The present study aimed to investigate the change of cytochrome c in postconditioning-attenuated ischemia-reperfusion (I/R)-induced mucosal apoptosis in rat intestine compared with ischemic preconditioning (IPC). Using rat model of intestine I/R injury, male Sprague-Dawley rats weighing 220-250 g were divided into 4 groups which were Sham operation group, I/R group, IPC group and ischemic postconditioning (IPOST) group. In these groups, I/R procedure was performed by the occlusion of the superior mesenteric artery (SMA) for 45 min followed by reperfusion for 1 h. In Sham group, there was no intervention. In IPC group, SMA was occluded for 5 min and reperfused for 5 min, for two cycles, before the prolonged occlusion. In IPOST group, three cycles of 30-s reperfusion and 30-s reocclusion were preceded at the start of reperfusion. After the reperfusion, the small intestines were sampled for experimental detection. Intestinal mucosal mitochondrial membrane potential was detected by confocal laser scanning microscopy. Expressions of cytochrome c and caspase-3 proteins were detected using Western-blot method. The apoptosis of intestinal mucosal cells was determined with agarose gel electrophoresis and deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) technique. Compared with I/R group, the mitochondrial membrane potentials and the expressions of cytochrome c protein were significantly increased, while the expressions of caspase-3 and the apoptotic rates were decreased in IPOST and IPC groups (P<0.05). There were no significant differences between IPOST and IPC groups (P>0.05). These data provide substantial evidence that IPOST attenuates I/R-induced mucosal apoptosis by reducing the release of cytochrome c from mitochondria in the rat small intestine.
Animals ; Apoptosis ; physiology ; Cytochromes c ; metabolism ; Intestinal Mucosa ; metabolism ; pathology ; Intestines ; blood supply ; Ischemic Postconditioning ; methods ; Male ; Membrane Potential, Mitochondrial ; Mitochondria ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control

OBJECTIVETo detect the incidence of the HFE gene C282Y and H63D mutations in patients with myelodysplastic syndromes (MDS) and aplastic anemia (AA), and analyze the relationship of these mutations with iron metabolism, and organs impairment from iron overload.

METHODSThe incidence of the C282Y and H63D mutations in 271 MDS, 402 AA patients and 1615 normal subjects was measured by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combining with DNA sequencing. Iron metabolism parameters and iron overload indices were retrospectively compared between HFE gene mutation and unmutation groups in MDS and AA patients with no transfusion history.

RESULTSNo C282Y and C282Y/H63D compound mutation was detected in all the three groups. The incidence of H63D heterozygous and homozygous genotype did not significantly differ between AA cases and controls (9.7% vs 10.2%, 0.25% vs 0.24% respectively, both P > 0.05). The frequency of H63D heterozygous genotype in MDS patients was significantly lower than that in controls (4.1% vs 10.2%, P = 0.002). H63D homozygous was not found in MDS patients. In both MDS and AA patients with no RBC transfusion history, serum ferritin (SF), transferrin saturation value (TS), serum iron concentration (SI) were close to or higher than normal; and unsaturated iron-binding capacity (UIBC) value was significantly lower. There was no significant difference in SF, SI, TS values between HFE-mutation and -unmutation MDS patients. For AA patients, only the level of SI was significantly higher in HFE-mutant group than in -unmutation group [42.6 (24.6-60.4) micromol/L vs 32.0 (8.4-63.3) micromol/L, P = 0.011]. There was no significant difference in the values of liver enzyme, fasting blood sugar (FBS), abnormal electrocardiogram (ECG), peripheral blood indices between HFE-mutation and -unmutation MDS and AA groups (all P > 0.05).

