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Biomedical subjects

Qing Su

Publications and source records attributed to Qing Su.

11 recordsLinked to original sources

Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.

BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged&#x2009;&#x2265;&#x2009;40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (<&#x2009;55, 55-<65, 65-<75, &#x2265;&#x2009;75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction&#x2009;<&#x2009;0.05). Among participants aged&#x2009;<&#x2009;75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged&#x2009;<&#x2009;65 years and 160 mmHg in those aged 65-<75 years. Among those aged&#x2009;&#x2265;&#x2009;75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c&#x2009;&#x2265;&#x2009;9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C&#x2009;<&#x2009;1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged&#x2009;&#x2265;&#x2009;75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.

Humans↗

Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo.

MAGE-D1 is a member of the MAGE family of proteins, and functions as an adaptor that mediates multiple signaling pathways. The current study for the first time provides evidence for a role of MAGE-D1 in the negative regulation of angiogenic activity in vitro and in vivo models. Our findings showed that MAGE-D1 over-expression significantly suppressed the angiogenic key events such as endothelial cell migration and invasion, adhesion on collagen I substrate, and in vitro differentiation into tube-like structures under both normoxic and hypoxic conditions. MAGE-D1 over-expression also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. With further experiments, we revealed that MAGE-D1 over-expression disrupted actin cytoskeleton organization and lamellipodia formation, and down-regulated HIF-1-dependent gene expression in endothelial cells under hypoxic conditions. These findings demonstrate a new function of MAGE-D1 in the regulation of angiogenesis and provide new insight into the ability of MAGE-D1 to suppress the growth and angiogenic response of endothelial cells by interfering with HIF-1-dependent gene expression, and actin cytoskeleton reorganization, suggesting that MAGE-D1 might be a novel inhibitor of angiogenesis in vitro and in vivo.

Actins↗

Deletion of the V2 vasopressin receptor gene in two Chinese patients with nephrogenic diabetes insipidus.

BACKGROUND: Congenital nephrogenic diabetes insipidus (NDI) is a rare X-linked inherited disorder characterized by the excretion of large volumes of diluted urine and caused by mutations in arginine vasopressin receptor 2 (AVPR2) gene. To investigate the mutation of AVPR2 gene in a Chinese family with congenital NDI, we screened AVPR2 gene in two NDI patients and eight family members by PCR amplification and direct sequencing. RESULTS: Five specific fragments, covering entire coding sequence and their flanking intronic sequences of AVPR2 gene, were not observed in both patients, while those fragments were all detected in the control subjects. Several different fragments around the AVPR2 locus were amplified step by step. It was revealed that a genomic fragment of 5,995-bp, which contained the entire AVPR2 gene and the last exon (exon 22) of the C1 gene, was deleted and a 3-bp (GAG) was inserted. Examination of the other family members showed that the mothers and the grandmother were carriers for this deletion. CONCLUSION: Our findings suggest that the two patients in a Chinese family suffering from congenital NDI had a 5,995-bp deletion and 3-bp (GAG) insertion at Xq28. The deletion contained the entire AVPR2 gene and exon 22 of the C1 gene.

Adult↗

QSAR modeling of AT1 receptor antagonists using ANN.

Multiple linear regression (MLR) and artificial neural networks (ANN) have been used for structure-activity relationship analysis for a set of 113 AT1 receptor antagonists. The ANN model showed better performance with a 6-6-1 architecture than MLR. The results obtained from this study indicate that three descriptors, hydration energy (EH), n-octanol/water partition (LOGP), and energy of the lowest unoccupied molecular orbital (LUMO), play an important role on the activity of AT1 receptor antagonists with biphenyltetrazole structures. This information is pertinent to the further design of new AT1 receptor antagonists. 1 A plot of observed versus predicted PIC50 produced from the best nonlinear model using 6-6-1 architecture.

Angiotensin II Type 1 Receptor Blockers↗

Cysteine 390 mutation of the TSH receptor modulates its ectodomain as an inverse agonist on the serpentine domain with decrease in basal constitutive activity.

