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Biomedical subjects

Ming He

Publications and source records attributed to Ming He.

33 records · Page 2Linked to original sources

Macrocycle-derived functional xanthenes and progress towards concurrent detection of glucose and fructose.

The detection of saccharides in biological media is of great current importance for the monitoring of disease states. We have previously reported that solutions of boronic acid-functionalized macrocycles form acyclic oligomeric materials in situ. The oligomers contain fluorescent xanthene moieties. Current efforts are aimed at modulating the spectroscopic responses of these materials for the analysis of specific sugars. We describe conditions whereby the xanthene boronic acids exhibit high colorimetric fructose selectivity. In contrast, at physiological levels selective glucose monitoring can be achieved via fluorescence. Additionally, we describe a method which exhibits promise for detecting both glucose and fructose at dual wavelengths in the UV-Vis region. Mechanistic rationale for each of these findings is presented.

Blood Glucose↗

Effects of sasanquasaponin on ischemia and reperfusion injury in mouse hearts.

We investigated effects of sasanquasaponin (SQS), a traditional Chinese herb's effective component, on ischemia and reperfusion injury in mouse hearts and the possible role of intracellular Cl- homeostasis on SQS's protective effects during ischemia and reperfusion. An in vivo experimental ischemia model was made in mice (weight 27-45 g) using ligation of left anterior descending coronary artery, and in vitro models were made in perfused hearts by stopping flow or in isolated ventricular myocytes by hypoxia. The in vivo results showed that SQS inhibited cardiac arrhythmias during ischemia and reperfusion. Incidence of arrhythmias during ischemia and reperfusion, including ventricular premature beats and ventricular fibrillation, was significantly decreased in the SQS-pretreated group (P<0.05). Results in perfused hearts showed that SQS suppressed the arrhythmias, prevented against ischemia-induced decrease in contract force and promoted the force recovery from reperfusion. Furthermore, intracellular Cl- concentrations ([Cl-]i) were measured using a MQAE fluorescence method in isolated ventricular myocytes in vitro. SQS slightly decreased [Cl-]i in non-hypoxic myocytes and delayed the hypoxia/reoxygenation-induced increase in [Cl-]i during ischemia and reperfusion (P<0.05). Our results showed that SQS protected against ischemia/reperfusion-induced cardiac injury in mouse hearts and that modulation of intracellular Cl- homeostasis by SQS would play a role in its anti-arrhythmia effects during ischemia and reperfusion.

Action Potentials↗

[Protective effect and mechanism of pharmacologic preconditioning induced by sodium ferulate on primary cultured myocardial cell injury by anoxia/reoxygenation].

AIM: To study the preconditioning effects and mechanism of action of sodium ferulate (SF) on primary cultured myocardial cell injury induced by anoxia/reoxygenation. METHODS: Cultured myocardial cells of neonatal SD rats were randomly divided into ten groups: control group: without any treatment; anoxia/reoxygenation group (A/R), reoxygenation of 1 h following anoxia of 3 h; anoxia preconditioning group (AP), reoxygenation of 30 mins following anoxia of 30 mins, three times before the same procedure as group A/R; SF preconditioning groups, 20 mins of SF (1.68, 0.42, 0.105 mmol x L(-1) in final concentration) preconditioning followed by 10 mins wash out before A/R; K+ATP channel blocker group, NOS inhibitor group and PKC inhibitor group, adding gliberclamide, L-NAME, ploymyxin B at final concentration of 12 g x mL(-1), 50 micromol x L(-1), 50 micromol x L(-1), to culture medium respectively 10 min before the same procedures as SF preconditioning group (1.68 mmol x L(-1)). Myocardial cells pulse rate and rhythm, myocyte viability, the activity of LDH and CK in culture, the contents of intracelluar MDA, LD in myocardial cells, the activity of SOD and GSH-Px of the cultured myocardial cell were measured at the end of experiment. RESULTS: Compared with control group, anoxia/reoxygenation caused great increases of levels of LDH, CK, MDA and LD (P < 0.01), decreases of myocardial cells pulse rate, cell viability, SOD and GSH-Px (P < 0.01); SF preconditioning significantly attenualed these increases and decreases. Glib, L-NAME, and Ploy B partly abolished the effects of SF preconditioning. CONCLUSION: SF preconditioning is effective in protecting myocardial cells from anoxia injury. The cardioprotective effect of SF preconditioning is produced by multiple factors.