CONCLUSIONThe distribution of C282Y and H63D mutations has ethnic and genetic disparity, the frequency in Chinese population is lower than that in Caucasian. It seems that MDS and AA patients are susceptible to iron overload, in the diseases itself and the mutations of HFE gene are not the major factor for iron overload in the patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; complications ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; China ; Female ; Genotype ; Hemochromatosis Protein ; Histocompatibility Antigens Class I ; genetics ; Humans ; Iron ; blood ; Iron Overload ; etiology ; genetics ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Myelodysplastic Syndromes ; complications ; genetics ; Young Adult

Objective To investigate the early diagnosis and surgery timing of strangulated intestinal obstruction.Methods The clinical data of 90 patients with strangulated intestinal obstruction who were admitted into our hospital from January 2013 and January 2016 were retrospectively analyzed.And these patients were divided into the early stage group (28 cases) and the later stage group (62 cases).The rate of mortality and the rate of necrotic bowel resection of the two groups were analyzed.Results Among the 90 patients underwent emergency surgery,there were 88 cases cured and 2 cases died,and there were 10 cases (11.11％) of necrotic bowel resection among the survivor.In the early stage group,there were 8 cases of necrotic bowel resection and 1 case of death.In the later stage group,there were 2 cases of necrotic bowel resection and 1 case of death.Conclusion Early diagnosis and prompt surgical treatment can reduce the mortality of strangulation obstruction and necrosis of bowel resection.

OBJECTIVETo investigate the preventive effects and possible underlying mechanism of different extracts of Kanggushu () on osteoporosis in ovariectomized rats.

METHODSOne hundred and sixtyfive female SD rats were divided into 11 groups: control, sham, model, Xianling Gubao Capsule (), nilestriol, Kanggushu aqueous extract high-, medium-, and low-dose and suet extract high-, medium-, and low-dose groups. The osteoporosis model was made by ovariectomizing the rats. The latter 8 groups were administered intragastricly with Xianling Gubao Capsule, nilestriol, Kanggushu aqueous extract and suet extract for 12 weeks, respectively, while the other 3 groups were administered orally saline. The whole body bone mineral density, bone mineral content, organ coefficient of uterus, serum estradiol and alkaline phosphatase contents, blood calcium, phosphorus, interleukin 6 and bone Gla-protein levels after treatment were monitored. Additionally, three-point bending test of femur, HE staining, and scanning electron microscope were performed to explore the pharmacodynamics and underlying mechanisms.

RESULTSIn comparison with ovariectomized rats of model group, Kanggushu aqueous extract high-dose resulted in an increased bone mineral density, bone mineral content and organ coefficient of uterus, improved estradiol level, and improved maximum load and structural stiffness (P<0.05 or P<0.01). Two-dimensional and three-dimensional trabecular structure was also observed under HE staining and scanning electron microscopy, and the number and thickness of trabecular bone in Kanggushu aqueous extract high-dose group was significantly increased compared to the model group, while the lipid droplets in bone marrow cavity were significantly less. However, there were no significant differences in blood calcium, total serum alkaline phosphatase and bone Gla protein among different treatment groups. Overall, the osteoprotective effects of Kanggushu aqueous extract were comparable to those of nilestriol and were significantly more effective than those of Xianling Gubao Capsule.

CONCLUSIONThe preventive effects of Kanggushu aqueous extract might be partly due to the increased estradiol level, accelerated restoration of bone trabecular reticulate structure, and accordingly increased bone mineral density in osteoporosis rats.

Alkaline Phosphatase ; metabolism ; Animals ; Biomechanical Phenomena ; drug effects ; Body Weight ; drug effects ; Bone Density ; drug effects ; Calcium ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; blood ; Female ; Femur ; drug effects ; pathology ; physiopathology ; ultrastructure ; Interleukin-6 ; metabolism ; Organ Size ; drug effects ; Osteocalcin ; metabolism ; Osteoporosis ; blood ; drug therapy ; pathology ; physiopathology ; Ovariectomy ; Phosphorus ; metabolism ; Rats ; Rats, Sprague-Dawley ; Uterus ; drug effects ; pathology

Histone deacetylases(HDAC)and its inhibitors have been the hot spots in the field of cancer-treatment.At pres?ent,six HDAC inbibitors(HDACi)have been approved by FDA for the treatment of various hematological neoplasms and solid tu?mors.Besides,a number of new HDACi are undergoing clinical trials in different stages or preclinical experiments,which have shown great inhibitory activities.However,a series of side effects and dose-dependent problems have appeared due to the poor selectivity of inhibitors in HDAC subtypes.So a new HDACi with high-selectity to HDAC subtypes or drug-combination will be of importance to im?prove the therapeutic effect.This review highlights the structure modification in HDACi and multiple drugs combination to summarize the latest evolution of HDACi.