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Biomedical subjects

Gang Hu

Publications and source records attributed to Gang Hu.

At least 73 records · Page 4Linked to original sources

6-Hydroxydopamine-induced glutathione alteration occurs via glutathione enzyme system in primary cultured astrocytes.

AIM: To define the role of enzymes involved in glutathione metabolism in 6-hydroxydopamine (6-OHDA)-induced glutathione alteration in primary cultured astrocytes. METHODS: Total glutathione (GSx) levels were determined using the modified enzymatic microtiter plate assay. The mRNA levels of gamma-glutamylcysteine synthetase (gammaGCS), gamma-glutamyltransferase (gammaGT), glutathione peroxidase (GPx), GR(glutathione reductase), and glutathione transferases (GST) were determined using RT-PCR. gammaGT activity was determined using gammaGT assay kits. RESULTS: In primary cultured astrocytes, 6-OHDA induced a significant elevation of cellular GSx levels after treatment for 24 h. However, the GSx levels decreased after 24 h and the values were even lower than the value in the control group without 6-OHDA at 48 h. RT-PCR data showed that the mRNA levels of gammaGCS, the rate-limiting enzyme of gamma-L-glutamyl-L-cysteinylglycine (GSH) synthesis, were increased by 6-OHDA after treatment for 24 h and 48 h; the mRNA levels of GPx, GR, and GST did not alter in 6-OHDA-treated astrocytes after treatment for 24 h and 48 h; and 6-OHDA increased the mRNA levels and the activity of gammaGT after treatment for 48 h, which induced a decrease in GSx levels, despite the up-regulation of gammaGCS after exposure to 6-OHDA for 48 h. CONCLUSION: The change in gammaGCS correlated with the increase in GSH levels induced by 6-OHDA after treatment for 24 h. GSx levels decreased because of increased gammaGT mRNA levels and gammaGT activity induced by 6-OHDA after treatment for 48 h.

Animals↗

Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes.

OBJECTIVE: The aim of this study was to examine both single and joint associations of physical activity and conventional cardiovascular risk factors with total and cardiovascular mortality among patients with diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 3,708 Finnish patients with type 2 diabetes aged 25-74 years. Physical activity, smoking status, blood pressure, height, weight, and serum cholesterol level were determined at baseline. Cox proportional hazard models were used to estimate single and joint effects of physical activity and other cardiovascular risk factors on the risk of mortality. RESULTS: During a mean follow-up of 18.7 years, 1,423 deaths were recorded, 906 of which were due to cardiovascular disease. Moderate or high levels of physical activity were associated with decreased total and cardiovascular mortality, whereas higher levels of BMI and blood pressure and current smoking were associated with increased total and cardiovascular mortality. High serum cholesterol levels also increased cardiovascular mortality. The protective effect of physical activity was consistent in diabetic patients with any levels of BMI, blood pressure, total cholesterol, and smoking. CONCLUSIONS: A moderate or high level of physical activity was associated with a reduced risk of total and cardiovascular mortality among patients with type 2 diabetes. The favorable association of physical activity with longevity was observed regardless of the levels of BMI, blood pressure, total cholesterol, and smoking.

Adult↗

[Effects of enalapril on plasma Ang II level and the expression of AT1 in blood vessel and kidney of type 2 diabetic rats].

AIM: To study the plasma angiotensin II (Ang II) levels and the expressions of angiotensin II1 receptor (AT1) in blood vessels and kidneys in diabetic and high fat diet rats, and the effects of enalapril on plasma Ang II levels and the expressions of AT1 in blood vessels and kidneys in diabetic rats. METHODS: The plasma Ang II level was assayed with 125I-Ang II radioimmunoassay, and the expression of AT1 in blood vessel and kidney was analyzed with immunohistochemical technique. RESULTS: The plasma Ang II level was significantly higher in type 2 diabetic rats (241 +/- 49) pg x mL(-1) than that in the control (71 +/- 22) pg x mL , high fat diet group (151 +/- 29) pg x mL(-1) (P < 0.01) , and enalapril-treated groups (136 +/- 25) pg x mL(-1) (P < 0.05). The plasma Ang II levels in high fat diet and in enalapril-treated groups were also significantly higher than that in control group ( P < 0.01 ). With immunohistochemical technique, it was found that the expression of AT1 in endothelial cells of blood vessels, vascular smooth muscle cells, and kidneys in diabetic group increased. The expression of AT1 in endothelial cells of blood vessels, vascular smooth muscle cells, and kidney in enalapril-treated group was similar to that in control group. CONCLUSION: The plasma Ang II levels and the expression of AT1 in type 2 diabetic and high fat diet rats increased. Enalapril was shown to decrease the plasma Ang II level and downregulate the expression of AT1 in blood vessels and kidneys in type 2 diabetic rats.

