Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews.

AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC). METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs). RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs. CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.

The Associations between Helicobacter Pylori immunoglobulin G seropositivity and body mass index in adults.

OBJECTIVES: Inconsistent evidence currently exists regarding the associations between Helicobacter Pylori (H. pylori) infection and body mass index (BMI). The goal of the current study was to examine independent associations of H. pylori immunoglobulin G (IgG) seropositivity and BMI in a U.S.-based population sample. METHODS: The US National Health and Nutrition Examination Survey (NHANES) with 2,576 subjects from 1999 to 2000 were analyzed. Using multivariate logistic regression models, associations between H. pylori IgG seropositivity and BMI were calculated after potential confounders were taken into account. Subgroup analyses were conducted furtherly stratified by sex, age, and race. RESULTS: H. pylori IgG seropositivity was not associated with BMI in the general population (OR = 0.998; 95% CI = 0.977-1.019; P = 0.842). In the subgroup analyses stratified by race, a negative correction was found between the H. pylori IgG seropositivity and BMI among other races (OR = 0.873; 95% CI = 0.795-0.959; P = 0.004) except non-Hispanic white (OR = 1.006, 95% CI 0.966 to 1.048, P = 0.762), non-Hispanic black (OR = 1.021, 95% CI 0.979 to 1.065, P = 0.335), and Mexican American (OR = 1.010, 95% CI 0.966 to 1.055, P = 0.665). CONCLUSIONS: In the general population, H. pylori IgG seropositivity is not associated with increased BMI, which provides a new perspective on obesity management.

The Correlation between Helicobacter pylori Immunoglobulin G Seropositivity and Plasma Homocysteine Levels in Adults.

Objectives: Helicobacter pylori (H. pylori) immunoglobulin G (IgG) seropositivity is prevalent, but its correlation with homocysteine (Hcy), a biomarker of vascular risk events, is unclear. This study is aimed at exploring the correlation of H. pylori IgG seropositivity and plasma Hcy levels in adults. Methods: Data was obtained from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Hcy was measured by the Abbott homocysteine assay, and H. pylori IgG was measured by enzyme-linked immunosorbent assays. The weighted multiple logistic regression analyses with adjustments for potential confounders were conducted. Subgroup analyses stratified by gender, age, and race were performed. Results: A total of 4029 subjects aged 20-85 years were included. Population prevalence of H. pylori IgG seropositivity was 44.7% in the overall population with higher prevalence found in those with older age, Mexican Americans, lower education, and lower household income. Levels of plasma Hcy were not elevated in those with H. pylori IgG seropositivity versus seronegativity (ß -0.120 (-0.438, 0.199) P = 0.462). This difference was not significant after stratifying by gender and age. However, in the subgroup analyses stratified by race, a negative correlation between H. pylori seropositivity and plasma Hcy levels was observed in Mexican Americans (ß -0.802 (-1.253, -0.352) P < 0.001). Conclusions: H. pylori IgG seropositivity was not associated with plasma Hcy levels in the general population, but there may be a negative correlation in Mexican Americans. These findings provide new insights to advance the research of the link between plasma Hcy levels and stomach health.

Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.

BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research. MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software. RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3 years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields. CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.

The Association between Helicobacter pylori Seropositivity and Bone Mineral Density in Adults.

Objectives: Current evidence on the associations between Helicobacter pylori (H. pylori) infection and bone mineral density (BMD) is conflicting. Therefore, a nationally representative sample of adults was analyzed to investigate the associations of H. pylori seropositivity and BMD in this study. Methods: A retrospective cross-sectional study was conducted with 2555 subjects aged 40-85 years in the US National Health and Nutrition Examination Survey (NHANES) 1999-2001. Multivariable logistic regression models were performed to evaluate the associations between H. pylori seropositivity and BMD. Subgroup analyses stratified by sex, age, race, and body mass index (BMI) were performed. Results: No association was found between H. pylori seropositivity and BMD (ß = 0.006, 95% CI: -0.003 to 0.015, P = 0.177). In the subgroup analyses stratified by age, a positive association was observed between the H. pylori seropositivity and total BMD among subjects aged 40-55 years (ß = 0.018, 95% CI: 0.004 to 0.033, P = 0.012); in the subgroup analyses stratified by sex, a positive association was observed between the H. pylori seropositive and total BMD in male (ß = 0.019, 95% CI: 0.007 to 0.032, P = 0.003); in the subgroup analyses stratified by age and sex, the total BMD was higher in men aged 40-55 years with H. pylori seropositive than those with H. pylori seronegative (ß = 0.034, 95% CI: 0.013 to 0.056, P = 0.002). Conclusions: In conclusion, no association between H. pylori seropositive and total BMD was demonstrated among most middle-aged and elderly adults. H. pylori infection may not be one key factor in the loss of BMD.

