LncRNA TUG1 Exacerbates Myocardial Fibrosis in Diabetic Cardiomyopathy by Modulating the microRNA-145a-5p/Cfl2 Axis.

ABSTRACT: Nowadays, there is limited prevention and treatment for myocardial fibrosis in diabetic cardiomyopathy (DCM). Our study aimed to depict the mechanism of the lncRNA TUG1/miR-145a-5p/Cfl2 axis in DCM and to provide a molecular basis for the study of this disease. Male C57BL/6J mice were intraperitoneally injected with streptozotocin to establish DCM mouse models. The expression levels of lncRNA TUG1, miR-145a-5p, and Cfl2 in myocardial tissues of mice were tested by RT-qPCR or Western blot. Cardiac function was assessed by echocardiography. The contents of Ang-II, TNF-α, and IL-1ß were measured using ELISA. The histopathological observation was performed by HE staining and Masson staining. The expression levels of myocardial fibrosis-related genes COL1A1, MMP2, and FN1 were determined by RT-qPCR. In addition, bioinformatics website, RIP assay, pull-down assay, and luciferase activity assay were conducted to verify the relationships of lncRNA TUG1, miR-145a-5p, and Cfl2. In the DCM mouse model, lncRNA TUG1 and Cfl2 expression levels were upregulated and miR-145a-5p expression was downregulated. Downregulation of lncRNA TUG1 improved cardiac function and myocardial fibrosis; decreased COL1A1, MMP2, and FN1 expression levels; as well as TNF-α, IL-1ß, and Ang-II contents in myocardial tissues of DCM mice. Upregulation of miR-145a-5p showed the same trend as downregulation of lncRNA TUG1. In addition, upregulating miR-145a-5p reversed the promotion roles of lncRNA TUG1 on myocardial fibrosis in DCM mice, and upregulating Cfl2 compromised the improvement effect of downregulated lncRNA TUG1 on myocardial fibrosis in DCM mice. Mechanistically, there was a binding site between lncRNA TUG1 and miR-145a-5p, and miR-145a-5p had a targeting relationship with Cfl2. This study highlights that lncRNA TUG1 sponges miR-145a-5p to aggravate myocardial fibrosis in DCM mice by promoting Cfl2.

Development and validation of a prediction model for in-hospital death in patients with heart failure and atrial fibrillation.

BACKGROUND: To develop a prediction model for in-hospital mortality of patients with heart failure (HF) and atrial fibrillation (AF). METHODS: This cohort study extracted the data of 10,236 patients with HF and AF upon intensive care unit (ICU) from the Medical Information Mart for Intensive Care (MIMIC). The subjects from MIMIC-IV were divided into the training set to construct the prediction model, and the testing set to verify the performance of the model. The samples from MIMIC-III database and eICU-CRD were included as the internal and external validation set to further validate the predictive value of the model, respectively. Univariate and multivariable Logistic regression analyses were used to explore predictors for in-hospital death in patients with HF and AF. The receiver operator characteristic (ROC), calibration curves and the decision curve analysis (DCA) curves were plotted to evaluate the predictive values of the model. RESULTS: The mean survival time of participants from MIMIC-III was 11.29 ± 10.05 days and the mean survival time of participants from MIMIC-IV was 10.56 ± 9.19 days. Simplified acute physiology score (SAPSII), red blood cell distribution width (RDW), beta-blocker, race, respiratory rate, urine output, coronary artery bypass grafting (CABG), Charlson comorbidity index, renal replacement therapies (RRT), antiarrhythmic, age, and anticoagulation were predictors finally included in the prediction model. The AUC of our prediction model was 0.810 (95%CI: 0.791-0.828) in the training set, 0.757 (95%CI: 0.729-0.786) in the testing set, 0.792 (95%CI: 0.774-0.810) in the internal validation set, and 0.724 (95%CI: 0.687-0.762) in the external validation set. The calibration curves of revealed that the predictive probabilities of our model for the in-hospital death in patients with HF and AF deviated slightly from the ideal model. The DCA curves revealed that the use of our prediction model increased the net benefit than use no model. CONCLUSION: The prediction model had good discriminative ability, and might provide a tool to timely identify patients with HF complicated with AF who were at high risk of in-hospital mortality.

