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ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
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ObjectiveTo evaluate the efficacy and safety of Linggui Zhugantang in the treatment of heart failure. MethodCNKI，Wanfang Data，VIP，CBM，PubMed，ClinicalKey，Cochrane Library ，Web of Science ，Medline and Embase were systematically searched to screen randomized controlled trials（RCT）of Linggui Zhugantang in the treatment of heart failure. Meta-analysis was performed on the included studies using RevMan 5.3 ResultTwenty-seven studies were included with a total sample size of 3 569 cases，including 1 816 in experimental group and 1 753 in control group. Meta-analysis showed that compared with conventional drugs alone，combination of Linggui Zhugantang and conventional drugs improved the marked effective rate [relative risk（RR）=1.41，95% confidence interval（CI）[1.29，1.54]，P<0.000 01] and the total effective rate（RR=1.21，95%CI[1.17，1.25]，P<0.000 01），decreased the levels of serum B-type brain natriuretic peptide （BNP）[mean difference（MD）=-390.08，95%CI[-538.84，-241.52]，P<0.000 01] and serum N-terminal pro-brain natriuretic peptide（NT-proBNP）（MD=-713.83，95%CI[-828.41, -599.25]，P<0.000 01）， left ventricular end-diastolic diameter（LVDD）（MD=-5.23，95%CI[-7.18, -3.29]，P<0.000 01）, left ventricular end-systolic diameter（LVSD）（MD=-4.54，95%CI[-6.75，-2.33]，P<0.000 01）, tumor necrosis factor-α（TNF-α）（MD=-37.53，95%CI [-50.72，-24.34]，P<0.000 01）and interleukin-6（IL-6）（MD=-23.64，95%CI [-47.40，0.11]，P=0.05）, increased left ventricular ejection fraction（LVEF）（MD=5.73，95%CI [3.33，8.14]，P<0.000 01），and cardiac output [stroke volume (SV) ]（MD=5.90，95%CI[4.56，7.25]，P<0.000 01）. In addition, the combination prolonged the 6 minute walking test distance（MD=51.08，95%CI [33.01，69.16]，P<0.000 01），reduced the traditional Chinese medicine (TCM) syndrome score（MD=-3.50，95%CI [-4.92，-2.07]，P<0.000 01），and improved quality of life（MD=-7.26，95%CI [-10.43，-4.09]，P<0.000 01），with higher safety（RR=0.36，95%CI [0.17，0.79]，P=0.01）. ConclusionLinggui Zhugantang combined with conventional drug therapy could improve cardiac function，reduce cardiac fibrosis，and improve prognosis, with high safety.
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ObjectiveTo investigate the protective effect of Linggui Zhugantang （LGZGT）-medicated serum against H2O2-induced injury in H9c2 cells and its relationship with the phosphatidylinositol 3- kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodThe LGZGT-medicated serum and blank serum were prepared based on serum pharmacology. H9c2 cells were cultured in vitro and divided into a normal group， an H2O2 group， a 20% blank serum group， and a 20% LGZGT-medicated serum group. The cells were treated with corresponding drugs for 12 h and cultured with 100 μmol·L-1 H2O2 for another 6 h. The effect of 20% LGZGT-medicated serum on the proliferation activity of H9c2 cells induced by H2O2 was detected by cell counting kit-8 （CCK-8） assay. Mitochondrial reactive oxygen species （ROS） level was detected by the fluorescence probe. The levels of malondialdehyde （MDA）， lactate dehydrogenase （LDH）， catalase （CAT）， and glutathione peroxidase （GSH-Px） were detected by colorimetry. Western blot was used to detect the protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated-PI3K （p-PI3K）， protein kinase B （Akt）， and phosphorylated-Akt （p-Akt）. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of PI3K and Akt. Flow cytometry was used to detect the apoptosis rate. After the addition of PI3K inhibitor LY294002， the levels of mitochondrial ROS， LDH， and GSH-Px， protein expression of PI3K， p-PI3K， Akt， and p-Akt， and cell apoptosis rate were detected. ResultCompared with the normal group， the H2O2 group showed blunted cell viability （P<0.01）， increased levels of mitochondrial ROS， MDA， and LDH （P<0.01）， decreased levels of CAT and GSH-Px （P<0.01）， reduced phosphorylation and mRNA expression of PI3K and Akt （P<0.05， P<0.01）， and increased apoptosis rate （P<0.01）. Compared with the H2O2 group， the 20% LGZGT-medicated serum group showed potentiated cell viability， reduced levels of mitochondrial ROS， MDA， and LDH （P<0.01）， increased levels of CAT and GSH-Px （P<0.01）， up-regulated phosphorylation and mRNA expression of PI3K and Akt （P<0.05， P<0.01）， and decreased apoptosis rate （P<0.01）. The combined use of LGZGT-medicated serum and inhibitor LY294002 reversed the above-mentioned effects of LGZGT-medicated serum on H9c2 cells （P<0.05， P<0.01）. ConclusionThe protective effect of LGZGT-medicated serum on H2O2-induced H9c2 cell injury may be related to the regulation of the PI3K/Akt signaling pathway to reduce oxidative stress and apoptosis.
