COMMD proteins function and their regulating roles in tumors.

The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

BNIP3 contributes to silibinin-induced DNA double strand breaks in glioma cells via inhibition of mTOR.

BNIP3 is found to eliminate cancer cells via causing mitochondrial damage and endoplasmic reticulum stress, but it remains elusive of its role in regulating DNA double strand breaks (DSBs). In this study, we find that silibinin triggers DNA DSBs, ROS accumulation and expressional upregulation of BNIP3 in glioma cells. Mitigation of ROS with antioxidant GSH significantly inhibits silibinin-induced DNA DSBs and glioma cell death. Then, we find knockdown of BNIP3 with SiRNA obviously prevents silibinin-induced DNA DSBs and ROS accumulation. Mechanistically, BNIP3 knockdown not only reverses silibinin-triggered depletion of cysteine and GSH via maintaining xCT level, but also abrogates catalase decrease. Notably, silibinin-induced dephosphorylation of mTOR is also prevented when BNIP3 is knocked down. Given that activated mTOR could promote xCT expression and inhibit autophagic degradation of catalase, our data suggest that BNIP3 contributes to silibinin-induced DNA DSBs via improving intracellular ROS by inhibition of mTOR.

An essential technique for modern hepato-pancreato-biliary surgery: minimally invasive biliary reconstruction.

Introduction: Minimally invasive reconstruction of the biliary tract is complex and involves multiple steps. The procedure is challenging and has been an essential technique in modern hepato-pancreato-biliary surgery in recent years. Additionally, the quality of the reconstruction directly affects long-and short-term complications and affects the prognosis and quality of life. Various minimally invasive reconstruction methods have been developed to improve the reconstruction effect; however, the optimal method remains controversial. Areas covered: In this study, were viewed published studies of minimally invasive biliary reconstruction within the last 5 years and discussed the current status and main complications of minimally invasive biliary reconstruction. More importantly, we introduced the current reconstruction strategies and technical details of minimally invasive biliary reconstruction, which may be potentially helpful for surgeons to choose reconstruction methods and improve reconstruction quality. Expert opinion: Although several improved and modified methods for biliary reconstruction have been developed recently, no single approach is optimal or adaptable to all situations. Patient-specific selection of appropriate technical strategies according to different situations combined with sophisticated and skilled minimally invasive techniques effectively improves the quality of anastomosis and reduces complications.

LncRNA LINC00668 promotes cell proliferation, migration, invasion ability and EMT process in hepatocellular carcinoma by targeting miR-532-5p/YY1 axis.

Liver cancer is now one of the most lethal and commonest cancers in the world, among which over 90% is hepatocellular carcinoma (HCC). Recent studies have confirmed long non-coding RNAs (lncRNAs) are implicated in carcinogenesis. It has been reported lncRNA LINC00668 serves as an oncogene in several cancers. However, the mechanism where LINC00668 regulates HCC is still unclear. qRT-PCR analysis was adopted to detect the expression of relative RNAs. Cytoplasmic and nuclear RNA fraction analysis was conducted to verify the underlying molecular mechanism. Cell colony formation was carried out to test cell colony formation ability and transwell assays were performed to testify cell migratory and invaded abilities. Relevant protein expression level was measured by Western blot assay. LINC00668 was significantly up-regulated in HCC tissues and cell lines. LINC00668 knockdown inhibited cell proliferative, migratory and invasion abilities and slowed down the epithelial-mesenchymal transition (EMT) process. Mechanistically, LINC00668 positively modulates the expression of YY1 by competitively binding to miR-532-5p. It was revealed that LINC00668 up-regulation accelerated cell proliferation and motility in HCC and suggested LINC00668 could be a potential therapeutic target for HCC.

Influence of pregabalin on post-operative pain after laparoscopic cholecystectomy: A meta-analysis of randomised controlled trials.

