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Diabetic cardiomyopathy (DCM) is characterized by structural and functional changes in the myocardium. Several studies have revealed that myocardial apoptosis and fibrosis occur during DCM. Studies have also indicated that oxidative stress may be a major factor associated with the development of DCM. Protein kinase C (PKC)β2 has been demonstrated to be activated in diabetic rats, and overexpression of PKCβ2 in the myocardium may result in cardiac hypertrophy and fibrosis. The P66shc adaptor protein, which is mediated by PKCβ, serves an important role in apoptosis during oxidative stress. The aim of the present study was to investigate whether the PKCβ2/P66shc oxidative stress pathway is associated with DCM, and to investigate the role and mechanisms of carvedilol in preserving cardiac function. Experimental diabetic rat models were induced by streptozotocin treatment accompanied by high energy intake. Carvedilol was orally administrated at a dose of 1 or 10 mg/kg/day. Cardiac function was evaluated by serum N-terminal pro-B-type natriuretic peptide level and cardiac ultrasound. Myocardial inflammation, oxidative stress, apoptosis and fibrosis were assessed by histopathological and echocardiographic analyses and tests for oxidative markers. Associated proteins and factors were examined by immunohistochemical and western blot analyses. Rats in the diabetes mellitus group exhibited significantly decreased systolic cardiac function along with elevated expression levels of phosphorylated (p)-PKCβ2, phos-P66shc, caspase-3, malondialdehyde, collagen type I, tumor necrosis factor-α and interleukin-1β, which were accompanied by disorder in metabolic processes. Treatment with carvedilol reversed these changes. Thus, the present results suggest that the PKCβ2/P66shc signaling pathway may be associated with diabetic cardiomyopathy; furthermore, carvedilol, as a novel β-receptor blocker, may protect the myocardium from injury by suppressing the myocardial inflammatory response, fibrosis, P66shc-mediated oxidative stress and subsequent apoptosis in myocardial tissue. Consequently, carvedilol may have potential as a therapy for the treatment of DCM. [ABSTRACT FROM AUTHOR]

Donor organ rejection remains a significant problem. The present study aimed to assess whether transferring a donor's major histocompatibility complex (MHC) genes to the recipient could mitigate rejection in organ transplantation. Seven loci of MHC genes from donor mice were amplified and ligated into vectors; the vectors either contained one K locus, seven loci or were empty (control). The vectors were subsequently injected into the thymus of recipients (in heterotransplants, recipient rats received the vector containing one K locus), following which donor mouse hearts were transplanted. Following the transplantation of allograft and heterograft, electrocardiosignals were viable for a significantly longer duration in recipient mice and rats receiving the donor histocompatibility-2 complex (H-2)d genes compared with those in controls, and in mice that received seven vectors compared with those receiving one vector. Mixed lymphocyte cultures containing cells from these recipients proliferated significantly less compared with mixed lymphocyte cultures containing controls. Also, hearts from H-2d genes-treated recipients demonstrated less lymphocyte infiltration and necrosis compared with the control recipient. The present study concluded that allograft and heterograft rejection may be mitigated by introducing the donor's MHC into the recipient; transferring seven loci has been demonstrated to be more effective than transferring one locus. [ABSTRACT FROM AUTHOR]

Cerebral ischemia is one of the most common clinical diseases characterized by high morbidity and mortality. Neurocyte apoptosis and a cascade of inflammatory signals following cerebral ischemia-reperfusion injury (IRI) may contribute to secondary brain damage, resulting in severe neurological damage. It has been reported that dioscin, a natural steroid saponin, exerts anti-inflammatory properties against different diseases. The present study aimed to investigate the role of dioscin in oxygen-glucose deprivation/reperfusion (OGD/R) induction in hippocampal cells in vitro and in vivo. For the in vitro study, hippocampal cells were collected from rat embryos of gestational age of E18. The oxygen-glucose deprivation model in primary hippocampal neurons was used to mimic cerebral IRI in vitro. To select the optimum dioscin concentration and acting time, cell viability was evaluated by a Cell Counting Kit-8 (CCK-8) assay. Neurons subjected to OGD/R were treated with dioscin and the inflammatory cytokines, high mobility group box chromosomal protein 1 (HMGB-1)/receptor for advanced glycation end products (RAGE) signaling molecules and apoptosis-associated genes were determined. The intracellular reactive oxygen species (ROS) generation was detected. Furthermore, the effects of dioscin on the antioxidant defense mechanisms were evaluated by measuring the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the glutathione (GSH)/glutathione disulphide (GSSG) ratio. In addition, OGD/R-induced cells were transfected with pcDNA3.1-HMGB-1 and treated with dioscin, and the neuronal cell apoptosis rate was determined using a terminal deoxynucleotidyl transferase-mediated 2-deoxyuridine 5-triphosphate-biotin nick-end labeling (TUNEL) assay. The mRNA and protein expression levels of the inflammatory factors were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo investigation, the oxidation and anti-oxidation system in rat hippocampal tissue was evaluated by detecting the expression of the aforementioned oxidative stress-associated proteins, 3-NT as well as 8-oxo-deoxyguanosine (8-OHdG). In the hippocampal region, the apoptotic rate was determined using a TUNEL assay. The results demonstrated that dioscin at a dose of 400 ng/ml significantly reversed the increase in the expression levels of the inflammatory factors and attenuated those of apoptotic cytokines induced by OGD/R. Additionally, dioscin notably reversed the OGD/R-mediated activation of the HMGB-1/RAGE signaling pathway in vitro and in vivo. Cell treatment with dioscin significantly attenuated ROS production and increased the activity of antioxidant enzymes. Additionally, increasing the expression of HMGB-1 inhibited the protective effects of dioscin on cell apoptosis in the OGD/R-induced neurons. Furthermore, HMGB-1 overexpression reversed the antiapoptotic and anti-inflammatory effects of dioscin on neurons. The results of the present study indicated that dioscin exerted anti-inflammatory, antiapoptotic and antioxidant effects via the HMGB-1/RAGE signaling pathway. These results suggest a novel perspective of the protective effects of dioscin as a prospective remedial factor for IRI. [ABSTRACT FROM AUTHOR]