Diabetic cardiomyopathy (DCM) is a common cause of heart failure worldwide. The pathological mechanisms underlying DCM are intricate, involving factors such as oxidative stress, inflammation, and mitochondrial dysfunction. USP18 is a deubiquitinating enzyme that mediates the stability of target proteins. In this study, high glucose (HG)-induced AC16 cells and STZ-induced rats were used as in-vitro and in-vivo DCM models to investigate the role of USP18 in DCM and its related mechanisms. We found that HG stimulation led to abnormal production of reactive oxygen species (ROS), accumulation of inflammation, and mitochondrial damage in AC16 cells. However, these pathological lesions were mitigated after USP18 overexpression. For in-vivo studies, the elevated blood sugar, abnormal heart function, and damage to myocardial tissue were observed in DCM rats. Similar to in-vitro experiments, overexpression of USP18 ameliorated these phenotypes. Mechanistically, immunofluorescence confirmed the binding of USP18 and Notch1 and USP18 mediated the stability of Notch1 with the evidence of Western blot. USP18 was able to restore the level of AKT phosphorylation at Ser473 site in HG-induced AC16 cells and DCM rats. In conclusion, our study demonstrated that USP18 alleviated the myocardial damage by promoting the stability of Notch1, thereby activating AKT signaling pathway in cardiac tissue of DCM rats.

Background - This study aims to evaluate the correlation between miRNAs and known nerve injury markers neuron-specific enolase (NSE) and S100 beta in ischemic stroke (IS) patients, exploring its efficacy. Methods - We retrospectively analyzed 86 IS patients and 32 healthy controls. Clinical and neurological examinations were performed in the admitted patients and the severity of neurological deficits was assessed by National Institutes of Health Stroke Scale (NIHSS). Plasma extraction and serum isolation were performed on all subjects before and 2 weeks after admission. miR-142-5p in serum, and NSE and S100 beta contents were measured by RT-qPCR and ELISA. Results - Ischemic lesions were more severe in IS patients, and NSE and S100 beta were abnormally elevated. miR-142-5p in the serum of IS patients was 2.85 times higher. After 2 weeks of treatment, serum miR-142-5, NSE, and S100 beta decreased. Patients' serum levels of miR-142-5p were 57.5% lower. Serum miR-142-5, NSE, and S100 beta were lower in patients with disease improvement than in patients with poor recovery. Additionally, miR-142-5 was positively correlated with NSE (P < 0.0001) and S100 beta (P = 0.0147), and also with the NIHSS score (P = 0.0004). Conclusions - miR-142-5p, NSE, and S100 beta in peripheral blood (PB) of IS patients are elevated, and miR-142-5p is positively correlated with NSE and S100 beta.

Adipose tissue-derived mesenchymal stem cells (ADSCs) have promising effects on nerve repair due to the differentiation ability to neural cells. Ghrelin has been shown to promote the neural differentiation of ADSCs. This work was designed to explore its underlying mechanism. Herein, we found high expression of LNX2 in ADSCs after neuronal differentiation. Knockdown of LNX2 might block neuronal differentiation of ADSCs, as evidenced by the decreased number of neural-like cells and dendrites per cell, and the reduced expressions of neural markers (including β-Tubulin III, Nestin, and MAP2). We also demonstrated that LNX2 silencing suppressed the nuclear translocation of β-catenin in differentiated ADSCs. Luciferase reporter assay indicated that LNX2 inhibited wnt/β-catenin pathway by reducing its transcriptional activity. In addition, results showed that LNX2 expression was increased by ghrelin, and its inhibition diminished the effects of ghrelin on neuronal differentiation. Altogether, the results suggest that LNX2 is involved in the role of ghrelin to facilitate neuronal differentiation of ADSCs.

