Long noncoding RNAs (lncRNAs) are regarded as crucial regulators in tumor progression. Potassium two pore domain channel subfamily K member 15 and WISP2 antisense RNA 1 (KCNK15-AS1) has been confirmed to inhibit the migration and invasion of pancreatic cancer (PC) cells. However, its downstream mechanism and effect on other cellular functions in PC remain unknown. This study probed the function and potential mechanism of KCNK15-AS1 in PC cell growth. RT-qPCR and western blot were employed to measure gene expression in PC cells. ISH was applied to analyze KCNK15-AS1 expression in PC tissues. Functional assays were utilized to evaluate PC cell proliferation, apoptosis, migration and EMT. Mechanical experiments were adopted to detect gene interaction in PC cells. The obtained data indicated that KCNK15-AS1 was down-regulated in PC cells and tissues. Overexpressing KCNK15-AS1 hindered cell proliferation, migration and EMT while facilitated cell apoptosis in PC. Mechanically, alkylation repair homolog protein 5 (ALKBH5) was verified to induce m6A demethylation of KCNK15-AS1 to mediate KCNK15-AS1 up-regulation. KCNK15-AS1 combined with KCNK15 5’UTR to inhibit KCNK15 translation. Moreover, KCNK15-AS1 recruited MDM2 proto-oncogene (MDM2) to promote RE1 silencing transcription factor (REST) ubiquitination, thus transcriptionally upregulating phosphatase and tensin homolog (PTEN) to inactivate AKT pathway. In conclusion, our study first confirmed that KCNK15-AS1 hinders PC cell growth by regulating KCNK15 and PTEN, suggesting KCNK15-AS1 as a potential biomarker of PC.
Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. This study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 over-expression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 over-expression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.
Objective. Currently, the therapeutic effect and outcomes of US-PCD in patients with liver abscess and septic shock remain unclear. This study is aimed at investigating the effects of ultrasound-guided percutaneous catheter drainage (US-PCD) on the prognosis of patients with liver abscess complicated with septic shock. Method. We retrieved and assessed the data of 120 patients with liver abscess complicated with septic shock diagnosed at our hospital from January 2019 to March 2021. The patients underwent US-PCD in the observation group or conventional surgical incision and drainage in the control group. After treatment, we determined the levels of liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), and alkaline phosphatase (ALP) as well as the levels of inflammatory cytokines IL-6, IL-8, and TNF-α in serum using ELISA on postoperative days 0, 2, 4, and 6. The postoperative body temperature recovery, peripheral white blood cell count recovery, extubation, postoperative length of stay, and complications were recorded, with a 12-month follow-up to calculate their survival rate. Results. After treatment, the ALT, AST, TBIL, DBIL, and ALP levels and inflammatory factor levels in the two groups were gradually reduced over time and returned to the normal range with a better recovery trend in the observation group. US-PCD was associated with better postoperative body temperature recovery, peripheral white blood cell count recovery, shorter extubation time, hospital stay, lower postoperative rate, and a higher survival rate. Conclusion. US-PCD may be effective in treating liver abscess and can significantly improve the prognosis of patients.
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