Association of Helicobacter pylori infection with colorectal polyps/adenomas: A single-center cross-sectional study.

BACKGROUND: Helicobacter pylori (H. pylori) infection may be associated with colorectal polyps/adenomas, but the current evidence remains controversial. METHODS: We retrospectively screened the medical records of 655 participants who underwent both colonoscopy and H. pylori test from June 15, 2020 to April 30, 2023. The number, size, location, and pathological type of colorectal polyps/adenomas were compared between H. pylori positive and negative groups. Adjusting for age, gender, smoking, drinking, hypertension, diabetes, fatty liver, body mass index, and inflammatory and metabolic indicators, multivariate logistic regression analyses were performed to evaluate the association of H. pylori infection with the number, size, location, and pathological type of colorectal polyps/adenomas, where no polyp/adenoma was used as reference. RESULTS: Overall, 508 participants were included, of whom 154 and 354 were divided into H. pylori positive and negative groups, respectively. H. pylori positive group had significantly higher colorectal polyps/adenomas (74.7 % vs. 65.8 %, P=0.048), low-grade adenomas (55.7 % vs. 47.6 %, P=0.026), advanced adenomas (22.6 % vs. 13.3 %, P=0.008), and colorectal polyps/adenomas with sizes of ≥6 mm (61.7 % vs. 48.5 %, P=0.002) and ≥10 mm (25.2 % vs. 14.6 %, P=0.004) than H. pylori negative group. In multivariate logistic regression analyses, H. pylori infection was independently associated with low-grade adenomas (OR=2.677, 95 %CI=1.283-5.587, P=0.009), advanced adenomas (OR=3.017, 95 %CI=1.007-9.036, P=0.049), right-side colon polyps/adenomas (OR=5.553, 95 %CI=1.679-18.360, P=0.005), and colorectal polyps/adenomas with sizes of ≥10 mm (OR=4.436, 95 %CI=1.478-13.310, P=0.008), but not number of colorectal polyps/adenomas. CONCLUSION: H. pylori infection is associated with increased risk of colorectal polyps/adenomas, especially low-grade adenomas, advanced adenomas, right-side colon polyps/adenomas, and large colorectal polyps/adenomas.

The role of glycogen synthase kinase 3 beta in neurodegenerative diseases.

Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and so on. They are characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system and share several cellular and molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, and chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3ß) is a serine/threonine kinase that is believed to play a pivotal role in the pathogenesis of NDDs. Here we summarize the structure and physiological functions of GSK3ß and explore its involvement in NDDs. We also discussed its potential as a therapeutic target.

14-Day Vonoprazan-Based Bismuth Quadruple Therapy for Treatment-Naïve Patients with Helicobacter pylori Infection: A Retrospective Comparative Study.

Background: Until now, there is little evidence regarding clinical efficacy of 14-day vonoprazan-based bismuth quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication. Methods: Overall, 65 treatment-naïve patients with H. pylori infection who received 14-day vonoprazan-based BQT regimen (VBCA, n=17) or pantoprazole-based BQT regimen (PBCA, n=48) for H. pylori eradication were retrospectively included. Results: Neither successful H. pylori eradication (88.2% versus 91.7%, p=1.000) nor adverse event (52.9% versus 64.6%, p=0.397) was significantly different between VBCA and PBCA groups. Conclusion: Vonoprazan seems to be as effective and safe as pantoprazole during a 14-day BQT regimen in treatment-naïve patients with H. pylori infection.

The γ-Adducin 1-357 fragment promotes tau pathology.

Background: Tau phosphorylation is a pathological hallmark of Alzheimer's disease (AD). Previously, we reported that the γ-adducin 1-357 fragment is present in the brains of AD patients. However, it remains unknown how γ-adducin regulates tau phosphorylation. Objective: The aim of this project is to investigate the effects of the γ-adducin 1-357 fragment on tau phosphorylation and the kinases involved in this process. Methods: Full-length γ-adducin or the γ-adducin 1-357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length γ-adducin or γ-adducin 1-357 fragment to determine the phosphorylation of tau. Results: The γ-adducin 1-357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the γ-adducin 1-357 fragment leads to the activation of glycogen synthase kinase-3ß (GSK-3ß). This effect was mitigated by the GSK-3ß inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). Conclusion: The γ-adducin 1-357 fragment enhances tau phosphorylation by activating GSK3ß. These results support that the fragmentation of γ-adducin may play a pivotal role in tau pathology.

A Novel Angiogenesis-Related Prognostic Signature Associated with the Hepatocellular Carcinoma Immune Microenvironment and Survival Outcome.