Angiotensin II↗

[Expression and genetic immunization of hantaan virus G2 recombinant adenovirus].

AIM: To express hantaan virus(HTNV) envelope glycoprotein G(2) recombinant adenovirus(Adeno-G(2)) in vero E6 cells and explore its property of inducing immune response. METHODS: Vero E6 cells were infected with the HTNV Adeno-G(2) (100 MOI). The expression of Adeno-G(2) in the infected Vero E6 cells was detected by IFA. BALB/c mice were immunized with HTNV Adeno-G(2), then the immune response to Adeno-G(2) was tested by ELISA, microcell-culture neutralizing experiment and lymphocyte proliferation test (MTT colorimetry). RESULTS: IFA detection showed the expression of Adeno-G(2) in the infected Vero E6 cells. The titer of specific antibody was 1:40; The low-titer neutralization antibody was also detected. But the lymphocyte proliferation reaction was not notable. CONCLUSION: The HTNV Adeno-G(2) can stimulate BALB/c mice to develop specific humoral immune response instead of specific cell-mediated immunity. This study provides the experimental basis for the development of gene engineering vaccine of HFRS.

Adenoviridae↗

DRO1, a gene down-regulated by oncogenes, mediates growth inhibition in colon and pancreatic cancer cells.

Neoplastic progression in human tissues appears to be paralleled by a series of genetic and epigenetic alterations. In human colorectal cancers, defect Wnt/beta-catenin/T-cell factor and RAS/RAF signaling pathways have a major contributing role in tumor initiation and progression. To date, much of the research on the consequences of beta-catenin activation has been focused on genes whose expression is believed to be activated by beta-catenin-associated T-cell factor-dependent transcription. Little is known about genes whose expression may be down-regulated secondary to beta-catenin activation. Using a subtractive suppression hybridization approach, we identified a gene with markedly decreased expression in rat RK3E epithelial cells neoplastically transformed by beta-catenin. Because expression of this gene was also down-regulated in RK3E transformed by several other oncogenes, the gene was named DRO1 for "down-regulated by oncogenes 1." Compared with corresponding normal tissues, DRO1 expression was found to be very reduced in colon and pancreatic cancer cell lines as well as in most colorectal cancer specimens. The predicted DRO1 protein contains three repetitive elements with significant similarity to the carboxyl-terminal regions of the predicted proteins from DRS/SRPX/ETX1 and SRPUL genes, suggesting the existence of a new protein family. Ectopic expression of DRO1 in neoplastically transformed RK3E or colorectal and pancreatic cancer cell lines lacking endogenous DRO1 expression resulted in substantial inhibition of growth properties. DRO1 was found to suppress anchorage independent growth and to sensitize cells to anoikis and CD95-induced apoptosis. Our findings suggest that inhibition of DRO1 expression may be an important event in the development of colorectal and pancreatic cancers.

Amino Acid Sequence↗

Drift of rigidly rotating spirals under periodic and noisy illuminations.

Under the weak deformation approximation, the motion of rigidly rotating spirals induced by periodic and noisy illuminations are investigated analytically. We derive an approximate but explicit formula of the spiral drift velocity directly from the original reaction-diffusion equation. With this formula we are able to explain the main features in the periodic and noisy illuminations induced spiral drift problems. Numerical computations of the Oregonator model are carried out as well, and they agree with the main qualitative conclusions of our analytical results.

Journal Article↗

Effects of iptakalim hydrochloride, a novel KATP channel opener, on pulmonary vascular remodeling in hypoxic rats.

