To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

Adult ; Cladribine/therapeutic use* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.

Objective To establish a rat model of craniocerebral blast injury caused by the shock wave of cabin explosion.Methods Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups (10 each):3g,5g,8g TNT with vest groups,5g TNT without vest group and control group.Uncased explosives of different equivalent were suspended in the cabin center.After anesthesia,with exception of control group,the rats were placed in prone position about 31 cm below the explosive,facing the explosive with or without vest.After the explosion,the survived rats were observed,serological and pathological examinations were performed at 3h,1d and 3d after the explosion.Results In terms of tissue damage and mortality,compared with the control group,no obvious injury formed in rats of the 3g TNT with vest group,and all of them survived;Rats in 5g TNT with vest group showed mild lung injury,brain tissue edema,enlarged blood vessel,patchy hemorrhage on the brain surface,and with a mortality of 30％;Rats in 8g TNT with vest group showed serious organ damage with a mortality of 80％;Rats in 5g TNT without vest group suffered from severe lung injury,almost all died right after the explosion.Therefore,rats in 5g TNT with vest group were more in line with the experimental needs.Further serum and pathologic examinations showed that the brain water content increased,the serum neuron specific enolase (NSE) and S-100β protein also increased markedly,and necrotic or apoptotic changes happened in the cortex and hippocampus neurons.Conclusion A stable animal model of craniocerebral blast injury may be established with rats in the case of chest and abdomen protected and then exposed to 5g TNT explosion in cabin.

β3-adrenoceptor (β3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of β3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis assay. Furthermore, we investigated the NE-induced expression of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a β3-AR agonist and antagonist on expression of these marker genes. β3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the β3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti-apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK.
Adrenergic Agonists ; pharmacology ; Adrenergic Antagonists ; pharmacology ; Animals ; Apoptosis ; Cells, Cultured ; Myocytes, Cardiac ; drug effects ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

Vascular endothelial growth factor (VEGF) plays an important role in tissues angiogenesis. The adaptation of animals to hypoxic environment is relative to the microvessel density (MVD) in tissues. To further explore the adaptation mechanisms of plateau zokor (Myospalax baileyi) to the hypoxic-hypercapnic burrows, the VEGF mRNA and the MVD in cerebral tissues of the plateau zokor were studied. Total RNA was isolated from liver, and VEGF cDNA was obtained by RT-PCR, then the VEGF cDNA was cloned and sequenced. The coding sequence of plateau pika (Ochotona curzniae), rat (Rattus norvegicus) and mouse (Mus musculus) VEGF cDNA are obtained from GenBank, and the nucleotide and amino acid sequence homology of plateau zokor VEGF cDNA coding sequence with that of plateau pika, rat and mouse were analyzed and compared by using of bioinformatics software. The VEGF mRNA was detected by real-time PCR, and the MVDs in cerebral tissues of the plateau zokor, plateau pika and Sprague-Dawley (SD) rat were measured by immunohistochemical staining. The results showed that the open reading frame of the plateau zokor VEGF was 645 bp, and the coding sequence of the plateau zokor VEGF cDNA shared 92.1%, 93.6% and 93.8% nucleotide sequence homology to that of the plateau pika, rat and mouse, respectively. The deduced amino acid sequence of the plateau zokor VEGF cDNA was composed of 188 amino acids and the amino acids from 1 to 26 were signal peptide sequence. The plateau zokor VEGF188 was 90.2%, 94.9% and 94.4% homologous to that of plateau pika, rat and mouse. The level of VEGF mRNA in brain of the plateau zokor was significantly lower than that of SD rat, but there was no obvious difference in VEGF mRNA level between plateau zokor and plateau pika. The MVD in brain of the plateau zokor was markedly higher than that of plateau pika and SD rat. In conclusion, plateau zokor enhances its adaptation to the hypoxic environment by increasing the MVD. The level of VEGF mRNA in the brain of plateau zokor is lower than that of SD rat, which may be as a result of inhibition by the higher concentration of carbon dioxide in the burrow.
Adaptation, Physiological ; physiology ; Amino Acid Sequence ; Animals ; Arvicolinae ; physiology ; Base Sequence ; Brain ; blood supply ; metabolism ; Hypoxia ; physiopathology ; Microvessels ; anatomy & histology ; Molecular Sequence Data ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo investigate the association between matrix metalloproteinase 9 gene (MMP9) -1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.

METHODSA total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed.

RESULTSThe results showed that the frequency of CT and TT genotypes in patients with MI (27.67%) was significantly higher than that in controls (14.14%). The frequencies of the -1562T allele were 15.71% and 7.56% in the MI group and the control group respectively (chi-square=24.57, P<0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2.009, 95%CI: 1.250-3.230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3.714, 95%CI: 1.299-10.773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (chi-square=0.491, P=0.782).