Exploring the Immune Landscape of Disulfidptosis in Ulcerative Colitis and the Role of Modified Gegen Qinlian Decoction in Mediating Disulfidptosis to Alleviate Colitis in Mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC), a recurrent inflammatory bowel disease, continues to challenge effective pharmacologic management. Disulfidptosis, a recently identified form of cell death, appears implicated in the progression of various diseases. Scientific studies have demonstrated that Modified Gegen Qinlian decoction (MGQD) alleviates UC symptoms. However, the underlying mechanisms remain inadequately elucidated. AIM OF THE STUDY: This study investigated the role of disulfidptosis in UC and explored the potential of MGQD to ameliorate UC by mediating disulfidptosis. METHODS: Microarray data were utilized to identify disulfidptosis-related genes stably expressed in UC, and integrated genomic analyses were conducted to elucidate the landscape of disulfidptosis in UC. Subsequently, C57BL/6J mice were administered 3% dextran sodium sulfate (DSS) to induce experimental colitis and treated with MGQD. Quantitative real-time polymerase chain reaction and immunohistochemical analysis of colonic tissues from colitis mice were performed to validate the microarray data findings. Finally, molecular docking was employed to explore the binding interactions between MGQD components and disulfidptosis biomarkers. RESULTS: Myosin heavy chain 10 (MYH10) and filamin A (FLNA) were identified as stably expressed in UC, demonstrating high diagnostic value for the disease. Correlation analysis indicated that disulfidptosis-related genes are associated with elevated levels of immune cells in UC. Single gene set enrichment analysis further clarified that these genes might be involved in the pathological processes of UC via immune-related pathways. Subsequent animal experiments revealed that MYH10 and FLNA were significantly upregulated in mice with colitis, a condition reversed by MGQD treatment. Molecular docking results showed that MYH10 and FLNA serve as stable binding targets for the primary components of MGQD. CONCLUSIONS: The study identified a connection between the disulfidptosis-related landscape and immune infiltration in UC, suggesting that MGQD may modulate disulfidptosis by inhibiting MYH10 and FLNA, thereby alleviating UC.

Uncovering the shared molecule and mechanism between ulcerative colitis and atherosclerosis: an integrative genomic analysis.

Background: Ulcerative colitis (UC) and atherosclerosis (AS) are closely related. However, the pathologic mechanisms underlying the co-occurrence of UC and AS are not well understood. Objects: To reveal the hub molecule and mechanism involved in the co-occurrence of UC and AS. Methods: Differentially expressed genes (DEGs) of UC and AS were obtained, and the shared DEGs of UC and AS were explored for biological function. Next, the hub genes were explored using the cytoHubba plugin. The predictive ability of the hub genes was measured by constructing the receiver operating characteristic curve. Analyses of immune infiltration and the single-gene gene set enrichment analysis (GSEA) for the hub genes were further carried out. Results: Identification of 59 DEGs (55 were upregulated and four were downregulated) shared by both UC and AS was performed. Enriched pathways of the shared DEGs were mainly related to immunity and inflammation. Protein tyrosine phosphatase, receptor type, C (PTPRC) was identified as the hub crosstalk gene for the comorbidity of UC and AS. The upregulation of PTPRC was correlated with mast cells resting, T cells CD4 memory resting, macrophages M0, and macrophages M1. Pathways of immune and inflammatory processes, including NF-kappa B, viral protein interaction with cytokine and cytokine receptor, and cytokine-cytokine receptor interaction, were significantly correlated with high expression of PTPRC in UC and AS. Conclusion: At the transcriptional level, our study reveals that imbalanced inflammatory and immune responses are the key pathological mechanisms underlying the comorbidity of UC and AS and that PTPRC is a key biomarker for the comorbidity of UC and AS.

Macrophages in ulcerative colitis: A perspective from bibliometric and visual analysis.

