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Abstract Objective Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia–reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia–reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia–reperfusion injury and the O-GlcNAcylation level of COX10. Methods We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia–reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. Results Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia–reperfusion injury. In vivo, MTH effectively alleviates ischemia–reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. Conclusions In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia–reperfusion injury, which provides important theoretical basis for the clinical application of MTH.

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

Abstract Background Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Results In the present study, bromide does not affect cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic (Hk2 and Pkm2) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes (Bmal1, Cry1 and Rorα) and glycolytic genes (Hk2 and Pkm2). Conclusions Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.

Abstract Background Extensor apparatus rupture is a severe complication after knee arthroplasty, but there have not been many reports on how to perform knee arthroplasty after chronic patellar ligament rupture. We reported a case of total knee arthroplasty (TKA) in a patient with severe osteoarthritis (OA) complicated by chronic patellar ligament rupture. Case presentation In this case, a 67-year-old male patient suffered from patellar ligament rupture due to trauma more than 20 years ago and did not undergo any formal treatment. Physical examination revealed a small amount of fluid and extension lag, and the patella was displaced upward by approximately 5.5 cm. The quadriceps were atrophic and weak. There was significant tenderness on the medial side of the left knee joint. Passive motion of the left knee joint ranged from full extension to 120° of flexion with discomfort during excessive flexion. Active flexion of the knee joint to 120°, and extensor lag was approximately 90°. We reconstructed the extensor apparatus through a quadriceps tendon V-Y quadricepsplasty and Krackow suture technique of the patellar ligament, and osteoarthritis was resolved with TKA. The visual analogue scale (VAS) score decreased from 5 points to 1 point after surgery. Six weeks later, the patient was able to walk normally without a walking stick, and the knee joint could stretch actively to approximately 30°. However, he had obvious extension lag. This problem improved 10 months after surgery. The AKS score increased from 35 to 95 10 months after surgery. The HSS score increased from 43 to 93. Conclusions TKA and ligament reconstruction are options for the treatment of knee OA with chronic patellar ligament rupture. V-Y lengthening of the quadriceps femoris tendon after the Krackow suture technique of the patellar ligament with transpatellar tunnels may be a reasonable choice during TKA.

Abstract Background Transmissible gastroenteritis virus (TGEV) infection can cause acute inflammation. Long noncoding RNAs (lncRNAs) play important roles in a number of biological process including inflammation response. However, whether lncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells (IPECs) is largely unknown. Results In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of lncRNAs in Mock and TGEV-infected porcine intestinal epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 106 lncRNAs were differentially expressed. Many differentially expressed lncRNAs act as elements to competitively attach microRNAs (miRNAs) which target to messenger RNA (mRNAs) to mediate expression of genes that related to toll-like receptors (TLRs), NOD-like receptors (NLRs), tumor necrosis factor (TNF), and RIG-I-like receptors (RLRs) pathways. Functional analysis of the binding proteins and the up/down-stream genes of the differentially expressed lncRNAs revealed that lncRNAs were principally related to inflammatory response. Meanwhile, we found that the differentially expressed lncRNA TCONS_00058367 might lead to a reduction of phosphorylation of transcription factor p65 (p-p65) in TGEV-infected IPEC-J2 cells by negatively regulating its antisense gene promyelocytic leukemia (PML). Conclusions The data showed that differentially expressed lncRNAs might be involved in inflammatory response induced by TGEV through acting as miRNA sponges, regulating their up/down-stream genes, or directly binding proteins.