Objective:To study the effect of β-sheet blocking peptide H102 on the expression of AMPK-mTOR autophagy pathway-related protein in APP/PS1 double transgenic AD mice. Methods: Thirty male APP/PS1 transgenic male AD mice of 6 months old were randomly divided into AD group and H102 intervention group, and C57BL/6J male mice of the same age were used as control group (n=15). The mice in the HF group were administered with 5 μl (5.8 mg/kg) of H102 polypeptide solution through the nasal cavity at the same time period, and the mice in the control group and the AD group were given the same amount of blank adjuvant solution daily. The memory recognition ability was tested by a new object recognition experiment 30 days after continuous administration. Immunohistochemistry and Western blot were used to detect the expressions of phosphorylated AMP-activated protein kinase(P-AMPK),phosphorylated mammalian target of rapamycin (P-mTOR) and ratio of LC3Ⅱto LC3Ⅰ(LC3II/I )in brain tissue. Results: Compared with the control group, the new object recognition index (RI) of the AD group was significantly lower (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain of the mice were significantly lower (P＜0.05). The expression of P-mTOR protein was increased significantly (P＜0.05). Compared with the AD group, the RI of the H102 intervention group was increased significantly (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain tissue of the mice were increased significantly (P＜0.05). The expression of P-mTOR protein was decreased significantly (P＜0.05). Conclusion: H102 can improve the recognition and memory ability of AD mice by activating the AMPK-mTOR autophagy-related pathway.

Objective:To investigate the expression of EGR1 gene and the localization of EGR1 protein in bovine skeletal muscle-derived satellite cells (MDSCs), as well as to investigate the mechanism that EGR1 protein enters the nucleus. Methods: Bovine MDSCs were cultured in differentiation medium for 1 day, 3 days and 5 days, respectively, and each group was triplicate. The expression of EGR1 gene and the localization of EGR1 protein were studied at different differentiation period in MDSCs by qRT-PC and Western blot. Moreover, the changes on the expression of endogenous EGR1 gene and EGR1 proteins were explored by CRISPRi, site-directed mutagenesis and laser confocal method. Results: The results from the qRT-PCR and Western blot showed that the expressions of EGR1 gene on transcription level and translation level were significantly higher in differentiated cells than those in undifferentiated cells. The highest expression was found on the third day after the differentiation, and then began to decline. Immunofluorescence assays showed that EGR1 proteins were preferentially expressed in differentiated MDSCs, and increased along with the increase of number of myotubes. Confocal observation revealed that some EGR1 proteins were transferred into the nucleus in the differentiation of cells, however, the EGR1 proteins would not be detected in the differentiated MDSCs nuclei if a site directed mutagenesis (serine₅₃₃) on EGR1 protein occurred. Conclusion: During the differentiation of bovine skeletal muscle satellite cells, the transcriptional level of EGR1 gene is increased, and some EGR1 proteins are transferred into the nucleus. The serine phosphorylation at position 533 of the C terminal of EGR1 protein is necessary for the nucleus transfer.

Objective:Yun Kang oral liquid is a listed proprietary Chinese Medicine. To further evaluate its efficacy, this experiment established a kidney deficiency and luteum inhibition threatened abortion rat model to observe the effects of Yun Kang oral liquid. Methods: Sixty pregnant rats were randomly divided into normal control group (NC), model group (MG), dydrogesterone group (DT, 3.02 mg/kg), and Yun Kang oral liquid low-dose group (YK-L, 4 ml/kg), medium dose group (YK-M, 6 ml/kg), high dose group (YK-H, 9 ml/kg), 10 in each group. On the first day of pregnancy, each administration group was treated with the test drug at the prescribed dose every morning, and the NC group and the MG group were given an equal volume of purified water for 10 days; the rats were intragastrically administrated every afternoon, except for the NC group. In addition, the other groups were intragastrically administered with hydroxyurea at a dose of 450 mg/kg for 9 days, and mifepristone was administered at a dose of 4.0 mg/kg on the 10th day. On the 9th day of pregnancy, behavioral signs such as back temperature, grasping force, pain threshold, and autonomic activity were measured in each group. On the 11th day of pregnancy, blood was collected from the abdominal aorta in each group to determine serum levels of estradiol (E₂) , progesterone (P) and thromboxane B₂ (TXB₂) . Ovary and fetal uterus were removed, the number and diameter of embryos were observed, and the ovary and uterus indexes were calculated. Results: Compared with the NC group, the back temperature, grip, pain threshold, number of spontaneous activities, number of embryos, embryo diameter, uterus index and serum E₂, P, TXB₂ levels in the MG group were decreased significantly (P＜0.05, 0.01). Compared with the MG group, the back temperature, grasping force, number of embryos, embryo diameter and serum E₂ and P levels were increased significantly in each dose group (P＜0.05, 0.01); the pain threshold, autonomic activity, and uterus index of YK-M and YK-H group were increased significantly (P＜0.05); serum level of TXB₂ in YK-H group were increased significantly (P＜0.05). Conclusion: Yun Kang oral liquid has a clear kidney-filling effect on rats with threatened abortion caused by kidney deficiency-luteal suppression. The mechanism may be related to raising serum E₂, P, TXB₂ levels, improving kidney deficiency and improving embryo quality.

