Interleukin-22 Ameliorates Cerulein-Induced Pancreatitis in Mice by Inhibiting the Autophagic Pathway

Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-XL, which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis

Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma

Background Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. Methods The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. Results Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of “E2F TARGETS”, “G2M CHECKPOINT”, “MYC TARGETS V1” and “DNA REPAIR” pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group. Conclusions Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients

Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by many cytokines and growth factors and plays a key role in cell survival, proliferation, and differentiation. STAT3 activation is detected virtually in all rodent models of liver injury and in human liver diseases. In this review, we highlight recent advances of STAT3 signaling in liver injury, steatosis, inflammation, regeneration, fibrosis, and hepatocarcinogenesis. The cytokines and small molecules that activate STAT3 in hepatocytes may have therapeutic benefits to treat acute liver injury, fatty liver disease, and alcoholic hepatitis, while blockage of STAT3 may have a therapeutic potential to prevent and treat liver cancer.</p

Tissue-Specific Expression of the Terpene Synthase Family Genes in Rosa chinensis and Effect of Abiotic Stress Conditions

International audienceRose (Rosa chinensis) is one of the most famous ornamental plants worldwide, with a variety of colors and fragrances. Terpene synthases (TPSs) play critical roles in the biosynthesis of terpenes. In this work, we report a comprehensive study on the genome-wide identification and characterization of the TPS family in R. chinensis. We identified 49 TPS genes in the R. chinensis genome, and they were grouped into five subfamilies (TPS-a, TPS-b, TPS-c, TPS-g and TPS-e/f). Phylogenetics, gene structure and conserved motif analyses indicated that the RcTPS genes possessed relatively conserved gene structures and the RcTPS proteins contained relatively conserved motifs. Multiple putative cis-acting elements involved in the stress response were identified in the promoter region of RcTPS genes, suggesting that some could be regulated by stress. The expression profile of RcTPS genes showed that they were predominantly expressed in the petals of open flowers, pistils, leaves and roots. Under osmotic and heat stresses, the expression of most RcTPS genes was upregulated. These data provide a useful foundation for deciphering the functional roles of RcTPS genes during plant growth as well as addressing the link between terpene biosynthesis and abiotic stress responses in roses

Prevalence and associated risk characteristics of HIV infection based on anal sexual role among men who have sex with men: a multi-city cross-sectional study in Western China

Background: The HIV prevalence among men who have sex with men (MSM) in Western China is substantial and increasing at an alarming rate. The current HIV infection prevalence among MSM in Western China and its associated risk characteristics were explored by looking at different anal sexual roles separately. Methods: A total 1245 MSM recruited by convenience sampling from multiple sources and areas in the Chongqing and Sichuan region were interviewed using an anonymous self-administered questionnaire with the assistance of investigators and then underwent HIV testing. Multivariate logistic regression was used to identify factors independently associated with HIV infection. Results: Of the 1235 respondents who reported their sexual roles during anal sex with men, the overall HIV antibody positive rate was 21.21% (262/1235). With regard to the different anal sex roles, HIV-positive rates were significantly higher among men who played the ‘0.5’ role (versatile, equal) and ‘0’ role (only bottom or versatile, but mostly bottom) during anal sex with men than among those who played the ‘1’ role (only top or versatile, but mostly top) (26.41% for ‘0.5’ role, 26.20% for ‘0’ role, and 15.19% for ‘1’ role; Chi-square = 22.66, p  0.05). The ‘1’ role MSM who had an education level lower than senior high school, a rural household registration, and low self-perceived severity status of AIDS, the ‘0.5’ role MSM who had an education level lower than senior high school and had not undergone HIV testing in the recent 1 year, and the ‘0’ role MSM who were retired or unemployed and had been diagnosed with a sexually transmitted disease by a doctor in the recent 6 months were more likely to be HIV-infected. Conclusions: In this study, the HIV prevalence among MSM was alarmingly high. Moreover, the ‘0.5’ and ‘0’ role MSM were found to have a higher risk of infection compared to the ‘1’ role MSM, while respective risk characteristics were not completely the same across the three groups. Along with routine preventive intervention services, more focused and specific interventions are needed to target anal sex role classes separately

Prognostic Impact of Cirrhosis in Patients with Intrahepatic Cholangiocarcinoma following Hepatic Resection

Background. Prognostic impact of cirrhosis in patients with intrahepatic cholangiocarcinoma (ICC) upon hepatic resection remains unclear due to lack of studies in the literature. Methods. A total of 106 resected patients with ICC were reviewed, including 25 patients (23.6%) with cirrhosis and 81 noncirrhotic patients (76.4%). Subgroups of cirrhotic patients with and without hepatitis B virus (HBV) infection were studied. Results. The impact of cirrhosis on the overall survival (OS) (hazard ratio [HR], 0.901; 95% confidence interval [CI], 0.510 to 1.592; P=0.720) and the relapse-free survival (RFS) (HR, 0.889; 95% CI, 0.509 to 1.552; P=0.678) revealed no statistical significance. Furthermore, HBV-associated cirrhotic patients and the other cirrhotic patients demonstrated no statistical difference on survival outcomes (1 yr OS, 60.0% versus 70.0%; 5 yr OS, 10.0% versus 0%; P=0.744; 1 yr RFS, 53.3% versus 30.0%; 5 yr RFS, 10.0% versus 0%; P=0.279). In patients with cirrhosis, tumor size larger than 5 cm was found to be the foremost factor that was independently associated with poor prognosis. Conclusion. The presence of liver cirrhosis did not significantly affect prognosis of patients with ICC after resection. Downstaging modality may be in need for patients with ICC underlying cirrhosis, which remains to be validated in future studies