Objective The purpose of this study was to investigate the effect of pinacidil, an ATP-sensitive K + channel opener in protecting myocardium of immature rabbit heart from ischemia-reperfusion injury.Methods Fifty-two rabbits of 3-4 weeks old, weighing 350-450g were anesthetized with intraperitoneal pentobarbital sodium(50mg/kg). Hearts were excised and connected to modified Langendorff perfusion system and passively perfused with Krebs-Henseleit buffer(KHB) at 76 cmH 2O. Hearts were made globally ischemic for 30 min by aortic crossclamping and then reperfused for 30min. During ischemia the hearts received 20-25 ml cardioplegic solution of diferent constituents every 15 min. There were four groups with 13 hearts in each group based on the diferent constituents of cardioplegic solution: group Ⅰ(control, no cardioplegic solution); group Ⅱ(KHB+K + 16mmol/l); group Ⅲ(KHB+K +16mmol/L+pinacidil 50?mol/L); group Ⅳ (KHB+K +16mmol/L+glibenclamide 10?mol/L). Left ventricle developed pressure (LVDP), left ventricle diastolic pressure (LVEDP),?dp/dtmax, coronary flow (CF), and the levels of CK, LDH and AST in coronary sirnus veneous effluent and by myocardial ultrastructural changes. Myocardial ultrastructure was examined before and after ischemia.Results Before myocardial ischemia, there were no significant differences in the above mentioned parameters among four groups. Group Ⅲ was the best in terms of postischemic recovery of LVDP, LVEDP,?dp/dtmax and CF. The changes in CK,LDH,AST levels and myocardial ultrastructure were the least in group Ⅲ.Conclusions Pinacidil can afford best myocardial protection against ischemia-reperfusion injury in immature rabbit hearts.

Traumatic optic nerve injury ( TON) is caused by direct or indirect optic nerve trauma, which is one of a serious complication of craniocerebral trauma. lts prognosis poor and usually bring permanent vision damage. At present, optic nerve injury and regeneration is hot in neurobiology research. To build an ideal experimental animal model is extremely important in research and development in the treatment of optic nerve injury. ln this article, we review the methods of making rat models of traumatic optic neuropathy, clinical similarities, advantages and disadvantages of among these models, to provide reference for more experimental study.

Tezepelumab(AMG 157/MEDI9929)is a human monoclonal antibody against the epithelial cell-derived cytokine thymic stromal lymphopoietin(TSLP).It is primarily used to treat moderate to severe asthma,particularly in patients with a non-eosinophilic inflammatory phenotype,whose asthma remains uncontrolled despite the use of long-acting beta-agonists and moderate to high doses of inhaled glucocorticoids.This article will summarise the mechanism of action,clinical trial efficacy and safety and tolerability of Tezepelumab in order to provide a comprehensive understanding of the drug and inform clinical work.

OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).

METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.

RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.

CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism

Stress cardiomyopathy is an atypical myocardial disease induced by emotional or physical stress, with the characteristic of left ventricular systolic dysfunction, transient imaging and electrocardiogram (ECG) changes. Sudden cardiac death can occur in severe cases. Clinical symptoms are likely to appear on acute myocardial infarction, but the exact pathological mechanism is unclear. In the present study, we perform a systematic review of the literature on the clinical manifestations, epidemiological characteristics, ECG, imaging and laboratory tests of stress cardiomyopathy, in order to provide the values for forensic pathology diagnosis.
Death, Sudden, Cardiac ; Diagnostic Imaging ; Electrocardiography ; Humans ; Myocardial Infarction ; Stress, Psychological ; Takotsubo Cardiomyopathy/physiopathology*

Objective To observe the effect of allogenic bone marrow mononuclear cells(BM-MNCs) transplantation on myocardial apoptosis after acute myocardial infarction(AMI) in rats.Methods 40 Wistar rats were randomly divided into control group(n=20) and transplantation group(n=20).Myocardium around the infarcted left ventricular area of the rats in transplantation group were injected with BM-MNCs suspension beneath the epicardium.Myocardium the area of control group was injected with culture solution.Results After 4 weeks of the operation,the myocardial apoptosis index,the TNF-? content and the PDCD5 mRNA of transplantation group were all notably less than those of control group(P