Background: Pregabalin may have some potential in reducing post-operative pain after laparoscopic cholecystectomy. However, the results remain controversial. We conduct a systematic review and meta-analysis to explore the influence of pregabalin on post-operative pain after laparoscopic cholecystectomy. Materials and Methods: PubMed, Embase, Web of science, EBSCO and Cochrane Library databases have been systematically searched. Randomised controlled trials (RCTs) assessing the effect of pregabalin versus placebo on post-operative pain after laparoscopic cholecystectomy are included. The primary outcomes are pain scores at 8-12 h and 20-24 h. Secondary outcomes include sedation score, intraoperative fentanyl requirement, post-operative analgesic requirement, operative duration, post-operative nausea and vomiting, as well as respiratory depression. This meta-analysis is performed using the random-effect model. Results: Eight RCTs involving 528 patients were included in the meta-analysis. Overall, compared with control intervention after laparoscopic cholecystectomy, pregabalin treatment is found to significantly reduce pain scores at 20-24 h (Standard Mean difference [Std. MD] = -0.46; 95% confidence interval [CI] = -0.82--0.10), and post-operative analgesic requirement (Std. MD = -2.64; 95% CI = -3.94--1.33), but cannot substantially decrease pain scores at 8-12 h (Std. MD = -0.71; 95% CI = -1.70-0.27). In addition, pregabalin results in improved sedation score (Std. MD = 0.92; 95% CI = 0.55-1.29), but has no remarkable influence on intraoperative fentanyl requirement (Std. MD = 0.04; 95% CI = -0.30-0.39), operative duration (Std. MD = 0.34; 95% CI = -0.10-0.77), post-operative nausea and vomiting (Std. MD = 0.79; 95% CI = 0.59-1.11) as well as respiratory depression (Std. MD = 0.71; 95% CI = 0.17-3.02). Conclusions: Compared to control intervention after laparoscopic cholecystectomy, pregabalin treatment can significantly decrease pain scores at 20-24 h and post-operative analgesic requirement, with no increase in adverse events.

Relationship of genetic polymorphisms in CTLA-4 and IL-18 with viral hepatitis: evidence from a meta-analysis.

Relationship of genetic polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and interleukin-18 (IL-18) with susceptibility to viral hepatitis was already investigated by many association studies. The aim of this study was to more comprehensively analyse associations between genetic polymorphisms in CTLA-4/IL-18 and viral hepatitis by combing the results of all relevant association studies. We searched Pubmed, Embase, Web of Science and CNKI for eligible studies. We used Review Manager to combine the results of eligible studies. Thirty-seven studies were finally included in this meta-analysis. Combined results demonstrated that CTLA-4 rs231775 (recessive comparison: OR 1.31, 95% CI 1.11-1.55), IL-18 rs1946518 (dominant comparison: OR 0.82, 95% CI 0.75-0.90; recessive comparison: OR 1.29, 95% CI 1.11-1.50; allele comparison: OR 0.76, 95% CI 0.68-0.86) and IL-18 rs187238 (dominant comparison: OR 1.25, 95% CI 1.03-1.52; allele comparison: OR 1.20, 95% CI 1.05-1.37) polymorphisms were all significantly associated with viral hepatitis in the general population. Further subgroup analyses revealed that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were significantly associated with susceptibility to hepatitis B virus (HBV), especially among East Asians. Moreover, CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were also significantly associated with susceptibility to hepatitis C virus (HCV), especially among South Asians. So to conclude, this meta-analysis demonstrated that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HBV in East Asians, while CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HCV in South Asians.

LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/ß-Catenin Pathway.

BACKGROUND: To date, although several long noncoding RNAs (lncRNAs) are reported to regulate hepatocellular carcinoma (HCC) development, their relationship still remains elusive. ASB16-AS1 is a poorly researched novel lncRNA. We aimed to investigate its function in HCC progression. METHODS: qRT-PCR and in situ hybridization (ISH) were used to analyze ASB16-AS1 expression in HCC tissues. CCK8, Edu incorporation and colony formation were used to determine cell proliferation. Transwell assay was used to examine migration and invasion. Luciferase reporter assay was used to analyze the interactions among ASB16-AS1, miR-1827 and FZD4. RESULTS: Bioinformatics analysis identified ASB16-AS1 was overexpressed in HCC tissues, which was further validated by qRT-PCR and in situ hybridization (ISH). Besides, ASB16-AS1 was demonstrated to be a potential indicator for HCC prognosis. Functional studies showed ASB16-AS1 knockdown attenuated proliferation, migration and invasion of HCC cells. Mechanistically, ASB16-AS1 directly interacted with miR-1827 and promoted FZD4 expression by sponging miR-1827. Overexpressed FZD4 eventually activated Wnt/ß-catenin pathway and contributed to HCC progression. CONCLUSION: Our work is the first to identify ASB16-AS1 as an oncogene that enhances HCC progression by modulating miR-1827/FZD4/Wnt/ß-catenin pathways.