Mutations of individual cysteine residues at codon 301, 390, 398 and 408 of the thyrotropin receptor (TSHr) to serine resulted in cell surface expression of only C301S and C390S mutants. C390S mutation was a silencing mutation with decreased basal constitutive activity. Although the C301S and C390S mutants did not show any significant TSH binding, they generated cyclic AMP upon TSH stimulation. These mutants were also able to interact with stimulating and blocking anti-TSHr antibodies. In fact, C390S receptor is a more sensitive tool for blocking antibody detection than wild type receptor. Introduction of C390S to activating mutations in the ectodomain (S281N), exloop (I486F) and transmembrane (D633H) segments could not mute/nullify receptor activation. These data indicate that the C390S ectodomain behaves as a more effective inverse agonist on the noisy transmembrane segment and suggest that the basal and activated states of the receptor operate through two independent pathways.

Animals↗

[Studies on fingerprints of ant nest of Macrotermes annadalei from different areas].

OBJECTIVE: To study comparatively the fingerprint of zhuang medicinal material-ant nest of Macrotermes annadalei from different areas in Guangxi. METHOD: The fingerprint of total amino acid of 12 lots of ant nest of M. annadalei from different areas was determined by high speed amino acid analyzer. Separation was perform on anylytical column (4.6 mm x 40 mm), column temperature at 57 degrees C. The flow rate of buffering solution was 0.4 mL x min(-1), and the flow rate of ninhydrin was 0.3 mL x min(-1). RESULT: 18 characteristic peaks in the fingerprints were identified in 12 lots of samples, the chromatographic overlap rate was 89.4%-100.0%, and the total relative peak area of 7 lots of samples was over 52% in eight main peaks. CONCLUSION: The components of amino acid of ant nest of M. armadalei from different areas in Guangxi are very similar. The qualities of majority samples are good as well. The fingerprints can provide the useful information for the quality evaluation and the identification of ant nest of M. annadalei.

Amino Acids↗

Paraoxonase activity in Greek migrants and Anglo-Celtic persons in the Melbourne Collaborative Cohort Study: relationship to dietary markers.

BACKGROUND: Greek migrants to Australia have low all-cause and cardiovascular disease (CVD) mortality. This may be partly due to maintenance of a traditional Mediterranean diet and its interaction with CVD risk factors. The enzyme paraoxonase-1 (PON1) is thought to contribute to the anti-atherogenic properties of high density lipoproteins (HDL) by metabolizing lipid peroxides. PON1 activity is subject to modulation by dietary and genetic factors. AIMS: To determine PON1 activity in Greek migrants and Anglo-Celtic subjects recruited from the Melbourne Collaborative Cohort Study, and its relationship to coronary risk factors and dietary markers. METHODS: Greek (n = 127) and Anglo-Celtic (n = 128) participants in the MCCS were recruited. By design, there were approximately equal numbers of men and women and of diabetic and non-diabetic subjects. Subjects were screened for glucose tolerance, dyslipidaemia, hypertension and coronary heart disease. Plasma markers of diet (carotenoids, retinol, tocopherol, homocysteine) and inflammation (C-reactive protein) were assessed. Serum PON1 activity was determined spectrophotometrically using two substrates: paraoxon (paraoxonase) and phenylacetate (arylesterase). RESULTS: PON1 activity was significantly higher in the presence of hyperlipidaemia but otherwise did not vary by ethnicity, presence of coronary heart disease, diabetes, hypertension or smoking. Among subjects with the high activity phenotype (defined by the ratio of paraoxonase:arylesterase activity), paraoxonase activity correlated directly with circulating diet-derived carotenoid concentrations for Greeks, and inversely with homocysteine and C-reactive protein for Anglo-Celtics. No such associations were seen among subjects with the low activity phenotype. CONCLUSIONS: The data suggest that dietary modulation of atherosclerotic risk may vary according to PON1 phenotype.

Aryldialkylphosphatase↗

Inflammation and vascular endothelial activation in an Aboriginal population: relationships to coronary disease risk factors and nutritional markers.

OBJECTIVE: To describe the levels of inflammation and vascular endothelial activation in an Aboriginal community, and the relationship of these factors to coronary heart disease (CHD) risk factors and markers of nutritional quality. DESIGN AND PARTICIPANTS: A cross-sectional survey of 95 women and 76 men participating in a chronic-disease prevention program. SETTING: A remote Aboriginal community in Western Australia in 1996. MAIN OUTCOME MEASURES: Concentrations of markers of inflammation (C-reactive protein [CRP]) and vascular endothelial activation (soluble E-selectin [sE-selectin]); presence of metabolic syndrome; concentrations of diet-derived antioxidants. RESULTS: Participants exhibited very high plasma concentrations of CRP (mean, 5.4 mg/L; 95% CI, 4.6-6.3 mg/L) and sE-selectin (mean, 119 ng/mL; 95% CI, 111-128 ng/mL). Both CRP and sE-selectin concentrations were significantly higher in the presence of the metabolic syndrome. There were significant inverse linear relationships between concentrations of CRP and plasma concentrations of the antioxidants lycopene, beta-carotene, cryptoxanthin and retinol. Even stronger inverse associations were evident between concentrations of sE-selectin and lycopene, beta-carotene, cryptoxanthin and lutein. CONCLUSIONS: Vascular inflammation and endothelial activation may be important mediators of elevated CHD risk in Aboriginal people. Inadequate nutrition and physical inactivity may contribute to this process.

