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Objective To investigate the effect of CA3(CIL56) on the proliferation and apoptosis of hepatocellular carcinoma HepG2 cells and its mechanism. Methods HepG2 cells were cultured in vitro and treated with different concentrations of CA3 (0, 0.25, 0.5, 1.0, 2.0, 4.0 mmol/L) for 24 and 48 hours, respectively. Enhanced CCK-8 reagent was used to detect the effect of CA3 on cell proliferation. Flow cytometry was utilized to detect cell apoptosis rate. We detected the changes of intracellular reactive oxygen species (ROS). Western blot was utilized to analyze the expression of YAP1, Bcl-2, Bax and Caspase-3 protein. Results The enhanced CCK-8 reagent test results showed that after 0.25, 0.5, 1.0, 2.0, 4.0 mmol/L CA3 treatment for 24 and 48 hours, the cell proliferation rates were (80.5±0.3)%, (79.4±0.2)%, (76.2±0.2)%, (76.4±0.1)%, (49.3±0.4)% and (75.3±0.2)%, (64.8±0.3)%, (48.4±0.2)%, (32.2±0.4)%, (31.9±0.2)%, respectively. Flow cytometry results showed that when CA3 concentration was increased to 2 mmol/L, the apoptosis rate was increased to 58.48%. CA3 could significantly increase the content of reactive oxygen species in HepG2 cells, reduce the expression of YAP1 and Bcl-2 protein, and increase the expression of Bax and Caspase-3. Conclusion CA3 could inhibit the proliferation and induce the apoptosis of HepG2 cells. The mechanism may be related to the increase of intracellular reactive oxygen species production and the regulation of YAP1, Bcl-2, Bax and Caspase-3 protein expression.

A nonhomogeneous hidden Markov model (NHMM) is used to stochastically simulate summer (June–August) daily precipitations in the middle and low reaches of the Yangtze River in Eastern China, with driving forcing from three global climate models (GCMs). Simulations cover the historical period from 1961 to 2005 and from 2006 to 2100 following the RCP4.5 scenario. The model is first evaluated against data from the regional observation network. The results show that NHMM effectively enhances the ability of GCMs in simulating summer daily rainfall in the region. For future projection at different time horizons of the 21st century, the spectral distribution of regional precipitations (in function of their intensity) shows consistent changes with a decrease of occurrence probability for light rain (<10 mm/day) and an increase for heavy rain (>10 mm/day). Among variables of interest, total precipitation (PRCPTOT), precipitation intensity, the number of rainy days for daily precipitation exceeding 10 mm (R10mm) and 95th percentile of precipitation (P95), all show a gradually increasing trend in the 21st century, and geographically an eastward gradient with smaller increase (or even weak decrease) for the west and larger increase for the east. It is noted that obvious changes occur in the eastern region with 95% significance level, and PRCPTOT or R10mm increases by 40–60% in the late 21st century. Further quantitative assessment is performed for global warming of 1.5 and 2°C. The half‐degree additional warming makes R10mm change by −3.7, 2.4 and 12.1% over western, central and eastern regions, respectively. Figure Boxplots showing the distribution of relative changes (in %) of R10mm (number of rainy days for daily precipitation more than 10mm, a), P95 (95th percentile of precipitation, b) and CDD (maximum consecutive dry days, c) in the three sub‐regions, western (light grey, 110–114°E), central (dark grey, 114–118°E) and eastern (black, 118–122°E), under the global warming of 1.5, 2°C and half‐degree warming from 1.5 to 2°C. The upper and lower limits of box indicate the 75th and 25th percentiles among stations; the horizontal line inside box indicates the 50th percentiles among stations; the asterisk inside box represents multi‐station ensemble median (mean); and the whiskers show the range among stations. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the most common malignant tumors in the world, which brings great challenges to people's life and health. The purpose of this study was to investigate immune related-lncRNAs and identify new biomarkers for the prognosis of gastric cancer (GC)., Methods: We downloaded data from The Cancer Genome Atlas (TCGA) and used R software to determine the ESTIMATEScore, ImmuneScore, and StromalScore of each tumor sample. We performed prognostic analysis and identified the differentially expressed lnRNAs, which were then used to construct a prognostic model. Among the 44 hub genes in the competitive endogenous RNA (ceRNA) network, 3 differentially expressed genes were verified by qPCR., Results: Based on the degree of immune infiltration, cluster A had a higher ESTIMATEScore, ImmuneScore, and StromalScore and higher expression levels of PD-L1 ( CD274 ) and CTLA4 than cluster B. Univariate Cox analysis was conducted for these differential lncRNAs, and 57 lncRNAs were found to have prognostic value (P<0.05). gene cluster A had a worse prognosis than gene cluster B (P=0.021). Then, a prognostic model was constructed. The low-risk group had a significantly higher survival rate. Finally, the qPCR results showed that the expression levels of BMPER , PRUNE2 , and RBPMS2 were low in GC cell lines., Conclusions: We identified a risk score of 19 lncRNAs as a prognostic marker of GC. There was a relationship between these 19 prognostic-related lncRNAs and the subtypes of infiltrating immune cells. An approach for predicting the prognosis of GC was therefore provided in this study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-833/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: Colon adenocarcinoma (COAD) is globally one of the most frequently occurring malignant tumors. The patients' 5-year survival rate with colon cancer was poor. There is a usual form of mRNA modification called N6-methyl adenosine (m6A). It is adjusted by the m6A RNA methylation modulator. Nevertheless, few studies of COAD can fully discuss m6A-related lncRNAs' prognostic function., Methods: From The Cancer Genome Atlas (TCGA) database, this study of COAD samples discussed 23 m6A regulator-related lncRNAs systemically. 2 m6A patterns with various clinical results were recognized, and a remarkable correlation between various m6A clusters and tumor immune microenvironment was discovered., Results: According to prognostic analysis, cluster1 had a higher immune checkpoint programmed death-ligand 1 (PD-L1) expression and a better prognosis. A 6 m6A-related lncRNAs model was constructed through least absolute shrinkage and selection operator (LASSO), univariate, multivariate Cox regression and stratified analysis. The outcomes reported that compared with the low-risk group, high-risk groups that were based on model closely were related to poor overall survival (OS). The study ensured a risk model consisting of 6 m6A-related lncRNAs as independent prognosis predictors. For the expression differences between the two groups, Genomes Pathway Analysis, Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) biological process analyses were conducted. In addition, on the basis of full analysis of OS, a nomogram based on gender, age, lncRNA feature and the stage was constructed. One year, two years, and three years are the periods when the calibration chart performed best., Conclusions: The outcomes of the study confirmed the underlying function of m6A-related lncRNAs and offered fresh perspectives to COAD prognosis.

