Molecular mechanism of Qishen Yiqi Dripping Pills in treating myocardial ischemia:a study based on HIF-1 signaling pathway / 中国中药杂志

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.

An investigation on the chromosomal damage in nurses occupationally exposed to antineoplastic drugs / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate their genotoxic risk in nurses occupationally exposed to antineoplastic drugs with chromosomal aberration test and cytokinesis-block micronucleus (CBMN) test.</p><p><b>METHODS</b>Sixteen nurses in the exposure group were selected from the oncology department of the same hospital, with an average length of exposure of 5.5 years and daily making 8.25 chemotherapeutic preparations in average. The controls were students from a nursing school. Peripheral blood from both groups was cultured at 37 degrees C for 48 h and 72 h, respectively, and then slides were prepared for conventional chromosomal aberration test and CBMN test. One hundred blood cells in metaphase and 1 000 binuclear lymphocytes in each sample were observed under microscope.</p><p><b>RESULTS</b>The results showed that the mean chromosomal aberration rate in the exposure group was (6.38 +/- 3.30)%, significantly higher than that in the controls (1.25 +/- 0.93)% (P < 0.01). And, the mean micronucleated cell rate in the exposure group was (15.06 +/- 5.30) per thousand, very significantly higher than that in the controls (4.56 +/- 1.67) per thousand (P < 0.01).</p><p><b>CONCLUSIONS</b>The investigation indicated that chromosome damage rate in the nurses from oncology department was higher than that in the controls, which may be related to their occupational exposure to antineoplastic drugs.</p>

Detection for DNA Damage in Human Lymphocytes Induced by Four Chemicals Using Comet Assay / 环境与健康杂志

Objective To validate feasibility of comet assay as a tool for detecting DNA damage induced by various types of chemical mutagens.Study of DNA damage induced by4chemicals on human lymphocytes was carried out in vitro.Methods Human lymphocytes were exposed to4-nitroquinoline-1-oxide(4NQO,a UV-mimetic agent ),methyl methanesulfonate(MMS,an alkylating agent ),Bleomycin(BLM,a radiamimetic agent )and Mitomycin(MMC,a DNA crosslink agent )for3h,the DNA single strand breaks(SSB)induced by4chemicals were measured immediately(0h-incubation)and21h-incubation after3h-exposure to the chemicals with comet assay.Results It was found that the SSB induced by4NQO,MMS and BLM,which revealed a dose-response relationship(P