Splicing factor proline- and glutamine-rich (SFPQ) can interact with RNAs to regulate gene expression. The function of SFPQ in the immunotherapy of non-small cell lung cancer (NSCLC) is investigated in this study. H1299 and A549 cells were transfected with shSFPQ plasmid. Cell counting kit-8 (CCK-8) and cell clone formation were utilized to detect survival and proliferation. Programmed death-ligand 1 (PD-L1) and SFPQ were detected in NSCLC patients treated with anti-PD-L1 antibody. Dual-luciferase assays, RNA immunoblotting, RNA pull-down, and mRNA stability assay were applied to verify the regulation of PD-L1 with SFPQ. Human peripheral blood mononuclear cells (PBMC)-derived dendritic cells were loaded with irradiated A549 and H1299 cells, which were cultured with autologous CD8+T cells and tumor cells to perform in vitro tumor-specific cytotoxic T lymphocytes (CTL) cytotoxicity analysis. SFPQ silencing inhibited the survival and proliferation of H1299 and A549 cells with down-regulated PD-L1 expression. PD-L1 and SFPQ expression were markedly higher in anti-PD-L1 antibody treatment responders compared to non-responders, which showed a positive Pearson correlation (R = 0.76, P < .001). SFPQ up-regulated the relative mRNA and protein expression of PD-L1 by binding to the PD-L1 3'UTR to slow the decay of PD-L1 mRNA. SFPQ silencing promoted the killing effect of CTL on A549 and H1299 cells. SFPQ up-regulates PD-L1 expression by binding with PD-L1 3'UTR to slow the decay of PD-L1 mRNA, and SFPQ silencing promotes CTL-mediated cytotoxicity on NSCLC cells.

Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.

目的 探究miRNA-21对2型糖尿病心肌病(Diabetic Cardiomyopathy,DCM)心肌纤维化的影响.方法 将32只雄性SD大鼠随机分为四组:对照组、DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组,每组8只.各组大鼠高糖高脂饮食4周后,腹腔注射25mg/kg链脲佐菌素(STZ),每2周进行体重、空腹血糖测量,第8周时经尾静脉对DCM+干扰miRNA-21组、DCM+干扰对照组进行慢病毒转染,第12周时所有试验动物处死,进行指标检测:qRT-PCR检测大鼠心肌组织中miRNA

目的 探究微小RNA-30c(miRNA-30c,miR-30c)是否能够通过调控p53来减轻高糖诱导的H9c2大鼠心肌细胞损伤.方法 应用35 mM高糖(high glucose,HG)培养H9c2大鼠心肌细胞48 h,建立高糖诱导的心肌细胞损伤模型,5.0 mM葡萄糖处理48 h作为阴性对照(NG组),检测高糖环境对大鼠心肌细胞miR-30c表达水平的影响.然后将miR-30c mimics和阴性对照mimics control转染到H9c2心肌细胞内,转染后各组细胞给予35 mM HG孵育48 h.根据不同的处理方法将所有细胞分为四组:5.0 mM葡萄糖对照组(NG组);35 mM葡萄糖刺激组(HG组);转染miR-30c mimics再进行35 mM高糖刺激组(miR-30c mimics+HG组);转染mimics control再进行35 mM高糖刺激组(mimics control+HG组).应用CCK-8检测各组心肌细胞的活力,DCFH-DA检测各组细胞活性氧水平的高低,JC-1荧光探针检测各组活细胞线粒体膜电位高低,An-nexin V-FITC试剂盒检测各组凋亡细胞的情况.Western blot技术检测并分析各组心肌细胞中相关的凋亡蛋白p53、Bcl-2和Cleaved Caspase-3的表达水平,以β-actin为内参.结果 高糖处理可以明显下调H9c2细胞中miR-30c表达,降低细胞活力和线粒体膜电位的表达水平,提高细胞内活性氧和凋亡的水平,促进凋亡相关蛋白p53和Cleaved Caspase-3的表达,抑制抗凋亡相关蛋白Bcl-2的表达;miR-30c模拟物转染后可以抑制上述高糖诱导的H9c2细胞损伤.结论 在高糖诱导的H9c2大鼠心肌细胞中miR-30c低表达,而p53蛋白高表达;过表达的miR-30c可负性调节p53蛋白,可减轻高糖诱导的H9c2大鼠心肌细胞凋亡损伤.