To investigate whether pulmonary artery remodeling could be prevented or not in hypoxic pulmonary hypertensive rats by treatment, the effects of iptakalim hydrochloride, a novel KATPCO, were evaluated. Iptakalim hydrochloride was orally administered at the doses of either 1.5 mg/kg/day or 0.75 mg/kg/day before their 4-week exposure to hypoxia (10% oxygen). It was demonstrated that iptakalim hydrochloride could reverse all pathological indices of pulmonary arterial remodeling and significantly reduce right ventricular hypertrophy in hypoxic rats. The reversal of hypoxic indices was dose-dependent, in which the higher dose of iptakalim hydrochloride reversed pathological indices more effectively than the lower dose did. This was further confirmed electrophysiologically using whole cell patch-clamp technique, which revealed that the outward potassium currents could be enhanced by iptakalim hydrochloride, and the decrease of K+ current density and increase of membrane capacitance could be reversed by chronic iptakalim hydrochloride treatment. These findings implied that iptakalim hydrochloride could play its role through activating plasmalemmal K+ channels of pulmonary arterial SMCs. The results indicated that iptakalim hydrochloride had anti-remodeling properties of pulmonary artery in hypoxic pulmonary hypertensive rats. It is therefore suggested that KATPCOs might be promising in the treatment of patients with hypoxic, and even possibly other forms of, pulmonary hypertension.

Analysis of Variance↗

Activities of cAMP-dependent protein kinase and protein kinase C are modulated by desensitized nicotinic receptors in the rat brain.

When rats were treated with different dosages of nicotine, nicotinic acetylcholine receptors (nAChRs) were observed in activated, sub-acute desensitized, acute desensitized, and chronic desensitized states. The activities of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) were assayed in the respective rat brains. The results showed that the activities of PKA and PKC could not be modified when brain nAChRs were in an activated state. However, the activities of PKA and PKC decreased when brain nAChRs were in a sub-acute state, an acute state or a chronic desensitized state induced by repeated administration of nicotine. These results suggest that desensitized nAChRs in the rat brain can inhibit the activities of PKA and PKC, which may be responsible for nicotine dependence.

Animals↗

Targeting ischemic stroke with a novel opener of ATP-sensitive potassium channels in the brain.

During cerebral ischemia, the opening of neuronal ATP-sensitive potassium channels (K(ATP) channels) affords intrinsic protection by regulating membrane potential. To augment this endogenous mechanism, we have synthesized iptakalim, a K(ATP) opener. Through K(ATP) channel activation, iptakalim affected multiple pathways of the glutamatergic system, limiting glutamate release and receptor actions, which are involved in excitotoxicity during ischemic damage. The molecule readily penetrated the brain and showed low toxicity in animal experiments. In different animal models of stroke as well as in cell cultures, iptakalim provided significant neuroprotection, not only in promoting behavioral recovery but also in protecting neurons against necrosis and apoptosis. This compound thus has promise as a neuroprotective drug for the treatment of stroke and other forms of neuronal damage.

Animals↗

Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from PC12 cells.

Parkinson's disease is characterized by an extensive loss of dopaminergic neurons in the substantia nigra pars compacta. The final common pathway in the demise of these cells may involve dopamine-dependent oxidative stress. Previous studies revealed a new neuronal protective role of ATP-sensitive potassium channel openers. But the exact mechanism is still unknown. In the present study, the neuroprotective effect of iptakalim, a novel ATP-sensitive potassium channel opener, was studied against rotenone-induced cytotoxicity in rat dopaminergic PC12 cells. Rotenone decreased cell viability significantly after 48 h exposure and induced dopamine release from PC12 cells concentration-dependently. Iptakalim significantly enhanced dopamine uptake and alleviated rotenone-induced PC12 cells death and reduced dopamine release induced by rotenone or GBR-12909, a classical dopamine transporter inhibitor. These results suggest that iptakalim may open mitochondrial K(ATP) channels to modulate dopamine transporter and reduce extracellular dopamine levels, thereby it protecting PC12 cells against rotenone-induced injury.

Adenosine Triphosphate↗

Occupational, commuting, and leisure-time physical activity in relation to total and cardiovascular mortality among Finnish subjects with type 2 diabetes.

