The regulation of epigenetics on bone marrow mesenchymal stem cells (BMSCs) has been a research hot spot in medical area. This paper mainly summarizes the progress of the regulation of DNA methylation, histone acetylation, small interfering RNA (siRNA) induced gene silence and microRNA (miRNA) on BMSCs. Our analysis shows that the regulation of epigenetics on BMSCs plays a significant role in the repair of bone tissue, nervous tissue and cardiac muscle.
Acetylation ; Bone and Bones ; DNA Methylation ; Epigenesis, Genetic ; Hematopoietic Stem Cells ; Histones ; Humans ; Mesenchymal Stromal Cells ; cytology ; MicroRNAs ; Myocardium ; RNA, Small Interfering ; Wound Healing

Objective To investigate the effect of ischemic preconditioning ( IP) on the content of myocardial mitochondria cardiolipin and the heart function in isolated rat hearts. Methods Seventy-two healthy SD rats of both sexes ( 36 males,36 females) weighing 200 to 300 g were randomly divided into 4 groups ( n =18 for each group) : normal group,control group,IP group ( IP) and 5-hydroxydecanoate ( 5-HD) plus IP group ( HD) . Langendorff apparatus were used to establish the model of ischemia/reperfusion in isolated rat hearts. The hearts were perfused for 20 min to get stabilization followed by continuous perfusion in normal group for 100 min. In control group,after perfusing of 20 min for stabilization followed by continuous perfusion for 30 min,the hearts were then reperfused for 30 min after 40 min ischemia. In IP group,the hearts were given a 5-minute ischemia and 5-minute reperfusion for twice in order within a brief intermittent period,and ischemia reperfusion was carried out in the same way as that in control group. In HD group,the hearts were perfused with 100 ?mol/L 5-HD before IP,and the following procedures were carried out as those in IP group. HR,left ventricular end-diastolic pressure ( LVEDP) ,left ventricular developed pressure ( LVDP) were recorded at the end of stable perfusion ( T1) ,immediately before ischemia ( T2) and at the end of reperfusion ( T3) in all the groups. The content of myocardial mitochondria cardiolipin was measured with HPLC. Results When theparameters at T3 were compared with those at T1 and T2,HR and LVDP were decreased,LVEDP was increased and the content of myocardial mitochondria cardiolipin was decreased. All these changes were significant ( P

The myocardial protective effect of continuous infusion with normothermic oxygenated crystalloid solution or blood cardioplegia during normothermic CPB was studied in 15 dogs. Ultrastructure. levels of adenine nucleotides,lipid peroxide (LPO),water content of heart musle,hemodynamics were observed. Dogs were randomly divided into three groups. Group Ⅰ: intermittent infusion with cold crystsalloid cardioplegia during hypothermic CPB (n=5); Group Ⅱ: continuous infusion with normothermic oxygenated blood cardioplegia during normothermic CPB(n=5); Group Ⅲ: continuous infusion with normothermic oxygenatde crystalloid cardioplegia duriug normothermic CPB((n=5). The normal mitochandria contents and glycogen stores in group Ⅱ and Ⅲ were significantly higher than those in group Ⅰ(P

Objective To evaluate the myocardial protective effect of hyperpolarized heart arrest at different temperature during cardiopulmonary bypass CPB.Methods Eighteen dogs were randomly allocated to be infused with St.Thomas solution containing 50?mol/L pinacidil and 5mmol/L K + at 37℃ (group A) or 4℃ (group B), or the standard St.Thomas solution containing K + 16mmol/L at 4℃ (group C) respectively, through aortic root after aortic clamping . The global surgical ischemia lasted 60min with the declamping of 20min .The activities of serum myocardial enzymes, and levels of lipid peroxide and adenine nucleotide of myocardium were measured.Results All paramaters showed to occur serious ischemic and reperfusion damages during the whole procedures in group C, while there were the mild damages in two hyperpolarized groups, especially in group B.Conclusions Myocardial protective effect of hyperpolarized arrest induced with pinacidil, an ATP sensitive potassium channel opener, is superior to that of traditional hyperkalemic cardioplegia , which is much more prominent in hypothermic state.

