[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Esophageal squamous cell carcinoma transformed into neuroendocrine carcinoma after neoadjuvant immunochemotherapy: A case report.

Immunotherapy provides durable responses for locally advanced esophageal carcinoma clinical therapy in numerous patients. However, the mechanisms of resistance to immunotherapy have not been elucidated. The phenomenon of the histological transformation of non-small cell lung cancer to small cell lung cancer resulting in resistance to immune checkpoint inhibitors (ICIs) has been reported. It remains unclear whether ICIs or chemotherapy could cause a similar transformation from esophageal squamous cell carcinoma (ESCC) to esophageal neuroendocrine carcinoma (ENEC). The present study report the case of a patient initially diagnosed with stage II ESCC who underwent radical surgery after three cycles of neoadjuvant therapy with cisplatin, albumin bound paclitaxel and ICIs. Immunohistochemical staining confirmed the absence of the SCC component and the presence of the NEC component, with negativity for CK5/6 and tumor protein p40, but positive expression of tumor protein p53, pan-cytokeratin, synaptophysin and CD56. The patient was followed up for 5 months with no treatment or postoperative complications. In conclusion, histological transformation to ENEC is a potential mechanism of acquired resistance to ICIs in ESCC. Prospective larger studies are warranted to further characterize ESCC-to-NEC transformation on use of ICIs.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

Shuangshen ningxin formula attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial function.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen Ningxin Formula (SSNX) is a traditional Chinese medicine formula used to treat myocardial ischemia-reperfusion injury (MIRI). A randomized controlled trial previously showed that SSNX reduced cardiovascular events, and experiments have also verified that SSNX attenuated ischemia-reperfusion (I/R) injury. However, the mechanism of SSNX in the treatment of microvascular I/R injury is still unclear. AIM OF THE STUDY: To determine whether SSNX protects the microvasculature by regulating I/R induction in rats and whether this effect depends on the regulation of NR4A1/Mff/Drp1 pathway. METHODS: The anterior descending coronary artery was ligated to establish a rat MIRI model with 45 min of ischemia and 24 h of reperfusion. The rats were subjected to a 7-day pretreatment with SSNX and nicorandil, after which their cardiac function and microvascular functional morphology were evaluated through diverse methods, including hematoxylin and eosin (HE) staining, wheat germ agglutinin (WGA) staining, and transmission electron microscopy. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Additionally, serum levels of ET-1 and eNOS were determined through an enzyme-linked immunosorbent assay (ELISA). The expression levels of NR4A1, Mff, and proteins related to mitochondrial fission were examined by Western blot (WB). Cardiac microcirculation endothelial cells (CMECs) were cultured and the oxygen-glucose deprivation/reoxygenation (OGD/R) model was duplicated. Following treatment with SSNX and DIM-C-pPhOH, an NR4A1 inhibitor, cell viability was assessed. Fluorescence was used to evaluate mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening. Moreover, vascular endothelial function was evaluated through transendothelial electrical resistance (TEER), Transwell assays and tube formation assays. RESULTS: The results showed that SSNX reduced the infarction area and no-flow area, improved cardiac function, mitigated pathological alterations, increased endothelial nitric oxide synthase expression, protected endothelial function, and attenuated microvascular damage after I/R injury. I/R triggered mitochondrial fission and apoptotic signaling in CMECs, while SSNX restored mitochondrial fission to normal levels and inhibited mitochondrial apoptosis. A study using CMECs revealed that SSNX protected endothelial function after OGD/R, attenuating the increase in NR4A1/Mff/Drp1 protein and inactivating VDAC1, HK2, cytochrome c (cyt-c) and caspase-9. Research also shows that SSNX can affect CMEC cell migration and angiogenesis, reduce mitochondrial membrane potential damage, and inhibit membrane opening. Moreover, DIM-C-pPhOH, an NR4A1 inhibitor, partially imitated the effect of SSNX. CONCLUSION: SSNX has a protective effect on the cardiac microvasculature by inhibiting the NR4A1/Mff/Drp1 pathway both in vivo and in vitro.

Investigation of the active ingredients of Shuangshen Ningxin Fomula and the mechanism underlying their protective effects against myocardial ischemia-reperfusion injury by mass spectrometric imaging.