BACKGROUND: Some previous studies have assessed the association between leisure-time physical activity and mortality among patients with diabetes, but the potential effect of occupational and commuting physical activity remains uncertain. METHODS AND RESULTS: We prospectively followed up 3316 Finnish participants 25 to 74 years of age with type 2 diabetes. The association of different types of physical activity with mortality was examined with Cox proportional-hazard models. During a mean follow-up of 18.4 years, 1410 deaths were recorded, 903 of which were due to cardiovascular disease (CVD). The multivariate-adjusted (age, sex, study year, body mass index, systolic blood pressure, cholesterol, smoking, and the 2 other types of physical activity) hazard ratios associated with light, moderate, and active work were 1.00, 0.86, and 0.60 (P(trend)<0.001) for total mortality and 1.00, 0.91, and 0.60 (P(trend)<0.001) for CVD mortality, respectively. The multivariate-adjusted hazard ratios associated with low, moderate, and high leisure-time physical activity were 1.00, 0.82, and 0.71 (P(trend)<0.001) for total mortality and 1.00, 0.83, and 0.67 (P(trend)=0.005) for CVD mortality, respectively. Active commuting had significant inverse associations with total and CVD mortality, but these relations were no longer significant after additional adjustment for occupational and leisure-time physical activity. CONCLUSIONS: Moderate or high levels of physical activity reduce total and CVD mortality among patients with type 2 diabetes. Not only leisure-time physical activity but also occupational and commuting physical activities are important components of a healthy lifestyle among patients with diabetes.

Cardiovascular Diseases↗

Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women.

BACKGROUND: Few studies have evaluated the associations between the metabolic syndrome (by any definition) and mortality. This study examined the age- and sex-specific prevalence of the metabolic syndrome and its association with all-cause and cardiovascular mortality in nondiabetic European men and women. METHODS: The study was based on 11 prospective European cohort studies comprising 6156 men and 5356 women without diabetes and aged from 30 to 89 years, and had a median follow-up of 8.8 years. A modification of the World Health Organization definition of the metabolic syndrome was used. The subjects were considered to have the metabolic syndrome if they had hyperinsulinemia and 2 or more of the following: obesity, hypertension, dyslipidemia, or impaired glucose regulation; however, other definitions were also studied. Hazard ratios for all-cause and cardiovascular mortality were estimated with Cox models in each cohort. Meta-analyses were performed to assess the overall association of the metabolic syndrome with mortality risk. RESULTS: The age-standardized prevalence of the metabolic syndrome was slightly higher in men (15.7%) than in women (14.2%). Of the 1119 deaths recorded during follow-up, 432 were caused by cardiovascular disease. The overall hazard ratios for all-cause and cardiovascular mortality in persons with the metabolic syndrome compared with persons without it were 1.44 (95% confidence interval [CI], 1.17-1.84) and 2.26 (95% CI, 1.61-3.17) in men and 1.38 (95% CI, 1.02-1.87) and 2.78 (95% CI, 1.57-4.94) in women after adjustment for age, blood cholesterol levels, and smoking. CONCLUSIONS: The overall prevalence of the metabolic syndrome in nondiabetic adult Europeans is 15%. Nondiabetic persons with the metabolic syndrome have an increased risk of death from all causes as well as cardiovascular disease.

Adult↗

Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation.

BACKGROUND: Sedentary lifestyle, obesity, and impaired glucose regulation are associated with the risk of type 2 diabetes. However, the joint associations of these risk factors are not known. METHODS: We prospectively followed up 2017 Finnish men and 2352 Finnish women aged between 45 and 64 years without a history of known or newly diagnosed diabetes at baseline. Single and joint associations of physical activity, body mass index (BMI), and blood glucose levels with risk of type 2 diabetes were examined using Cox proportional hazards models. RESULTS: During a mean follow-up of 9.4 years, there were 120 incident cases of type 2 diabetes. After adjustment for confounding factors (age, study year, sex, systolic blood pressure, smoking, and education), physical activity was found to be inversely associated with the risk of type 2 diabetes. This association was persistent in subjects with (1) both obesity and impaired glucose regulation, (2) either obesity or impaired glucose regulation, and (3) a normal BMI and glucose regulation. Similarly, the multivariate-adjusted positive association between BMI and risk of type 2 diabetes was consistently observed. Obesity in subjects who reported being inactive and had normal glucose levels was associated with an increased risk of diabetes compared with a normal BMI in subjects who reported being active and had impaired glucose regulation. CONCLUSIONS: Increasing physical activity can reduce the risk of type 2 diabetes. The protective effect of physical activity was observed in subjects with an excessive BMI and elevated glucose levels. Physical activity and weight control are critical factors in diabetes prevention in subjects with both normal and impaired blood glucose regulation.

Blood Glucose↗

Propagation of desynchronous disturbances in synchronized chaotic one-way coupled map lattices.