CONCLUSIONThe -1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI. The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.

China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Matrix Metalloproteinase 9 ; genetics ; Middle Aged ; Myocardial Infarction ; enzymology ; genetics ; Polymorphism, Single Nucleotide

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling and development of atherosclerotic lesion. The potentially functional MMP-9 gene polymorphism may contribute to the susceptibility of acute coronary syndrome (ACS). This study aimed to investigate the association between two single nucleotide polymorphisms (-1562C>T, R279Q) of the MMP-9 gene in patients with ACS in the Uygur population of China. METHODS: This case-control study was composed of 361 ACS patients and 432 control subjects, who had undergone coronary angiography. Among the ACS patients, 162 (44.9％) had single-vessel disease, 145 (40.2％) had two-vessel disease, and 54 (14.9％) had three-vessel disease. The genotypes of the two selected SNPs were determined by the method of polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR). The relationship between the polymorphism of the MMP-9 gene and the severity of coronary arterial stenosis was analyzed. RESULTS: Analysis of the two SNPs showed that the frequency of CT and TT genotypes in patients with ACS was significantly higher than that in the control group (ACS vs. controls; CT+TT:25.5％ vs. 15.8％, P=0.001). And the -1562 gene allele (C/T) was significantly associated with acute coronary syndrome (ACS vs. controls; C allele: 85.7％ vs. 91.5％, T allele: 14.3％ vs. 8.5％, P<0.001). But the frequencies of CT+TT and CC genotypes were not statistically different among ACS patients with one, two and three or more significantly diseased vessels (P=0.55). The R279Q polymorphism site with regard to the association with ACS was not significant (P>0.05). The presence of CT or TT genotypes, assuming codominant effect of the T allele, was independently associated with increased risk of coronary artery disease when adjustment was made for age, body mass index, smoking, hypertension and diabetes mellitus [odds ratio=1.737 (95％ confidence interval, 1.337-2.257), P=0.018]. CONCLUSIONS: MMP-9-1562C>T polymorphism is associated with the susceptibility to ACS in the Uygur population of China. However, this mutation apparently is not related to the severity of coronary arterial stenosis. Another SNP (R279Q) polymorphism of MMP-9 is not significantly associated with the risk of ACS.

Objective To investigate the relationship between stroke and ankle-brachial index (ABI), pulse wave velocity (PWV) in Han, Uighur, and Kazakh populations of Xinjiang. Methods Data was from the investigation of cardiovascular risk survey (CRS) program among different nationalities in Xinjiang from October 2007 to March 2010. A total of 14 618 samples aged over 35 with complete data dimension were surveyed. Results ( 1 ) There were 633 patients with stroke, including 258 Hans (4.48%), 247 Uighurs (5.18%), and 128 Kazakhs (3.13%). The incidence of stroke was significant different in the three ethnic groups (P＜0.001). (2)Compared to the Han population, the incidence of stroke was higher ( OR= 1.304) in Uighur but lower (OR=0.794) in Kazakh. (3) PWV was significant different between stroke and non-stroke patients. After adjustment for age, body mass index, systolic blood pressure, triglyceride, total cholesterol and other risk factors, the difference remained significant, indicating that PWV (OR=1.001, P＜0.001) might associate with the occurrence of stroke. Conclusion The results of this study showed that the incidence of stroke was significantly different in the three ethnic groups. PWV might associate with the occurrence of stroke.

Objective To investigate the prevalence and distributing feature of chronic heart failure (CHF) in adult population of Xinjiang. Methods Four-stage random sampling method was used to analyze the prevalence and distributing feature of self-reported congestive heart failure among different nationalities in adult (35 years and over) population of Xinjiang. Sampling was collected from 6 localities ( Urumqi, Kelamayi, Fukang, Turfan Basin, Hetian, Yili Hazakh). Results A total of 8459 adults were surveyed. The prevalence of CHF was 1.26% in this cohort The prevalence of CHF was 0.89% , 1. 11% and 2. 14% * in Han, Uygur and Hazakh population, respectively ( * P <0. 05 vs. Han and Uygur). The risk of CHF was higher in the males than in the females ( 1. 61% vs. 0. 93% , u = 2. 79, P < 0. 05 ) . The prevalence of CHF increased in proportion with aging and was 0. 29% , 0. 60% , 1. 32% , 2. 55% and 4. 10% in 35 - 44, 45 - 54, 55 - 64, 65 - 74, 75 years and over age groups, respectively. Common complications of CHF were hypertension ( 63. 55% ), coronary heart disease ( 42. 99% ) , diabetes (18.69%), valvular heart disease (5.61%) and atrial fibrillation (4.67%). Conclusion The prevalence of CHF in Xinjiang was higher than the average level in China (0. 9% ) and was the highest in the Hazakh population.