BACKGROUND: Traditional Chinese medicine, particularly Shuangshen Ningxin Capsule (SSNX), has been studied intensely. SSNX includes total ginseng saponins (from Panax ginseng Meyer), total phenolic acids from Salvia miltiorrhiza Bunge, and total alkaloids from Corydalis yanhusuo W. T. Wang. It has been suggested to protect against myocardial ischemia by a mechanism that has not been fully elucidated. METHODS: The composition and content of SSNX were determined by UHPLC-Q-TOFQ-TOF / MS. Then, a rat model of myocardial ischemia-reperfusion injury was established, and the protective effect of SSNX was measured. The protective mechanism was investigated using spatial metabolomics. RESULTS: We found that SSNX significantly improved left ventricular function and ameliorated pathological damages in rats with myocardial ischemia-reperfusion injury. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the protective mechanism of SSNX was examined by comparing the monomer components of drugs targeted in myocardial tissue with the distribution of myocardial energy metabolism-related molecules and phospholipids. Interestingly, some lipids display inconsistent content distribution in the myocardial ischemia risk and non-risk zones. These discrepancies reflect the degree of myocardial injury in different regions. CONCLUSION: These findings suggest that SSNX protects against myocardial ischemia-reperfusion injury by correcting abnormal myocardial energy metabolism, changing the levels and distribution patterns of phospholipids, and stabilizing the structure of the myocardial cell membrane. MALDI-TOF MS can detect the spatial distribution of small molecule metabolites in the myocardium and can be used in pharmacological research.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Shuangshen Ningxin capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy: network pharmacology and experiments in vivo.

BACKGROUND: Myocardial ischemia/reperfusion injury (MI/RI) is involved in a variety of pathological states for which there is no effective treatment exists. Shuangshen Ningxin (SSNX) capsule which is developed by Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine has been demonstrated to alleviate MI/RI, but its mechanism remains to be further elucidated. METHODS: The MI/RI miniature pigs model was constructed to assess the pharmacodynamics of SSNX by blocking the proximal blood flow of the left anterior descending branch of the cardiac coronary artery through an interventional balloon. The principal chemical compounds and potential targets of SSNX were screened by HPLC-MS and SwissTargetPrediction. The targets of MI/RI were identified based on Online Mendelian Inheritance in Man (OMIM) and GeneCards. Cytoscape 3.9.0 was applied to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using metascape. To further validate the mechanism of SSNX, Molecular docking, Transmission electron microscopy, and Western blot analysis were used to test the effectiveness of targets in related pathways. RESULTS: Our results indicated that SSNX significantly improved cardiac function, attenuated myocardial I/R injury. Through network analysis, a total of 15 active components and 201 targets were obtained from SSNX, 75 of which are potential targets for the treatment of MI/RI. KEGG and MCODE analysis showed that SSNX is involved in the mitophagy signaling pathway, and ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rb2 are key components associated with the mitophagy. Further experimental results proved that SSNX protected mitochondrial structure and function, and significantly reduced the expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1), Parkin, FUN14 domain containing 1 (FUNDC1) and Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) in MI/RI miniature pigs. CONCLUSION: In our study, the integration of network pharmacology and experiments in vivo demonstrated that SSNX interfered with MI/RI by inhibiting mitophagy.

Synthesis, structures and properties of two donor-acceptor acridone-based compounds.

Two donor-acceptor acridone-based compounds, namely, 2-{10-[4-(diphenylamino)phenyl]acridin-9-ylidene}malononitrile (TPA-AD-DCN), C34H22N4, and 2-{10-[4-(9H-carbazol-9-yl)phenyl]acridin-9-ylidene}malononitrile (CzPh-AD-DCN), C34H20N4, have been synthesized in high yield and their structures determined. TPA-AD-DCN and CzPh-AD-DCN crystallized in the centrosymmetric space groups P-1 and P21/c, respectively. Both molecules adopt a `butterfly-like' configuration of the common part of the structure and differences occur within the substituents on the acridine N atom. A Hirshfeld surface analysis showed that the H...H and C...H/H...C contacts constitute a high percentage of the intermolecular interactions. The optical and electrochemical properties, as well as theoretical calculations, of TPA-AD-DCN and CzPh-AD-DCN support the structural characterization of these materials. As crystallization-induced emission materials, TPA-AD-DCN and CzPh-AD-DCN are anticipated to be of potential use in the construction of promising optoelectronic materials.

Case report: Anterior mediastinal mass in a patient with pleural effusion and dyspnea.

