MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q-markers in Paris polyphylla var. yunnanensis.

To enhance the quality evaluation and control of traditional Chinese medicine (TCM) and ensure the safety and efficacy of clinical medication, it is imperative to establish a comprehensive quality assessment method aligned with TCM efficacy. This study uses a representative Chinese medicine with multi-origin and multi-efficacy, Paris polyphylla var. yunnanensis (PY), as an illustrative example. Surprisingly, despite the high fingerprint similarity among the 12 batches of PY samples collected from various regions in Yunnan, a notable variation in the composition and content of components was observed. The chromatographic analysis identified seven common peaks, namely, polyphyllin I, polyphyllin II, polyphyllin V, polyphyllin VI, polyphyllin VII, polyphyllin H, and polyphyllin D. In the bioactivity evaluation, an in vitro antiplatelet aggregation model induced by adenosine diphosphate was established, showcasing excellent stability. The maximum antiplatelet aggregation inhibition rate for all PY samples consistently remained stable at 73.1%-99.1%. However, the 50% inhibitory concentration (IC50 ) values exhibited a range from 1.615 to 18.200 mg/mL. This approach not only meets high-throughput screening requirements but also demonstrates remarkable discrimination. The results of chemical and bioactivity evaluations were analyzed using hierarchical cluster analysis and canonical correlation analysis. Polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin H, and polyphyllin D were identified as the Q-markers for antiplatelet aggregation in PY samples. Validation of the bioactivity for these monomer components aligned with the previously mentioned findings. Notably, this study established a spectrum-effect model for PY samples, enhancing the scientific robustness of the quality evaluation method. Furthermore, these findings offer valuable research insights for improving the quality assessment of other TCMs.

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma.

The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC.

Insight into increased risk of portal vein thrombosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases with increased morbidity and mortality rates for extrahepatic diseases (including cardiovascular disease, portal vein thrombosis, etc.). There is an increased risk of thrombosis in both the portal and systemic circulation in patients with NAFLD, independent of traditional liver cirrhosis. However, increased portal pressure, the most critical factor, is frequently observed in NAFLD patients, predisposing them to portal vein thrombosis (PVT). It has been reported that there is an 8.5% incidence of PVT among patients with non-cirrhotic NAFLD in a prospective cohort study. Based on the prothrombotic status of NAFLD itself, patients combined with cirrhosis may accelerate the development of PVT and lead to a poor prognosis. Moreover, PVT has been shown to complicate the procedure and adversely affect the outcome during liver transplantation surgery. NAFLD is in a prothrombotic state, and its underlying mechanisms have not been fully understood so far. Particularly noteworthy is that gastroenterologists currently overlook the higher risk of PVT in NAFLD. We investigate the pathogenesis of NAFLD complicated with PVT from the perspective of primary, secondary, and tertiary hemostasis, and also summarize relevant studies in humans. Some treatment options that may affect NAFLD and its PVT are also explored to improve patient-oriented outcomes.

Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer.

BACKGROUND: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. METHODS: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). RESULTS: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. CONCLUSION: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.

The prognostic role and metabolic function of GGPS1 in oral squamous cell carcinoma.

Background: GGPS1(geranylgeranyl diphosphate synthase 1) is a member of the prenyltransferase family. Abnormal expression of GGPS1 can disrupt the balance between protein farnesylation and geranylgeranylation, thereby affecting a variety of cellular physiologic and pathological processes. However, it is still unknown how this gene could contribute to the prognosis of oral squamous cell carcinoma (OSCC). This study aimed to explore the prognostic role of GGPS1 in OSCC and its relationship with clinical features. Methods: The RNA-seq data and clinical data were obtained from TCGA. The survival analyses, Cox regression analyses, ROC curves, nomograms, calibration curves, and gene function enrichments were established by R software. Results: The results showed that the high expression of GGPS1 in OSCC is related to poor prognosis. At the same time, multivariate Cox regression analyses showed that GGPS1 could be an independent prognostic biomarker, and its gene expression level is closely related to the histological stage of cancer. GGPS1 may promote tumorigenesis because of its metabolic function. Conclusion: This study came to a conclusion that GGPS1, whose high expression has a significantly unfavorable meaning toward the prognosis of OSCC, can act as a novel independent biomarker for OSCC.