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Objective:To build a performance evaluation index system of family doctor contracting service for urban communities, so as to evaluate the effects of such service.Methods:Based on the conceptual framework of performance appraisal of family doctor contracting service, such means as Delphi method and analytic hierarchy process were employed to evaluate the performance appraisal system of such service. A measured simulation test was made in Guangzhou.Results:A library of performance appraisal candidate indexes for such service was established, based on the performance appraisal concept framework of " structure, input, output, result" of such service. A questionnaire made based on such a library was developed for correspondence inquiry of 20 experts from December 2018 to June 2019. Based on results of such inquiry, a performance appraisal system for family doctor contracting service in Guangzhou was developed, consisting of 4 level-1 indexes, 10 level-2 indexes and 34 level-3 indexes. In the system, level indexes include organizational structure and management(weight 0.21), resource input(weight 0.24), contracting service process(weight 0.19), and contracting service effect(weight 0.36). A community health center in Guangzhou was used as the measurement site, for adjustment and improvement of data acquisition methods of individual indexes or scoring criteria.Conclusions:The index system is developed scientifically; appraisal tools are designed focusing on results and outputs, ensuring the appraisal of contracting service quality from multiple perspectives of supply-demand sides and health management patterns; the system can provide appraisal tools for policy appraisal authorities to evaluate the performance of contracting service reform.
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Objective To investigate the contribution of hypoxia-inducible factor inhibitor YC-1 to cisplatin chemo-sensitivity to human ovarian cancer cells A2780s in vitro. Methods Ovarian cancer cells were divided into four groups which were treated with saline, YC-1, cisplatin, and YC-1+cisplatin, separately, mRNA of HIF-1αand VEGF in the A2780s cells were detected by real-time fluorescence quantitative PCR by calculating 2-△△CT;the protein were detected by Western blot, to evaluate the change of hypoxia and angiogenesis capabilities under the ovarian cancer microenvironment. Results Compared with the control group, mRNA and protein of HIF-1αand VEGF expressed less in the group of YC-1, cisplatin and YC-1+cisplatin;while, those in the group of YC-1+cisplatin were lower than the monotherapy (P<0. 05), but no significant difference was detected between the YC-1 and cisplatin groups, and the expression of HIF-1αand VEGF mRNA were positively related(r=0. 830 5)in each group. Conclusion YC-1 exerts the antitumor effect and may contribute to sensitivity to cisplatin in the therapy of ovarian cancer.
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Over the last few years,elevated phospholipase D(PLD)expression and activity found to be mediated by Wnt/ β-catenin and NF-κB signaling axis sharing the same downstream genes have been involved in tumorigenesis,controlling cancer cell invasion and metastasis. New studies have revealed that Wnt signaling/ NF-κB signaling can induce PLD upregulation and increased enzymatic activ-ity. PLD/ PLD-generated phosphatidic acid( PA),as a critical regulator,might positively modulate β-catenin-dependent T-cell factor and NF-κB transcriptional activity via a targeted motif and a positive feed-back loop to reinforce pathway output including cyclin D1 ,c-myc,survivin,vascular endothelial growth factor and cyclooxygenase-2,while PLD/ PA inhibitors can reverse all the effect mentioned above and achieve significantly better anticancer effects. The PLD/ PA signaling pathway can be a novel therapeutic target for the treatment of cancer.