Objective:To investigate the effects of central nucleus of amygdala (CeA) lesion on the initiation and expression of sodium appetite in sodium-deficient rats. Methods: Three groups of SD rats (n=6 in each group) were treated with bilateral CeA lesion, sham lesion or no lesion. After the recovery, the rats were fed with low-sodium diets for 14 days to establish a sodium-deficient rat model. The double-bottle selection in single cage test was used to observe the intake of 0.3 mol/L NaCl and DW in 5 timepoint with 24 hours in sodium-deficient rats. Immunofluorescence staining of aldosterone-sensitive neurons in the nucleus tractus solitarii (NTS)was used to investigate the effect of CeA lesion or not on the activity of aldosterone-sensitive neurons in rats with or without sodium deficiency. Results: After fed with low-sodium diet for14 days, the volume and preference rate of 0.3 mol/L NaCl intake of the rats within 24 h were significantly increased compared with those before low-sodium diet (P＜0.01). The intake volume and the preference rate of 0.3 mol/L NaCl in CeA lesion rats were significantly decreased than those in CeA sham lesion rats and normal rats in the sodium-deficient condition (P＜0.01). The CeA lesion had no effects on the activity of aldosterone-sensitive neurons in NTS in rats with low-sodium diet. Conclusion: Low-sodium diet induces an increase in the expression of sodium appetite in rats. CeA lesions inhibit the behavioral expression of sodium appetite in sodium-deficient rats but have no effects on the initiation of sodium appetite in rats with sodium-deficient rats.

Objective:To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. Methods: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. Results: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. Conclusion: Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.

Objective:To establish an arterial remodeling model of rats and to investigate the expression and role of Hippo signaling pathway in this model. Methods: In the model group (n=40), the left common carotid artery was removed through the median incision of the neck. The 6-0 non-absorbable line was used to ligate the carotid artery near the proximal end as far as possible, completely blocking the blood flow. The common carotid artery of rats in control group (n=20) was not ligated using the operative line. After 14 days, the animals were sacrificed and the common carotid arteries were separated through the original surgical pathway and the arteries from the ligature to the distal end were collected. Arterial morphology and fibrosis were observed by HE and MASSON staining. Immunohistochemical staining was used to detect the expressions of anti-α smooth muscle actin (α-MSA) and proliferating cell nuclear antigen (PCNA) in the carotid artery. Western blot was used to detect the expressions of yes associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), TEAD1, Bcl-2-like protein 4 (Bax), and B-cell lymphoma-2 (Bcl-2). Results: Compared with the control group, the HE staining showed that the vascular remodeling was obvious, the ratio of the neointima/middle membrane was increased significantly, and the MASSON staining indicated that the fibrosis was significantly increased in model group. The immunohistochemical staining suggested that the expressions of α-SMA and PCNA were increased significantly; Western blot suggested that the expressions of YAP, TAZ, TEAD1, and Bcl-2 were increased in carotid artery of the model group. While the expression of Bax and the ratio of Bax/Bcl-2 were decreased. Conclusion: A rat model of arterial remodeling mediated by carotid artery ligation was established successfully in this study. Hippo signaling pathway was proved to be activated in the arterial remodeling model induced by carotid artery ligation in rats, and might regulate the change of Bax/Bcl-2 ratio related to proliferation and apoptosis, and subsequently involved in the proliferation of smooth muscle cells to promote vascular remodeling.

