Recent progress on cGAS-STING pathway in tumor radiotherapy / 中华放射肿瘤学杂志

Radiotherapy is widely used in the treatment of primary and metastatic malignant tumors. It is traditionally believed that the killing effect of radiotherapy on tumor is based on the direct or indirect damage of ionizing radiation to DNA. In recent years, the anti-tumor role and mechanism of anti-tumor immune response induced by ionizing radiation have captivated widespread attention and achieved significant progress. Among them, Cyclic GMP-AMP synthase (cGAS)-stimulator of interference genes (STING) pathway is considered to be one of the key regulatory hubs. cGAS is a cytoplasmic DNA receptor that can bind to tumor-derived double-stranded DNA and activate the downstream STING, thereby activating anti-tumor immune response of the host. In view of the latest progress in this field, the important role and potential mechanism of cGAS-STING pathway in radiotherapy immune effect were mainly summarized, and the application prospect of targeting cGAS-STING pathway in radiotherapy sensitization was explored.

Research progress on metabolic regulating cell fate / 国际生物医学工程杂志

The close link between metabolism and cell death has been getting more and more attention.Many metabolically related proteins play a key role in the programmed cell death pathway.Several proteins classically regulating cell death have been found to regulate metabolism.In addition,many metabolic intermediates are closely involved in the cascade of signal transduction pathways that influence cell death.Some metabolic checkpoints not only receive information from metabolic variables,but also transmit signals that regulate cell survival.Typically,these checkpoints respond to metabolic imbalances by activating an organelle specific or by initiating an adaptive response at the overall level of the cell,and attempts to establish a new homeostasis.However,when the metabolic disorders are extravagantly serious or prolonged in time,these checkpoints will initiate apoptosis or programmed cell death.The cross-regulation of cellular metabolism and death pathways was discussed,so as to provide clues for the development of novel pharmacological approaches by regulating the metabolism to block or induced cell death.

Effects of serum cytokines on antipsychotic medication treatment in schizophrenia patients / 国际检验医学杂志

Objective To study the levels of serum cytokines in schizophrenic patients and their changes in antipsychotic medica-tion treatment .Methods The levels of serum cytokines including IL-10 ,IL-6 ,IL-13 ,IL-4 ,IFN ,TNF-α,IL-1a and IL-1RA were de-tected in 34 healthy adults and 53 schizophrenia patients by adopting the flow fluorescence method .Results The serum levels of IL-6 ,IL10 and TNF-αbefore treatment in schizophrenic patients were significantly higher than those in the control group (P<0 .05) . After treatment ,the levels of serum IL-1a ,IL-6 and TNF-α in schizophrenic patients were significantly lower than those before treatment(P<0 .05) .Conclusion Serum IL-6 and TNF-α levels are correlated with the disease condition of schizophrenia .IL-10 plays a role in early anti-inflammation of schizophrenia .

Detection of breast cancer metastasis-related genes by co-word analysis and network analysis / 中华医学图书情报杂志

Objective To provide the reference for early diagnosis and treatment of breast cancer by detecting its metastasis-related genes.Methods Breast cancer metastasis-related genes were searched from PubMed-covered papers with their conception matched according to the MetaMap.A gene-gene matrix was generated using data a-nalysis software.An interaction network of breast cancer metastasis-related genes was established using Ucinet 6 and its related indexes were analyzed.Results tp53, thra, erbb2, esr1, cdh1, egfr, nr4al and cd69 were the core genes for breast cancer metastasis.Conclusion Co-word analysis can show breast cancer metastasis-related genes. However, the role of cd69 in breast cancer metastasis remains unclear and is thus necessary to be further confirmed.

Research progress on anticancer therapeutics targeting telomere/telomerase / 中国肿瘤临床

Telomeres are protective caps located at the ends of human chromosomes. Telomeres shorten with each successive cell di-vision in normal human cells, whereas they are continuously elongated by human telomerase in over 85%of tumors. This simple and attractive difference steers the development of anticancer drugs targeting telomeres and telomerase. Many promising current telo-mere/telomerase-targeting agents, such as GRN163L and GV1001, showed good therapeutic effect both in preclinical studies and phaseⅠ/Ⅱclinical trials. These agents have even entered phaseⅢclinical trials in patients with various tumors. Most therapeutics are more effective when used in combination with standard chemotherapies. Moreover, pharmacological interference with tumor-cell telomere biology to reduce telomere length and/or telomere stability could enhance the effectiveness and safety of radiotherapy. Therapeutics targeting telomere/telomerase may play a key role in radiotherapy in the era of personalized medicine in the future.

