The association between non-alcoholic fatty liver disease and urinary incontinence among adult females in the United States.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and urinary incontinence (UI) are both highly prevalent and age-related diseases. Nevertheless, the link between NAFLD and UI is unclear. Hence, the study was designed to evaluate the association between the NAFLD and UI (including UI types) in a nationally representative sample of United States (US) female adults. METHODS: We conducted this study used data from U.S. female adults in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) cycles. The diagnosis of NAFLD is based on Vibration controlled transient elastography (VCTE) and absence of know liver diseases and significant alcohol consumption. The diagnosis and types of UI were assessment using a self-report questionnaire. Multivariable logistic regression models were used to analyze the association between NALFD and UI. Stratified analyses based on age, obesity, race, educational level, married status, PIR, and smoking status were conducted. RESULTS: Of the 2149 participants, the mean (95% CI) age was 53.9 (52.7-55.0), 686 (61.1%) were Non-Hispanic White. UI was significantly more common in participants with NAFLD [490 (64.7%)] than those without NAFLD [552 (44.9%)]. Adjusted for age, race/ethnicity, marital status, educational level, family poverty income ratio (PIR) status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking status, obesity, type 2 diabetes mellitus (T2DM), hypertension and insulin resistance (IR) in a multivariable logistic regression model, NALFD were associated with UI [OR: 1.93, 95%CI 1.23-3.02, P = 0.01] and urge UI [OR: 1.55, 95%CI 1.03-2.33, P = 0.03], while patients with NAFLD did not show an increased odds in stress UI and mixed UI when compared with those without NAFLD subject (P > 0.05). In the subgroup analyses, NAFLD remained significantly associated with UI, particularly among those participants without obesity (OR: 2.69, 95% CI 1.84-4.00) and aged ≥ 60 years (OR: 2.20, 95% CI 1.38-3.51). CONCLUSIONS: Among US female adults, NAFLD has a strong positive correlation with UI. Given that NAFLD is a modifiable disease, these results may help clinicians to target female patients with NAFLD for treatments and interventions that may help prevent the occurrence of UI and reduce the symptoms of UI.

Hsa_circ_0016788 regulates hepatocellular carcinoma progression via miR-506-3p/poly-adenosine diphosphate-ribose polymerase.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of HCC, but the mechanism is still indistinct. In this work, we explored the roles of circRNA_0016788 in HCC. METHODS: The levels of hsa_circ_0016788, microRNA-506-3p (miR-506-3p), and mRNA of poly-adenosine diphosphate-ribose polymerase, member 14 (PARP14) were detected by quantitative real-time reverse transcription-polymerase chain reaction in HCC tissues. Meanwhile, the level of PARP14 was quantified by Western blot analysis. Besides, the cell functions were examined by commercial kit, Cell Counting Kit-8 assay, EdU assay, colony formation assay, flow cytometry assay, Western blot, and transwell assay. Furthermore, the interplay between miR-506-3p and hsa_circ_0016788 or PARP14 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of hsa_circ_0016788. RESULTS: The levels of hsa_circ_0016788 and PARP14 were upregulated, and the miR-506-3p level was decreased in HCC tissues in contrast to that in normal tissues. For functional analysis, hsa_circ_0016788 deficiency inhibited cell glycolysis metabolism, cell vitality, cell proliferation, colony formation, and invasion in HCC cells whereas promoted cell apoptosis. Moreover, miR-506-3p was confirmed to repress the progression of HCC cells by suppressing PARP14. In mechanism, hsa_circ_0016788 acted as a miR-506-3p sponge to regulate the level of PARP14. In addition, hsa_circ_0016788 knockdown also inhibited tumor growth in vivo. CONCLUSION: Hsa_circ_0016788 facilitates the development of HCC through increasing PARP14 expression by regulating miR-506-3p, which also offered an underlying targeted therapy for HCC treatment.

Epstein-Barr virus-associated gastric cancer: A distinct subtype.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a common malignant tumor associated with EBV infection. The molecular classification of gastric carcinoma indicates that EBVaGC is a distinct subtype in terms of oncogenesis and molecular features. Viral proteins, Bam-HI-A rightward transcripts (BART) miRNAs, and Bam-HI A rightward frame 1 (BARF1) promote oncogenesis after EBV infection via the induction of methylation, regulation of host gene expression, and malignant transformation. Together with abnormal mutations and amplification of the host genome as driving factors, interactions between the EBV genome and host genome accelerate carcinogenesis. The molecular profile of EBVaGC is that of EBV driving DNA hypermethylation, frequent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, and the overexpression of Janus kinase 2 (JAK2), programmed death ligand-1 (PD-L1), and PD-L2. Clinically, the frequency of lymph node metastasis is lower, and the prognosis is better for EBVaGC than EBV-negative gastric cancer (EBVnGC). Pathologically, EBVaGC is a gastric adenocarcinoma with lymphoid stroma. This review interprets how the EBV genome is involved in the oncogenesis of gastric cancer and describes the molecular and clinicopathological features of EBVaGC.

Integrated Analysis of RNA-Binding Proteins Associated With the Prognosis and Immunosuppression in Squamous Cell Carcinoma of Head and Neck.

