Mechanism of Zhishi Xiebai Guizhi Decoction on myocardial infarction based on network pharmacology and experimental validation / 中国药理学通报

Aim To explore the effects of Zhishi Xiebai Guizhi Decoction (ZXGD) in the treatment of myocardial infarction (MI) using the network pharmacology method and verifying by in vivo experiments and to reveal the underlying mechanism. Methods The chemical components of ZXGD and related targets were retrieved from the TCMSP database. The targets of MI were searched from the GeneCards, OMIM and DisGeNET databases, with the keywords " myocardial infarction" and "MI", and removing duplicates. The intersection of ZXGD and MI targets were obtained, and a protein-protein interaction (PPI) network based on the intersection of active ingredients and disease targets was constructed. The DAVID database was used to conduct GO and KEGG pathway enrichment analysis on the intersection targets. Combined with STRING database and Cytoscape 3.7.2 software, the intersection targets were visualized as a " medicine-component-target-disease" network. The MI mouse model was established by ligation of the left anterior descending coronary artery of the heart. ZXGD was given once a day for 14 days. The cardioprotective effects of ZXGD were examined by ultrasound cardiogram and Western blot. Results The results of network pharmacology analysis showed that the pharmacological components of ZXGD such as quercetin, naringenin, β-sitosterol, and luteolin maybe work on the targets like TNF-α, IL-1β, IL-6, VEGFA, and IL-10. Animal experiments found that compared with the model group, ZXGD significantly increased the left ventricular cardiac function, outflow tract blood flow, and other ultrasound indexes of the mice (P < 0.05). Moreover, the expression levels of IL-1β, TNF-α and IL-6 in myocardial infarction tissue were significantly down-regulated by ZXGD (P < 0.05), while the expression level of IL-10 was significantly up-regulated (P < 0.05). Conclusion ZXGD protects against MI and improves heart function by regulating inflammatory factors including TNF-α, IL-1β, IL-6, and IL-10.

Drug selection for simultaneous treatment of tuberculosis combined with hepatitis C virus infection / 中华肝脏病杂志

Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.

Toxicity comparison of psoralen in 2D /3D hepatocyte models and its effect on mitochondrial fusion and fission / 中国药理学通报

Aim To evaluate and compare the toxicity of psoralen on two-dimensional(2D)and three-dimensional(3D)cultured human hepatocyte HepG2 models. Methods The 3D cell model of HepG2 cells was constructed by low adsorption U-shaped bottom porous plate method. After treated with psoralen for 24 hours, the cell viabilities of 2D and 3D HepG2 cells were detected by CCK-8 assay, LDH leakage was detected by kit, and the mitochondrial membrane potential was detected by TMRM staining. The effect of psoralen on the mRNA of mitochondrial fusion-fission proteins DRP1, Mfn-2 and OPA1 was detected by Q-PCR. Results 3D model maintained a high level of albumin and urea secretion for a long time. And the expression levels of CYP1A2, CYP2E1, CYP3A4 and UGT1A1 in 3D model were higher than those in 2D model. In 3D model lower concentrations of psoralen showed a significant decrease in cell viability, a significant increase in LDH leakage, and a decrease in mitochondrial membrane potential. Q-PCR results showed that psoralen induced a marked increase in the expression of mitochondrial fission protein DRP1, while a significant decrease in mitochondrial fusion protein OPA1. Conclusions A 3D HepG2 cell model is successfully constructed and applied to the evaluation of psoralen hepatotoxicity; the 3D cell culture model is more sensitive to psoralen toxicity, and mitochondria may play a key role in psoralen-induced cell damage.

GRP78 upregulation-induced increase in cisplatin sensitivity of SPCA1 lung cancer cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, plays a critical role in chemotherapy resistance in a variety of cancers. In this study, we investigated the up-regulation of GRP78 induced by A23187 and its association with the chemotherapeutical sensibility to cisplatin in human lung cancer cell line SPCA1.</p><p><b>METHODS</b>SPCA1 cells were pretreated with A23187 at different concentrations. The expression of GRP78 at the mRNA level was analyzed by RT-PCR; the expression of GRP78 at the protein level was determined by Western blotting and immunofluorescence assay. Cell survival was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry.</p><p><b>RESULTS</b>The expression of GRP78 at both the mRNA and protein levels was obviously induced by A23187 in SPCA1 cells, with an elevation of GRP78 by 2.1-fold at the mRNA level and by 3.8-fold at the protein level compared to the control. There was a dose-dependent response. Survival curve analysis demonstrated that A23187 induction caused a significant reduction of survival for the cells subjected to cisplatin treatment (P < 0.05). After treatment by cisplatin, the percentage of apoptotic cells in the A23187 pretreated group increased about three fold compared with the control group ((27.53 ± 4.32)% vs. (9.25 ± 3.64)%, P < 0.05).</p><p><b>CONCLUSIONS</b>A23187 treatment was fairly effective for the induction of GRP78 in SPCA1 cells at both the mRNA and protein levels. To a certain extent, GRP78 up-regulation by A23187 was associated with the enhancement of drug sensitivity to cisplatin in human lung cancer cell line SPCA1.</p>

Pain in human skin caused by laser stimulation / 军事医学科学院院刊

Laser techniques are widely applied in medical research and military affairs. The characters of laser make it the best way to evoke pain.Pain induced by laser stimuli is influenced by laser parameters such as wavelength, pulse duration and stimulus area in addition to the properties of skin such as the distance from the brain, type and color of skin. In this review,both laser evoked pain and factors influencing it are discussed.

The relationship between coronary atherosclerotic stenosis and cerebral atherosclerotic stenosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the relationship between coronary and carotid/cerebral atherosclerotic stenosis.</p><p><b>METHODS</b>Carotid/aortocranial angiography and coronary angiography were performed in 34 CAD patients complicated with symptomatic cerebral ischemia. Patients were divided into 3 subgroups according to the extent of arterial stenosis determined by angiography. There were 5 light, 4 moderate and 25 severe stenosis determined by coronary angiography and there were 6 light, 6 moderate and 24 severe stenosis determined by carotid/aortocranial angiography.</p><p><b>RESULTS</b>The extent of coronary artery stenosis was parallel to the carotid artery or vertebral artery stenosis. Twenty-four patients out of 25 patients with severe coronary stenosis had severe cerebrovascular stenosis (P = 0.873). The coincident rate was as high as 92% for patients with moderate or severe cerebrovascular stenosis whose Califf risk scores of coronary artery were more than or equal to 2. The follow-up study showed the incidence of cardiovascular event and cerebrovascular event increased significantly in the patients with moderate to severe coronary and cerebral arteries stenosis and 3 patients with severe stenosis found in both coronary and cerebral arteries died during follow up.</p><p><b>CONCLUSION</b>The incidence and severity of coronary artery stenosis is parallel with carotid artery or vertebral artery stenosis.</p>