To evaluate the pattern and prevalence trends of liver cirrhosis caused by specific etiologies. Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The ASR increased 0.75 per year. The most pronounced increases were found in middle-high and high socio-demographic index (SDI) regions, especially in the Caribbean and Latin America. Among the etiologies, non-alcoholic steatohepatitis (NASH) related liver cirrhosis accounted for 59.46% of the cases. The ASR increased 1.74 per year, and the increase was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol also increased in both sexes and all SDI regions. In contrast, the ASR of liver cirrhosis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) decreased, especially in middle and low-middle SDI regions. Though the number of people suffering from HBV and HCV decreases, liver cirrhosis is still a major threat to health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continues to grow. Thus, more targeted and specific strategies should be established based on etiology and prevalence trends of liver cirrhosis. We collected data based on Global Burden of Disease (GBD) 2017 study. The age standardized prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trends in prevalence by population, etiologies and regions.

Heat shock protein B8 (HSPB8) has been recently discovered to be participated in the regulation of tumor progression. However, the function of HSPB8 in intrahepatic cholangiocarcinoma (ICC) has not yet been elucidated. This study studied the function of HSPB8 in ICC progression. ICC patients (n = 150) were enrolled. The relationship between clinicopathological characteristics and HSPB8 expression was analyzed. RBE cells were transfected and treated by 3-MA. The RBE cells morphology was observed under a transmission electron microscope. Cell counting kit-8 assay, wound healing assay and Transwell experiment was conducted to detect RBE cells proliferation, migration and invasion. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blot and immunofluorescence were used for genes detection in clinical tissues and RBE cells. HSPB8 was up-regulated in ICC tissues than that in adjacent normal tissues. High HSPB8 expression in ICC indicated poor prognosis of patients. HSPB8 expression was mainly expressed in cell cytoplasm and aberrantly increased in RBE cells (P < 0.01). HSPB8 up-regulation promoted RBE cells proliferation, migration and invasion (P < 0.05). HSPB8 down-regulation reduced RBE cells proliferation, migration and invasion (P < 0.01). HSPB8 overexpression facilitated Vimentin expression, LC3-II/LC3-I ratio and inhibited E-cadherin, p62 expression in RBE cells (P < 0.05). Treatment of 3-MA partially reversed HSPB8 promotion on RBE cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < 0.05 or P < 0.01). HSPB8 promoted ICC progression by enhancing EMT and autophagy. HSPB8 might be an effective target for ICC treatment.

Molecular Mechanisms of Gynostemma pentaphyllum in Prevention and Treatment of Non-Small-Cell Lung Cancer: Objective. Lung cancer represents the leading cause of cancer death on a global scale. Gynostemma pentaphyllum (G. pentaphyllum), a traditional medicinal material with a high medicinal and health value, has recently been reported for its anticancer activity. However, the pharmacological mechanism of G. pentaphyllum in non-small-cell lung cancer (NSCLC) remains to be elucidated. Methods. The active ingredients of G. pentaphyllum were obtained from the TCMSP database and known therapeutic targets of NSCLC from the GeneCards and OMIM databases. Disease-drug common targets are subjected to protein-protein interaction (PPI), GO enrichment analysis, and KEGG pathway enrichment analysis. A molecular docking strategy was performed to verify the interaction between molecules. Results. We found a total of 24 compounds of G. pentaphyllum fulfilling OB30 concomitant with DL0.18 and corresponding 81 target genes in the TCMSP database, with 5062 NSCLC-related genes collected in the GeneCards and OMIM databases. The network consisting of the disease-target compound was obtained, including 8 active ingredients and 69 common targets. The PPI network with 65 nodes and 645 edges was visualized. After functional enrichment analysis, it was revealed that the therapeutic effects of G. pentaphyllum on NSCLC were achieved through response to ketone, gland development, and cellular response to xenobiotic stimulus. After molecular docking analysis, it was revealed that the two active ingredients of G. pentaphyllum, quercetin and rhamnazin, bound well and stably to their targets (MYC, ESR1, and HIF1A). Conclusion. Our study, based on network pharmacology, identifies active ingredients, targets, and pathways model mechanism of G. pentaphyllum when it is used to treat NSCLC.

Background: Natural products and their bioactive components serve as valuable resources for anticancer drug discovery. Eucommia ulmoides, a medicinal and edible plant widely used in traditional medicine, contains functionally significant compounds in its seeds, particularly Eucommia ulmoides seed oil (EUSO). Previous studies have demonstrated EUSO’s promising preventive and therapeutic potential against metabolic disorders, including hypertension, diabetes, and obesity. However, its therapeutic effects on malignancies, particularly digestive system cancers, remain unexplored.Methods: To evaluate the antitumor effects of EUSO, we performed in vitro and in vivo functional analyses using Cell viability, clone formation, migration capacities, and apoptosis rates were assessed through CCK-8 assays, colony formation assays, Transwell assays, and flow cytometry in hepatocellular carcinoma (HCC) and pancreatic cancer cell models. In vivo antitumor efficacy was further validated using subcutaneous xenograft models in nude mice. Mechanistically, transcriptomic profiling (RNA-seq) and Western blotting were conducted to identify EUSO-regulated signaling pathways.Results: EUSO exhibited dose-dependent suppression of HCC and pancreatic cancer cell proliferation, colony formation, and migration. Flow cytometry confirmed EUSO-induced apoptosis. In vivo, EUSO administration suppressed tumor growth in xenograft models. Mechanistic studies revealed that EUSO downregulated PI3K-AKT-mTOR pathway activation, evidenced by reduced phosphorylation of AKT (Ser473) and mTOR (Ser2448).Conclusion: EUSO attenuates the malignant progression of digestive system cancers by inhibiting the PI3K-AKT-mTOR pathway. These results provide mechanistic evidence supporting the potential application of EUSO as an adjuvant therapeutic agent in cancer management and warrant further clinical investigation into its chemopreventive and complementary therapeutic value.

Background Liver cirrhosis is a major health issue worldwide. Few studies have explored the prevalence trends caused by specific etiologies. This study was conducted to evaluate the pattern and prevalence trends. Methods We collected detailed data on liver cirrhosis based on GBD 2017 study. The ASR and EAPC were used to estimate the trends in prevalence by population, etiology and region. Results Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The worldwide ASR increased 0.75 per year. The increasing pattern was heterogeneous. The most pronounced increases were found in middle-high and high SDI regions, especially in the Caribbean, Andean Latin America and Southern Latin America. Among the etiologies, NASH-related liver cirrhosis accounted for 59.46% of the cases in 2017. The ASR increased 1.74 per year, and the increase was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol use also increased in both sexes and all 5 SDI regions. In contrast, the ASR of liver cirrhosis caused by HBV and HCV decreased, especially in the middle and low-middle SDI regions. Conclusions By using vaccine and direct-acting antiviral therapy, the number of people suffering from HBV and HCV decreased, but liver cirrhosis was still a major threat to human health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continued to grow. Thus, more targeted and specific strategies should be established in countries based on the etiology and prevalence trends for liver cirrhosis.