Objective To evaluate the myocardial protective effect of hyperpolarized arrest induced with ATP-sensitive potassium channel opener ,pinacidil in vitroMethods Twenty-four rabbit hearts were randomly divided into three groups : hypothermic hyperpolarized group (LH group), normothermic hyperpolarized group ( WH group), and hyperkalemic control group (group C) The isolated rabbit hearts with a Langendorff apparatus were perfused oxygenated Krebs-Henseleit's solution (K-H) for 10 min and followed by cardioplegia The cardioplegia consisted of StThomas solution with either traditional high potassium (16mmol/L KCl, 4 ℃, group C), or pinacidil 50?mol/L (4 ℃ in LH group or 37 ℃ in WH group ) with 5mmol/L KCl The hearts were subjected to 40 min perfusional occlusion and followed by 20 min reperfusionResults Hearts were arrested quickly in LH group, and a little slowly in WH group, but rebeated quickly , which were different significantly from those in group C ; Recovery of LVP and left ventricle contracility in LH group and WH group were remarkedly faster than those in group C (P

Objective To compare the myocardial protective effect of hyperpolarized cardioplegic arrest with pinacidil against that of depolarized hyperkalemic arrest during cardiopulmonary bypass Methods Eighteen healthy mongrel dogs of both sexes weighing 10 15kg were divided into three groups of six each, according to the cardioplegic solution infused into aortic root after aortic cross clamp was applied; group A received 4℃ standard St Thomas solution (K +16mmol/L); group B 37℃ St Thomas solution (K +5mmol/L) containing pinacidil (50?mol/L) mixed with blood (the ratio was 1:1);group C 4℃St Thomas solution (K + 5mmol/L) containing pinacidil(50?mol/L) mixed with blood (1∶1) The global ischemic time was 60min followed by 30min reperfusion Myocardial tissue was taken before and 30min, 60min after aortic cross clamping and 30min after reperfusion for determination of myocardial content of adenine nucleotide and MDA and ultrastructure examination with electron microscope Hemodynamics (BP,CVP,PCWP,CO,CI and LVSW) was also measured before aortic cross clamping and 15,30min after declamping Results Significant ischemic and reperfusion damages were found in group A, while there were only mild damages in group B and C Hemodynamics recovery after aortic declamping was significantly better in group C than that in group A and B Conclusions Myocardial protective effect of hyperpolarized arrest produced by blood cardioplegic solution containing pinacidil is superior to that of traditional depolarized hyperkalemic arrest and hypothermic hyperpolarized cardioplegia is better than normothermic

Objective To compare the myocardial protective effect of pinacidil-induced hyperpolarized and hyperkalemic depolarized cardiac arrest on isolated rabbit heart under different temperature. Methods Forty-eight rabbits of both sexes weighing 2.0-2.5 kg were sacrificed by a knock on the head. Their hearts were excised and perfused in a Langendorff apparatus with an oxygenated Krebs-Hensleit buffer (KHB)(37℃). The study was divided into six groups: A normothermic hyperkalemic cardioplegia; B normothermic hyperkalemic blood cardioplegia; C hypothermic hyperkalemic cardioplegia; D hypothermia hyperkalemic blood cardioplegia; E normothermic hyperpolarizing blood cardioplegia; F hypothermic hyperpolarizing blood cardioplegia. Three pieces of myocardial tissue were obtained from apex of left ventricle at the end of the study for determination of myocardial adenine nucleotide and lipid peroxide content and microscopic examination. The following were recorded : (1) cardiac arrest time: the time from perfusion with cardioplegic solution to the beginning of cardiac arrest. (2) heart beat recovery time ;the time from reperfusion with KHB to the beginning of normal heart beat. (3) changes in HR, left ventricle developed pressure and myocardial contractility before and after cardiac arrest. Results The cardiac arrest time was longer and the time for the heart to restart was shorter in the two hyperpolarizing blood cardioplegia groups (group E and F) than that in the other 4 groups. No arrhythmia occurred in group E and F. Left ventricle developed pressure(LVDP) and left ventricle contractility recovered quickly after reperfusion with KHB was started and were restored to the pre-ischemia level after 20 min in group E and F. The levels of ATP, TAN and EC were higher and the MDA level was lower in group E and F than those in the other 4 groups. Myocardial structure was less injuried in group E and F. Conclusion The myocardial protection effect of hyperpolarizing blood cardioplegia with pinacidil is superior to traditional hyperkalemic depolarizing cardioplegia.