Objectives: Despite the many reported studies on macrophages in ulcerative colitis (UC), the overall research trends in this field are unclear. This study evaluates the research trends and hotspots regarding macrophages in UC using bibliometric analysis. Methods: A systematic search was conducted in the Web of Science database to identify publications related to macrophages in UC from 2012 to 2021. R package 'bibliometrix', VOSviewers, CiteSpace and Microsoft Excel were utilised for the bibliometric analysis. Results: 1074 articles published between 2012 and 2021 were analysed. The number of publications on macrophages in UC showed a consistently increasing trend, with USA and China as the leading contributors to this field. Notably, Georgia State University and Nanjing University contributed significantly to this field. Among the authors, Wang Y had the highest productivity, while Wu X received the most citations. The journal Gut was identified as the most authoritative journal in this field. Co-citation analysis revealed that the exploration of the mechanisms of macrophages in UC through in vivo and in vitro experiments was the primary focus of research. Moreover, the emerging research hotspots included keywords such as 'macrophage polarization', 'gut microbiota' and 'NLRP3 inflammasome'. Conclusions: Research on macrophages in UC holds significant value and practical implications. Additionally, China demonstrated prolific output in this field, while the USA had the most influential contributions. Currently, research hotspots are centred around the modulation of gut microbiota to regulate macrophage polarization and macrophage pyroptosis as potential strategies for mitigating UC.

Identifying biomarkers associated with the diagnosis of ulcerative colitis via bioinformatics and machine learning.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic inflammatory disease with an increasing incidence. This study aimed to identify potential UC biomarkers and associated immune infiltration characteristics. METHODS: Two datasets (GSE87473 and GSE92415) were merged to obtain 193 UC samples and 42 normal samples. Using R, differentially expressed genes (DEGs) between UC and normal samples were filtered out, and their biological functions were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Promising biomarkers were identified using least absolute shrinkage selector operator regression and support vector machine recursive feature elimination, and their diagnostic efficacy was evaluated through receiver operating characteristic (ROC) curves. Finally, CIBERSORT was used to investigate the immune infiltration characteristics in UC, and the relationship between the identified biomarkers and various immune cells was examined. RESULTS: We found 102 DEGs, of which 64 were significantly upregulated, and 38 were significantly downregulated. The DEGs were enriched in pathways associated with interleukin-17, cytokine-cytokine receptor interaction and viral protein interactions with cytokines and cytokine receptors, among others. Using machine learning methods and ROC tests, we confirmed DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 to be essential diagnostic genes for UC. Immune cell infiltration analysis revealed that all five diagnostic genes were correlated with regulatory T cells, CD8 T cells, activated and resting memory CD4 T cells, activated natural killer cells, neutrophils, activated and resting mast cells, activated and resting dendritic cells and M0, M1 and M2 macrophages. CONCLUSIONS: DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 were identified as prospective biomarkers for UC. A new perspective on understanding the progression of UC may be provided by these biomarkers and their relationship with immune cell infiltration.

Overlapping Symptoms of Functional Gastrointestinal Disorders: Current Challenges and the Role of Traditional Chinese Medicine.

Several functional gastrointestinal disorders (FGIDs) have overlapping symptoms, and, consequently, developing treatment strategies based on symptomatology poses a challenge for the clinical management of complex FGIDs. The significant overlap in the symptoms of FGIDs caused by the shared pathophysiological mechanisms is both a challenge and an excellent target for therapeutic development, since treatment strategies focused on shared pathophysiological mechanisms can treat the associated underlying diseases rather than just alleviating the primary symptoms. Owing to its multi-targeted approach, traditional Chinese medicine (TCM) has garnered immense interest worldwide; however, the quality of the data demonstrating its effectiveness is generally weak. Additionally, the causal link between the intrinsic mechanisms of action of TCM and its clinical benefits remains obscure. Systems biology is characterized by holistic and dynamic research, which corresponds to the holistic, multi-targeted, and syndrome-based approach of TCM. Therefore, high-throughput analysis techniques can be employed to describe and comprehend the genesis and progression of diseases, as well as the impacts of TCM on the organism, which may aid in elucidating the pathogenic mechanisms of the diseases as well as the mechanism of action of TCM.

GPER governs the immune infiltration of gastric cancer and activates the NF-κB/ROS/Apoptosis pathway in gastric mucosal epithelium.