Background: Compound lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent B- and T-cell tumors are relatively rare. Case Summary: A 41-year-old man was presented with a 1-month history of progressively worsening cough, chest tightness, and dyspnea after exercise, which could be relieved following rest. Contrast-enhanced computed tomography scan demonstrated a 7.4 × 4.9 cm2 heterogeneous mass in the anterior mediastinum, where a large area of cystic liquid existed, and multiple enlarged lymph nodes in the mediastinum. Since the biopsy failed to yield an exact diagnosis and there was no sign of metastasis, the tumor was surgically resectioned. Surgical findings included obscure boundaries and consistent tumor stiffness with pericardial and pleural invasion. Further pathological examination combined with immunophenotype and gene rearrangement test found the mass composite of angioimmunoblastic T-cell lymphoma (AITL) and B-cell lymphoma. The patient recovered well after R0 resection and received chemotherapy with four cycles of CHOP combined with chidamide 2 weeks after surgery. The patient has had a complete response for over 60 months. Conclusion: In conclusion, we reported a composite lymphoma of AITL combined with B-cell lymphomas. Our experience provides the first successful attempt to treat this rare disease with combined surgery and chemotherapy.

[Effect of Jinzhen Oral Liquid on cough after lipopolysaccharide-induced infection in rats and mechanism].

This study aims to explore the effect of Jinzhen Oral Liquid(JOL) on cough after infection in rats and the mechanism. To be specific, a total of 60 male SD rats were classified into 6 groups: normal group(equivalent volume of distilled water, ig), model group(equivalent volume of distilled water, ig), Dextromethorphan Hydrobromide Oral Solution group(3.67 mL·kg~(-1), ig), high-, medium-, and low-dose JOL groups(11.34, 5.67, and 2.84 mL·kg~(-1), respectively, ig). Lipopolysaccharide(LPS, nasal drip), smoking, and capsaicin(nebulization) were employed to induce cough after infection in rats except the normal group. Administration began on the 19 th day and lasted 7 days. Capsaicin(nebulization) was used to stimulate cough 1 h after the last administration and the cough frequency and cough incubation period in rats were recorded. The pathological morphology of lung tissue was observed based on hematoxylin-eosin(HE) staining. Immunohistochemistry(IHC) was used to detect the specific expression of transient receptor potential vanilloid 1(Trpv1), nerve growth factor(NGF), tropomyosin receptor kinase A(TrkA), and phosphorylated-p38 mitogen-activated protein kinase(p-p38 MAPK) in lung tissue, Western blot the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and real-time fluorescent quantitative polymerase chain reaction(real-time PCR) the mRNA expression of Trpv1, NGF, and TrkA. The results showed that model group demonstrated significantly high cough frequency, obvious proliferation and inflammatory cell infiltration in lung tissue, significantly enhanced positive protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue and significant increase in the mRNA expression of Trpv1, NGF, and TrkA compared with the normal group. Compared with the model group, JOL can significantly reduce the cough frequency, alleviate the pathological changes of lung tissue, and decrease the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and high-dose and medium-dose JOL can significantly lower the mRNA expression of Trpv1, NGF, and TrkA. This study revealed that JOL can effectively inhibit Trpv1 pathway-related proteins and improve cough after infection. The mechanism is that it reduces the expression of NGF, TrkA, and p-p38 MAPK in lung tissue, thereby decreasing the expression of Trpv1 and cough sensitivity.

Proteomic analysis revealed the pharmacological mechanism of Xueshuantong injection in preventing early acute myocardial infarction injury.

