Multiple characteristic alterations and available therapeutic strategies of cellular senescence / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Given its state of stable proliferative inhibition, cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis. Cells undergoing senescence are often associated with the alteration of a series of specific features and functions, such as metabolic shifts, stemness induction, and microenvironment remodeling. However, recent research has revealed more complexity associated with senescence, including adverse effects on both physiological and pathological processes. How organisms evade these harmful consequences and survive has become an urgent research issue. Several therapeutic strategies targeting senescence, including senolytics, senomorphics, immunotherapy, and function restoration, have achieved initial success in certain scenarios. In this review, we describe in detail the characteristic changes associated with cellular senescence and summarize currently available countermeasures.

Protective effect of Ganoderma lucidum spore glycopeptide on liver injury in mice / 中国药科大学学报

@#Models of acute and chronic liver injury in mice were established using carbon tetrachloride (CCl4) and ethanol to explore the protective effects of Ganoderma lucidum spore glycopeptide on liver injury.Different dosage of Ganoderma lucidum spore glycopeptide (65,130,260 mg/kg) were given by gavage.The liver index and the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined.The contents of liver interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) were tested by enzyme-linked immunosorbent assay (ELISA).The pathological injury of liver tissue was observed by HE staining.The results showed that Ganoderma lucidum spore glycopeptide could significantly reduce the liver index and the contents of serum AST and ALT in mice of acute and chronic liver injury.In mice of chronic liver injury induced by CCl4, Ganoderma lucidum spore glycopeptide could significantly decrease the contents of liver IL-6, TNF-α and iNOS, and alleviate the pathological damage of liver tissue.Results suggested that Ganoderma lucidum spore glycopeptide might reduce acute and chronic liver injury with anti-inflammatory effects in mice.

Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer / 中国药科大学学报

@#To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.

Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

Research progress on the role of heat shock protein 27 in prostate cancer / 中国药科大学学报

@#Prostate cancer is one of the most common cancers in adult men. Heat shock proteins (HSPs),as molecular chaperones widely involved in the pathogenesis,diagnosis,treatment and prognosis of various cancers,play crucial biological functions in prostate cancer and it can be considered as valuable biomarkers for cancer therapy, such as prostate-specific membrane antigen. As a member of the heat shock protein family, HSP27 is related to prostate cancer castration resistance,and its expression can promote tumor resistance,invasion and bone metastasis,making prostate cancer more invulnerable to treatments. Therefore,targeting HSP27 in prostate cancer can be perceived as one promising cancer treatment strategy. This article reviews the structure and function of HSP27,and its potential role on castration resistance and targeted therapy in order to provide a new theoretical basis for the clinical treatment of prostate cancer.

Advances of Src kinase family and paclitaxel resistance / 中国药科大学学报

Src family kinase (SFK) highly expresses in many types of cancers,broadly adjusting their malignant behaviors.Paclitaxel is a widely used chemical agent.However,because of constant resistance,the effect of paclitaxel has been greatly attenuated.The present review summaries the recent research progress of the structure and adjustment of SFK and the molecular mechanism of paclitaxel resistance,as well as the regulation of SFK on paclitaxel resistance,in order to provide new references and evidences upon the paclitaxel-based tumor therapy.

Advances of Hedgehog pathway in tumor resistance / 中国药科大学学报

@#Hedgehog pathway regulates the physiological process of tumor cells, including proliferation, cycle, invasion and metastasis, and maintains tumorigenesis and development. With abnomal activation of Hedgehog pathway, most tumors response poorly to chemotherapy, which is mediated by Hedgehog pathway through activation of target gene and crosstalk with other pathways. Herein, Hedgehog pathway has been an important target for reversing resistance. In this study, the Hedgehog pathway and role of Hedgehog-mediated resistance in recent years are reviewed.

Correlation between optical density and colony forming units of Mycobac-terium tuberculosis suspension / 中国感染控制杂志

Objective To establish a reliable approach for quantification of colony forming unit(CFU)of Mycobac-terium tuberculosis (M.tb)by measuring optical density(OD).Methods M.tb suspension H37Ra was prepared using low-power ultrasonic or glass bead beating methods,and was two-fold serially diluted,OD at 600nm (OD600)of each dilution ratio was measured respectively,OD600 and dilution curve were analyzed to determine the optimum approach for preparing bacterial suspension,linear range of OD600,as well as linear relationship between OD600 and CFU.Results OD600 was 0.1 -0.6,linear regression analysis of OD600 and dilution ratio within linear range revealed that correlation coefficient (R2 )of glass bead beating and low-power ultrasonic methods were 0.98 and 1 .00 respectively,both presented a good correlation,low-power ultrasonic method was better than glass bead beat-ing method,bacterial suspension dispersed more evenly.Linear regression analysis results of OD600 and CFU val-ues showed that the regression equation of glass bead beating method and low-power ultrasonic method were CFU=2.35×107 ×OD600+4.42×105 and CFU=3.26×107 ×OD600+6.89×105 respectively.Conclusion Low-power ultrasonic method is a good method for preparation of M.tb suspension,combined the measurement of OD600 value, it can be a reliable and rapid method for quantitative analysis of M.tb.