Objective:To evaluate the effects of 12 weeks high intensity interval training(HIIT) on serum lipids profile in patients with dyslipidemia of different apolipoprotein E(ApoE) genotypes. Methods: Eighty-eight patients with dyslipidemia were screened by fasting blood lipid as subjects. Apolipoprotein E genotypes were detected in oral mucosa of subjects. Serum lipids before and after 12 weeks high intensity interval training were measured to analysis the effect of high intensity interval training on serum lipids. Results: Five genotypes were detected in 88 cases of dyslipidemia. The distributions were ApoE3/3＞ApoE3/4＞ApoE2/3＞ApoE2/2＞ApoE2/4,and allele ε3＞ε2=ε4. Before exercise intervention, the level of total cholesterol in patients with ε4 allele was significant higher than those in patients with ε2 and ε3 (P＜0.01), low density lipoprotein cholesterol in patients with ε4 was significant higher than that of patients with ε2 (P＜0.05), and the other indexes had no significant difference among the groups (P＞ 0.05). After 12 weeks high intensity interval training, the levels of total cholesterol, triglyceride and low density lipoprotein cholesterol were decreased significantly ,while the level of high density lipoprotein cholesterol was increased in those patients with ε3 genotype. For those individuals with ε4 genotype , their serum levels of total cholesterol and low density lipoprotein cholesterol were reduced after 12 weeks high intensity interval training , but there was no changes in serum levels of triglyceride and high density lipoprotein cholesterol. For those individuals with ε2 genotype, there was no significant improvement in serum lipids after 12 weeks high intensity interval training interventions. Conclusion: The polymorphisms of apolipoprotein E gene resulted in different effects of exercise interventions on serum lipids of dyslipidemia. Twelve weeks high intensity interval training can be used as an intervention method to regulate serum lipids of dyslipidemia with ε3 and ε4 alleles.

Objective:To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. Methods: Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Results: Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P＜0.05 or P＜0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P＜0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P＜0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P＜0.05orP＜0.01). Conclusion: Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.

Objective:To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% Ⅲ° scald, and to provide experimental basis for the prevention and control of enterogenic infection. Methods: A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. Results: Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P＜0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P＜0.05 or P＜0.01). Conclusion: Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.

Objective:To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD). Methods: The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes. Results: Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P＜0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P＜ 0.05), and the neural network and dendritic junction were improved significantly. Conclusion: Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.

Objective:To clarify whether lycium barbarum polysaccharides (LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process. Methods: Eighteen SD rats were randomly divided into 3 groups ( n= 6): normal control group (NC), diabetes mellitus group (DM) and LBP-treatment group (DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin (STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage, once a day for 12 weeks. After the treatment, the weight and blood glucose, the generation of reactive oxygen species (ROS), the surviving retinal ganglion cells (RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected. Results: The successful rate of diabetic model was 100%. Compared with NC group, the rats of DM group caused weight loss, elevated blood glucose, a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells (P＜0.01), and these effects were diminished or abolished by LBP treatment. Meanwhile, LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats (P＜0.01). Conclusion: LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats, and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.

Objective:To observe the effects of AdipoRon orally on the functions of spleen and pancreas in type 2 diabetic mice, in order to present data for clinical application.Methods: Forty C57/BL6 male mice were randomly divided into 2 groups: normal control group (n=10) and model group (n=30), the former group was fed normally, while the later group was fed with high fat and sugar for 4 weeks.After that, type 2 diabetes model was established in DM group induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg).As type 2 diabetes model established successfully, the model mice were randomly divided into three groups (n=10): diabetes mellitus (DM) group, high dose of AdipoRon group (DM + H) and low dose of adiponRon group (DM + L).All the four groups were treated with saline, saline, AdipoRon at the doses of 20 mg/kg and 50 mg/kg by gavages respectively, once a day for 10 days.And then put them to death for collecting blood, pancreas and spleen.Pathological changes of pancreas were observed with a light microscope after HE staining.Protein contents of insulin receptor (INSR), insulin receptor substrate 1( IRS-1) and tumor necrosis factor-α(TNF-α) in pancreatic and spleen tissues were detected by ELISA.The protein level of phosphorylation insulin receptor substrate 1(p-IRS-1) in pancreas was determined by Western blot, and the expression of insulin mRNA in pancreas was tested by RT-PCR.Results: Under the light microscope, it was visible that the pancreatic tissue in NC group was full and closely packed, and the islet was big.Pancreatic tissue of DM mice was incompact and the islet of DM mice was smaller than that of normal mice.As for the mice treated with AdipoRon orally, the pancreatic tissue was full and closely arranged, and the islet was slightly smaller.Compared with NC group, the levels of TNF-α in pancreas and spleen of DM group were increased markedly, the levels of INSR and IRS-1 were decreased, the spleen coefficient, p-IR-1 protein level and insulin mRNA expression in pancreas were decreased, all were significant statistically (P＜0.05).Compared with DM group, the levels of TNF-α in pancreas and spleen of AdipoRon groups were decreased, the levels of INSR and IRS-1 in pancreas and spleen of AdipoRon groups were increased, while the spleen coefficient was increased (P＜0.05).The p-IRS-1 protein level and insulin mRNA expression in pancreas in DM+H group were increased (P＜0.05).Compared with DM + L group, the level of TNF-α was decreased, and the levels of INSR and IRS-1 were significantly increased (P＜0.05) in DM + H group (P＜0.05).Conclusion: Oral administration of AdipoRon can protect the spleen and pancreas of diabetic mice by decreasing the inflammatory response, up-regulating the expression of INSR, and increasing p-IRS-1 level in diabetic mice.