Propagations of desynchronous perturbations in synchronization processes of spatiotemporal chaos are investigated by considering chaotic one-way coupled map lattices. Under large coupling approximation the desynchronous area in time space is analytically calculated, based on the concepts of comoving Lyapunov exponent and absolute largest Lyapunov exponent. The ideas used in this paper are expected to be applicable to synchronizations of spatiotemporally chaotic systems of coupled maps and coupled oscillators with convective instability.

Journal Article↗

Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women.

CONTEXT: Only a few studies of coffee consumption and diabetes mellitus (DM) have been reported, even though coffee is the most consumed beverage in the world. OBJECTIVE: To determine the relationship between coffee consumption and the incidence of type 2 DM among Finnish individuals, who have the highest coffee consumption in the world. DESIGN, SETTING, AND PARTICIPANTS: A prospective study from combined surveys conducted in 1982, 1987, and 1992 of 6974 Finnish men and 7655 women aged 35 to 64 years without history of stroke, coronary heart disease, or DM at baseline, with 175 682 person-years of follow-up. Coffee consumption and other study parameters were determined at baseline using standardized measurements. MAIN OUTCOME MEASURES: Hazard ratios (HRs) for the incidence of type 2 DM were estimated for different levels of daily coffee consumption. RESULTS: During a mean follow-up of 12 years, there were 381 incident cases of type 2 DM. After adjustment for confounding factors (age, study year, body mass index, systolic blood pressure, education, occupational, commuting and leisure-time physical activity, alcohol and tea consumption, and smoking), the HRs of DM associated with the amount of coffee consumed daily (0-2, 3-4, 5-6, 7-9, > or =10 cups) were 1.00, 0.71 (95% confidence interval [CI], 0.48-1.05), 0.39 (95% CI, 0.25-0.60), 0.39 (95% CI, 0.20-0.74), and 0.21 (95% CI, 0.06-0.69) (P for trend<.001) in women, and 1.00, 0.73 (95% CI, 0.47-1.13), 0.70 (95% CI, 0.45-1.05), 0.67 (95% CI, 0.40-1.12), and 0.45 (95% CI, 0.25-0.81) (P for trend =.12) in men, respectively. In both sexes combined, the multivariate-adjusted inverse association was significant (P for trend <.001) and persisted when stratified by younger and older than 50 years; smokers and never smokers; healthy weight, overweight, and obese participants; alcohol drinker and nondrinker; and participants drinking filtered and nonfiltered coffee. CONCLUSION: Coffee drinking has a graded inverse association with the risk of type 2 DM; however, the reasons for this risk reduction associated with coffee remain unclear.

Adult↗

Reconstructing the diversification of subtilisins in the pathogenic fungus Metarhizium anisopliae.

Fungi secrete subtilisin proteinases to acquire nutrients and breach host barriers. Here we sought a global characterization of the diversity of subtilisins in the insect pathogen Metarhizium anisopliae. Expressed sequence tag (EST) analyses showed that a broad host range strain of M. anisopliae sf. anisopliae (strain 2575) expressed 11 subtilisins during growth on insect cuticle, the largest number of subtilisins reported from any fungus. Polymerase chain reaction amplified 10 of their orthologs from a second strain with multiple hosts (strain 820) and seven from the locust specialist M. anisopliae sf. acridum (strain 324). Analyses based on sequence similarities and exon-intron structure grouped M. anisopliae subtilisins into four clusters-a class I ("bacterial") subtilisin (Pr1C), and three clusters of proteinase K-like class II subtilisins: extracellular subfamily 1 (Pr1A, Pr1B, Pr1G, Pr1I and Pr1K), extracellular subfamily 2 (Pr1D, Pr1E, Pr1F and Pr1J) and an endocellular subtilisin (Pr1H). Phylogenetic analysis of homologous sequences from other genera revealed that this subdivision of proteinase K-like subtilisins into three subfamilies preceded speciation of major fungal lineages. However, diversification has continued during the evolution of Metarhizium subtilisins with evidence of gene duplication events after divergence of M. anisopliae sf. anisopliae and M. anisopliae sf. acridum. Comparing alignments and nonsynonymous/synonymous rates for Pr1 isoenzymes within a lineage and between lineages showed that while overall divergence of subtilisins followed neutral expectations, amino acids involved in catalysis were under strong selective constraint. This suggests that each Pr1 paralog contributes to the pathogens fitness. Furthermore, homology modeling predicted differences between the Pr1's in their secondary substrate specificities, adsorption properties to cuticle and alkaline stability, indicative of functional differences.

Amino Acid Sequence↗