BACKGROUND: Gastric cancer (GC) is with high mortality and morbidity. The GC morbidity of males is twice as high as that of females. G-protein estrogen receptor (GPER) bears on this phenomenon. METHODS: Networks and experiments assessed the GPER expression in different validity and content. The evidence-based practice involved accessing the clinical relevance of GPER by UALCAN and Kaplan-Meier plotter. Enrichment analyses contributed to guide further experimental validations. Activation of the NF-κB/ROS/Apoptosis pathway was analyzed by WB, immunofluorescence (IF), microplate reader and flow cytometry. TISIDB and TIMER identified the immune infiltration investigations, with credibility boosted by the Kaplan-Meier plotter. RESULTS: The appraisers revealed that GPER significantly decreased in GC at both gene and protein levels with highly approved prognosis value (P < 0.05). GPER was a significant fate determinant governing the inner part of gastric glands. NF-κB pathway and the following ROS in gastric cells were activated after MNU stimulation (20 µM, 24 h), and the GPER antagonist G15 strengthened the effect of MNU. Furthermore, GPER expression positively correlated with immune cells and various immune markers in GC patients, with highly approved clinical relevance. For example, type-2 helper cells enriched GC patients had a lower survival rate in the GPER-high expression group (P < 0.05). CONCLUSION: We demonstrated that GPER governs the GC progression by activating the NF-κB/ROS/Apoptosis pathway in gastric cells and regulating the immune environment around them.

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells.

BACKGROUND: Current therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PURPOSE: We aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. METHODS: The protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. RESULTS: MGQD alleviated DSS­induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. CONCLUSION: The mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

Modified Gegen Qinlian decoction ameliorated ulcerative colitis by attenuating inflammation and oxidative stress and enhancing intestinal barrier function in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Gegen Qinlian decoction (MGQD), which was first documented in Treatise on Febrile Disease, is recognized as a classic prescription to treat ulcerative colitis (UC). However, its protective mechanism against UC remains to be fully elucidated. AIM OF THE STUDY: To explore the impact and the potential molecular mechanism of MGQD on dextran sodium sulfate (DSS)-induced UC mice and tumor necrosis factor alpha (TNF-α)-induced Caco-2 cell monolayer model of intestinal barrier. MATERIALS AND METHODS: The chemical components of MGQD and MGQD drug containing serum (MGQD-DS) were characterized by LC-MS/MS. The therapeutic effect of MGQD on DSS-induced UC was evaluated based on body weight, disease activity index (DAI), colon length, colonic histopathological injury, inflammatory cytokines, oxidative stress response and intestinal barrier function. Cell Counting Kit (CCK)-8 assay was applied to detect the effect of MGQD-DS on the viability of Caco-2 cells. Additionally, TNF-α-induced Caco-2 cell monolayer model of intestinal barrier was established in vitro. The Caco-2 cell monolayers were administered blank serum or MGQD-DS to observe the effects of MGQD-DS on transepithelial electrical resistance (TEER), permeability of fluorescein isothiocyanate (FITC)-dextran, inflammatory cytokines, oxidative stress indicators and intestinal epithelial barrier (IEB). RESULTS: MGQD significantly improved symptoms and pathological damage in UC mice by downregulating the expression of interleukin (IL)-1ß and malondialdehyde (MDA), attenuating the loss of goblet cells and the destruction of intestinal epithelial ultrastructure, and upregulating the expression of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), zonula occludens-1 (ZO-1), Occludin, Claudin-1 and E-cadherin. In vitro, MGQD-DS significantly reduced the flux of FITC-dextran, increased the TEER, inhibited the expression of IL-21, IL-17A and MDA, and promoted the expression of IL-4, IL-10, transforming growth factor-ß (TGF-ß), SOD, CAT, GSH, Occludin and E-cadherin in TNF-α-induced Caco-2 cell monolayer model of intestinal barrier. CONCLUSION: MGQD can ameliorate DSS-induced UC mice and TNF-α-induced Caco-2 cell monolayer model of intestinal barrier, and the protective effect is related to its inhibition of inflammation, alleviation of oxidative stress, and repair of intestinal barrier damage.

Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis.

Objectives: Cuproptosis is a recently discovered form of programmed cell death; however, its role in ulcerative colitis (UC) remains a void. Methods: Three gene expression profiles were acquired from the GEO database. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify the immune infiltration characteristics of UC. Correlation analysis between cuproptosis and immune infiltration was further conducted, and the cuproptosis-related genes were applied to construct a UC diagnostic model. Subsequently, analysis results of microarray data were experimentally validated by DSS-induced colitis in mice. Finally, therapeutic agents for the cuproptosis-related genes were screened owing to the gaping field of therapeutic agents on cuproptosis. Results: Three gene expression profiles with 343 samples (290 UC and 53 healthy samples) were included. Immune infiltration revealed that UC patients had a higher level of DCs, B cells, CD8+ T cells, iDCs, Macrophages, neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg than normal subjects. Moreover, almost all cuproptosis-related genes were significantly negatively associated with immune infiltration in UC patients. The risk prediction model based on cuproptosis-related genes showed an excellent discrimination for UC. Animal experiments revealed significant alterations in genes essential for cuproptosis between DSS-induced colitis mice and healthy controls, providing experimental validation for the analysis results of microarray data. Further analysis revealed that latamoxef, vitinoin, clomipramine, chlorzoxazone, glibenclamide, pyruvic acid, clindamycin, medrysone, caspan, and flavin adenine dinucleotide might be the target agents for cuproptosis-related genes. Conclusions: In conclusion, cuproptosis was significantly associated with immune infiltration in UC, and the cuproptosis-related genes showed an excellent discrimination for UC.