Focusing on discoidin domain receptors in premalignant and malignant liver diseases.

Discoidin domain receptors (DDRs) are receptor tyrosine kinases on the membrane surface that bind to extracellular collagens, but they are rarely expressed in normal liver tissues. Recent studies have demonstrated that DDRs participate in and influence the processes underlying premalignant and malignant liver diseases. A brief overview of the potential roles of DDR1 and DDR2 in premalignant and malignant liver diseases is presented. DDR1 has proinflammatory and profibrotic benefits and promotes the invasion, migration and liver metastasis of tumour cells. However, DDR2 may play a pathogenic role in early-stage liver injury (prefibrotic stage) and a different role in chronic liver fibrosis and in metastatic liver cancer. These views are critically significant and first described in detail in this review. The main purpose of this review was to describe how DDRs act in premalignant and malignant liver diseases and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for cancer treatment and accelerate translation from bench to bedside.

Focusing on Helicobacter pylori infection in the elderly.

As a confirmed carcinogen, Helicobacter pylori (H. pylori) is the main cause of inflammatory diseases of the upper digestive tract and even gastric cancer. There is a high prevalence of H. pylori infection among the elderly population, which may cause adverse clinical outcomes. Particularly noteworthy is that guidelines or expert consensus presently available on H. pylori infection overlook the management of the elderly population as a special group. A brief overview of H. pylori in the elderly is as follows. The detection of H. pylori infection can be divided into invasive and non-invasive techniques, and each technique has its advantages and shortcomings. There may be more side effects associated with eradication treatment in elderly individuals, especially for the frail population. Physical conditions and risk-benefit assessments of the elderly should be considered when selecting therapeutic strategies for H. pylori eradication. Unless there are competing factors, elderly patients should receive H. pylori eradication regimens to finally reduce the formation of gastric cancer. In this review, we summarize the latest understanding of H. pylori in the elderly population to provide effective managements and treatment measures.

Antibiotics Resistance Prevalence of Helicobacter pylori Strains in Northwest China.

Purpose: This study aims to estimate the resistance rate of Helicobacter pylori (HP) to commonly used antibiotics and analyze the potential influencing factors in northwest regions of China. Patients and Methods: HP-positive patients visiting the outpatient department of multiple hospitals were enrolled in the study. Then, gastric mucosal biopsy specimens were collected for HP isolation, culture, and investigation of the resistance rate of HP to amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin by Epsilometer test (E-test) antibiotic susceptibility testing. In addition, multi-drug resistance, the influence of HP eradication history, age, and region of residence on drug resistance rate were analyzed. Results: In total, 198 HP clinical strains were successfully isolated and cultured. The resistance rates of amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin were 16.16%, 85.86%, 7.58%, 46.46%, and 55.05%, respectively. The multi-drug resistance rates demonstrated that dual and triple resistances were 30.30% and 22.73%, respectively. The quadruple resistance rate reached 9.60%. Our results revealed that the prior eradication history of HP significantly increased levofloxacin and clarithromycin resistance. Metronidazole and levofloxacin resistances significantly differed among different age groups, which presented an upward trend with increasing age. Drug resistance rates varied with geographic regions, especially amoxicillin and clarithromycin resistance, which were highest in Hexi Corridor and Longnan regions. Conclusion: The current situation of HP resistance to common antibiotics is severe. Tetracycline is the most sensitive antibiotic, followed by amoxicillin, the first choice for HP eradication. However, the eradication failure of HP may lead to an increase in the resistance rate. Therefore, it is necessary to strengthen the standardized diagnosis and treatment of HP to improve the primary eradication rate.

[Research progress of targeting macrophage surface receptors in the treatment of inflammatory bowel disease].

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract with unknown etiology and pathogenesis. In the intestinal tissues of IBD patients, dysregulation of macrophages results in persistent intestinal inflammation. Macrophages are highly adaptable and their phenotypes and functions could be regulated by various factors in the microenvironment via ligand-receptor binding, thus affecting the progression of the disease.

