S100 calcium binding protein a8 (S100a8) and a9 (S100a9) belong to the S100 family of calcium-binding proteins and have important roles in inflammation. They increase endothelial cell proliferation, thereby affecting inflammation, angiogenesis and tumorigenesis. However, the mechanism of action of S100a8/9 in endothelial cells needs further study. Therefore, the present study sought to investigate the effects of S100a8/9 on the proliferation and angiogenesis of human umbilical vein endothelial cells (HuVecs) and their mechanism of action. The viability of HuVecs was determined through a cell counting Kit-8 assay. The effect of S100a8/9 on the proliferation of HuVecs was detected by flow cytometry. Migration was evaluated by a Transwell migration assay. apoptosis was evaluated by annexin V-FiTc and Pi staining via flow cytometry. Western blot analysis and reverse transcription-quantitative polymerase chain reaction assays were performed to evaluate the activation of the phosphatidylinositol 3-phosphate kinase (Pi3K)/akt/mTor pathway and mTor complex 2 (mTorc2). We previously confirmed that S100a8/9 were consistently overexpressed at 1 and 7 days post-surgery in a rabbit vein graft model, which is the period when apoptosis changes to proliferation in neointimal hyperplasia. in the present study, proliferation, viability and migration were increased after treating HuVecs with S100a8/9. S100a8/9 stimulated the Pi3K/akt/mTOR pathway and mTORC2, which was significantly suppressed by a receptor for advanced glycation end products (raGe)-blocking antibody. Furthermore, depleting expression of raGe or mTorc2 protein components (rapamycin-insensitive companion of mTor) by small interfering rna was found to reduce the cell viability, migration and angiogenesis of S100a8/9-treated HuVecs. The development of neointimal hyperplasia is a complex process initiated by damage to endothelial cells. in conclusion, S100a8/9 has an important role in intimal hyperplasia by promoting cell growth and angiogenesis via raGe signaling and activation of mTorc2.

Mounting evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and tumor progression. SNHG12 has been identified in multiple types of malignant tumors. However, the role of SNHG12 in human non-small cell lung cancer (NSCLC) is poorly characterized, and the relevant underlying mechanism remains unclear. The expression levels of SNHG12, miR-101-3p, and CUL4B in collected human NSCLC tumor tissues and NSCLC cell lines were tested via qRT-PCR.Then, NSCLC cellular proliferation, migration and invasion were determined, followed by MTT, scratch and Transwell assays. Dual-luciferase reporter assays and RNA pulldown assays were adopted to explore the target site. Moreover, western blotting was performed to detect the relevant protein expression concerning the CUL4B/ PI3K/AKT pathway. This study clarified that SNHG12 knockdown significantly reduced proliferation, migration, invasion and EMT of NSCLC cells. Our data indicated that SNHG12 targeted and negatively regulated miR-101-3p, and this depletion reversed the inhibitory effect of si-SNHG12 on NSCLC cells. Furthermore, CUL4B was confirmed as a functional target of miR-101-3p, and its knockdown resulted in a strong alleviation of the NSLCL cell phenotype, which was enhanced by the silencing of miR-101-3p. Mechanistically, we found that SNHG12 regulated miR-101-3p to modulate the PI3K/AKT pathway mediated by CUL4B.These observations suggested that lncRNA SNHG12-mediated miR-101-3p downregulation regulated the malignant phenotype of NSCLC cells by targeting CUL4B through the PI3K/AKT pathway, which may present a path to novel therapeutic strategies for NSCLC therapy.

Background Organ failure (OF) and death are considered the most significant adverse outcomes in necrotizing pancreatitis (NP). However, there are few NP-related studies describing the clinical traits of OF and aggravated outcomes. Purpose An improved insight into the details of OF and death will be helpful to the management of NP. Thus, in our research, we addressed the risk factors of OF and death in NP patients. Methods We performed a study of 432 NP patients from May 2017 to December 2021. All patients with NP were followed up for 36 months. The primary end-points were risk factors of OF and death in NP patients. The risk factors were evaluated by logistic regression analysis. Results NP patients with OF or death patients were generally older, had a higher APACHE II score, longer hospital stay, longer ICU stay, as well as a higher incidence of severe acute pancreatitis (SAP), shock and pancreatic necrosis. Independent risk factors related to OF included BMI, APACHE II score and SAP (P < 0.05). Age, shock and APACHE II score (P < 0.05) were the most significant factors correlated with the risk of death in NP patients. Notably, increased mortality was linked to the number of failed organs. Conclusions NP is a potentially fatal disease with a long hospital or ICU stay. Our study indicated that the incidence of OF and death in NP patients was 69.9% and 10.2%, respectively. BMI, SAP, APACHE II score, age and shock are potential risk factors of OF and death in NP patients. Clinicians should focus on these factors for early diagnosis and appropriate therapy.

IntroductionAortic dissection (AD) is a critical cardiovascular system disease caused by blood in the aortic cavity penetrating into the middle layer of the aortic wall through the intimal rift and extending along the long axis of the aorta. Studies have shown that long noncoding RNAs (lncRNAs) can bind to microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) and further affect the levels of target mRNAs. The purpose of this study was to construct and analyse the lncRNA-miRNA-mRNA ceRNA network in AD.Material and methodsWe first downloaded the AD expression data of five normal samples and seven AD samples from the Gene Expression Omnibus (GEO) database (GSE52093) and identified differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEmRNAs were performed using the DAVID and KOBAS online databases. The ceRNA network was constructed by using the miRcode, miRDB, miRTarBase, and TargetScan databases and visualised by Cytoscape v3.6.1. In addition, a protein-protein interaction (PPI) network of DEmRNAs was also constructed.ResultsIn total, 13 lncRNAs and 472 mRNAs were identified as significantly differentially expressed between the AD and normal samples (|logFC| > 1.0, false discovery rate (FDR) < 0.05). In addition, seven lncRNAs, 18 miRNAs, and 48 mRNAs contributed to the construction of the ceRNA network.ConclusionsWe confirmed the DElncRNAs and DEmRNAs in AD and constructed a lncRNA-miRNA-mRNA ceRNA network by using bioinformatics methods, which may provide a novel perspective for the diagnosis of, and potential therapeutic targets for, AD.

Background: Acute pancreatitis in pregnancy (APIP) with organ failure (OF) is a rare but serious disease. Here, we describe the primary characteristics associated with APIP, and explore potential predictors for early recognition of OF among the patients. Methods: A total of 3154 patients with AP from January 2018 to December 2021 were retrospectively reviewed. After screening, we enrolled 49 patients with APIP and 184 non-pregnant AP patients. Clinical characteristics and blood biochemical information were assessed using IBM SPSS 26.0 software and the rms package in R. Results: The most primary cause of APIP was hypertriglyceridemia (59.2%), while respiratory failure (46.9%) was the main type in all OF patients. Age, hemoglobin (Hb), hematocrit (HCT), aminotransferase (ALT), creatinine (Cr), blood urea nitrogen (BUN), albumin (ALB) and sodium ion (Na+) in the pregnant group were lower than in the non-pregnant group (P<0.05), while body mass index (BMI), triglyceride (TG) and total cholesterol (TC) in the pregnant group were higher (P<0.05). Among the APIP patients, BUN, TG and TC were independent risk factors for predicting OF, (P < 0.05) and they were used to create a nomogram with accurate prediction performance. (AUC=0.941) Conclusions: APIP was highly correlated with hypertriglyceridemia and respiratory failure. Higher BMI was a distinguishing feature of OF-APIP patients. The data indicate that close monitoring of BUN, TG and TC levels is essential for early prevention of OF in APIP patients.