Animals↗

[Frequency stabilization of diode laser using zeeman spectra].

Zeeman split takes place for the hyperfine level structure of neutral atoms where magnetic field exists. In addition, being excited by right circularly polarized light and left circularly polarized light, atoms obey different transition rules. So, the absorption peak between the hyperfine Zeeman level shifts with respect to the absorption peak without magnetic field. Accordingly, the authors demonstrated a kind of simple and flexible method to stabilize the frequency of diode laser. The linewidth of diode laser was reduced to less than 1 MHz using this method. Through analyzing the experiment results, the authors found that when the sum of both shifts of the hyperfine level of atoms excited by right circularly polarized light and left circularly polarized light was equal to the FWHM (Full Width at Half Maximum) of the saturated absorption peak, the laser frequency was stabilized best.

Electrochemistry↗

Soluble CD40 ligand induces beta3 integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling.

We earlier reported that the soluble form of the CD40 ligand (sCD40L), is involved in thrombosis by stabilizing platelet thrombi. In this article, we have determined the mechanism by which this protein affects platelet biology. Addition of sCD40L to washed platelets was found to activate the receptor function of alphaIIbbeta3 as measured by the induction of fibrinogen binding and the formation of platelet microparticles. Mutation in the KGD sequence (D117E) of sCD40L, the alphaIIbbeta3-binding domain in the N terminus of the protein resulted in a loss of the platelet-stimulatory activity of this protein. Integrilin, a alphaIIbbeta3 antagonist, but not an antibody to CD40 that blocked the ligand-binding activity, inhibited these platelet-stimulatory events. CD40-/- platelets bound fibrinogen and formed microparticles similar to WT platelets, again indicating that CD40 is not involved in sCD40L-induced platelet activation. Exposure of platelets to sCD40L, but not D117E-sCD40L-coated surfaces, induced platelet thrombi formation under arterial shear rate. sCD40L-induced platelet stimulation resulted in the phosphorylation of tyrosine-759 in the cytoplasmic domain of beta3. Platelets from the diYF mouse strain, expressing beta3 in which both cytoplasmic tyrosines are mutated to phenylalanine, were defective in sCD40L-induced platelet stimulation. These data indicate that sCD40L is a primary platelet agonist and that platelet stimulation is induced by the binding of the KGD domain of sCD40L to alphaIIbbeta3, triggering outside-in signaling by tyrosine phosphorylation of beta3.

Animals↗

[The association of cyclin D1 (A870G) polymorphism with susceptibility to esophageal and cardiac cancer in north Chinese population].

OBJECTIVE: To investigate the association of Cyclin D1 (A870G) single nucleotide polymorphism (SNP) with the susceptibility to esophageal and cardiac cancer in northern Chinese population. METHODS: By polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP), the Cyclin D1 (A870G) genotyping was performed among 178 patients with esophageal or esophageal -gastric junction carcinoma (120 with esophageal squamous cell cancer and 58 with cardiac adenoma cancer) and 122 health controls. RESULTS: There were no significant differences in Cyclin D1 (A870G) allele frequencies between cancer patients and health controls (P = 0.075). There is no genotype distribution difference was found between non-smoker patients and controls (P > 0.05). The risk for esophageal and cardiac cancer is 2.5 times higher in A/A genotype carried smokers than that in A/G or G/G genotype carried non-smokers, with the adjusted Odd Ratio of 2.57 (95% confidence interval is 1.19 approximately 5.57). The G/G genotype reduces the susceptibility to esophageal cancer, with the adjusted Odd Ratio of 0.39 and 95% confidence interval of 0.18 - 0.82. The A/A frequency in cardiac patients (34.48%) is higher than that in health controls (23.77%) but the difference does not reach significant (P = 0.212). CONCLUSION: In northern Chinese population, the smoking individuals carrying Cyclin D1 (A870G) A/A genotype increase the susceptibility to esophageal and cardiac cancer. The G/G genotype probably plays a protecting role in the occurrence of esophageal cancer.

