit the growth and metastasis of CRC by exerting the antiinflammatory,anti-oxidative or pro-oxidative,and pro-apoptotic effects,which are achieved by modulations at multiple levels.Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells,including the mitogen-activated protein kinase pathway,phosphatidylinositol-3 kinase/Akt pathway,Wnt/β-catenin pathway,and 67 kDa laminin receptor pathway,to inhibit proliferation and promote cell apoptosis.In addition,novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses.Molecular pathological epidemiology,a novel multidisciplinary investigation,has made great progress on CRC,and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC.This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.

Morin enhances hepatic Nrf2 expression in a liver fibrosis rat model

AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.

Dairy product consumption and gastric cancer risk: A meta-analysis

AIM: To investigate whether dairy product consumption is a risk factor for gastric cancer. METHODS: We searched the Pub Med and Web of Science databases for English-language studies on dairy product consumption and gastric cancer risk that were published between October 1980 and September 2013. One author independently extracted data and assessed study quality. Based on the heterogeneity results, we used either the fixed effects model or the random effects model to compute the summary relative risks and 95% confidence intervals(CIs). We also analyzed subgroups according to the study design, geographic region, sex, and whether there were adjustments for confounders(smoking and drinking) with respect to the sources of heterogeneity.RESULTS:We found 39 studies that were potentiallyeligible for inclusion in this meta-analysis,including 10cohort studies and 29 case-control studies.The summary relative risk for gastric cancer,comparing the highest and lowest dairy product consumption categories,was 1.06(95%CI:0.95-1.18).Specific analyses for milk,butter,and margarine yielded similar results,but the results for cheese and yogurt were different.There was significant heterogeneity for all studies(Q=112.61;P=0.000;I2=67.1%).No publication bias was observed(Egger’s test:P=0.135;Begg’s test:P=0.365).There was a nonsignificant association between dairy product consumption and gastric cancer risk in the subgroup analysis for the study design,sex,geographic region,and whether there were adjustments for confounders(smoking and drinking).CONCLUSION:In our meta-analysis,dairy product consumption was associated with a nonsignificantly increased risk of gastric cancer.However,this result should be verified using large,well-designed prospective studies.

Angiopoietin and vascular endothelial growth factor expression in colorectal disease models

AIM:To investigate angiopoietin(Ang) and vascular endothelial growth factor(VEGF) expression in rats with ulcerative colitis(UC) and colorectal cancer(CRC).METHODS:Dysplasia and cancer were investigatedin rats that received three cycles of 3.5% dextran sulfate sodium(DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine(DMH)(CRC group).Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline(UC group).Rats without DSS or DMH treatment served as controls.Expression of the tyrosine kinase with immunoglobulinlike and EGF-like domains(Tie)-2 and its ligands,Ang-1 and Ang-2,as well as VEGF were evaluated in the colorectum by Western blotting.RESULTS:Compared with rats in the control group,rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea,rectal bleeding,wasting,and loss of body weight(P < 0.05).In addition,the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats(8.29 ± 0.21 and 8.31 ± 0.86,respectively,vs 12.34 ± 0.12 cm; P < 0.05).Furthermore,rats in the CRC group,but not in the UC or control groups,developed multiple tumors in the colorectal region.Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1,Ang-2,Tie-2,and VEGF in the colorectum compared to rats in the control group.CONCLUSION:Increased expression of Ang-1,Ang-2,Tie-2,and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.

Isoflavones and inflammatory bowel disease

Isoflavones constitute a class of plant hormones including genistein,daidzein,glycitein,formononetin,biochanin A,and irilone,and the major source of human intake is soybeans.Inflammatory bowel disease(IBD)is a chronic recurrent inflammatory disease including ulcerative colitis,Crohn’s disease,and indeterminate colitis,which seriously affects the quality of life of patients and has become a global health problem.Although the pathogenesis of IBD is not very clear,many factors are thought to be related to the occurrence and development of IBD such as genes,immunity,and intestinal flora.How to control IBD effectively for a long time is still a problem for gastroenterologists.Diet has an important effect on IBD.Patients with IBD should pay more attention to diet.To date,many studies have reported that isoflavones have both good and bad effects on IBD.Isoflavones have many activities such as regulating the inflammatory signal pathways and affecting intestinal barrier functions and gut flora.They can also act through estrogen receptors,as they have a similar structure to estrogen.Isoflavones are easy to get from diet for human.Whether they are valuable to be applied to the treatment of IBD is worth studying.This review summarizes the relationship between isoflavones and IBD.

Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses

AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P < 0.05 each), but enhanced the expression of IL-10 and Foxp3(P < 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

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.

Chymase inhibitor TY-51469 in therapy of inflammatorybowel disease

AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups(control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium(DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4+CD25+ Tregs in peripheral blood; colon tissues of rats were collected to measure m RNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin(IL)-10, transforming growth factor(TGF)-β1 and IL-17A were detected by ELISA. RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group(P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group(P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d(P < 0.05). The proportion of CD4+CD25+ Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4+CD25+ Tregs than that in the model group(P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group(P < 0.05). Cytokines IL-10, TGF-β1 and IL-17 A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group(P < 0.05). CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines(IL-10, TGF-β1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS-induced colitis possibly by increasing the expression of Tregs and cytokines.

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 resistance,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.

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.

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

Correction to:Cheng FS,Pan D,Chang B,Jiang M,Sang LX.Probiotic mixture VSL#3:An overview of basic and clinical studies in chronic diseases.World J Clin Cases 2020;8:1361-1384.We are the team of Min Jiang and Li-Xuan Sang from the First Affiliated Hospital,China Medical University.Now we solemnly declare that the studies mentioned in this article[1]evaluated the probiotic formulation known as VSL#3 before January 31,2016.The probiotic formulation is now commonly referred to as De Simone Formulation.In addition,the product currently known as VSL#3 is not the same as De Simone Formulation.De Simone Formulation is now available as Visbiome in the United States and Vivomixx in Europe.

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.