Background: Acute myocardial infarction (AMI) is a common and life-threatening cardiovascular disease. However, there is a lack of pathology and drug studies on AMI within 20 min. Xueshuantong injection (XST) is mainly composed of Panax notoginseng saponins, which can dilate blood vessels and improve blood circulation, and is clinically used in the treatment of cardiovascular and cerebrovascular diseases. Purpose: The study aimed to investigate the protective mechanism of Xueshuantong injection against acute myocardial infarction within 20 min in rats by proteomic methods and molecular docking. Method: The male Sprague-Dawley rat acute myocardial infarction model was established by LAD ligation, and Xueshuantong injection (38 mg/kg) was injected into the caudal vein 15 min before surgery. Cardiac function evaluation, morphological observation, label-free quantitative proteomics, Western blotting analysis, molecular docking, and affinity measurement were applied in this study. Results: In a span of 20 min after acute myocardial infarction, the model group showed significant cardiac function impairment. Xueshuantong injection can significantly improve cardiac function and prevent pathological injury of myocardial tissue. A total of 117 vital differentially expressed proteins were identified by proteomic analysis, including 80 differentially expressed proteins (DEPs) in the sham group compared with model rats (Sham: model) and 43 DEPs in model rats compared with the Xueshuantong injection group (Model: XST). The treatment of Xueshuantong injection mainly involves "poly(A) RNA binding" and "cadherin binding involved in cell-cell adhesion." The differentially expressed levels of the pathways related to proteins Echdc2, Gcdh, Dlst, and Nampt, as well as 14-3-3 family proteins Ywhaz and Ywhab, could be quantitatively confirmed by WB. Molecular docking analysis and SPR analysis revealed that Ywhaz has a generally stable binding with five Xueshuantong injection components. Conclusion: Xueshuantong injection (XST) could protect rat myocardial function injury against AMI in 20 min. Echdc2, Ywhaz, Gcdh, Ywhab, Nampt, and Dlst play an essential role in this protective effect. In particular, Ywhaz might be the core target of Xueshuantong injection when treating acute myocardial infarction in the early stage. This study promoted the understanding of the protective mechanism of Xueshuantong injection in 20 min injury of acute myocardial infarction and contributed to the identification of possible targets of Xueshuantong injection.

[Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris].

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

Mechanism of 'Invigorating Qi and Promoting Blood Circulation' Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology.

OBJECTIVE: Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD). METHODS: The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated. RESULTS: Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications. CONCLUSION: The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

[Research progress of traditional Chinese medicine in regulating autophagy and ischemic heart disease].

Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.

[Salvianolic acid B regulates mitochondrial autophagy mediated by NIX to protect H9c2 cardiomyocytes from hypoxia/reoxygenation injury].

The aim of this paper was to investigate whether the mechanism of salvianolic acid B in protecting H9 c2 cardiomyocytes from hypoxia/reoxygenation injury is related to the regulation of mitochondrial autophagy mediated by NIX. H9 c2 cardiomyocytes were cultured in vitro and divided into normal group, model group and salvianolic acid B group(50 µmol·L~(-1)). Hypoxia/reoxygenation injury model was established by hypoxia for 4 h and reoxygenation for 2 h. In normal group, high glucose DMEM medium was used for culture. Those in model group were cultured with DMEM medium without glucose and oxygen, and no drugs for hypoxia and reoxyge-nation. In salvianolic acid B group, salvianolic acid B prepared by glucose-free DMEM medium was added during hypoxia, and the other process was as same as the model group. The cell viability was evaluated by CCK-8 assay. The leakage of lactate dehydrogenase(LDH) was detected by microplate method. The levels of intracellular reactive oxygen species(ROS) and mitochondrial membrane potential(ΔΨm) were measured by chemical fluorescence method. The level of intracellular adenosine triphosphate(ATP) was mea-sured by fluorescein enzyme method. The autophagy related proteins LC3-Ⅰ, LC3-Ⅱ, apoptosis related protein cleaved caspase-3 and mitochondrial autophagy receptor protein NIX were detected by Western blot. As compared with the normal group, the activity of H9 c2 cardiomyocytes and ATP level were decreased(P<0.05); LDH leakage and ROS production were increased(P<0.01); ΔΨm was decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio, cleaved caspase-3 and NIX protein expression levels were increased(all P<0.05) in the model group. As compared with the model group, the activity of cells and ΔΨm were significantly increased(P<0.01); ATP level was increased(P<0.05); LDH leakage and ROS generation were decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio was decreased(P<0.01); cleaved caspase-3 and NIX expression levels were decreased(P<0.05) in the salvianolic acid B group. The protective effect of salvianolic acid B on hypoxia/reoxygenation injury of H9 c2 cardiomyocytes may be associated with inhibiting mitochondrial auto-phagy. The specific mechanism may be related to inhibiting the activation of mitochondrial autophagy mediated by NIX, increasing ΔΨm, reducing ROS production, reducing the expression of cleaved caspase-3, LC3-Ⅱ, and increasing cell viability.

[Protective effect of safflower yellow injection against rat MIRI by TLR-NF-κB inflammatory pathway].

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.