Objective:To observe the effects of Shenmai injection(SM) on p38MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion (I/R) in rats and to investigate the protective mechanism of SM. Methods: Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery (SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group, intestinal ischemia/reperfusion group(I/R group), Shenmai injection treated group (SM+I/R group). Lung wet/dry weight ratio(W/D), the contents of phosphatidylcholine (PC) and total phospholipid(TPL) which are the major ingredients of pulmonary surfactant were measured, as well as the expression levels of p38MAPK, Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method. Results: Compared with control group, lung W/D was significantly increased, the contents of PC and TPL were significantly decreased, the protein expression levels of p38MAPK, Bcl-2 and Bax were significantly increased in I/R group (all P＜0.01). But Bax protein expression was much greater than Bcl-2 protein expression, the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group (P＜0.01). Compared with I/R group, lung W/D was significantly decreased, while the contents of PC and TPL were significantly increased, the p38MAPK and Bax protein expression levels were significantly decreased in SM+I/R group (all P＜0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group (P＜0.01). The correlation analysis indicated that the expression level of p38MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax (r is -0.787 and -0.731, all P＜0.01). Conclusion: SM can protect the lung injury induced by intestinal I/R injury, which may be mediated by inhibiting the activation of p38MAPK, improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.

Objective:To investigate the effects of dexmedetomidine (DEX) on hippocampal neuron development process and the expressions of molecules in brain-derived neurotropic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. Methods: The hippocampal neurons were isolated from neonatal rats and cultured in vitro. The cells were seeded in 96-well plates,which were divided into 4 groups (control group, 1 μmol/L DEX treatment group, 5 μmol/L DEX treatment group, 50 μmol/L DEX treatment group), six wells were set in each group, and different concentrations of dexmedetomidine 1, 5 and 50 μmol/L were administered respectively. Cell viability was detected at 2, 4, 6, 8, and 10 d after treatment, and apoptosis was detected 10 days after treatment. The mRNA expression levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) were detected by q-PCR, and the expressions of BDNF, TrkB and N-methyl-D-aspartate receptor (NMDAR) protein were analyzed. Results: Compared with the control group, there was no significant difference in neuronal cell viability between the different doses of DEX treatment group. There was no significant difference in the expression of SYN and PSD95 mRNA and TrkB protein between the 1 μmol/L and 5 μmol/L DEX treatment groups (P＞0.05). The expression levels of SYN and PSD95 mRNA in the 50 μmol/L DEX group were increased significantly (P＜0.01), and the expression level of BDNF protein was up-regulated significantly (P＜0.01), the expression of the p-N-methyl-D-aspartate receptor was increased (P＜0.01). Conclusion: 50 μmol/L DEX has a certain effect on rat hippocampal neurons, which may be achieved by up-regulating the expression of BDNF and the phosphorylation level of N-methyl-D-aspartate receptor.

Objective:To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.Methods: The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively.Results: The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P＜0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P＜0.05).Conclusion: Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.

Objective:To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism.Methods: Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot.Results: Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups.Conclusion: These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.

Objective:To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test. Methods: The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed. Results: The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P＜0.05). The ARR difference value before and after captopril challenge test was lower ( P＜0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P＜0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors. Conclusion: The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.

Objective:To screen genes associated with poor prognosis of hepatocellular carcinoma (HCC) and to explore the clinical significance of these genes. Methods: The proper expression profile data of HCC was obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified by differential expression analysis. The DAVID and String database were used for function enrichment analysis and to construct the protein-protein interaction (PPI) network respectively. The Cancer Genome Atlas (TCGA) database and the Cox Proportional Hazard Model were used for prognosis analysis of the DEGs. Results: A eligible human HCC data set (GSE84402) met the requirements. A total of 1141 differentially expressed genes were identified, including 720 up-regulated and 421 down-regulated genes. The results of function enrichment analysis and PPI network performed that CDK1、CDC6、CCNA2、CHEK1、CENPE 、PIK3R1、RACGAP1、BIRC5、KIF11 and CYP2B6 were prognosis key genes. And the prognosis analysis showed that the expressions of CDC6、PIK3R1、KIF11 and RACGAP1 were increased, and the expression of CENPE was decreased, which was closely related to prognosis of HCC. Conclusion: CDC6、CENPE、PIK3R1、KIF11 and RACGAP1 may be closely related to poor prognosis of HCC, and can be used as molecular biomarkers for future research of HCC prognosis.