In-depth Understanding of Camellia oleifera Self-incompatibility by Comparative Transcriptome, Proteome and Metabolome.

Oil-tea tree (Camellia oleifera) is the most important edible oil tree species in China with late-acting self-incompatibility (LSI) properties. The mechanism of LSI is uncertain, which seriously hinders the research on its genetic characteristics, construction of genetic map, selection of cross breeding parents and cultivar arrangement. To gain insights into the LSI mechanism, we performed cytological, transcriptomic, proteomic and metabolomic studies on self- and cross-pollinated pistils. The studies identified 166,591 transcripts, 6851 proteins and 6455 metabolites. Transcriptomic analysis revealed 1197 differentially expressed transcripts between self- and cross-pollinated pistils and 47 programmed cell death (PCD)-control transcripts. Trend analysis by Pearson correlation categorized nine trend graphs linked to 226 differentially expressed proteins and 38 differentially expressed metabolites. Functional enrichment analysis revealed that the LSI was closely associated with PCD-related genes, mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, ATP-binding cassette (ABC) transporters and ubiquitin-mediated proteolysis. These particular trends in transcripts, proteins and metabolites suggested the involvement of PCD in LSI. The results provide a solid genetic foundation for elucidating the regulatory network of PCD-mediated self-incompatibility in C. oleifera.

Dynamic changes in inflammatory responses and 3-year clinical outcomes of XINSORB scaffolds in coronary stenting.

BACKGROUND: Inflammation is known to play a crucial role in the development of coronary atherosclerosis and vascular healing after stenting. This study aimed to investigate the dynamic changes in inflammatory responses between XINSORB and TIVOLI scaffolds and their correlation with 3-year clinical outcomes. METHOD: A total of 140 patients in the XINSORB group and 42 patients in the TIVOLI group were included in this prospective, single-center study, conducted in Shanghai tenth People's Hospital. Blood samples were collected at baseline, 24 h, 6 months, and 12 months after stent implantation to measure high sensitivity C-reactive protein (hsCRP), fibrinogen (FBG), white blood cell count (WBC), tumor necrosis factor (TNF), and interleukin-6 (IL-6). Receiver-operating characteristic curves and proportional hazards models were generated to evaluate the relationship between 24-h postoperative inflammatory indicators and 3-year patient-oriented composite endpoints (POCE). RESULT: The levels of hsCRP, FBG, WBC, TNF, and IL-6 reached their peak levels 24 h after stenting and then gradually decreased to levels comparable to baseline at 6 and 12 months. During the 3-year follow-up, 11.4 % of the XINSORB cohort and 9.5 % of the TIVOLI cohort experienced POCE (P = 0.948). High levels of hsCRP and IL-6 24 h after the procedure were associated with clinical endpoints, and the combination of these two biomarkers improved the predictive ability of prognosis. CONCLUSIONS: There were no significant differences between the changes in the concentration of inflammatory biomarkers after XINSORB stents or drug-eluting stent implantation. Reduction in postoperative inflammatory levels may decrease the occurrence of clinical outcomes. This study provides insights into the dynamic changes of inflammatory responses and their correlation with clinical outcomes, which could have implications for the management of patients undergoing coronary stenting. TRIAL REGISTRATION: The study has been registered on the official website of the China Clinical Trial Registry (ChiCTR1800014966).

Influence of Different Obstetric Factors on Early Postpartum Pelvic Floor Function in Primiparas After Vaginal Delivery.