Content Determination of Chlorogenic Acid,Protocatechuic Acid and Total Phenolics in Chaenomeles sinersis from Different Areas / 中国药房

OBJECTIVE:To establish a method for the content determination of chlorogenic acid,protocatechuic acid and total phenolics in Chaenomeles sinensis,compare the content of total phenolics and 2 phenolic acids from different areas. METHODS:Wavelength switching HPLC method was conducted to determine the chlorogenic acid and protocatechuic acid. The column was Shim-pack CLC-ODS(M)with the mobile phase of acetonitrile-0.1% phoephoric acid(15∶85,V/V),the detection wavelength was 259 nm(for protocatechuic acid)and 325 nm(for chlorogenic acid)and the switching time was 14 min. With the index of proto-catechuic acid,Folin-Ciocalteau colorimetric method was conducted to determine the total phenolics. RESULTS:The 2 methods of quantitative analysis showed that the precision,repeatability,recoveries and standard curves were all validated by methodology. The mass fraction of total phenolics was 0.87%-3.77% with the average of 2.16%;the chlorogenic acid was 0.053%-0.387% with the average of 0.192% and the protocatechuic acid was 0.024%-0.541% with the average of 0.087%. The order of total phenolics content in C. sinensis from different areas was Yunnan>Anhui Xuancheng>Sichuan>Hubei and the order of total amount of chlo-rogenic acid and protocatechuic acid from different areas was the same as the total phenolics. There were differences among the con-tents of C. sinensis from different areas,however,the positive correlation was found between the content of total phenolics and the total amount of chlorogenic acid and protocatechuic acid with the pearson correlation coefficient of 0.719(P<0.01).CONCLU-SIONS:The established method is simple,accurate and reproducible and can be used for the content determination of chlorogenic acid,protocatechuic acid and total phenolics in chaenomelis fructus.

Meta-Analysis of the SLCO1B1 c.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins

BACKGROUND: Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS: We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I 2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS: No significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS: No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.

Endoplasmic reticulum stress-mediated high-fat diet, palmitic acid-induced insulin resistance in skeletal muscle and interventional effects of fenofibrate / 中国药理学通报

Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.

Resveratrol improves vascular endothelial injury induced by high-calorie and high-cholestrol diet through reduced ERS and increased eNOS expression / 中国药理学通报

Aim To study whether the mechanisms in-volved in resveratrol′s protective effects on vascular en-dothelial injury induced by high-calorie and high-chol-estrol diet are concerned with ERS and the change of eNOS expression. Methods Twenty-four male C57BL/6 mice were randomly divided into standard control diet (SCD),high-calorie and high-cholestrol diet(HCD)and HCD group treated with resveratrol (HCD +RES,400 mg·kg -1 ·d -1 ,1 2 weeks).Then the thoracic aorta was separated,embedded and sliced to analyze the pathological changes by HE and resor-cinol staining.The protein distribution of eNOS was measured with immunohistochemical analysis.The up-stream and downstream genes of ERS in thoracic aorta were detected by RT-PCR.After the pretreatment with different concentrations of resveratrol,the mouse aortic endothelial cells (MAECs)were treated with palmitic acid,then the changes of cell proliferation in each group were compared.Western blot,immunofluores-cence and immunohistochemistry were used to deter-mine the protein expressions of GRP78,CHOP and eNOS respectively.Results Mice fed with HCD showed thickening of thoracic aortic wall and disorgan-ized elastic fibers as compared with those in SCD group.The mRNA levels of ERS related genes were all increased obviously (P <0.05),while the protein expression of eNOS was decreased.Compared with HCDgroup,the thickened wall and the disorganized elasticfibers were improved significantly,the mRNA levels ofERS related genes were all decreased obviously (P <0.05)and the expression of eNOS protein was increased in HCD +RES group.Compared with NCgroup, the cell proliferation was significantly decreased,meanwhile GRP78 and CHOP was significantly increased (P <0.05)and the protein expression ofeNOS was decreased in PA group.The cell proliferation was increased significantly (P <0.05),the mRNA and protein expression of GRP78 and CHOP wasobviously decreased (P <0.05),meanwhile the protein expression of eNOS was increased in the mediumand large dose of RES pretreatment groups.Conclusion Resveratrol has obvious effects of improving endothelial damages induced by HCD and decreasing cellproliferateion of MAECs induced by PA, and themechanisms are possibly related with decreased ERSand increased level of eNOS protein.

Effects and mechanism of TG6 on myocardial ischemia and reperfusion injury / 药学实践杂志

Objective To investigate the protective effects and mechanism of TG 6 on myocardial ischemia/reperfusion injury . Methods the protective effects of TG 6 on myocardial ischemia/reperfusion was investigated by setting up models of ischemia and reperfusion of rats induced by ligating the left coronary anterior descending artery in vivo,isolated rat hearts through an improved Lange-ndorff device, and hypoxia /reoxygenation injury of neonatal rat cardiomyocytes , and the serum CK,LDH,T-SOD, MDA were taken as research markers .Results TG6 significantly reduced the myocardial infarct size , decreased the activity of CK and the content of MDA in serum, reduced the activity of LDH, and increased the activity of T-SOD in vivo;TG6 obviously increased the coronary blood flow after low rate perfusion and reperfusion , decreased the content of MDA and the leakage of CK , LDH in myocardial tissue , elevated the activity of T-SOD in vitro of isolated rat hearts;TG6 had no effects on cells in normal growth condition , raised the viability of cardio-myocytes significantly, and reduced the rate of CK leakage and the content of [Ca2+]i obviously in Na2S2O4 treated cells in vitro of neonatal rat cardiomyocytes .Conclusion TG6 could effectively protect myocardial ischemia/reperfusion injury .