Adult↗

Association of cyclin D1 (G870A) polymorphism with susceptibility to esophageal and gastric cardiac carcinoma in a northern Chinese population.

Our aim was to investigate the association of cyclin D1 (G870A) single nucleotide polymorphism with susceptibility to esophageal and cardiac carcinoma in a northern Chinese population. By polymerase chain reaction-single strand conformation polymorphism analysis, cyclin D1 (G870A) genotyping was carried out among 120 patients with esophageal squamous cell carcinoma (ESCC), 87 patients with gastric cardiac adenocarcinoma (CAC), and 183 age- and gender-matched controls. The cyclin D1 genotype distribution among ESCC patients was significantly different from that among healthy controls (chi(2) = 7.372, p = 0.025). The G/G genotype was significantly less frequent among ESCC patients (9.2%) than among healthy controls (20.8%) (chi(2) = 7.192, p = 0.007). The G/G genotype significantly reduced risk for the development of ESCC compared to the combination of G/A and A/A genotypes (adjusted odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16-0.83). After stratification according to smoking status, the A/A frequency among smoking ESCC (34.3%) and CAC patients (35.7%) was significantly higher than that among smoking healthy controls (18.6%) (chi(2) = 5.426 and 5.599, p = 0.020 and 0.018, respectively). Smokers with the A/A genotype had an about 2-fold increased risk for both of ESCC and CAC compared to the G/A and G/G genotypes, with an adjusted OR of 2.26 in ESCC (95% CI = 1.14-4.49) and of 2.42 in CAC (95% CI = 1.17-4.98). No correlation between the cyclin D1 genotype and development of ESCC or CAC was found among nonsmokers. Determination of the cyclin D1 (G870A) single nucleotide polymorphism may be suitable to identify individuals with increased risk for ESCC or CAC in the northern Chinese population.

Adenocarcinoma↗

A T42M substitution in bacterial 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) generates enzymes with increased resistance to glyphosate.

Mutants of class I enolpyruvylshikimate 3-phosphate synthase (EPSPS) with resistance to glyphosate were produced in a previous study using the staggered extension process with aroA genes from S. typhimurium and E. coli. Two of these mutants shared a common amino acid substitution, T42M, near the hinge region between the large globular domains of EPSPS. Using site-directed mutagenisis, we produced the T42M mutants without the other amino acid changes of the original mutants. The T42M substitution alone produced enzymes with a 9- to 25-fold decreased K(m)[PEP] and a 21- to 26-fold increased K(i)[glyphosate] compared to the wild-type enzymes. These results provide more testimony for the powerful approach for protein engineering by the combination of directed evolution and rational design.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China.

AIM: To investigate the association of the NQO1 (C609T) polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China. METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls. RESULTS: The NQO1 C609T C/C, C/T and T/T genotype frequency among healthy controls was 31.5 %, 52.1 % and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (chi(2)=4.79, P=0.028). The NQO1 T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes, with an age, sex and smoking status adjusted odds ratio (OR) of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 % CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC. CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.

Adenocarcinoma↗

[p53 gene polymorphism with susceptibility to esophageal cancer and lung cancer in Chinese population].

OBJECTIVE: To investigate the association of p53 codon 72 polymorphism with susceptibility to esophageal cancer and lung cancer in the northern Chinese population. METHODS: p53 codon 72 genotyping was performed by amplifying DNA fragments with sequence specific primers among 173 patients with esophageal squamous cell carcinoma, 98 with non-small cell lung carcinoma as well as 136 healthy controls. RESULTS: No significant difference of p53 allelotype and genotype distribution was observed between esophageal cancer and lung cancer patients. The Pro allele frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.024 and 0.027 respectively). There were no significant differences in Pro/Arg and Arg/Arg genotype frequency among cancer patients and healthy controls (P > 0.05). However, the Pro/Pro genotype frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.041 and 0.026 respectively). The risk of Pro homozygotes for both esophageal cancer and lung cancer was about 2 times against Arg homozygotes with adjusted odds ratio of 2.12 (95% CI = 1.13 - 4.01) and 2.30 (95% CI = 1.13 - 4.93), respectively. There was no interaction between p53 Pro/Pro genotype and smoking status to the risk for esophageal cancer and lung cancer. CONCLUSION: In the northern Chinese population, p53 Pro/Pro genotype is an independent risk factor for both esophageal cancer and lung cancer. The possible common genetic basis of the development of these two cancers is suggested by this study.