Revealing immune infiltrate characteristics and potential diagnostic value of immune-related genes in ulcerative colitis: An integrative genomic analysis.

Objectives: Ulcerative colitis (UC) is an autoimmune disease of the colon. The aim of this study was to explore the characteristics of immune infiltrates in UC patients and identify immune-related diagnostic biomarkers for UC. Methods: Three gene expression profiles were acquired from the GEO database, followed by identification of differentially expressed genes (DEGs) by Linear Modeling of Microarray Data. Enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease Ontology (DO) were performed to analyze the biological functions of DEGs. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify immune infiltration characteristics of UC. Correlations between diagnostic genes and immune infiltration were explored to identify markers with the greatest diagnostic potential, and a UC diagnostic model was subsequently constructed. Finally, the prediction performance of the model was quantified by nomogram, non-correlated nomogram, and ROC curve. Results: A total of 3111 DEGs (1,608 up-regulated and 1,503 down-regulated genes) were identified. DEGs were significantly involved in the immune system and UC-related pathways. Immune infiltration profiles of colonic tissue were significantly different between healthy individuals and UC patients. High proportions of resting of aDCs, B cells, CD8+ T cells, DCs, iDCs, Macrophages, Neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg were found in UC samples. A 5-gene based diagnostic prediction model was constructed and the results of nomogram, non-correlated nomogram and ROC curve suggested the powerful diagnostic value of the model. Conclusions: This study identified the immune infiltrate characteristics and 5 immune-related genes for UC. The model based on the immune-related genes facilitates the early diagnosis of UC and provides a basis for the evaluation of the prognosis of UC.

Reliability of the Evidence to Guide Decision-Making in Acupuncture for Functional Dyspepsia.

Background and Aims: There has been a significant increase in the number of systematic reviews (SRs)/meta-analyses (MAs) investigating the effects of acupuncture for functional dyspepsia (FD). To systematically collate, appraise, and synthesize the current evidence, we carried out an umbrella review of SRs/MAs. Methods: Systemic reviews/meta-analyses on acupuncture for FD were collected by searching major medical databases. The included studies were evaluated in terms of methodological quality, reporting quality, and evidence quality using the criteria from the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Ten SRs/MAs were analyzed for this study. The methodological quality, reporting quality, and evidence quality of the included SRs/MAs were generally unsatisfactory. Lack of protocol registration, no list of excluded trials, or lack of a comprehensive search strategy were the main limitations. No high-quality evidence was found to support the effects of acupuncture for FD; the qualitative data synthesis relied on low quality trials with small sample sizes and was the main factor for evidence degradation. Conclusions: Acupuncture seems to have a promising efficacy in the treatment of FD. It provides a new and prospective therapeutic method for FD. Although the quality of the included SRs/MAs was generally low and defects were frequent, this umbrella review highlights areas where improvement in methodology is required.

Inhibiting Ferroptosis: A Novel Approach for Ulcerative Colitis Therapeutics.

Ulcerative colitis (UC) is a recurrent and persistent nonspecific inflammatory bowel disease (IBD) that greatly affects human survival and social wealth. Despite the advances in the treatment of UC, there is still a high demand for novel therapeutic strategies for UC patients. Cell death is critical to the development and progression of UC. Understanding how intestinal cells die and how to prevent damage to intestinal cells is of great interest for the diagnosis and early treatment of UC. Ferroptosis, a novel form of regulated cell death (RCD) manifested by iron accumulation, lipid peroxidation, and excessive reactive oxygen species (ROS) production, has been shown to contribute to the development and progression of UC. Inhibitors of ferroptosis have been validated in models of UC. Here, we reviewed the mechanisms of initiation and control of ferroptosis and summarize the therapeutic activity of ferroptosis inhibitors in models of UC. We further discussed the possibility of inhibiting ferroptosis as a novel therapeutic target for UC. These findings revealed novel mechanisms to protect the colonic mucosa and highlighted the importance of ferroptosis in the disease process.