Objective To investigate the mechanisms of pseudolaric acid B (PAB) blocks cell cycle and inhibits invasion and migration in human hepatoma HepG2 cells. Methods The proliferation effect of PAB on HepG2 cells was evaluated by MTT assay. The effect of PAB on the cell cycle of HepG2 cells was analyzed by flow cytometry. Immunofluorescence cytochemical staining was applied to observe the effect of PAB on the α-tubulin polymerization and expression in HepG2 cells. Transwell TM chamber invasion assay and wound healing assay were performed to detect the influence of PAB on the migration and invasion ability of HepG2 cells. Western blotting was used to determine the expressions of α-tubulin, E-cadherin and MMP-9 in HepG2 cells after treated with PAB. Results PAB inhibited the proliferation of HepG2 cells in a dose-dependent manner and blocked the cell cycle in G2/M phase. PAB significantly changed the polymerization and decreased the expression of α-tubulin. The capacities of invasion and migration of HepG2 cells treated by PAB were significantly depressed. The protein levels of α-tubulin and MMP-9 decreased while the E-cadherin protein level increased. Conclusion PAB can inhibits the proliferation of HepG2 cells by down-regulating the expression of α-tubulin and influencing its polymerization, arresting HepG2 cells in G2/M phase. Meanwhile, PAB also can inhibit the invasion and migration of HepG2 cells by lowering cytoskeleton α-tubulin and MMP-9, and increasing E-cadherin.

Picroside II, from the herb Picrorhiza scrophulariiflora Pennell , has antioxidant and anti-inflammatory activities. However, its function on severe acute pancreatitis (SAP) and molecular mechanism remains unknown. The effects of picroside II on the SAP induced by cerulean were investigated. SAP rats were treated with picroside II (25 mg/kg). The severity of SAP was evaluated by using biochemical and histological analyses. Pancreatic cancer cell PANC-1 was transfected with ptfLC3 (an indicator of autophagic activity), pcDNA3.1-NF- κ B (nuclear factor kappa B), and pTZU6+1-NF- κ B-shRNA and then treated with picroside II. Relative molecules related with NF- κ B-dependent autophagy were detected by using Western blot. Autophagic activities were observed by phase-contrast and fluorescent microscopes. Acetylated LC3 was detected by immunoprecipitation. The results showed that picroside II treatment reduced the level of ALT, AST, NF- κ B, IL-1 β , IL-6, TNF- α , and SIRT1 (NAD + -dependent deacetylase) and increased the level of SOD and GSH. The autophagic activity was reduced when NF- κ B was silenced, and the levels of TNF- α and SIRT1 were reduced. In contrast, the overexpression of NF- κ B increased autophagic activity and the level of TNF- α , which activated SIRT1. SIRT1 deacetylated LC3 and increased autophagic activities. Picroside II ameliorates SAP by improving antioxidant and anti-inflammtory activities of SAP models via NF- κ B-dependent autophagy.