Alleles↗

[The NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and susceptibility to esophageal cancer].

OBJECTIVE: To investigate the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern Chinese population. METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis in 193 patients with ESCC and 141 unrelated healthy controls. RESULTS: The frequency of the T allele (null) among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.86, P=0.028). The NQO1 C/C and C/T genotype distribution among ESCC patients was not significantly different from that among healthy controls (Chi-square= 2.27 and 0.127; P=0.132 and 0.721, respectively). However, the T/T genotype frequency among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.39, P=0.036). The NQO1 T/T genotype significantly increased the risk for developing ESCC, compared to the combination of C/C and C/T genotypes, with the adjusted odds ratio (OR) of 1.81 (95%CI: 1.04-3.15). This increased susceptibility exhibited pronouncedly in patients with family history of upper gastrointestinal cancers (adjusted OR=2.22, 95%CI 1.18-4.17). CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate high-risk individuals for ESCC.

Esophageal Neoplasms↗

Chromophore formation in resorcinarene solutions and the visual detection of mono- and oligosaccharides.

The colorimetric properties of resorcinarene solutions had not been investigated since Baeyer's initial synthesis. We recently reported that solutions containing resorcinarene macrocycles develop color upon heating or standing. In the presence of saccharides, these solutions exhibit significant color changes which are easily seen. We herein present strong evidence that the solution color is due to macrocycle ring opening and oxidation. The optical responses to saccharides are due to complexation of the sugar with the acyclic chromophores. We apply these mechanistic insights toward the challenging problem of the visual detection of neutral oligosaccharides by simple chromogens. In addition, we also report the first single-crystal X-ray crystal structure determination of a rarely observed "diamond" resorcinarene stereoisomer.

Boronic Acids↗

A mutant P53 can activate apoptosis through a mechanism distinct from those induced by wild type P53.

A common mutation in P53 protein occurs at amino acid residue 281 in the DNA binding domain (P53(gly(281))), which results in loss of transcriptional regulation of P53 target genes and has been reported to gain pro-oncogenic functions. In the present study, we investigated the activity of P53(gly(281)) in P53-null PC3 human prostate cancer cells and found that the P53(gly(281)) induced apoptosis as efficiently as the wild-type P53 (wtP53). However, in contrast to wtP53-induced apoptosis, the P53(gly(281))-induced apoptosis was insensitive to overexpression of bcl-2. Thus, our findings indicate that while a mutation in the DNA binding domain of p53 may result in a more oncogenic form of the protein, it may also paradoxically result in the 'gain' of a new, alternative pathway for apoptosis.

Apoptosis↗

CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism.

CD40L, a member of the tumor necrosis factor family of ligands, plays a major role in immune responses via its receptor, CD40. Recently, CD40L has been detected on the surfaces of activated platelets and shown to activate endothelium. Here we further addressed the function of platelet CD40L. We show that absence of CD40L affects the stability of arterial thrombi and delays arterial occlusion in vivo. Infusion of recombinant soluble (rs)CD40L restored normal thrombosis, whereas rsCD40L lacking the KGD integrin-recognition sequence did not. CD40-deficient mice exhibited normal thrombogenesis. rsCD40L specifically bound to purified integrin alphaIIbbeta3 and to activated platelets in a beta3-dependent manner and induced platelet spreading. In addition, rsCD40L promoted the aggregation of either human or mouse platelets under high shear rates. Thus, CD40L appears to be an alphaIIbbeta3 ligand, a platelet agonist, and necessary for stability of arterial thrombi.

Animals↗