Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4 / 中国药房

OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）. METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl- 2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2- induced myocardial cells were investigated. RESULTS Compared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜ 0.05）. CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.

Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Salvianolic acid B regulates bone metabolism through Nox4 pathway in HFD mice / 中国药理学通报

Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .

Association between speed and endurance performance with sleep duration in children and adolescents / 北京大学学报(医学版)

OBJECTIVE@#To analyze the association between sleep duration and athletic performance, and provide scientific basis to improve the 50 m and endurance performance in children and adolescents.@*METHODS@#All the 119 462 subjects aged 9-15 years in both genders were sampled from 2014 National Physical Fitness and Health Surveillance by using stratified random cluster sampling method, to measure the height, weight, 50 meters and endurance performance and investigate sleep duration with questionnaire. Their body mass indexes (BMI) were calculated and the students' 50 m, endurance run scores and sleep durations were assessed. Binary Logistic regression was used to analyze the difference between the different sleep groups, and multifactor Logistic regression was used to analyze the relationship between the sleep condition and athletic performance.@*RESULTS@#The prevalence of insufficient sleep was 94.67% in the total subjects, the prevalence was higher among the girls (95.26%)than the boys (94.09%, χ2=80.99, P<0.001), and higher among the urban (95.41%) than the rural students(93.93%, χ2=128.48, P<0.001).The children with sufficient sleep had better performance in 50 m and endurance run scores( χ250 m=10.10, P50 m＜0.01; χ2endurance run=21.76, P<0.001). Logistic regression analysis after controlling the gender, area, grade and BMI showed that children with adequate sleep showed better results(OR50 m=1.14, 95%CI50 m=1.05-1.23, P50 m<0.01; ORendurance run=1.21, 95%CIendurance run=1.11-1.31, Pendurance run<0.001). As for gender, the excellent rates of 50 m and endurance run scores in the boys with adequate sleep were higher (P<0.001), but there were no significant difference in 50 m and endurance run excellent rates in the girls of different sleep conditions. The excellent rates of 50 m and endurance run in the urban children and the endurance rate in the rural children and adolescents with adequate sleep were higher than those with insufficient sleep (P<0.01) while there were no significant difference in the 50 m excellent rates between the different sleep groups in rural areas. The 50 m and endurance run excellent rates of the children and adolescents with adequate sleep in each grade were higher than those of the children in the same grade with insufficient sleep (Pprimary students' endurance performance<0.001, and the rest P<0.05). Children and adolescents with normal BMI and overweight who slept well had better performance in 50 m (P<0.05). The endurance run excellent rate of children and adolescents with adequate sleep in each BMI group was higher than that in children and adolescents with insufficient sleep in the same BMI group (Pmalnutrition<0.01, Pnormal<0.01, Poverweight<0.05, Pobesity<0.05). The children and adolescents were divided into different groups according to the sleep duration,the one who slept less than 7 hours had lower 50 m excellent rate than the other groups with longer sleeping duration (P<0.01) and the rate in the ones who slept more than 9 hours was the highest (P<0.001).The endurance excellent rate in the children and adolescents who slept more than 9 hours was significantly higher than that in the other groups (P<0.001).There was no significant dose-response relationship in excellent rates and sleep durations.@*CONCLUSION@#The prevalence of insufficient sleep has increased, and the sleep condition in children and adolescents is severe. Children and adolescents with sufficient sleep have better athletic performance, so we should strengthen the prevention and control of the lack of sleep in children and adolescents.

Role of cell apoptosis regulated by P53 in treatment of hepatocellular carcinoma / 临床肝胆病杂志

P53 abnormality or mutation is commonly seen in patients with hepatocellular carcinoma (HCC), and therefore, restoration of P53 function has become a research hotspot in the treatment of HCC.This article reviews the association of P53 with Bcl-2 protein family, microRNA, TGFβ, HBV, HCV, and AKT and the role of P53 in regulating cell apoptosis, in order to provide clues for improving the therapeutic outcome of HCC.

Seropharmacological study on osteogenic effects of post-absorption ingredients of an osteoprotective herbal formula / 中国结合医学杂志

<p><b>OBJECTIVE</b>To further investigate the {ptin vitro} effects of an osteoprotective herbal formula "ELP" (Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae) using seropharmacological approach.</p><p><b>METHODS</b>Rats were fed with ELP or its individual component herbs for 2 days. The serum containing the postabsorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell (MSC) isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) of UMR106 and MSC as well as matrix metalloproteinase 9 (MMP-9), tartrate-resistant acid phosphatase (TRAP) and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction.</p><p><b>RESULTS</b>ELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4 %, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2 %. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively.</p><p><b>CONCLUSIONS</b>The serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis.</p>

Application of Chinese herbal medicines to revitalize adult stem cells for tissue regeneration / 中国结合医学杂志

It has been established in the recent several decades that adult stem cells play a crucial role in tissue renewal and regeneration. Adult stem cells locate in certain organs can differentiate into functional entities such as macrophages and bone cells. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are two of the most important populations of adult stem cells. The application of these stem cells offers a new insight in treating various pathological conditions, through replenishing cells of specific functions by turning on or off the differentiating program within quiescent stem cell niches. Apart from that, they are also capable to travel through the circulation, migrate to injury sites and differentiate to enhance regeneration process. Recently, Chinese medicine (CM) has shown to be potential candidates to activate adult stem cells for tissue regeneration. This review summarizes our own, as well as others' findings concerning the use of Chinese herbal medicine in the regulation processes of adult stem cells differentiation and their movement in tissue repair and rejuvenation. A number of Chinese herbs are used as therapeutic agents and presumably preventive agents on metabolic disorders. In our opinion, the activation of adult stem cells self-regeneration not only provides a novel way to repair tissue damage, but also reduces the use of targeted drug that adversely altering the normal metabolism of human subjects.