Research progress on cardiotoxicity mechanism of doxorubicin and prevention and treatment of traditional Chinese medicine

Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At present,the mechanism of doxorubicin induced cardiotoxicity has not been fully clarified.Reducing cardiotoxicity and improving the scope of clinical application have become the focus of research in recent years.This paper reviews the mechanism of doxorubicin cardiotoxicity and the prevention and treatment of doxorubicin cardiotoxicity with traditional Chinese medicine,in order to provide reference for the combined application of doxorubicin.

Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with Chrysanthemum indicum extract

AIM： To investigate the effects of Chrysanthemum indicum extract （CIE） on inhibition of proliferation and on apoptosis, and the underlying mechanisms, in a human hepatocellular carcinoma （HCC） MHCC97H cell line. METHODS： Viable rat hepatocytes and human endothelial ECV304 cells were examined by trypan blue exclusion and MTT assay, respectively, as normal controls. The proliferation of MHCC97H cells was determined by MTT assay. The cellular morphology of MHCC97H cells was observed by phase contrast microscopy. Flow cytometry was performed to analyze cell apoptosis with annexin V/propidium iodide （PI）, mitochondrial membrane potential with rhodamine 123 and cell cycle with PI in MHCC97H cells. Apoptotic proteins such as cytochrome C, caspase-9, caspase-3 and cell cycle proteins, including P21 and CDK4, were measured by Western blotting. RESULTS： CIE inhibited proliferation of MHCC97H cells in a timeand dose-dependent manner without cytotoxicity in rat hepatocytes and human endothelial ceils. CIE induced apoptosis of MHCC97H cells in a concentration-dependent manner, as determined by flow cytometry. The apoptosis was accompanied by a decrease in mitochondrial membrane potential, release of cytochrome C and activation of caspase-9 and caspase-3. CIE arrested the cell cycle in the S phase by increasing P21 and decreasing CDK4 protein expression. CONCLUSION： CIE exerted a significant apoptotic effect through a mitochondrial pathway and arrested the cell cycle by regulation of cell cycle-related proteins in MHCC97H cells without an effect on normal cells. The cancer-specific selectivity shown in this study suggests that the plant extract could be a promising novel treatment for human cancer.

Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief

Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12th, 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate sta-tistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in mul-tivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the oc-currence of post-traumatic stress disorder was the result of the interaction of multiple factors.

Effects of electroacupuncture of acupoints of the neiguan and ximen on ischemic myocardium energy metabolism with acute myocardial ischemia rats

Objective:To observe the effect of Electroacupuncture of Acupoints of the Neiguan(PC6)and Ximen(PC4)on its myocardial energy metabolism with acute myocardial ischemia rats caused by coronary artery ligation.Methods:Forty standard Spargue-Dawely(SD)rats were divided into four groups randomly,namely,group of Neiguan,group of Ximen,model group,sham group.The group of rats of myocardial ischemia were induced by coronary ligation,and the model rat of acute myocardial ischemia was prepared.The sham group had no ligation of the needle.After anesthesia was awakened,acupuncture was applied bilateral at Neiguan and Ximen of the group of Neiguan and Ximen,once a day at a fixed time for 14 days.The rats of model group and the sham group were not given acupunctured,but use the samely methods of Neiguan and Ximen groups to grap the rats at the same time everyday.After 14 days the experiment was over,observed the pathological changes of myocardial tissue by HE staining,detected the levels of free fatty acid(FFA),adenosine triphosphate(ATP)content,and the activities of Na^(+)-K^(+)-ATPase according to the reagents´demand.Results:Pathological results showed that acupuncuted at Neiguan and Ximen could improve the ischemic cardiomyocyte injury.Compared with the sham group,the levels of FFA in model group were increased(p<0.01),the levels of ATP,the activities of Na^(+)-K^(+)-ATPase were all decreased(p<0.01);Compared with the model group,the levels of FFA were decreased(p<0.05,p<0.01),the levels of ATP,the activities of Na^(+)-K^(+)-ATPase were improved.Conclusion:Acupuncturing at the Pericardium Meridian can alleviate the cell injury by myocardial ischemia,and also can improve the myocardial energetic metabolism in acute myocardial ischemia.

