Background Hepatitis B virus (HBV) infection is a crucial risk factor for hepatocellular carcinoma (HCC). However, its underlying mechanism remains understudied. Methods Microarray analysis was conducted to compare the genes and miRNAs in liver tissue from HBV-positive and HBV-negative HCC patients. Biological functions of these biomarkers in HBV-related HCC were validated via in vitro and in vivo experiments. Furthermore, we investigated the effect of HBV on the proliferation and migration of tumor cells in HBV-positive HCC tissue. Bioinformatics analysis was then performed to validate the clinical value of the biomarkers in a large HCC cohort. Results We found that a gene, MINPP1 from the glycolytic bypass metabolic pathway, has an important biological function in the development of HBV-positive HCC. MINPP1 is down-regulated in HBV-positive HCC and could inhibit the proliferation and migration of the tumor cells. Meanwhile, miRNA-30b-5p was found to be a stimulator for the proliferation of tumor cell through glycolytic bypass in HBV-positive HCC. More importantly, miRNA-30b-5p could significantly downregulate MINPP1 expression. Metabolic experiments showed that the miRNA-30b-5p/MINPP1 axis is able to accelerate the conversion of glucose to lactate and 2,3-bisphosphoglycerate (2,3-BPG). In the HBV-negative HCC cells, miRNA-30b-5p/MINPP1 could not regulate the glycolytic bypass to promote the tumorigenesis. However, once HBV was introduced into these cells, miRNA-30b-5p/MINPP1 significantly enhanced the proliferation, migration of tumor cells, and promoted the glycolytic bypass. We further revealed that HBV infection promoted the expression of miRNA-30b-5p through the interaction of HBV protein P (HBp) with FOXO3. Bioinformatics analysis on a large cohort dataset showed that high expression of MINPP1 was associated with favorable survival of HBV-positive HCC patients, which could lead to a slower progress of this disease. Conclusion Our study found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis contributes to the development of HBV-positive HCC cells through the glycolytic bypass. We also presented miRNA-30b-5p/MINPP1 as a novel biomarker for HBV-positive HCC early diagnosis and a potential pharmaceutical target for antitumor therapy.
Background: The major causes of morbidity and mortality of patients with chronic liver disease are liver fibrosis and cirrhosis. Previous studies have been concerned with immune dysfunction in the pathogenesis of cirrhosis progress. However, the potential molecular mechanism of how the liver's fibrotic state favors tumor progression is still unclear. We attempted to reveal deviations of the immune cell landscape between various liver tissues and identify key biomarkers associated with patients' outcomes.Method: CIBERSORT was used for estimating the proportions of immune cells in various liver tissues.Comparative studies were carried out by Kruskal-Wallis test and Wilcoxon test. For survival analyses, the Cox proportional hazard regression model, Kaplan-Meier estimates, and log-rank test were used.Results: Significantly different adaptive and innate immune cell types were selected, including T cells, plasma cells, and resting mast cells. Meanwhile, the immune cell landscapes in The Cancer Genome Atlas' (TCGA) hepatocellular carcinoma (HCC) patients with different degrees of fibrosis were also calculated.Comparative studies and survival analysis were carried out. Resting mast cell and activated NK cells in HCC patients with fibrosis was significantly lower than that in other HCC patients without fibrosis. Then, the potential genes involved in immune cells and significantly associated with patients' outcome were identified. These genes may be potential novel checkpoints for immunotherapy, including PVRIG related to NK resting/activated cells and T cell CD8+ infiltration which was recently targeted in breast cancer.Furthermore, Pearson correlation coefficient analysis suggested that PVRIG is significantly positively related to other checkpoint molecules and Teff gene signatures.Conclusions: Alternative treatments, including immunotherapies, are necessary and urgent for HCC.Although checkpoint inhibitors that block CTLA-4 and PD-1 have improved cancer immunotherapies, targeting additional checkpoint receptors may be required to broaden patient response to immunotherapy.Our studies may find possible ways to select novel targets and improve immunotherapy efficacy by disrupting their function and promoting immune infiltration in advanced HCC patients with higher fibrosis and even cirrhosis.
Objective: Data are limited on the psychological disorders of patients with cardiovascular disease during the post-COVID-19 period, although mental health status is associated with morbidity and mortality. We aimed to investigate the prevalence of anxiety and depression and risk factors among patients with cardiovascular disease in the post-pandemic period.Method: A cross-sectional survey was conducted through opportunistic and snowball sampling in southeast China from 10 October to 24 November. Anxiety and depression were assessed on the hospital anxiety and depression scale (HADS).Results: A total of 435 patients with hypertension (48.05%), atrial fibrillation (17.24%), coronary artery disease (14.48%), heart failure (9.89%) and other heart diseases (10.34%) completed the survey. Interestingly, most patients reported monthly income comparable to (90.11%) or even greater than (8.51%) pre-pandemic income. The occurrence of anxiety and depression was 11.72 and 9.20%, respectively. Marital status and treatment interruption during the pandemic were independent risk factors for both anxiety and depression. Moreover, current monthly income and access to telemedicine during the pandemic were independent risk factors for anxiety.Conclusion: Patients with cardiovascular disease may experience anxiety and depression not only because of disease complications but also because of the effects of the pandemic. In facing the global challenge posed by the coronavirus, efforts should be made to improve patients' psychological well-being in the management of populations with cardiovascular disease.
Objective: This study aimed to observe the effect of miR-9-5p and CPEB3 on hepatocellular carcinoma (HCC) cells, and investigate the underlying targeting regulatory mechanism. Materials & methods: Various experiments like CCK-8, colony formation assay, wound healing assay and Transwell were performed for cancer cell activities detection, including cell proliferation, growth activity, migration and invasion. Results: MiR-9-5p was found to be highly expressed in HCC cells, while CPEB3 was poorly expressed (p < 0.05). The overexpression of miR-9-5p and the silencing of CPEB3 both could significantly promote cell proliferation, migration and invasion (p < 0.05). In addition, miR-9-5p could target to downregulate CPEB3 expression, thus accelerating cell proliferation, migration, invasion and epithelial-mesenchymal transition process in HCC. Conclusion: MiR-9-5p can target CPEB3, thereby promoting cell proliferation, migration and invasion in HCC. The axis of miR-9-5p/CPEB3 is expected to become a potential therapeutic target beneficial for HCC patients.
The CLIF-C ACLF and CLIF-C AD are better prognostic scores than MELD, MELD-Na, and CP in predicting mortality of ACLF and no-ACLF patients. A combined use of CLIF- Sequential Organ Failure Assessment, CLIF-C ACLFs, and CLIF-C ADs could identify cirrhosis patients at high death risk and assist clinical decisions for management.
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