Adult ; Genotype ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; blood ; genetics ; Pneumoconiosis ; blood ; genetics ; Polymorphism, Single Nucleotide

Prolyl-4-hydroxylase domain (PHDs) family is one of the most important regulatory factors in hypoxic stress. PHD2 plays a critical role in cells and tissues adaptation to the low oxygen environment. Its hydroxylation activity regulates the stability and transcriptional activity of the hypoxia-inducible factor 1 (HIF-1), which is the key factor in response to hypoxic stress. Subsequently, PHD2 acts as an important factor in oxygen homeostasis. Studies have shown that PHD2, through its regulation on HIF-1, plays an important role in the post-ischemic neovascularization. Furthermore, under hypoxic condition, PHD2 also regulates other pathways that positively regulate angiogenesis factors HIF-1 independently. Moreover, recently, several evidences have also shown that PHD2 also affects tumor growth and metastasis in a tumor microenvironment. Based on these facts, PHD2 have been considered as a potential therapeutic target both in treating ischemic diseases and tumors. Here, we review the molecular regulation mechanism of PHD2 and its physiological and pathological functions. We focus on the role of PHD2 in both therapeutic angiogenesis for ischemic disease and tumor angiogenesis, and the current progress in utilizing PHD2 as a therapeutic target.
Animals ; Humans ; Hydroxylation ; Hypoxia-Inducible Factor 1 ; metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; antagonists & inhibitors ; physiology ; Neoplasms ; blood supply ; metabolism ; pathology ; therapy ; Neovascularization, Pathologic ; metabolism ; pathology ; Tumor Microenvironment ; Vascular Diseases ; pathology ; therapy

0.05);2)After 12,24,36 months' treatment,BP was decreased significantly in each group (P0.05).Conclusion Both combined spirono- lactone/HCTZ and captopril/HCTZ significantly reduced BP and LVMI or LVMI and the maguitude of reduction was further enhanced after prolonged treatment.

Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.

OBJECTIVETo identify the expression characteristics of the 1700001022RIK (RIKEN cDNA 1700001022) gene in mice and explore its function by bioinformatic analysis.

METHODSUsing the expression profile of gene microarray, we detected the expression of a new testis-specific gene, 1700001022RIK, in mice. We analyzed its expression characteristics in the testis tissue and their changes in different developmental stages of the testis by RT-PCR, real-time RT-PCR, Western blot, and immunohistochemistry. We performed bioinformatic analysis using a bioinformatic software.

RESULTSThe 1700001022RIK gene was specifically expressed in the mouse testis in an age-dependent manner, most highly in the adult mice. The 1700001022RIK protein was mainly expressed in the spermatogonia, spermatocytes, and round spermatids of the adult mice. Bioinformatic analysis showed that the 1700001022RIK protein amino acid sequence had a high similarity in human and mice, which indicated that this gene was highly conserved in mammals.

CONCLUSION1700001022RIK is a testis-specific gene mainly expressed in the spermatogonia, spermatocytes, and round spermatids of seminiferous tubules, which might be involved in the regulation of spermatogenesis.

Age Factors ; Animals ; Blotting, Western ; Computational Biology ; DNA, Complementary ; Gene Expression ; Genomics ; Male ; Mice ; Molecular Chaperones ; genetics ; Seminiferous Tubules ; Spermatids ; Spermatocytes ; Spermatogenesis ; genetics ; Spermatogonia ; Testis

Objectives:To investigate the correlation between the systolic blood pressure variability and glomerular filtration rate in the elderly. Methods:From retired employees who participated in the third time physical examination of Kailuan group to underwent 24-hour ambulatory blood pressure monitoring. A total of 3 064 subjects aged over 60 years were recruited by cluster sampling method. 2 464 participants who met the inclusion were included and tested the renal function, with estimated glomerular filtration rate (eGFR) as indicators of renal function evaluation. Finally, 1 382 cases up to the standard. Multiviate regression models were performed to analyze the correlataion beteen short-term MMD and eGFR. Results:The mean age of 1 382 participants was (67.16±5.86) years, and 905 individuals (65.5%) were male. Levels of eGFR decreased with the increased of MMD (P＜0.05). Pearson correlation analysis indicated that eGFR was positively correlated with 24 hr-MMD、day-MMD and night-MMD(P＜0.05). Multivarite linear regrsssion analysis indicated that 24 hr-MMD、day-MMD were correlated with eGFR. Conclusions:24 hr-MMD、day-MMD are correlated with eGFR.

OBJECTIVETo explore the association between G614T single nuclear polymorphism (SNP) of the alpha-adducin gene and the antihypertensive effect of hydrochlorothiazide (HCTZ) in essential hypertensive (EH) patients.

METHODSEight hundred twenty nine EH patients were given 12.5 mg HCTZ/d for six weeks. Alpha-adducin gene G614T SNP in the tenth exon was determined by PCR-RFLP in 754 patients with complete records. All the patients were grouped according to TT, GT and GG genotypes.

RESULTSAfter 6 weeks of HCTZ treatment, the decreases in DBP and MAP of patients carrying 614T allele of alpha-adducin were significantly greater than that of those carrying GG homozygotes (P < 0.05). The decreases in SBP and MAP were significantly greater in patients with the TT genotype as compared with GT or GG genotype (P < 0.05). The effective rate of BP fall by HCTZ was higher in patients with TT genotype than those with GT or GG genotype (P < 0.05). Multivariate stepwise regression analysis showed that the TT genotype and the baseline SBP were the two major predictors affecting the decrease in SBP.