PURPOSE: Hepatocellular carcinoma (HCC) is a highly vascularized solid tumor characterized by neovascularization and vascular invasion. Angiogenesis plays an essential role in the occurrence and development of liver cancer. Our study aimed to investigate the prognostic value of angiogenesis-related genes in liver cancer. PATIENTS AND METHODS: The transcriptome data and corresponding clinical information of patients with liver cancer were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. In the TCGA cohort, differential expression and prognostic analyses were used to screen angiogenesis-related candidate prognostic genes. We then used least absolute shrinkage and selection operator regression analysis to construct a prognostic signature using 10 angiogenesis-related prognostic genes. The reliability of the prognostic signature was assessed in the TCGA and ICGC cohorts. In addition, we comprehensively analyzed the correlation of the prognostic signature with the tumor microenvironment, chemotherapy drugs, and specific genes. RESULTS: We identified 37 angiogenesis-related differentially expressed genes that were remarkably associated with prognosis. Ten of these genes were used to establish a survival and prognostic signature. This signature can distinguish between high-risk and low-risk groups and performs well in overall survival prediction, as demonstrated by internal and external validations. In addition, we observed that the high-risk group was remarkably associated with immune infiltration in the tumor microenvironment and had a different sensitivity to chemotherapeutic agents compared with the low-risk group. Moreover, the high-risk population was positively correlated with the expression of several special genes, such as immune checkpoint-related genes. CONCLUSION: Our results demonstrated that prognostic signatures based on angiogenesis-related genes are involved in the development of HCC and may provide new insights into accurate clinical decision-making and therapeutic evaluation of patients with HCC.

Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

A Novel Autophagy-Related lncRNA Prognostic Signature Associated with Immune Microenvironment and Survival Outcomes of Gastric Cancer Patients.

PURPOSE: Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC. METHODS: RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan-Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups. RESULTS: We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high- and low-risk groups. CONCLUSION: The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.

Altered Fecal Microbiota Composition in Older Adults With Frailty.

Objective: Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome. Methods: We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers. Results: Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability. Conclusions: Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.

CSF1R is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in the Gastric Cancer Microenvironment.

PURPOSE: The tumor microenvironment (TME) plays a crucial role in the progression and prognosis of gastric cancer (GC). This study investigated TME-associated genes and explored their roles in the GC microenvironment. METHODS: A total of 330 GC samples were extracted from TCGA. ESTIMATE and CIBERSORT algorithms were utilized to evaluate the stromal and immune scores of GC samples and the fraction of 22 immune cells infiltrated in the TME. Then, the TME-related differentially expressed genes (DEGs) were determined through integrative analysis. Protein-protein interaction (PPI) network and Cox regression analysis were conducted to analyze DEGs, and CSF1R was determined as the most crucial gene. We further probed the role of CSF1R in the GC microenvironment and evaluated the prognostic value of CSF1R. RESULTS: We identified 560 TME-related DEGs and found CSF1R associated with the development and prognosis of GC. Further analysis showed that CSF1R was involved in immune-related signaling pathways. Furthermore, CIBERSORT analysis revealed that CSF1R expression correlated with several kinds of infiltrating immune cells, including tumor-associated macrophages (TAMs), B cells, NK cells, neutrophils, eosinophils, T cells, dendritic cells, and so on. CONCLUSION: In summary, CSF1R might take part in the modulation of immune-active status in the GC microenvironment and could be a promising biomarker for GC therapy and prognosis.

Transfer of CD11c+ lamina propria mononuclear phagocytes from post-infectious irritable bowel syndrome causes mucosal barrier dysfunction and visceral hypersensitivity in recipient mice.

The role of low-grade inflammation in the development of post­infectious irritable bowel syndrome (PI­IBS) has attracted increasing attention. Abnormal CD11c+ mononuclear phagocytes, such as dendritic cells (DCs), macrophages, and monocytes, are involved in the disruption of immune tolerance in organisms, which can lead to the development of chronic inflammatory diseases. The present study tested the hypothesis that CD11c+ lamina propria mononuclear phagocytes (CD11c+ LPMPs) contribute to increased mucosal permeability and visceral hypersensitivity in a PI­IBS mouse model. CD11c+ LPMPs were isolated and purified via the digestion of intestinal tissues and magnetic­activated cell sorting. We detected increased mucosal permeability, visceral hypersensitivity and intestinal inflammation during both the acute and chronic stages of Trichinella infection. Following the transfer of CD11c+ LPMPs from PI­IBS mice into normal mice, low­grade inflammation was detected, as demonstrated by increased IL­4 expression in the ileum, as well as enhanced mucosal permeability, as indicated by decreased transepithelial electrical resistance and the pre-sence of ultrastructural alterations. More importantly, the mice that underwent adoptive transfer of CD11c+ LPMPs from the PI­IBS mice also exhibited increased abdominal withdrawal reflex scores and a decreased threshold. Our data demonstrated that the CD11c+ LPMPs from this PI­IBS mouse model were not only able to transfer enteric inflammation to the normal mice but also caused abnormal intestinal function, characterized by epithelial barrier disruption and visceral hyperalgesia.

Expression of ß-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein.

This study aimed to investigate the expression of ß-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of ß-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between ß-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of ß-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of ß-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that ß-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of ß-catenin was predominant in HCC tissues. The abnormal expression of ß-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of ß-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased ß-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of ß-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of ß-catenin, which may account for the poor prognosis of AFP-associated HCC patients.