Kaohsiung Journal of Medical Sciences最新文献

Bone mesenchymal stem cell-derived exosome (BMSC-exosome) is a potential candidate for lung ischemia-reperfusion injury (LIRI) treatment. This study aims to investigate the anti-pyroptosis effect of BMSC-exosomes in LIRI. The LIRI cell model was established by hypoxia/reoxygenation (H/R) treatment. Interleukin (IL)-1β and IL-18 levels were examined by enzyme-linked immunosorbent assay. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Lactate dehydrogenase (LDH) release was examined using a LDH assay kit. The interaction between microRNA (miR)-202-5p and cytidine monophosphate kinase 2 (CMPK2) was analyzed using dual-luciferase reporter assay and RNA immunoprecipitation. BMSC-exosomes promoted cell viability and suppressed pyroptosis in H/R-treated mouse lung epithelial. miR-202-5p was enriched in BMSC-exosomes, and exosomal miR-202-5p inhibition upregulated pyroptosis-associated proteins, including cleaved N-terminal Gasdermin D, nucleotide-binding domain-like receptor family member pyrin domain-containing protein 3, and Caspase1. Meanwhile, miR-202-5p suppressed CMPK2 expression by directly targeting CMPK2. Expectedly, CMPK2 knockdown reversed the promoting effect of exosomal miR-202-5p inhibition on pyroptosis in LIRI. Therefore, BMSC-derived exosome miR-202-5p repressed pyroptosis to inhibit LIRI progression by targeting CMPK2.

Myocardial ischemia-reperfusion injury (MIRI) was often observed after surgeries, causing a lot of suffering to patients. Inflammation and apoptosis were critical determinants during MIRI. We conveyed experiments to reveal the regulatory functions of circHECTD1 in MIRI development. The Rat MIRI model was established and determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. We analyzed cell apoptosis using TUNEL and flow cytometry. Proteins expression was evaluated by western blot. The RNA level was determined by qRT-PCR. Secreted inflammatory factors were analyzed by ELISA assay. To predict the interaction sequences on circHECTD1, miR-138-5p, and ROCK2, bioinformatics analysis was performed. Dual-luciferase assay was used to confirm these interaction sequences. CircHECTD1 and ROCK2 were upregulated in the rat MIRI model, while miR-138-5p was decreased. CircHECTD1 knockdown alleviated H/R-induced inflammation in H9c2 cells. Direct interaction and regulation of circHECTD1/miR-138-5p and miR-138-5p/ROCK2 were confirmed by dual-luciferase assay. CircHECTD1 promoted H/R-induced inflammation and cell apoptosis by inhibiting miR-138-5p. miR-138-5p alleviated H/R-induced inflammation, while ectopic ROCK2 antagonized such effect of miR-138-5p. Our research suggested that the circHECTD1-modulated miR-138-5p suppressing is responsible for ROCK2 activation during H/R-induced inflammatory response, providing a novel insight into MIRI-associated inflammation.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can be complicated by intestinal mucosal barrier dysfunction (SAP&IBD). The current study sought to examine the diagnostic efficacy of miR-1-3p and T-synthase mRNA in SAP&IBD patients. First, SAP patients were assigned to SAP&IBD and SAP groups. Serum miR-1-3p expression and T-synthase mRNA expression patterns in peripheral blood B lymphocytes were measured using RT-qPCR. Pearson tests, ROC curve analysis, and multivariate logistic regression were used to analyze the correlation between miR-1-3p/T-synthase mRNA and clinical data, their diagnostic efficiency, and independent risk factors for SAP&IBD patients, respectively. The results showed that serum miR-1-3p in the SAP&IBD group was elevated, and T-synthase mRNA expression in peripheral blood B lymphocytes was diminished. Additionally, serum miR-1-3p expression in SAP&IBD patients was negatively correlated with T-synthase mRNA expression, and positively correlated with their Ranson score, CRP, IL-6, DAO, and D-Lactate levels. Meanwhile, T-synthase mRNA level was negatively correlated with IL-6, DAO, and D-Lactate levels. Both, serum miR-1-3p, T-synthase mRNA, and their combination were found to exhibit diagnostic efficiency for SAP&IBD patients, and were independently associated with IBD in SAP patients. Collectively, our findings suggest that miR-1-3p and T-synthase serve as independent risk factors for SAP&IBD patients and can aid the diagnosis of IBD in SAP patients.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 μg/kg/h DEX in combination with 0.03 μg/kg/h SUF in Group I (n = 150) or 0.11 μg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