MOF衍生Co_(3)O_(4)/ZrO_(2)介孔八面体:优化电荷转移和中间体转化用于高效CO_(2)光还原

调控电荷转移和反应路径是促进光催化CO_(2)还原的两种有效策略.本研究通过热解UIO-66@ZIF-67核壳八面体,合成了Co_(3)O_(4)/ZrO_(2)介孔八面体.该介孔八面体由高度分散的小尺寸纳米颗粒组装而成,平均颗粒尺寸为13 nm,平均孔径为5.8 nm,比表面积为43.11 m^(2)g^(-1).受益于活性位点设计,电荷转移动力学和CO_(2)吸附得以增强.此外,密度泛函理论计算结果显示,ZrO_(2)能够有效调控CO_(2)还原的反应路径,包括促进CO_(2)活化为*CO_(2)、中间体(*COOH和*CO)的形成、以及减小限速步(*CO→CO)的能垒.因此,Co_(3)O_(4)/ZrO_(2)介孔八面体的周转率高达28.82,是纯Co_(3)O_(4)的16.95倍.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide

Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Study on the Mechanism of Qingre Huoxue Prescription in the Intervention and Treatment of Acute Myocardial Infarction Based on Network Pharmacology

Objective:The objective is to study the mechanism of Qingre Huoxue prescription in the intervention and treatment of acute myocardial infarction(AMI)based on the method of network pharmacology.Materials and Methods:Five databases were used to screen the chemical compounds and targets of Ligusticum wallichii(chuanxiong),Radix Paeoniae Rubra(chishao),Lignum acronychiae(jiangxiang),Safflower(honghua),Salvia miltiorrhiza(danshen),Scutellaria baicalensis(huangqin),and Ilex pubescens(mao dong qing)in Qingre Huoxue prescription.Furthermore,Cytoscape-V3.2.1 software was used to construct the drug-component-target network.Functional protein association networks'database and the Database for Annotation,Visualization,and Integrated Discovery(DAVID)were used to visualize the protein interaction,pathway enrichment,and analysis.Results:A total of 44 active ingredients were screened out in Qingre Huoxue prescription.Among them,178 targets and 41 compounds related to Qingre Huoxue prescription's function in treating AMI were obtained.After the analysis of the drug-component-action target network on Qingre Huoxue prescription,14 key compounds and nine key targets with three scores above average were obtained.In addition,pathway enrichment and biological processes were conducted with the aid of the DAVID;and 8 related pathways and 10 biological processes were associated with AMI and related diseases;the PI3 K-AKT signaling pathway,MAPK signaling pathway,and HIF-1 signaling pathway are the main pathways of Qingre Huoxue prescription for the treatment of AMI and related diseases.Conclusion:Qingre Huoxue prescription could treat AMI by multiple components,targets,and pathways.This study provides ideas and theoretical basis for further clinical studies on Qingre Huoxue prescription in treating AMI.

Effects and Mechanisms of the Functional Parts of Dahuang Zhechong Pill(大黄虫丸) Containing Serum on Platelet-Derived Growth Factor-Stimulated Proliferation of Vascular Smooth Muscle Cells

Objective： To investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill （大黄〈庶虫〉虫丸, DHZCP）, including drugs with the function of removing blood stasis and promoting blood circulation （FP- I ）, drugs with the function of expelling heat and moistening dryness （FP-II）, and drugs with the function of nourishing yin and replenishing blood （FP-m） of DHZCP, on platelet-derived growth factor （PDGF）-stimulated vascular smooth muscle cells （VSMCs） proliferation with the method of serum pharmacology. Methods： VSMCs proliferation of rat was assayed by measuring the cell viability with the 3-（4, 5-dimethylthiazol-2yl）-2, 5-diphenyltetrazolium bromide （Ml-I＇） method. DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKC a, and phosphorylated extracollular signal regulated kinase 1/2 （ERK1/2） was quantified by the Western blotting method. Results： The FP- I and FP-m containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G1 phase, downregulated cycUn D1, and upregulated p27 expression （P〈0.01 or P〈0.05）. The FP- I and FP-11I containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCo~ expression （P〈0.01 or P〈0.05）. Conclusions： FP- I and FP-$ of DHZCP are able to inhibit VSMCs proliferation via interrupting PKC a-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G1 phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.