Diabetes is characterized by increased fracture risk. Evidence from in vivo studies is lacking for anti-fracture strategies in diabetes. Our microarray analyses predicted association of Toll-like receptor 9 (TLR9) with both diabetes and osteoporosis, which was the focus of this work in a murine model of type II diabetic osteoporosis (T2DOP). A T2DOP model with fracture was established in TLR9 knockout (TLR9−/−) mice, which were then treated with the NF-κB signaling pathway inhibitor (PDTC) and activator (TNF-α). The obtained data suggested that TLR9 knockout augmented regeneration of bone tissues and cartilage area in the callus, and diminished fibrous tissues in T2DOP mice. Moreover, TLR9 depletion significantly affected bone mineral density (BMD), bone volume/tissue volume (BV/TV), connectivity density, trabecular number, trabecular separation and trabecular thickness, thus promoting fracture recovery. Bone morphology and structure were also improved in response to TLR9 depletion in T2DOP mice. TLR9 depletion inactivated NF-κB signaling in T2DOP mice. PDTC was found to enhance fracture healing in T2DOP mice, while TNF-α negated this effect. Collectively, these data indicate that TLR9 depletion may hold anti-fracture properties, making it a potential therapeutic target for T2DOP.Abbreviations: Diabetic osteoporosis (DOP); bone mineral density (BMD); Toll-like receptors (TLRs); type 2 diabetes (T2D); Toll-like receptor 9 (TLR9); nuclear factor-kappaB (NF-κB); streptozotocin (STZ); type 2 diabetic osteoporosis (T2DOP); Gene Expression Omnibus (GEO); Kyoto encyclopedia of genes and genomes (KEGG); pyrrolidine dithiocarbamate (PDTC); computed tomography (CT); Hematoxylin–eosin (HE); bone morphogenetic protein 7 (BMP7); analysis of variance (ANOVA);

Diabetic patients often have a heightened risk of cardiomyopathy, even in the absence of traditional risk factors such as hypertension and atherosclerotic coronary artery disease. Diabetic cardiomyopathy is characterized by a typical cardiomyopathy specific to diabetes, the pathogenesis of which has yet to be fully elucidated. As a well-documented oncogenic long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in a variety of pathological processes, including diabetic complications. This study aimed to evaluate the functional roles of MALAT1 in the pathogenesis of diabetic cardiomyopathy. Spontaneously diabetic (db/db) C57BL/Ks mice were employed to establish diabetic cardiomyopathy models in vivo and high glucose (HG)-cultured mouse cardiomyocytes for myocardial damage models in vitro. Mouse left ventricular volume and function were evaluated by echocardiography, while the myocyte cross-sectional area was calculated to evaluate the degree of myocardial hypertrophy. TUNEL staining and flow cytometric analysis were performed to evaluate myocardial damage and cardiomyocyte apoptosis. Silencing of MALAT1 was found to attenuate cardiac dysfunction and inhibit cardiomyocyte apoptosis in db/db mice and HG-cultured mouse cardiomyocytes. MALAT1 recruited the histone methyltransferase EZH2 to the miR-22 promoter region and inhibited its expression. EZH2 induced an increased in the expression of ATP-binding cassette transporter A1 (ABCA1), which was identified to be a target gene of miR-22. Silencing of EZH2 was found to improve cardiac function and prevent cardiomyocyte apoptosis in db/db mice and HG-cultured mouse cardiomyocytes in the presence of MALAT1, suggesting that MALAT1 mediated myocardial damage by recruiting EZH2 to the miR-22 promoter. Taken together, this study's findings provide evidence confirming our hypothesis, suggesting the involvement of MALAT1 in the processes of cardiac function and cardiomyocyte apoptosis via the EZH2/miR-22/ABCA1 signaling cascade, which has potential therapeutic implications for the understanding of diabetic cardiomyopathy.