RNA-binding proteins (RBPs) interacting with target RNAs play essential roles in RNA metabolism at the post-transcription level. Perturbations of RBPs can accelerate cancer development and cause dysregulation of the immune cell function and activity leading to evade immune destruction of cancer cells. However, few studies have systematically analyzed the potential prognostic value and functions of RBPs in squamous cell carcinoma of head and neck (SCCHN). Here, for the first time, we comprehensively identified 92 differentially expressed RBPs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model was constructed with six RBPs, including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2, and validated by the TCGA test set, the TCGA all set, and the GEO data set. In addition, the risk score was related to the clinical stage, T classification, and N classification. Furthermore, the high-risk score was significantly correlated with immunosuppression, and low expression of EZH2 and AZGP1 and high expression of IGF2BP2 were the main factors. Thus, the risk model may serve as a prognostic signature and offer highlights for individualized immunotherapy in SCCHN patients.

Matrine Mediates Inflammatory Response via Gut Microbiota in TNBS-Induced Murine Colitis.

This study mainly investigated the effect of matrine on TNBS-induced intestinal inflammation in mice. TNBS treatment caused colonic injury and gut inflammation. Matrine (1, 5, and 10 mg/kg) treatment alleviated colonic injury and gut inflammation via reducing bleeding and diarrhea and downregulating cytokines expression (IL-1ß and TNF-α). Meanwhile, serum immunoglobulin G (IgG) was markedly reduced in TNBS treated mice, while 5 and 10 mg/kg matrine alleviated IgG reduction. Fecal microbiota was tested using 16S sequencing and the results showed that TNBS caused gut microbiota dysbiosis, while matrine treatment markedly improved gut microbiota communities (i.e., Bacilli and Mollicutes). Functional analysis showed that cell motility, nucleotide metabolism, and replication and repair were markedly altered in the TNBS group, while matrine treatment significantly affected cell growth and death, membrane transport, nucleotide metabolism, and replication and repair. In conclusion, matrine may serve as a protective mechanism in TNBS-induced colonic inflammation and the beneficial effect may be associated with gut microbiota.

Bioinformatic analysis suggests that UGT2B15 activates the Hippo­YAP signaling pathway leading to the pathogenesis of gastric cancer.

Gastric cancer (GC) is one of the most common malignancies that threatens human health. As the molecular mechanisms unerlying GC are not completely understood, identification of genes related to GC could provide new insights into gene function as well as potential treatment targets. We discovered that UGT2B15 may contribute to the pathogenesis and progression of GC using GEO data and bioinformatic analysis. Using TCGA data, UGT2B15 mRNA was found to be significantly overexpressed in GC tissues; patients with higher UGT2B15 had a poorer prognosis. It was further discovered that UGT2B15 and FOXA1 were both upregulated, and UGT2B15 and Foxa1 were positively correlated in GC. It is known that Foxa1 is a vital threshold to activate the Hippo­YAP signaling pathway. In addition, we suggest that a potential molecular mechanisms includes UGT2B15 which may upregulate Foxa1, activate the Hippo­YAP signaling pathway and contribute to the development of GC. Taken together, our findings demonstrate that UGT2B15 may be an oncogene in GC and is a promising therapeutic target for cancer treatment.

Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.

Long non-coding RNAs (lncRNAs) are important regulators of many cellular processes, and their aberrant expression and/or function is associated with many different diseases, including cancer. However, the identification of functional lncRNAs in gastric cancer is still a challenge. In this study, we describe a novel functional lncRNA, linc00483, that is upregulated and associated with tumorigenesis, tumour size, metastasis and poor prognosis in gastric cancer. In our study, linc00483 promoted gastric cancer cell proliferation, invasiveness and metastasis in vitro and in vivo. Mechanistically, upregulated expression of linc00483 in gastric cancer acts as a sponge to absorb endogenous tumour suppressor miR-30a-3p. Furthermore, it restores SPAG9 expression, which is negatively regulated by miR-30a-3p, and actives MAPK signaling pathway in gastric cancer cells. Thus, linc00483 is an oncogenic lncRNA in gastric cancer and targeting linc00483 or its pathway can potentially be useful in development of targeted therapies for patients with gastric cancer. Our results show that linc00483 is an important regulator in carcinogenesis and may be a useful biomarker to predict prognosis of gastric cancer patients. We believe our findings are novel and will be of interest to scientists working in many areas related to biomarkers in cancer.

High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma.

Golgi phosphoprotein 3 (GOLPH3) is recently demonstrated to function as an oncogene involved in the development and progression of cancers. However, little is known about GOLPH3 expression and its clinical significance in hepatocellular carcinoma (HCC). The levels of GOLPH3 messenger RNA (mRNA) and protein in HCC cell lines and fresh tissues were determined by quantitative RT-PCR and western blotting. Additionally, the protein expression of GOLPH3 was detected in 167 paraffin-embedded HCC samples by immunohistochemistry. GOLPH3 mRNA and protein was overexpressed in HCC cell lines and tissues than the immortalized normal hepatocyte cell line LO2 and the adjacent nontumorous live tissues, respectively. High GOLPH3 expression was positively correlated with high serum AFP level (P = 0.015) and more tumor recurrence or metastasis (P = 0.010). In addition, HCC patients with high GOLPH3 expression had poorer overall survival (hazard ratio (HR), 1.87; 95 % confidence interval (CI), 1.19-2.94; P = 0.006) and poorer disease-free survival (HR, 1.90; 95 % CI, 1.21-2.98; P = 0.005) than those with low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19 % (95 % CI, 26.18-44.20 %) in the high GOLPH3 expression group, whereas it was 55.93 % (95 % CI, 43.26-68.60 %) in the low GOLPH3 expression group. Furthermore, multivariate Cox regression analysis demonstrated that the expression of GOLPH3, tumor size, and tumor multiplicity were independent prognostic predictors for HCC patients. GOLPH3 was overexpressed in HCC at both the mRNA and protein levels, and high expression of GOLPH3 could be served as a novel and potential prognostic biomarker for HCC patients.