Objective To investigate the effectiveness of pinacidil,an opener of ATP-sensitive K+ channels,in protecting the myocardium of immature rabbit hearts from ischemic reperfusion injury.Methods Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 min of reperfusion on the modified Langendorff apparatus.Fifty-two isolated hearts of 3 - 4 week-old immature rabbits were divided into 4 groups randomly.During ischemia,3 different cardioplegic solutions were administered intermittently by infusion every 15 min(20-25 mi each time in all groups).Group 1:control group(n = 13);group 2:Krebs-Henseleit(K-H)solution with potassium(16 mmol/L)(n = 1:3);group 3:K-H solution with potassium(16 mmol/L)and pinacidil(50 μmol/L)(n = 13);group 4:K-H solution with potassium(16 mmol/L),pinacidil(50 μmol/L)and glibenclamide(10 μmol/L)(n = 13).The pre-ischemic and post-ischemic myocardial functions were assessed by the percentage recovery of the left ventricular developed pressure(LVDP);the left ventricular end-diastolic pressure(LVEDP);both the Positive peak and negative peaks of the first derivative of the left ventricular pressures(± dp/dtmax);coronary flow;the level of creatine kinase(CK),lactic dehydrogenase(LDH)and aspartate transcarbamoylase(AST)in coronary sinus venous effluent;and by myocardial ultrastructural changes. Results Before myocardial ischemia,there were no significant differences among the four groups in any of the parameters mentioned above.Post-ischemic recovery of LVDP,LVEDP,± dp/dtmax,coronary flow,the level of CK,LDH and AST,and myocardial ultrastructural changes were better in group 3 than those in the three other groups.Conclusions As a new and effective composition,pinacidil can significantly improve myocardial protection from cardioplegia for immature rabbit hearts.

Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .

Apoptosis ; physiology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Carrier Proteins ; biosynthesis ; genetics ; DNA-Binding Proteins ; metabolism ; Gene Targeting ; Humans ; Liver Neoplasms ; enzymology ; pathology ; RNA Interference ; Telomerase ; metabolism ; Tumor Cells, Cultured

OBJECTIVETo extract two kinds of phenols 4-hydroxy-3, 5-dimethoxy-4-(2-oxopropyl) cyclohexa-2, 5-dien-l-one and 6-methoxy-5,7-dihydroxy coumarin (named as I and H compounds respectively) from Ajania salicifolia and to investigate their antioxidation and cytotoxicity to tumors and explore their pro-apoptosis mechanism.

METHODSThe antioxidant activities of two compounds were assessed by ABTS and DPPH radical-scavenging assays. Two compounds were evaluated for their cytotoxicity against human chronic myelogenous leukemia (K562) cells using the MIT assay. The expression of NF-kappaB P65 mRNA in K562 apoptotic cells was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR. In addition, protein expression levels of the NF-ICB P65, p-Akt, Fas, P-catenina and E-cadherin were also measured by Western blot.

RESULTS(1) We found that compound I displayed significant inoxidizability, while compound II had no obvious antioxidizability. (2) In cytotoxicity experiments, compound I didn't display cytotoxicity while compound H displayed obvious cytotoxicity. (3) Compared with the blank group, the expression of NF-kappaB P65 mRNA in K562 cell after treatment with compound II was obviously up-regulated. (4) Compared with the blank group, the expression levels of NF-kappaB P65, Fas, beta-catenina and E-cadherin were significantly increased in compound II treated groups and it appeared obvious dose-effect relationship between the expression of protein and drug concentration.

CONCLUSIONTwo phenols have obvious antioxidizability and cytotoxicity respectively. On the one hand, the tumor-suppressing mechanism of compound II maybe act by up-regulation the expression of NF-kappaB P65 and Fas protein; thereby, affecting the classical Fas apoptosis signaling pathways. On the other hand, it can also up-regulate the expression of protein beta-catenin and E-cadherin, which participate in the adhesion between cells, and accordingly, playing an important role in preventing the proliferation and metastasis of cancer cells.

Apoptosis ; Asteraceae ; chemistry ; Cadherins ; metabolism ; Humans ; K562 Cells ; Oncogene Protein v-akt ; metabolism ; Phenols ; chemistry ; Signal Transduction ; Transcription Factor RelA ; metabolism ; Up-Regulation ; beta Catenin ; metabolism ; fas Receptor ; metabolism