Effects and mechanism of programmed cell death of human gastric cancer cell under the treatment of flavonoid compound GL-V9 / 中国药科大学学报

@#To investigate the apoptotic effect of flavonoid compound GL-V9 on human gastric cancer cells and its potential mechanism, MGC-803 and BGC-823 cells were treated with GL-V9. MTT assay was performed to assess the growth inhibition effects on MGC-803 and BGC-823 cells under different concentrations of GL-V9. Annexin V-FITC/PI staining assay was employed to observe the apoptotic rate of GL-V9 cells with the treatment of GL-V9. DAPI staining was performed to observe the nuclear morphological changes using fluorescence microscopy. Activation of caspase-9 and caspase-3 was analyzed by Western blotting. Ca2+ concentration in gastric cancer cells was detected by Fluo-3 AM staining assay. Results showed that GL-V9 could inhibitcell viability, change the nuclear morphologyl, activate caspase-9 and caspase-3 and induce the apoptosis in gastric cancer cells. The mechanism of the induction of apoptosis in MGC-803 cells under the treatment of GL-V9 may aetivate the Ca2+ associated mitochondrial apoptosis pathway.

Inhibitory effects on glucose metabolism of human gastric carcinoma MGC-803 cells induced by wogonin / 中国药科大学学报

@#To investigate the inhibitory effect of wogonin on glucose metabolism in human gastric carcinoma MGC-803 cells and its underlying mechanism, Amplex Red Glucose/Glucose Oxidase Assay Kit was used to explore the influence of wogonin on glucose uptake of MGC-803 cells and lactate assay kit was adopted to evaluate the lactate generation of MGC-803 cells. Annexin V/PI staining assay was performed to observe the apoptotic rate of MGC-803 cells. Changes in the expression of hexokinase 2(HK II), glucose transporter 1(GLUT1), pyruvate dehydrogenase kinase(PDHK)and lactate dehydrogenase A(LDH-A)were assessed by Western blot. These results demonstrated that wogonin significantly reduced glucose uptake of MGC-803 cells at certain concentration. Meanwhile, wogonin apparently reduced the lactate generation of MGC-803 cells, without inducing notable cell apoptosis. Besides, with the impact of wogonin, the expression of glucose metabolism related proteins declined obviously. In a word, wogonin could inhibit the glucose metabolism of MGC-803 cells without inducing apparent apoptosis, which may be related to its inhibitory influence on the proteins in glucose metabolism of MGC-803 cells.

Research advances in wogonin's anti-tumor effects / 中国药科大学学报

Latest researches have indicated that wogonin, a naturally occurring flavonoid, could sensitize tumor cells to apoptosis, selectively induce apoptosis in the malignant tumor cells, inhibit tumor angiogenesis, reverse drug resistance as well as promote tumor cell death synergistically with other anti-cancer agents. This paper sum-marizes the involving mechanisms of wogonin's anti-tumor effects.

Gene expression spectra in human hepatoma SMMC-7721 cells treated with gambogic acid / 中国药科大学学报

Aim: To investigate gene expression spectra in human hepatoma cell line SMMC-7721 treated with gambogic acid (GA).Methods:Human cDNA microarray and RT-PCR technology were used to detect the changes in gene expression. Results: 31 genes in groups exposed to gambogic acid for 24 h and 56 genes for 48 h group were expessed differentially in comparison to the control group. Conclusior:The antitumor mechanism of GA might focus on apoptosis,metastasis as well as interfering with the cell cycle.

Protective effect of TQ0701-2 on cerebral ischemia reperfusion injury in rats / 中国临床药理学与治疗学

AIM:To investigate the protective effect of a new type nerves protectant TQ0701-2,as the derivate of edaravone free radical scavenger,on cerebral ischemia reperfusion injury rat.METHODS:120 male SD rats were randomly divided into sham group,model group,edaravone group(3.0 mg/kg)and TQ0701-2 high-dose group(6.0 mg/kg),middle-dose(3.0 mg/kg)and low-dose group(1.5 mg/kg).Animals in the latter five groups were subjected to transient focal ischemia by the middle cerebral artery occlusion(MCAO)for 2 h before reperfusion,while the sham group wasn't ischemic.The rats were injected with edaravone or TQ0701-2 30 min before ischemic and 0 min,2 h after reperfusion in edaravone and TQ0701-2 groups,sham group and model group were treated with normal saline as well.After 24 h of reperfusion,the infarct ratio,neurological and histological deficient and the changes of pathohistology were evaluated.RESULTS:The infarct ratios and neurological deficit scores in the model group were increased(P

Effect of Exendin-4 on the glucose tolerance and serum glucose level in normal animals / 中国临床药理学与治疗学

AIM:To study the effect of Exendin-4 on the glucose tolerance and serum glucose level in normal animals. METHODS: The fasting blood glucose concentration was tested at 0,1,2,3,4 h and 2,4 week after the first administration of Exendin-4 (0.1, 0.3, 0.9 g/kg, 4 weeks, qd) in Wistar rats ,taking insulin as positive control. Before intragastric administration 2.5 g/kg glucose, Exendin-4 (0.2, 0.6, 1.8 g/kg) were subcutaneously injected, then the fasting blood glucose concentration was tested at 0.5, 1, 2 h after the glucose loading. After hypodermic administration of Exendin-4 (0.2, 0.6, 1.8 g/kg), half of the mice were subcutaneously administrated 2.5 g/kg glucose 15 min later, and the insulin was tested at the end of the experiment. RESULTS:Exendin-4 could not significantly change the fasting blood glucose concentration at different times. The fasting blood glucose concentration was significantly decreased after glucose loading by administration Exendin-4. Exendin-4 could increase the serum insulin concentration remarkably after glucose loading and could not change much without glucose loading. CONCLUSION: The results suggest that the blood glucose regulation of Exendin-4 was related to the concentration of glucose.