Purpose: This study sought to explore the obstetric factors affecting early postpartum pelvic floor function of primiparas after vaginal delivery. Patients and Methods: We included 3362 primiparas who underwent postpartum re-examination in International Peace Maternity and Child Health Hospital at 42-60 days after delivery. The Glazer Protocol was used to evaluate their pelvic floor function, and univariate and multivariate logistic regression analyses were performed to identify obstetric factors that might affect it. Results: Forceps-assisted delivery significantly increased the risk of the decline in fast- and slow-twitch muscle strength in the early postpartum period when compared with natural vaginal delivery (P < 0.05). Women with a pre-pregnancy body mass index (BMI) of ≥18.5 kg/m2 had a decreased risk of decline in fast-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). Women who had a pre-pregnancy BMI of 24.0 to <28.0 kg/m2 bore a decreased risk of decline in slow-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). The risk of decline in fast-twitch muscle strength and slow-twitch muscle in women with anemia during pregnancy was significantly increased (P < 0.05); women with second-stage labors of >2 h had an increased risk of fast-twitch and slow-twitch muscle strength decline than those with <2 h (P < 0.05). Conclusion: Both pre-pregnancy underweight and obesity may cause impairment of early postpartum pelvic floor function. Forceps delivery, anemia during pregnancy, and the length of second stage of labor are independent factors leading to pelvic floor function impairment.

Impact of the Xinsorb Scaffold-Related Parameters on Platelet Reactivity in Patients with Single De Novo Coronary Artery Lesions Undergoing Clopidogrel Treatment.

BACKGROUND: This study aimed to assess the relationship between stent parameters and platelet function, as well as the platelet reactivity profiles over time in patients treated with the Xinsorb scaffold. METHODS: Adenosine diphosphate-induced maximal amplitude was measured as clopidogrel on-treatment platelet reactivity using thrombelastography. High residual platelet reactivity was defined as MAADP > 47 mm. Platelet function testing was induced at baseline, discharge, and 6- and 12-month visits. RESULTS: A total of 40 individuals undergoing Xinsorb scaffold implantation and platelet function testing were included. No adverse events were recorded during follow-up. No correlation was observed among thrombelastography indices, stent diameters, and stent coverage surface area. Significant correlation was found between MAADP and lengths of stents (Spearman rank correlation = 0.324, P =.031). Multiple logistic regression analyses demonstrated that high levels of high-density lipoprotein cholesterol was an independent protective factor for high residual platelet reactivity (odds ratio = 0.049, 95% confidence interval = 0.011-0.296, P =.016). No significant risk factors were identified; MAADP presented to be 20.6 [13.1-36.2] mm, 26.8 [18.2-35.0] mm, and 30.0 [19.6-33.4] mm 48 hours, 6 months, and 12 months after procedure, respectively; 12-month MAADP was significantly higher than the 48-hour MAADP (P =.026). There was no obvious trend for platelet response status over time. CONCLUSION: Among patients on a clopidogrel-based dual antiplatelet treatment regimen following Xinsorb scaffold implantation, stent parameters had no significant effects on platelet reactivity. The high residual platelet reactivity phenotype is relatively stable over time. High residual platelet reactivity is more likely to occur in patients with lower high-density lipoprotein cholesterol levels.

Activation of GPR39 with the agonist TC-G 1008 ameliorates ox-LDL-induced attachment of monocytes to endothelial cells.

Attachment of monocytes to endothelial cells is a major event in the pathogenesis of atherosclerosis and cardiovascular disease. As atherosclerosis is considered to be an inflammatory disease, increased expression of proinflammatory cytokines greatly contributes to endothelial dysfunction and atherogenesis. Additionally, attachment of monocytes to endothelial cells triggered by cellular adhesion molecules such as vascular cellular adhesion molecule 1 (VCAM-1) and E-selectin plays a vital role in the development of atherosclerotic plaques. Zinc therapy has been suggested as a potential strategy for countering atherosclerosis. In the present study, for the first time to our knowledge, we investigated the potential role of the GPR39 zinc-sensing receptor in mediating the adhesion of monocytes to endothelial cells, oxidative stress and inflammation in human aortic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL). Our findings show that agonism of GPR39 by the selective agonist TC-G 1008 potently reversed the effects of ox-LDL including increased expression of proinflammatory cytokines and chemokines, markers of oxidative stress, and enhanced expression of cellular adhesion molecules. Importantly, we also show that this protective effect is mediated through the nuclear factor-κB (NF-κB) pathway. Taken together, our findings suggest a potential role of GPR39 as a novel therapeutic target for the treatment and prevention of atherosclerosis induced by ox-LDL.