Adult↗

Low plasma concentrations of diet-derived antioxidants in association with microalbuminuria in Indigenous Australian populations.

Microalbuminuria is a risk factor for renal and cardiovascular diseases. Oxidant stress may contribute to vascular disease risk by promoting damage to renal and vascular tissues. This study examined the associations of plasma levels of diet-derived antioxidants with albuminuria in Australian population groups at high risk of renal and cardiovascular disease. Data on microalbuminuria and diet-derived plasma antioxidants were drawn from results of cross-sectional community-based risk factor surveys of Aboriginal and Torres Strait Islander peoples (n =698, 15 years and older). Prevalence of microalbuminuria ranged from 17-21%. After adjustment for age, gender, body mass index, diabetes, smoking status, plasma lipids and blood pressure, microalbuminuria was associated with significantly lower plasma concentrations of lycopene (-29%; P <0.001), beta-carotene (-22%; P <0.001), alpha-carotene (-22%; P <0.001) and cryptoxanthin (-17%; P <0.001) compared with normalbuminuric persons. Significant associations of microalbuminuria with plasma concentrations of alpha-tocopherol, retinol, lutein plus zeaxanthin and homocysteine were absent. The data are consistent with a protective effect of diets rich in carotenoids on vascular endothelium and/or renal tissues, and support the need for interventions to address affordable food supplies and dietary quality among Indigenous Australians.

Adolescent↗

Carotenoids: separation methods applicable to biological samples.

Epidemiologic and clinical studies have shown that a high intake of vegetables and fruit, with consequently high intakes and circulating concentrations of carotenoids, is associated with reduced risk of cardiovascular and other chronic diseases. The antioxidant properties of carotenoids are thought to contribute to these effects. The analysis of carotenoids in plasma, foods and tissues has thus become of interest in studies examining the role of diet in chronic disease prevention and management. High-performance liquid chromatography with ultra-violet or photodiode array detection is most often employed in routine use. We review these and other current methods for carotenoid analysis and information on sample stability relevant to epidemiological studies. The carotenoids remain an important and intriguing subject of study, with relevance to prevention of several important "lifestyle-related" diseases. Research into their physiological functions and their use as dietary markers requires sensitive, accurate and precise measurement. Further advances in these methodological areas will contribute to basic, clinical and public health research into the significance of carotenoid compounds in disease prevention.

Carotenoids↗

Cyclosporin A enhanced protection of nimodipine against brain damage induced by hypoxia-ischemia in mice and rats.

AIM: To study whether P-glycoprotein (P-gp) inhibitor cyclosporin A (CsA) enhanced the protection of nimodipine (NMD) against brain damage. METHOD: (1) After mice were given ip NMD alone or co-administration of CsA, survival time of mice were recorded following decapitation and ip injection of NaNO2, respectively. (2) After rats were given ip NMD alone or co-administration of CsA, 20 min forebrain ischemia induced by the technique of two-carotid occlusion plus hypovolemic hypotension. Following reperfusion of 1 h, the content of malondialdehyde (MDA), lactic acid (LA) and activity of lactic dehydrogenase (LDH) in cortex tissue were measured. (3) NMD level in brain was also determined after ip injection of NMD 2 mg/kg alone and co-administration of CsA, respectively. RESULTS: NMD showed potent pharmacological activity in the three models. The survival time of mice by decapitation and ip NaNO2 were significantly (P <0.05) prolonged after co-administration of CsA. In rat forebrain ischemia/reperfusion, levels of MDA, LA, and LDH by co-administration of CsA were greatly modified, compared with those of NMD alone group. The level of NMD in rat brain was increased markedly after co-administration of CsA. CONCLUSION: P-gp inhibitor CsA may enhance the protection of NMD against brain damage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