Dahuang Zhechong Pill(大黄虫丸) Containing Serum Inhibited Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells Proliferation by Inducing G_1 Arrest Partly via Suppressing Protein Kinase C α-Extracellular Regulated Kinase 1/2 Signaling

Objective： To investigate effects of Dahuang Zhechong Pill （大黄庶虫丸, DHZCP） on the cell cycle and the related signal pathways in vascular smooth muscle cells （VSMCs） stimulated by platelet-derived growth factor （PDGF） with the method of serum pharmacology. Methods： DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. The cycle of VSMCs was evaluated with flow cytometry. Expressions of cyclin D1, p27, protein kinase C α （PKC α）, and phosphorylated extracellular signal regulated kinase 1/2 （ERK1/2） were quantified by Western blot method. Results： DHZCP containing serum significantly inhibited DNA synthesis of PDGF-stimulated VSMCs, arrested the cells in G1 phase, modulated the protein expressions of cyclin D1 and p27, and suppressed the activation of PKC α and ERK1/2. Conclusion： DHZCP containing serum inhibits VSMCs proliferation via modulating the expressions of cell cycle proteins to arrest the cell in G1 phase, which is attributed to, at least in part, suppressing PKC α -ERK1/2 signaling in VSMCs.

Mechanism of acupuncture on anti-neuronal apoptosis and the regulation of PI3K/AKT signaling pathway in heroin relapse rats

Objective:To explore the mechanism of acupuncture intervention on anti-neuronal apoptosis in heroindependent rats based on the PI3K/AKT signaling pathway.Methods:A total of 30 SD rats were randomly divided into a normal group,a model group and an acupuncture group,10 rats in each one.In the model group and the acupuncture group,the heroin relapse rat model was established by intramuscular incremental injection of heroin.In the model group,no any intervention was applied.In the acupuncture group,after modeling,acupuncture was applied at"Bǎihuì(百会GV20)"and"Dàzhuī(大椎GV14)".Transmission electron microscope(TEM)was adopted to observe neuronal apoptosis in the rats.The effect of acupuncture on anti-neuronal apoptosis was compared.Using reverse transcription-polymerase chain reaction(RT-PCR)and western blot methods,the mRNA and protein expressions of PI3 K and AKT were detected in ventral tegmental area(VTA).Results:It was found that edema was presented in VTA neuronal cytoplasm and organelles basically disappeared in the heroin relapse rats,nuclear chromatin aggregation,condensation and increased neuronal apoptosis were presented as well.After acupuncture at"Bǎihuì(百会GV20)"and"Dàzhuī(大椎GV14)",a small amount of mitochondria,rough endoiplasmic reticulum and glycogen granules were visible in the cytoplasm of VTA neurons.The nuclear membrane structure was clear and the chromatin in the nucleus was basically normal.The fluorescence quantitative polymerase chain reaction(PCR)and western blot methods were adopted to detect mRNA and protein expressions of PI3K and AKT.It was found that the mRNA and protein expressions of PI3K and AKT in the brain of the rats in the model group were lower than those in the normal group(all P<0.05).Compared with the model group,the mRNA and protein expressions of PI3K and AKT in the acupuncture group were increased(all P<0.05),tending to the levels as the normal group.Conclusion:The effect of acupuncture on anti-brain cell apoptosis in heroin relapse rats may be related to the inhibition of PI3K/AKT signaling pathway.