Objective To explore whether physiological doses of testosterone therapy can modulate cardiomyocyte aging via classical androgen receptor (AR) dependent pathways.Methods Male C57BL/6J mice and testicular feminized (Tfm) mice were divided into five experimental groups:the control group (n=8),the castrated group (n=8),the Tfm group (n=7),the testosterone treated castrated group (n=8),and the testosterone-treated Tfm group (n =8).After isolation of cardiomyocytes from the left ventricle,the activity of superoxide dismutase (SOD) and the amount of malondialdehyde (MDA) were measured using colorimetry,and the expression of the p16INK4a and retinoblastoma (Rb) proteins was detected by Western blotting.Results Compared with the control group,the activity of SOD in the castrated group and the Tfm group declined [(16.55±1.18) U/ml,(17.30±1.32) U/ml vs.(21.57±2.21)U/ml,P＜0.05)],the amount of MDA increased [(7.78±1.27)μmol/L,(6.52±0.82)μmol/L vs.(3.48±0.70)μmol/L],P＜0.01,and the expression of both the p16INK4aand Rb proteins increased [(0.37±0.08),(0.45±0.06) vs.(0.14±0.02),forp16INK4a,P＜0.05; (0.74±0.05),(0.79±0.08) vs.(0.40±0.05),for Rb,P＜0.05].Compared with the castrated group,the activity of SOD in the testosterone treated castrated group increased [(23.00±0.58)U/ml vs.(16.55±1.18) U/ml,P＜0.01],the amount of MDA decreased [(2.63±0.90) μmol/L vs.(7.78±1.27) μmol/L,P＜0.01],and the p16INK4a and Rb proteins were both downregulated (0.13 ± 0.03 vs.0.37± 0.08),for p16INK4a,P＜0.05; (0.45 ±0.05) vs.(0.79±0.08),for Rb P＜0.05.Compared with the Tfm group,the activity of SOD in testosterone-treated Tfm group increased,the amount of MDA decreased,and the p16IN4a and Rb proteins were both downregulated (P＜ 0.05).No significant differences in these markers were detected between the testosterone-treated castrated group and the testosterone-treated Tfm group.Conclusions Physiological doses of testosterone can retard cardiomyocyte aging via androgen receptor independent pathways.

Objective To investigate the apoptosis induced by adenovirus mediated PML growth suppressor in SGC-7901 gastric cancer cells. Methods Human full-length PML cDNA was cloned into shuttle plasmid pSGCMV, the constructed plasmid containing PML gene was co-transfected into 293 cells together with backbone plasmid pPE3 to obtain recombinant adenovirus Ad-pml. Ad-pml was used to infect SGC-7901 cells. The expression of p53 and bcl-2 in SGC-7901 cells and qualitative, quantitative index of cell apoptosis were detected with MTT, flow cytometry and immunohistochemical method. Results The growth of SGC-7901 cells was inhibited and the apoptosis rate was increased by adenovirus mediated PML in a MOI- dependent manner. The expression of p53 protein was increased and that of bcl-2 protein was unchanged in SGC-7901 cells after treated with adenovirus mediated PML. Conclusions Adenovirus mediated PML exerts its cytotoxic effect on SGC-7901 cells by inducing apoptosis. The increase of p53 protein expression is the mechanism inducing gastric cancer cell apoptosis.

Objective To investigate the expression of PCNA in gastric cancer and its relationship with telomerase activity of peritoneal washings and peritoneal dissemination, and to compare the efficacy of telomerase activity and cytology of peritoneal washings for prediction of peritoneal metastasis of gastric cancer. Methods Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity of peritoneal washings collected from 60 patients with gastric cancer. Exfoliate cytologic analysis of the corresponding samples was used for comparison.Expression of PCNA was measured with immunohistochemical staining.Their relationship with clinicopathologic features were evaluated. Results The positive rate of telomerase activity in peritoneal washing collected from patients with gastric cancer was 41.7%,which well related to serosal invasion, histology types, depth of infiltration and peritoneal metastasis of gastric cancer. The positive rate of telomerase activity increased with the increased depth of infiltration and serosal involvement areas (P

Objective To determine whether left ventricular Tei Index evaluate the cardiac function and prognosis of patients with sepsis-induced cardiomyopathy (SIC).Methods A total of 86 patients with septic shock combined with SIC in the emergency department of Beijing Chaoyang Hospital affiliated to Capital Medical University from July 2014 to June 2016 were recruited and divided into non-survival group (n=35) and survival group (n=51) according to 28-day follow-up.Left ventricular Tei Index, BNP, cTNI and left ventricular ejection fraction within the first 24 h after admisson were detected and compared between the two groups.The correlations of left ventricular Tei Index to BNP, cTNI and ejection fraction were analyzed.The receiver operating characteristic curves (ROC) were constructed to analysize the value of Tei Index in evaluating the cardiac function and prognosis.Results The patientsin the non-survival group had a higher Tei Index compared with that in the survival group [(0.75±0.13) vs.(0.51±0.09), P<0.05].The Tei Index of SIC patients was significantly positively correlated with BNP and cTNI (both P<0.05), and significantly negatively correlated with ejection fraction (P<0.05).The AUC of Tei Index for predicting 28-day mortality in SIC patients was high comapred with that of BNP, cTNI and ejection fraction.Conclusion The left ventricular Tei Index has a reliable value in evaluating the cardiac function and prognosis of patients with SIC.

Objective To investigate the regulation and the mechanism of Melatonin in calcium overload of pancreatic acinar cell in acute necrotizing pancreatitis (ANP). Methods Fifty-four Sprague-Dawley (SD) rats were equally divided into three groups:sham-operation group (SO group),ANP group (created with retrograde cholangiopancreatography injection of sodium taurocholate) and MT group (ANP model made after intra-peritoneal injection MT for 30 mins).Rats were sacrificed at 1,4 and 8hours after operation and pancreas tissues were underwent pathological examination.The free calcium concentration of pancreas tissues was determined by fluorescence minitoring method; and the expression of CaMK Ⅱ in pancreas tissues at mRNA and protein level was tested by real-time PCR and Western Blot.Results Pancreatic pathological injury in ANP groups was progressively severe as time extended,which was obviously ameliorated in MT group compared with ANP group (the t value of compared pathological score at 1,4 and 8 hour was:-7.95,-9.72 and -7.69,all P=0.00).Compared at same time point,the free Ca2+ concentration of pancreas tissues in ANP group was significantly higher than that of SO group (the t value of 1,4 and 8 hour was 13.09,18.58 and 16.56,all P=0.00).It was a little bit higher in MT group compared with that of SO group,however was significantly lower than that of ANP group (the t value of 1,4 and 8 hour was -10.03,-11.75 and -11.02,all P =0.00).Compared with SO group,the expression of CaMK Ⅱ at mRNA and protein level significantly increased in ANP group; MT significantly inhibited its expression.Conclusions The expression of CaMK Ⅱ may be inhibited by MT interfere,and then lower the calcium overload in pancreatic acinar cell,which play a role in pancreas tissue protection.

Objective:To evaluate the expression of CXCR4 and the migration rate of bone marrow stromal CD34+cells in differ-ent risk groups with myelodysplastic syndromes (MDS) using correlation analysis. Methods: Forty MDS patients were divided into low-and high-risk groups based on the International Prognosis Scoring System (IPSS). The former was composed of 20 patients with IPSS<1.5, whereas the latter was composed of 20 patients with IPSS≥1.5. Bone marrow (BM) samples of these patients and 10 nor-mal controls were collected. CD34+cells were separated and purified. The expression of CXCR4 was determined by flow cytometry. The migration rate of CD34+cells on the chemotactic effect of SDF-1αand on the effect of bone marrow stromal cells were measured. Results:The expression rate of CXCR4 was higher in the high-risk MDS group than in the low-risk and control groups (P<0.000 1). No significant differences existed between the low-risk and the control groups (P>0.05). The migration rate of CD34+cells on the ef-fects of SDF-1αand marrow stromal cells were significantly increased in the high-risk MDS group compared with those in the low-risk and control groups (P<0.000 1). Migration rate of CD34+cells on the effect of marrow stromal cells was positively correlated with CX-CR4 expression (P=0.000 1). Conclusion:The CXCR4 expression and migration rates of CD34+cells on the effect of marrow stromal cells are significantly higher in the high-risk MDS group than in the low-risk group. Migration rate has a positive correlation with the CXCR4 expression, which further indicates that MDS is a heterogeneous group of hematopoietic stem cell malignancies. The expres-sion and function of SDF-1 and its receptor CXCR4 differ within each group with various risks. SDF-1 and CXCR4 may be involved in MDS pathogenesis.

Objective To investigate the expression of protein tyrosine phosphatase(PTP)1B in pancreas of obese rats induced by high fat diet.Methods Twenty male SD rats were randomly divided into control group on regular diet(n=10),and obesity model group on high fat diet(n=10).After twelve weeks,fasting serum insulin,blood glucose,triglyceride,total cholesterol,epididymal fat weight were measured and the histomorphological change in liver were observed;glucose tolerance test and insulin releasing test were performed; The protein expression of PTP-1B in pancreas of rats was determined with Western blotting and immunohistochemistry.The phosphorylation of insulin receptor substrate-1(IRS-1)and insulin receptor(IR)were detected by immuno-precipitation.Results(1)The insulin sensitive index was significantly decreased in the high-fat-diet rats compared with the normal rats(0.36?0.18 vs 0.91?0.28,P

By analysing the anatomy of upper cervical segment, the atlas - axis relation in plain X - ray film in 3-1 cases revealed that the joint displacement is one of the important causes for vertebral artery type or sympathetic type cervical spondylopathy. The main manifestations for diagnosing atlas - axis displacement included headache, dizziness, unilateral protrusion and tenderness of the affected vertebra, displacement of tooth protrusion up to 1 mm at anterior mouth -open positions. The most effective therapy was accurate and dexterousmanipulation for reduction.

OBJECTIVETo investigate the protective effect of melatonin on residual hair follicle cells of scald rats at early stage.

METHODSEighteen male Sprague-Dawley rats were randomly divided into scald group, treatment group, sham group , with 6 rats in each group. The rats in scald group and treatment group were subjected to 30% TBSA partial thickness scald on the back, and were resuscitated with balanced solution after 1 hour, while those in sham group were immersed in water at 37 degrees C for 25 s to simulate scald, and did not receive fluid replacement. Rats in treatment group were intraperitoneally injected with 10 mg/kg melatonin solution at 1 minute, 8 hours and 12 hours after scald, while those in sham group and scald group were given equal volume of 1% alcohol sodium-isotonic saline instead. Tissue samples were harvested at 6, 12 and 24 post scald hours (PSH) for determination of MDA and GSH levels. Apoptosis of residul hair follicle was detected by TUNEL method and immunohistochemistry of caspase-3.

RESULTSThe level of MDA in scald group at each time point was much higher than that in sham group (P < 0.01) and treatment group (P < 0.05), and it peaked at 12 PSH. The changes in GSH were just opposite to that of MDA. Under fluorescence microscope, the residual hair follicle cells were blue, and the apoptotic cells appeared green. The apoptosis rate in scald group at 6, 12, 24 PSH was obviously higher than that in sham (P < 0.01) and treatment groups (P < 0.05), which was (20.2 +/- 3.4)% vs (4.3 +/- 2.3)% vs (10.9 +/- 3.2)%, (31.2 +/- 3.6)% vs (5.1 +/- 2.5)% vs (19.1 +/- 3.7)%, (22.4 +/- 2.7)% vs (4.1 +/- 2.4)% vs (13.1 +/- 3.4)%, respectively. The score of caspase-3 positive cell in scald group was higher than those in sham group (P < 0.01) and treatment group (P < 0.05).

CONCLUSIONSThere is obvious correlation between oxidative stress and apoptosis rate of hair follicle cells in rats with partial thickness scald. Early administration of melatonin may have anti-apoptosis ability for residual hair follicle cells by attenuation of oxidative stress.

Animals ; Apoptosis ; Burns ; drug therapy ; metabolism ; Hair Follicle ; cytology ; metabolism ; Male ; Melatonin ; therapeutic use ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley

Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.
Antimycin A ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzopyrans ; chemistry ; pharmacology ; Biphenyl Compounds ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Design ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gossypol ; chemistry ; pharmacology ; Humans ; Nitriles ; chemistry ; pharmacology ; Nitrophenols ; chemistry ; pharmacology ; Piperazines ; chemistry ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; pharmacology ; Structure-Activity Relationship ; Sulfonamides ; chemistry ; pharmacology ; Thiazoles ; chemistry ; pharmacology ; bcl-X Protein ; antagonists & inhibitors ; pharmacology