目的 探究miRNA-21对2型糖尿病心肌病大鼠心肌纤维化的影响.方法 将32只雄性SD大鼠随机分为四组:对照组、DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组,每组8只.给予DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组大鼠高糖高脂饮食4周后,腹腔注射25 mg/kg链脲佐菌素(STZ),每2周对各组大鼠进行体重、空腹血糖测量,第8周时经尾静脉对DCM+干扰miRNA-21组、DCM+干扰对照组进行慢病毒转染,第12周时所有试验动物处死,进行指标检测;qRT-PCR检测大鼠心肌组织中miRNA-21的表达;HE检测心肌细胞病理学改变;Masson检测心肌组织中胶原纤维的表达;免疫组织化学染色法观察α-SMA的表达.结果 与对照组相比,DCM组大鼠出现体重先增长后下降的趋势,其空腹血糖≥11.1 mmol/L,差异有统计学意义(P<0.05);在转染慢病毒后(注射STZ第8周),与DCM+干扰对照组相比,DCM+干扰miR-NA-21组大鼠体重有所增加,空腹血糖水平下降,差异有统计学意义(P<0.05).与对照组相比,DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组大鼠心肌组织中miRNA-21表达量增加;与DCM+干扰对照组比较,DCM+干扰miRNA-21组心肌中miRNA-21表达量下降,差异有统计学意义(P<0.05);与对照组相比,DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组大鼠出现心肌纤维断裂,周围有炎细胞浸润,且心肌中胶原纤维表达量增加;与DCM+干扰对照组比较,DCM+干扰miRNA-21组改善了心肌纤维的损伤,并降低了胶原纤维表达量,差异有统计学意义(P<0.05);与对照组相比,DCM组、DCM+干扰miRNA-21组、DCM+干扰对照组大鼠心肌组织中α-SMA表达量升高;与DCM+干扰对照组比较,DCM+干扰miRNA-21组的心肌组织中α-SMA表达量下降,差异有统计学意义(P<0.05).结论 miRNA-21参与了DCM的发展过程,抑制miRNA-21的表达可以改善DCM心肌纤维化.

BACKGROUND:LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways.METHODS:A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments.RESULTS:Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition.CONCLUSION:Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.

Although the abundance of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) in lung cancer has been well researched, the underlying mechanisms behind its effects were unknown. Here we investigated the molecular events regulating PVT1 in lung cancer. The pro-proliferative property of PVT1 was examined using a xenograft tumor model. Transwell chambers were used to analyze the impact of PVT1 expression on cell invasiveness and migration. In vivo metastasis was examined by tail-vein-injection in mice. Direct binding of miR-128 to PVT1 was investigated using a probe pulldown assay. The relative expression levels of miR-128 and PVT1 were quantified by real-time polymerase chain reaction and Western blotting. We show here that when PVT1 is amplified, there is a poor survival prognosis for patients with lung cancer. Elevated levels of PVT1 promoted lung cancer cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, we found that PVT1 competes endogenously with miR-128 in the regulation of vascular endothelial growth factor C (VEGFC) expression, which is significantly associated with an unfavorable prognosis in lung cancer. We identified that copy number amplification significantly contributes to the high level of PVT1 transcripts in lung cancer, which promotes cell proliferation and metastatic behavior via modulating VEGFC expression by endogenous competition with miR-128.

随着人类科学技术的发展,人类对基因组计划的完成并对基因组的进一步研究,发现存在不编码蛋白质的RNA,其相同特征是都能从基因组上转录而来,但是不能通过翻译转化成蛋白,在RNA水平上就能发挥各自的生物学效应,这一结果 产生,引起人们对于非编码RNA的研究兴趣,而又最新的研究表明,非编码RNA与糖尿病及其并发症具有一定的联系,然而合并心血管系统并发症的糖尿病患者致死率增加2倍以上.因此该文将针对非编码RNA对糖尿病心肌病的发病机制进行进一步的研究.

Abstract Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third‐passage ADSCs were used in this study. The isolated ADSCs were characterized by flow cytometry analysis for MSCs' surface expression markers as evidenced by positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD11b/2f/c. The multilineage differentiation of ADSCs was confirmed by adipogenic, osteogenic, and neural differentiation. After induction of neurogenesis, the differentiated cells were identified by development of neuron‐like morphology and expression of neural markers including glial fibrillary acidic protein, Nestin, MAP2, and β‐Tubulin III using immunofluorescence and western blot. Ghrelin concentration dependently elevated the proportion of neural‐like cells and branching dendrites, as well as upregulated the expression of neural markers. Further, the expression of nuclear β‐catenin, p‐GSK‐3β, p‐AKT, and p‐mTOR was increased by ghrelin, indicating an activation of β‐catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of β‐catenin or AKT/mTOR signaling suppressed ghrelin‐induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of β‐catenin and AKT/mTOR signaling pathways.

Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific short-hairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3′-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

我们借鉴现在教学改革的新思维,将TBL、CBL与PBL联合教学法应用于病理实习课,观察是否对学生学习效果的有所改善,目的是为在基础教学中锻炼学生的临床思维及分析解决问题的能力.如何有效将PBL,TBL及CBL三种教学方法融合在一起,让这些教学法的优势得以互补,更好地激发起学生的学习潜能,成为本文研究的焦点所在.

为了更好地推广数码互动系统的应用,通过"数码互动教学系统"体现"学生为中心,学生自主学习"的教育理念,本课题将在病理实验课中数码互动教学的成效进行分析,探索出一套适合我院的病理学实验课教学模式,这将推动病理教学法的改进,也将扩大数码互动在医学教学中影响范围.探讨是否可以依托实验室开放,基于"数码互动教学系统",把课内为主的教学模式,转化为课内课外相结合的教学空间.

Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring independently of a recognized cause such as hypertension or coronary artery disease. Liver X receptor α (LXRα), a subtype of ligand-activated transcription factors LXRs, has been considered as a potential pharmacological target in the pathogenesis of cardiovascular and metabolic diseases. However, the potential mechanism of how LXRα is regulated in cardiomyocytes is still unclear. This study investigated the effect of activating LXRα with GW3965 on cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells. Our data indicated that GW3965 up-regulated the expression of LXRα, inhibited cardiomyocyte apoptosis, and altered the apoptosis-related proteins in glucose-induced H9C2 cells. In addition, GW3965 restored the mitochondrial membrane potential level and decreased the ROS production induced by glucose. Moreover, LXRα was confirmed as a direct target of microRNA-1 (miR-1) that was involved in cardiomyocyte apoptosis of DCM, and overexpression of miR-1 abrogated the inhibiting effect of GW3965 on glucose-induced apoptosis in H9C2 cells. This study highlights an important role of LXRα in the development of DCM and brings new insights into the complex mechanisms involved in the pathogenesis of DCM.

Diabetic cardiomyopathy (DCM) is characterized by abnormal myocardial structure or performance. It has been suggested that microRNA-1 (miR-1) may be abnormally expressed in the hearts of patients with diabetes. In the present study, the role of miR-1 in glucose-induced apoptosis and its underlying mechanism of action was investigated in rat cardiomyocyte H9C2 cells. Cells were transfected with anti-miR-1 or miR-1-overexpression plasmids and the expression of miR-1 and liver X receptor α (LXRα) were determined by reverse transcription-quantitative polymerase chain reaction analysis. The proportion of apoptotic cells was determined using an Annexin-V-FITC apoptosis detection kit and the mitochondrial membrane potential (ΔΨ) was measured following staining with rhodamine 123. In addition, the expression of apoptosis-associated proteins was measured by western blot analysis. The results demonstrated that expression of miR-1 was significantly increased, whereas the expression of LXRα was significantly decreased in H9C2 cells following treatment with glucose. miR-1 knockdown significantly inhibited apoptosis, increased the ΔΨ and suppressed the cleavage of poly (adenosine diphosphate-ribose) polymerase, caspase-3 and caspase-9. It also significantly downregulated the expression of Bcl-2 and upregulated the expression of Bax. In addition, it was demonstrated that miR-1 regulates LXRα; transfection with anti-miR-1 significantly increased the expression of LXRα. Furthermore, treatment of cells with the LXR agonist GW3965 inhibited apoptosis in glucose-induced anti-miR-1 cells. These results suggest a novel function of miR-1: The regulation of cardiomyocyte apoptosis via LXRα, and provide novel insights into regarding the complex mechanisms involved in DCM.