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Objective To explore the effect of lipid raft on cervical cancer cell growth and its mechanisms Methods HeLa cells in logarithmic phase were divided into three groups including control group, lipid raft interference agent group,and NADPH oxidase inhibitors group.Cells were treated with fre sh medium,3 μmol/L Apocynin and 1 mmol/L M-beta CD, respectively, for 24 h.Cell survival rate was detected using the MTT method, and the HIF-1α level was examined by Western-blot. Results Cell growths of the lipid raft interference agent group and NADPH oxidase inhibitors group were significantly slower than control group,(0.612±0.051 vs 0.984±0.034,0.591 ±0.074 vs 0.984±0.034,t=4.062,P＜0.05).HIF-1α expression in the lipid raft interference agent group and NADPH oxidase inhibitors group was also significantly reduced compared with control group (1.79±0.14 vs 2.56±0.22 and 1.54±0.12 vs 2.56±0.22) and the difference was significant (t=2.423,P＜0.05). Conclusion Lipid raft-NADPH oxidase pathway may activate HIF-1α and downstream protocarcinogenic gene expression to promote the growth of cervical cancer cells. The inhibitors of lipid raft and NADPH oxidase may become a new research direction for cervical cancer chemotherapy.
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In this article, the authors firstly summarized the number of applications submitted to and projects supported by the National Natural Science Foundation of China (NSFC) in the field of traditional Chinese medicine research in 2010. Then they described the district distribution, research direction layout and allotment of the approved projects in the three primary disciplines (traditional Chinese medicine, Chinese materia medica and integrated traditional Chinese and Western medicine) and their 43 subdisciplines. The targeting suggestions for improvement were given respectively by concluding the reason of disapproved projects from the point of view of applicants and supporting institution, and by stating the common problems existing in the review process from the perspectives of fund managers and evaluation experts. Lastly, the major funding fields in the near future were predicted in the hope of providing guidance for applicants.
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Our work focuses on the quality control and structural identification of Photocyanine as a cancer therapeutic photosensitizer. Photocyanine is a mixture which contains four ZnPcS2P2 type substituted Phthalocyanine isomers. In order to obtain the single component from Photocyanine, the mixture of four isomers possessing the similar structures and chemical property had been isolated and purified. An HPLC method with a mixture of methanol-acetonitrile-ion-pair buffer as the mobile phase was applied to isolate the four isomers by means of a semi-preparative C18 column. To remove the salts which were mixed in the preparative product, a SPE C18 column was used to separate the salts by elution with water and then the marker component was eluted by methanol. Subsequently, a column of Sephadex LH-20 gel was applied to elute the crudes with methanol to desalination. The purity of the isolated compound was measured by TLC and four different isomers of phthalocyanine were obtained. The chemical structures of them were elucidated by 1H NMR spectra, gCOSY and NOE1D. An HPLC-DAD method was developed for simultaneously determination of four major isomers in Photocyanine with a C18 column (Grace Smart, 150 mm x 4.6 mm ID, 5 microm). The separation was carried out with a gradient program at a flow rate of 1.0 mL x min(-1). The mobile phase was a mixture of acetonitrile and ion-pair buffer (0.01 mol x L(-1) hexadecyl trimethyl ammonium bromide and 0.01 mol x L(-1) potassium dihydrogen phosphate, adjusted the pH value to 6.8 with potassium hydroxide solution). The resolution values of four isomers were 2.5, 1.20, 1.33, and 1.8. Linear regression analysis for four compounds was performed by the external standard method. Four constituents were linear in the concentration range of 0.005 to 10 microg. The values of relative standard deviation (RSD) of intra-day were 0.12%, 0.66%, 0.99%, and 1.21%, respectively. The limits of detection for four compounds were 15 ng, 20 ng, 12 ng, and 25 ng, respectively. This method was simple, accurate and reproducible. The developed method can be successfully applied to analyze isomers in Photocyanine.
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Objective To investigate the preventive and therapeutic effects of Shenlixin Granules on chronic renal failure rats.Methods The chronic renal failure rat models were caused by adenine.After the treatment of Shenlixin Granules,the body weight,urine volume and renal index of models were examined.Results Shenlixin Granules could obviously inhibit the decrease of body weight and urine volume,reduce the renal index and had obvious protective effect on the renal tissue.Conclusions Shenlixin Granules has a preventive and therapeutic effect on chronic renal failure.