CONCLUSIONThe present study suggests that the alpha-adducin G614T polymorphism is associated with the antihypertensive effect of HCTZ, which is more effective in patients with TT genotype.

Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; Calmodulin-Binding Proteins ; genetics ; Female ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Single-Blind Method ; Treatment Outcome

OBJECTIVETo explore the relation of angiotensin-converting enzyme (ACE) gene polymorphism, angiotensin II type I receptor (ATIR) gene polymorphism and other factors on cerebral infarction.

METHODSOne thousand three hundred fifty-one subjects from Tangshan coalmine were enrolled with study method of cluster sampling. Face to face interviews were conducted to fill in questionnaires by trained interviewers. ACE gene, ATIR gene and inflammation factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, IL-10, C reactive protein (CRP), fibrinogen (Fg), fibrin monome polymerized velocity (FMPV), absorbance maximum (A(max)), FMPV/A(max), were measured.

RESULTSNo different prevalence rates of ACE genotype were found on cerebral infarction. The distributions of AA genotype of ATIR gene in the cerebral infarction was higher than that of the controls. The prevalence of AA genotype was higher than other groups, but the prevalence of combined genotype did not show much difference. Under the existence of factors that related to cerebral infarction, AA genotype frequencies were higher than those of non-smoking and with hypertension. IL-6, ATIR gene polymorphism, sex, FMPV/A(max) were strongly related to cerebral infarction. The level of IL-6 was higher than the normal ones.

CONCLUSIONSThe prevalence of cerebral infarction obviously increased in the hypertensive groups having AA genotype of ATIR gene. In the cerebral infarction groups, the level of IL-6 was higher than that in the normal population, indicating that these can be resulted from local inflammation and immunity reactivity. Environmental and genetic factors in the pathogenesis of cerebral infarction might have coordinating functions.

Aged ; Cerebral Infarction ; genetics ; Cross-Sectional Studies ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1 ; genetics

OBJECTIVETo explore the association between polymorphism in the ACE I/D gene and blood pressure-lowering response to hydrochlorothiazide (HCTZ) in 829 patients.

METHODSHCTZ 12.5 mg was taken once a day for six weeks. The blood pressure reduction and ratio reaching target blood pressure were compared in different ACE genotype groups.

RESULTSThe reduction in SBP of patients carrying DD was greater than that in other groups carrying II or ID (12.2 mmHg versus 5.4 mmHg, 12.2 mmHg versus 4.4 mmHg, respectively, P<0.05). The reduction in MAP of patients carrying DD was also greater than that in other groups carrying II or ID (6.9 mmHg versus 3.9 mmHg, 6.9 mmHg versus 3.6 mmHg, respectively, P<0.05). The ratio reaching target blood pressure in DD groups was significantly higher than that in II or ID groups (P<0.05). The pre-treatment SBP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of SBP. The pre-treatment DBP, aldosterone levels, DD genotype entered the multi-linear regression model significantly and might affect the reduction of DBP. The pre-treatment MAP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of MAP.

CONCLUSIONACE genotyping is associated with blood pressure-lowering response to HCTZ. Specific genotypes might be associated with the response to specific antihypertensive treatment.

Aged ; Alleles ; Antihypertensive Agents ; therapeutic use ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics

OBJECTIVETo investigate the relationship between baseline heart rate(HR) and all-cause death(ACD)in general population.

METHODS93 716 workers with heart rate between 40 bpm/min-120 bpm/min and without histories of stroke were selected from the '2006-2007 health examination records' in Kailuan and completed the electrocardiogram exam. Related information were also gathered. These subjects were followed up from July 2006 to December 2010, with the mean time of follow-up as 47.5±4.3 months. During the follow-up period, the occurrence of all-cause death was observed every half a year.

RESULTS(1)The lowest cumulative mortality rate was 1.61% in the group with 60-69 bpm/min. The lowest cumulative mortality rate was 1.78% in the group of 60-69 bpm/min in men. There was no death events observed in women with less than 50 bpm/min and the lowest cumulative mortality rate was 0.60% in the group of 80-89 bpm/min in women. (2)Data from Cox proportional hazard regression analysis showed that the RR(95%CI)of cumulative mortality rates in general population were 1.187 (1.039-1.336), 1.392(1.185-1.636), 1.733(1.404-2.139)and 2.716 (2.171-3.398)in the groups of 70-79, 80-89, 90-99 and ≥100 bpm/min, respectively. The RRs (95% CI) of cumulative mortality in men were 1.227(1.067-1.410), 1.481(1.254-1.750), 1.754 (1.406-2.188)and 2.831 (2.245-3.571) respectively. In women, when comparing with the group of 80-89 bpm/min, the RRs (95%CI)of all-cause death were 0.671(0.568-0.793), 0.825(0.703-0.970) and 1.925 (1.512-2.453)respectively in the groups of 60-69, 70-79 and ≥100 bpm/min.

CONCLUSIONWhen HR exceeding ≥70 bpm/min, the increase of HR would also increase the rate of ACD. Results of our study also showed a J-shaped curve relation between HR and mortality.

Adult ; Aged ; Asian Continental Ancestry Group ; Cause of Death ; China ; epidemiology ; Cohort Studies ; Electrocardiography ; statistics & numerical data ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Physical Examination ; statistics & numerical data ; Risk Factors