Acute myocardial infarction (AMI) is the most important cause of death among cardiovascular diseases. Long noncoding RNAs (lncRNAs) have been widely implicated in the regulation of AMI progression. Discrimination antagonizing nonprotein coding RNA (DANCR) alleviated hypoxia-caused cardiomyocyte damages, and the underlying mechanisms remain unclear. Here, we investigated the function and mechanism of DANCR in hypoxia-induced cardiomyocytes and AMI model by enzyme-linked immunosorbent assay, reactive oxygen species and adenosine triphosphate measurement, and mitochondrial activity determination. Additionally, luciferase reporter assay, immunoblotting, and qRT-PCR were performed to validate the interactions between DANCR/miR-509-5p and miR-509-5p/Kruppel-like factor 13 (KLF13). The role of DANCR was also verified in AMI model by overexpression. Our results showed that DANCR expression was significantly downregulated in hypoxia-induced cardiomyocytes or AMI model. Overexpression of DANCR significantly alleviated mitochondrial damages, reduced inflammation, and improved cardiac function in the AMI model. Furthermore, we demonstrated that miR-509-5p/KLF13 axis mediated the protective effect of DANCR. The current study highlighted the critical role of DANCR in alleviating AMI progression through targeting the miR-509-5p/KLF13 signaling axis, suggesting that DANCR may serve as a potential diagnostic marker or therapeutic target for AMI.

13-Acetoxysarcocrassolide (13-AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13-AC against leukemia cells was previously reported but its mechanism of action is still unexplored. In the current study, we showed that 13-AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13-AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13-AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13-AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13-AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation.

Tanshinone IIA (Tan IIA) has an important role in treatment of cardiovascular diseases, including atherosclerosis. The vascular smooth muscle cells (VSMCs) are a major part of the atherosclerotic plaque. However, the biological functions of Tan IIA in regulating VSMCs function remain mostly unclear. This research aimed at identifying the explicit molecular mechanism that Tan IIA regulates oxidized low-density lipoprotein (ox-LDL)-mediated VSMC proliferation and migration. VSMCs challenged by ox-LDL were adopted as cellular model of atherosclerosis, and suffered from Tan IIA treatment. After that, cells proliferation, apoptosis or migration were measured. The expression levels of microRNA (miR)-137, transient receptor potential cation channel subfamily C member 3 (TRPC3) and proliferating cell nuclear antigen (PCNA) were measured. The targeting relationship between miR-137 and TRPC3 was determined. It was found that Tan IIA blunted VSMC proliferation, PCNA expression and migration mediated by ox-LDL. Tan IIA promoted miR-137 level, and miR-137 knockdown reversed the influences of Tan IIA on VSMC proliferation, PCNA expression and migration in the presence of ox-LDL. TRPC3 was verified to be targeted by miR-137. Moreover, TRPC3 silencing exacerbated the influences of Tan IIA on VSMC proliferation, apoptosis and migration, and it mitigated the inhibitive effects of miR-137 knockdown on function of Tan IIA. We confirmed for the first time that Tan IIA constrained ox-LDL-stimulated VSMC proliferation and migration via regulating the miR-137/TRPC3 axis, which provided a theoretical basis for the research and promotion of Tan IIA as a therapeutic drug.

Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription-polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x-ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x-ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh-ERP29 or sh-NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x-ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen-sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription.