Aim To research the protective effect and mechanisms of taurine on myocardial ischemia and reperfusion injury in rats. Methods Myocardial ischemia reperfusion models were established in SD rats. The effects of taurine on the size of myocardial infarction and the changes of activity of SOD , and the levels of MDA and NO in myocardium and plasma of rats with myocardial ischemia and reperfusion injury were observed. Results In rats with myocardial ischemia and reperfusion injury, the taurine could reduce the size of myocardial infarction (P

To investigate the existence of nongenomic action of 17β-estradiol (E(2)) in the delayed implantation mouse endometrial stromal cells, the changes in intracellular calcium concentration ([Ca(2+)](i)) and the upstream of calcium signal in vitro were detected. The experiment was composed of two parts. Firstly, the change in [Ca(2+)](i) in endometrial stromal cells induced by E(2) under different conditions was detected. The mice were divided into 6 groups as follows: 0.1% dimethylsulfoxide (DMSO) control group, 1×10(-8) mol/L bovine serum albumin (BSA) control group, 1×10(-8) mol/L E(2) group, 1×10(-8) mol/L E(2) conjugated with BSA (E(2)-BSA) group, 1×10(-8) mol/L E(2) + calcium-free medium group, 1×10(-8) mol/L E(2) + 5 mg/mL tamoxifen group, with 4 mice in each group. The endometrial tissue was obtained from delayed implantation mice at pregnant day 7, and digested by incubation of tissue minces in Hankos balanced salts (HBSS, pH 7.2), which contained glucose (1 g/L), and collagenase I (0.125%), for 1 h at 37 degrees C. The stromal cells were preloaded with 2.5 mmol/L Fluo-3/AM, a fluorescent probe of calcium, for 30 min. A confocal laser scanning microscope, which fixed the wave length of excitation and emission at 488 nm and 526 nm, respectively, was used to detect the change in [Ca(2+)](i). Secondly, the mechanism of E(2) effects in endometrial stromal cells was investigated. Immunofluorescent method was used to detect the change in phosphorylation of phospholipase C (PLC) before and after the stromal cells were treated with E(2) for 5 min, 15 min, and 30 min. Seven delayed implantation mice were used. The results were as follows. [Ca(2+)](i) increased immediately and reached the maximum at 15 min after the stromal cells were treated with 1×10(-8) mol/L E(2) and returned to the normal level at 30 min. In E(2)-BSA group and E(2) + calcium-free medium group the same results were obtained as that in E(2) group, but there was no increase of [Ca(2+)](i) in DMSO and BSA groups. Tamoxifen, a traditional antagonist of estrogen receptor, did not inhibit the increase in [Ca(2+)](i) induced by E(2). Immunofluorescent results showed that the change in phosphorylated-PLC level had the same trend as [Ca(2+)](i) after the cells were treated with E(2). Compared with that in the control group, the immunofluorescent intensity increased at the beginning and achieved the maximum at 15 min (P<0.001), then declined to the normal level at 30 min. These results suggest that the rapid response of [Ca(2+)](i) induced by E(2) in the endometrial stromal cells in delayed implantation mice is possibly carried out through a nongenomic pathway, and the transmembrane signal transduction is related to the phosphorylation of PLC in this process.
Animals ; Calcium ; chemistry ; Culture Media ; Cytosol ; chemistry ; Endometrium ; cytology ; Estradiol ; pharmacology ; Female ; Mice ; Phosphorylation ; Pregnancy ; Receptors, Estrogen ; Signal Transduction ; Stromal Cells ; cytology ; drug effects ; Tamoxifen

OBJECTIVETo investigate quinalizarin-induced apoptosis in gastric cancer cells in vitro and explore the molecular mechanisms.

METHODSMTT assay was used to determine the cytotoxic effects of quinalizarin on human gastric cancer AGS, MKN-28 and MKN-45 cells. Annexin V-FITC/PI staining and flow cytometry were used to assess quinalizarin-induced apoptosis in AGS cells and its effect on intracellular ROS levels; the expression levels of apoptotic proteins in the cells were determined with Western blotting.

RESULTSQuinalizarin dose-dependently reduced the cell viabilities of the 3 gastric cancer cells (P<0.05). The ICvalues of quinalizarin in AGS, MKN-28 and MKN-45 cells were 7.07 µmol/L, 22.55 µmol/L and 14.18 µmol/L, respectively. Quinalizarin time-dependently induced apoptosis of AGS cells and potentiated the generation of intracellular reactive oxygen species (ROS) levels. Pretreatment with NAC, a scavenger of ROS, inhibited quinalizarin-induced apoptosis (P<0.001). Western blotting results showed that quinalizarin also up-regulated the expression levels of the apoptotic proteins including p-p38, p-JNK, Bad, cleaved caspase-3, and cleaved PARP-1 (P<0.05), and down-regulated the expression of the anti-apoptotic proteins p-Akt, p-ERK, and Bcl-2 (P<0.05).

CONCLUSIONQuinalizarin inhibits the proliferation and induces apoptosis in gastric cancer cells in vitro through regulating intracellular ROS levels via the MAPK and Akt signaling pathways.

BACKGROUNDAmong patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined.

METHODSAmong 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined.

RESULTSAmong 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%.

CONCLUSIONAmong individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.

Aged ; Coronary Angiography ; Coronary Disease ; pathology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Ventricular Dysfunction, Left ; pathology ; physiopathology

Enhancer of zeste homolog 2(EZH2) is a histone methyltransferase which regulate gene expression through epigenetic machinery. The abnormal expression of EZH2 has been described in many cancer types. With in-depth study, it was found that EZH2 is involved in the occurrence and development in many kinds of malignant hematologic disease which may play a dual role of oncogenes and tumor suppressor genes. In recent years, the emergence of EZH2 inhibitors provide a new option for the future treatment of hematological malignancies. In this review, the expression and clinical significance of EZH2 in various of hematological tumors were summarized briefly.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Hematologic Neoplasms/genetics* ; Humans ; Neoplasms ; Oncogenes ; Research

OBJECTIVE: Discuss the working ideas of the dynamic adjustment mechanism of medical device classification in the United States, and provide reference for the construction of medical device related mechanisms in China. METHODS: Collect and interpret the documents of regulatory background, procedures and orders of the dynamic adjustment mechanism of the medical device classification in the United States, and summarize the overall situation and specific cases of the medical device classification adjustment under this mechanism in recent years. RESULTS: The US work idea of the medical device classification dynamic adjustment mechanism is based on the latest valid scientific evidence, conducting risk analysis and identification, and determining the corresponding measures. CONCLUSIONS During the adjustment process, industry stakeholders have repeatedly discussed and achieved final agreement. Its procedures and working ideas can be used as a reference for China's work.
China ; United States ; United States Food and Drug Administration

ObjectiveThe study of the treatment of hypertriglyceridemia with scutellaria baicalensis stem-leaf total flavonoid (SSTF) are rarely reported.The objective of this study is to investigate the effects of SSTF on lipid metabolism and oxidative stress in rats with hypertriglyceridemia.Methods60 SD rats were randomly divided into normal group, model group, fenofibrate group (100 mg·kg-1), SSTF groups with low, medium and high doses (50,100,200 mg·kg-1, respectively). All rats, except those of the normal group, were fed with high-fat diet and given corresponding drug intervention for 6 weeks. Then the body masses at the 2nd, 4th and 6th weeks as well as wet weight of the liver at the end of 6th week were recorded, and liver index was calculated. The serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected. The levels of TG, TC, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver tissue were determined, and liver histopathological changes were observed by hematoxylin-eosin (HE) staining.ResultsIn the model group, compared with the normal group, the body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week were increased, the serum levels of TG, TC and LDL-C got increased with decreased HDL-C level, and the levels of TG[（1.603±0.146）mmol/L], TC[（3.474±0.356）mmol/L] and MDA[（10.288±1.979）nmol/mg] in liver tissue were increased with decreased levels of SOD[（106.840±24.014）U/mg] and GSH-PX[（9.278±2.079）U/mg]. Compared with the model group,the fenofibrate group and all SSTF groups showed decreased body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week, decreased serum levels of TG, TC and LDL-C with increased level of HDL-C, and decreased levels of TG, TC and MDA with increased levels of SOD and GSH-PX in liver tissue. The comparsion between the fenofibrate group and the high-dose SSTF group revealed that the body masses at the 4th and 6th weeks and liver index at the end of 6th week were decreased, the serum levels of TG, TC and LDL-C were decreased with increased level of HDL-C, and the levels of TG[（0.718±0.135）mmol/L] and MDA[（5.071±1.305）nmol/mg] in liver tissue got decreased with increased levels of SOD[（172.210±30.214）U/mg] and GSH-PX[（14.623±2.418）U/mg] in the latter group. All the above-mentioned differences were statistically significant (all P<0.05).ConclusionSSTF can regulate lipid metabolism and improve pathological injury of liver in hypertriglyceridemia rats, which may be related with inhibition of lipid peroxidation and reduction of oxidative stress.

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

OBJECTIVETo investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML).

METHODSFourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients.

RESULTSAll of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors.

CONCLUSIONThe induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Decitabine ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Middle Aged ; Remission Induction ; Treatment Outcome

Epigenetic abnormalities play an important role in the pathogenesis of hematological malignancies, especially acute leukemia (AL). Similar to DNA methylation and histone modifications, RNA methylation is another important epigenetic modification. m6A methylation is one of the most prevalent and extensively studied RNA methylation. m6A methylation is involved in many biological and pathological process. Recent studies have found that m6A methylation is involved in the occurrence, development and drug-resistance of AL. This review focuses on the research progress of m6A methylation in AL.
DNA Methylation ; Epigenesis, Genetic ; Humans ; Leukemia