Objective To investigate the effect of heart preservation solution containing pinacidil on mitochondrial function in isolated rat hearts. Methods One hundred and twenty pathogen-free SD rats of both sexes weighing 250-350 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 65 mg/kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Left ventricular enddiastolic pressure was measured from a fluid-filled latex balloon inserted in the left ventricle. The isolated hearts were randomized into 5 groups (n = 24 each):group Ⅰ was perfused with cardioplegic solution HTK; group Ⅱ with HTK containing pinacidil (a non-specific sarcKATP and mitoKATP channel opener) 0.5 mmol/L; group Ⅲ with HTK containing pinacidil 0.5 mmol/L + 5-HD (a selective mitoKATP channel blocker) 100 μmol/L; group Ⅳ with HTK containing pinacidil 0.5 mmol/L + HMR-1098 100 μmol/L (a selective sarcKATP channel blocker) and group Ⅴ with HTK containing pinacidil 0.5 mmol/L + 5-HD 100 μmol/L + HMR-1098 100μmol/L. The isolated hearts were perfused with simple HTK or HTK containing pinacidil or pinacidil + 5-HD and/or HMR 20 ml/kg at 10 ml/min and then removed from Langendorff apparatus and dipped into the same HTK solution for 8 h at 4 ℃followed by 60 min reperfusion. The respiratory function of mitochondria (respiratory control rate (RCR), the rate of oxygen consumption in state 3/state 4 and P/O) was measured at the end of equilibration (T1) after 8 hpreservation (T2) and at the end of 60 min reperfusion (T3). The CK-MB and LDH activities and cTnI expression in myocardium was detected at T1 and T3. The ultrastructure of myocardium was examined at T3. Results Perfusion suspension-reperfusion (PS/R) significantly decreased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and increased myocardial cTnI concentration and CK-MB and LDH activities at T3 compared with baseline at T1 in group Ⅰ. Pinacidil significantly increased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and decreased myocardial cTnI concentration and CK-MB and LDH activities in group Ⅱ as compared with group Ⅰ-indicative of protective effect of pinacidil on mitochondria against PS/R injury. The protective effect of pinacidil against PS/R injury was attenuated by 5-HD and/or HMR1098. The myocardial damage was slightest in group Ⅱ . Conclusion Both sarcolemmal and mitochondrial KATPchannel are involved in the protective effect of pinacidil against PS/R-induced myocardial damage during heart preservation.

BACKGROUND:Silk fibroin/mesoporous glass ceramic composites have been reported to exert satisfactory repair outcomes in bone defects and hold good biocompatibility. However, the biosafety and preparation methods are rarely reported. OBJECTIVE:To investigate the preparation method and treatment outcomes of silk fibroin/mesoporous bioactive glass ceramic in skul repair. METHODS:Thirty-two Sprague-Dawley rats were enrol ed to establish the skul defect models and were thenrandomized into two groups:fibroin/mesoporous glass ceramic materials and silk fibroin were respectively implanted into the defect region in experimental and control groups. At 4 and 8 weeks after implantation, the CT examination and histological observation were performed. RESULTS AND CONCLUSION:CT examination showed that at 4 weeks after implantation, the defect area in the experimental group diminished in size, showing more dense new bones. The defect area of the control group was reduced, and a smal amount of new bones were observed. At 8 weeks after implantation, bone defect repair was completed in the experimental group, but not in the control group. The bone volume in the experimental group was significantly larger than that in the control group at different time points after implantation (P<0.05). Hematoxylin-eosin staining found that at 4 weeks after implantation, in the experimental group, there was new bone between the implant and the bone, which did not cause inflammation;there were few new bones and fibrous tissues in the control group. At 8 weeks after implantation, many new bones formed in the experimental group, with similar morphology to the host bone and the scaffold was degraded completely. Conversely, the implant material stil existed in the control group. In conclusion, the silk fibroin/mesoporous glass ceramic composite can promote bone repair.

Objective: To investigate the effect of ischemic postconditioning on myocardial infarction and myocardial apoptosis in ischemia-reperfusion injury of rats, and the protective mechanisms thereof. Methods:Thirty-six healthy male Wistar rats(230-280 g) were randomly divided into three groups, ischemia-reperfusion group(Group I-R), ischemia 30 min and reperfusion 120 min without additional intervention; myocardial ischemic postconditioning group(Group Post), after 30 min ischemia, the rats were comprised 3 cycles of 10 seconds reperfusion followed by 10 seconds ischemia, and then the rats were reperfused 120 min; myocardial ischemic postconditioning+AG490(JAK2-STAT3 pathway inhibitor) group(Group Post+AG490), rats were treated with AG490 5 minutes before reperfusion, followed by myocardial ischemic postconditioning and 120 min reperfusion. The myocardial infarct size was measured by TTC staining. Apoptotic index of cardiomyocyte was detected by TUNEL. Results: Myocardial infarct size and myocardium apoptotic index were significantly reduced in Group Post compared to those in Group I-R(P ＜ 0.05). AG490 inhibited cardioprotective effect of ischemic postconditioning. Conclusion: Ischemic postconditioning provides potent cardioprotective effect. JAK2-STAT3 pathway mediates the cardioprotective effects of ischemic postconditioning.