Treatment of the Gastroesophageal Reflux Disease with Chinese Herbal Medicine (BanxiaXiexin Decoction): Evidence from Meta-Analysis.

Objectives: Systematic reviews/meta-analyses (SRs/MAs) are still controversial on the effectiveness of Banxia Xiexin decoction (BXD) to treat gastroesophageal reflux disease (GERD). To assess the evidence reliability and inform the clinical use of BXD, we performed a meta-analysis from previous SRs/MAs to collate, critically appraise, and synthesize the effectiveness of BXD treatment in GERD. Methods: SRs/MAs were collected by searching major medical databases. The included studies were evaluated in terms of methodological quality and quality of evidence using criteria from the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Six SRs/MAs were included in this study. The methodological quality of SRs/MAs was generally unsatisfactory. Unregistered protocols, failure to provide a list of excluded trials, and lack of a comprehensive search strategy were the main limitations of previous SRs/MAs. No high-quality evidence was found to support the effect of BXD on GERD patients. The qualitative data synthesis relied on low-quality trials with a small sample size, which was the main factor for evidence degradation. Conclusions: BXD seems to have promising efficacy to treat GERD patients. Although the quality of SRs/MAs was generally low and defects were frequent, our study highlights areas where methodologies need to be improved.

Development of a Dendritic Cell/Tumor Cell Fusion Cell Membrane Nano-Vaccine for the Treatment of Ovarian Cancer.

Ovarian cancer (OC) is a malignant tumor that seriously affects women's health. In recent years, immunotherapy has shown great potential in tumor treatment. As a major contributor of immunotherapy, dendritic cells (DCs) - based tumor vaccine has been demonstrated to have a positive effect in inducing immune responses in animal experiments. However, the effect of tumor vaccines in clinical trials is not ideal. Therefore, it is urgent to improve the existing tumor vaccines for tumor treatment. Here, we developed a fusion cell membrane (FCM) nano-vaccine FCM-NPs, which is prepared by fusing DCs and OC cells and coating the FCM on the poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with the immune adjuvant CpG-oligodeoxynucleotide (CpG-ODN). The fusion process promoted the maturation of DCs, thus up-regulating the expression of costimulatory molecule CD80/CD86 and accelerating lymph node homing of DCs. Furthermore, FCM-NPs has both the immunogenicity of tumor cells and the antigen presenting ability of DCs, it can stimulate naive T lymphocytes to produce a large number of tumor-specific cytotoxic CD8+ T lymphocytes. FCM-NPs exhibited strong immuno-activating effect both in vitro and in vivo. By establishing subcutaneous transplanted tumor model, patient-derived xenograft tumor model and abdominal metastatic tumor model, FCM-NPs was proved to have the effect of delaying the growth and inhibiting the metastasis of OC. FCM-NPs is expected to become a new tumor vaccine for the treatment of ovarian cancer.

Molecular Mechanism of the Effect of Zhizhu Pill on Gastroesophageal Reflux Disease Based on Network Pharmacology and Molecular Docking.

Background: To investigate the pharmacological mechanism of Zhizhu pill (ZZP) against gastroesophageal reflux disease (GERD), network pharmacology in combination with molecular docking was applied in this study. Methods: Active compounds of ZZP and target genes related to GERD were identified through public databases. Subsequently, the obtained data were used as a basis for further network pharmacological analysis to explore the potential key active compounds, core targets, and biological processes involved in ZZP against GERD. Finally, the results predicted by network pharmacology were validated by molecular docking. Results: Twenty active components of ZZP were identified to act on 59 targets related to GERD. Enrichment analysis revealed that multiple biological processes including response to oxygen levels, response to oxidative stress, and response to reactive oxygen species were involved in the GERD ZZP treatment with ZZP. ZZP had an impact on the prognosis of GERD mainly through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and pathways in cancer. Further analysis identified the key components and core targets of ZZP against GERD, of which nobiletin, didymin, luteolin, and naringenin were key components, and PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA were the core targets. Molecular docking verified the stable bonds formed between the key components and the core targets. Conclusions: The results of this study predict that the therapeutic effects of ZZP in GERD are mediated at least in part via PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA. These results may be useful in providing an experimental basis and new ideas for further research on ZZP in GERD.