Identification of therapeutic targets and prognostic biomarkers among frizzled family genes in glioma.

Background: The biological functions of the Frizzled gene family (FZDs), as the key node of wingless-type MMTV integration site family (Wnt) and mammalian target of rapamycin signaling pathways, have not been fully elucidated in glioma. This study aims to identify novel therapeutic targets and prognostic biomarkers for gliomas, which may help us understand the role of FZDs. Methods: RNA-sequence data were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Survival analyses, Cox regression analyses, nomograms, calibration curves, receiver operating characteristic (ROC) curves, gene function enrichment analyses, and immune cell infiltration analyses were conducted using R. Results: High expressions of FZDs were positively associated with the activation of mTOR signaling. FZD1/2/3/4/5/7/8 was significantly highly expressed in tumor tissues, and the high expression of FZD1/2/5/6/7/8 was significantly positively associated with poorer prognosis. FZD2 and FZD6 positively served as independent predictors of poor prognosis. Gene function analysis showed that FZDs were associated with mTOR signaling, immune response, cytokine-cytokine receptor interaction, extracellular matrix organization, apoptosis, and p53 signaling pathway. Conclusions: Our finding strongly indicated a crucial role of FZDs in glioma. FZD1/2/5/6/7/8 could be an unfavorable prognostic factor in glioma and FZD2 and FZD6 may be novel independent predictors of poor prognosis in glioma.

Evidence Mapping of Proton Therapy, Heavy Ion Therapy, and Helical Tomotherapy for Gastric Cancer.

PURPOSE: This study aimed to systematically present application situation and therapeutic effect of proton therapy (PT), heavy ion therapy, and helical tomotherapy (TOMO) for gastric cancer (GC), and to find gaps of existing studies. METHODS: PubMed, EMBASE, the Cochrane Library, Web of Science, and Chinese Biological Medical Database were searched. Tables, bubble plot, and heat map were conducted to display results. RESULTS: Fourteen studies were included. About PT, 7 single-arm studies showed median overall survival (OS) within 2-66 months and 1 study reported 40% of patients happened moderate degree of radiation gastritis. About TOMO, 1 study reported longer median OS and progression-free survival, lower occurrence of Grade III toxicity, and late toxicity compared to 3D-CRT, while another study remained neutral. About heavy ion therapy, there was no clinical study was found. CONCLUSIONS: Existing studies presented good clinic treatment effect about PT and TOMO for GC, and furthermore clinical studies are needed.

The efficacy and safety comparison of PD-1/PD-L1 antibody, chemotherapy and supportive treatment for pretreated advanced esophagogastric cancer: a network meta-analysis.

BACKGROUND: Immunotherapy is important for the treatment of esophagogastric cancer. The purpose of this study is to compare the efficacy and safety of PD-(L)1 antibody, chemotherapy, and supportive treatment in the management of pretreated advanced esophagogastric cancer. METHODS: The randomized controlled trials were identified by searching electronic databases including PubMed, Cochrane Library and Embase database. The network meta-analysis (NMA) was carried out using software R 3.3.2. Main outcomes including overall survival (OS), progression-free survival (PFS), all grades and serious treatment-related adverse events (TRAEs) were extracted and analyzed. The ranking results for all outcomes were performed to identify the best treatments. RESULTS: Seven high-quality RCTs involving 1,891 patients were taken into analysis. Compared with supportive treatment, PD-(L)1 antibody and chemotherapy both had a significantly longer OS time. Chemotherapy could obvious improve PFS than supportive treatment, but it had more all grades and serious TRAEs than PD-(L)1 antibody and supportive treatment. No significant difference was found in other comparisons. The probabilities of rank plot showed that PD-(L)1 antibody was the best in the outcome of OS. Chemotherapy ranked first in PFS and ranked last in all grades and serious TRAEs. CONCLUSIONS: According to our results, PD-(L)1 antibody had excellent survival benefits and tolerable TRAEs for pretreated advanced esophagogastric cancer. It might be a suitable potential choice, especially for patients with high PDL1 CPS or with gastroesophageal junction cancer.