Publications by authors named "YaoGang Zhang"

8 Publications

  • Page 1 of 1

Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes.

Mol Genet Genomic Med 2021 Aug 22;9(8):e1728. Epub 2021 Jun 22.

ChinovoLaboratory, Beijing, P. R. China.

Background: Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost-effective clinical diagnostic method.

Methods: A 4-year-old boy was preliminarily diagnosed with putative Leigh syndrome based on the clinical presentation. PDHC activity in peripheral blood leukocytes and a corresponding gene analysis were subsequently undertaken. Sodium pyruvate 1- C was used for the analysis of PDHC activity in peripheral leukocytes. The genes encoding PDHC were then scanned for mutations.

Results: The results showed that the corresponding PDHC activity was dramatically decreased to 10.5 nmol/h/mg protein as compared with that of healthy controls (124.6 ± 7.1 nmol/h/mg). The ratio of PDHC to citrate synthase was 2.1% (control: 425.3 ± 27.1). The mutation analysis led to the identification of a missense mutation, NM_000284.4:g214C>T, in exon 3 of PDHC.

Conclusion: The peripheral blood leukocyte PDHC activity assay may provide a practical enzymatic diagnostic method for PDHC-related mitochondrial diseases.
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http://dx.doi.org/10.1002/mgg3.1728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404224PMC
August 2021

Lactate Modulates Cellular Metabolism Through Histone Lactylation-Mediated Gene Expression in Non-Small Cell Lung Cancer.

Front Oncol 2021 2;11:647559. Epub 2021 Jun 2.

Department of Scientific Research Office, Affiliated Hospital of Qinghai University, Xining, China.

Lactate has been observed to fuel TCA cycle and is associated with cancer progression in human lung cancer, the leading cause of cancer deaths worldwide, but the effect of lactate on lung cancer metabolism is rarely reported. In this study, disordered metabolism in non-small cell lung cancer was demonstrated by increased G6PD and SDHA protein levels immunofluorescence, and up-regulated lactate dehydrogenase was found to be associated with poor prognosis. Then flow cytometry and Seahorse XFe analyzer were utilized to detect the effect of lactate on glycolysis and mitochondrial function in non-small cell lung cancer cells. The results show that in non-small cell lung cancer cells lactate attenuates glucose uptake and glycolysis while maintaining mitochondrial homeostasis as indicated by improved mitochondrial membrane potential. Further exploration found that mRNA levels of glycolytic enzymes (, ) and TCA cycle enzymes (, ) are respectively down-regulated and up-regulated by lactate, and increased histone lactylation was observed in promoters of and chromatin immunoprecipitation assay. Taken together, the above results indicate that lactate modulates cellular metabolism at least in part through histone lactylation-mediated gene expression in non-small cell lung cancer.
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http://dx.doi.org/10.3389/fonc.2021.647559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208031PMC
June 2021

microRNA-125b-5p is a promising novel plasma biomarker for alveolar echinococcosis in patients from the southern province of Qinghai.

BMC Infect Dis 2021 Mar 7;21(1):246. Epub 2021 Mar 7.

The Echinococcosis Key Laboratory of Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai Province, China.

Background: Alveolar echinococcosis (AE) is caused by parasitic infection by Echinococcus multilocularis. Its diagnosis is usually based on clinical symptoms, ultrasound, and other imaging methods. MicroRNAs (miRNAs) play important roles in disease processes and can exist in a highly stable cell-free form in body fluids. It is important to identify specific, sensitive diagnostic markers for early diagnosis and evaluation of AE. In this study, we examined hsa-miR-125b-5p as a potential plasma biomarker of E. multilocularis infection.

Methods: Plasma samples from patients with AE and healthy individuals were screened for the presence of five miRNAs using miRNA chips. We used quantitative polymerase chain reaction to measure miRNA expression levels in plasma and liver tissue samples from patients with AE.

Results: hsa-miR-125b-5p was stably upregulated in the plasma and liver tissue samples from patients with AE.

Conclusions: The results suggest that hsa-miR-125b-5p may be a promising biomarker for early, non-invasive diagnosis of AE.
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http://dx.doi.org/10.1186/s12879-021-05940-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938541PMC
March 2021

High-concentration homocysteine inhibits mitochondrial respiration function and production of reactive oxygen species in neuron cells.

J Stroke Cerebrovasc Dis 2020 Oct 28;29(10):105109. Epub 2020 Jul 28.

Central Laboratory, Affiliated Hospital of Qinghai University, Tongren Road 29, Xining, Qinghai Province, China, 810000. Electronic address:

Objective: Homocysteine plays critical roles in cellular redox homeostasis, and hyperhomocysteinemia has been associated with multiple diseases, including neurological disorders involving reactive oxygen species-inducing and pro-inflammatory effects of homocysteine that are related to mitochondria. This study investigated the role of homocysteine in regulating mitochondria of neuron cell lines.

Methods: Neuron cells were pre-treated with homocysteine, and then flow cytometry was used to detect reactive oxygen species production and mitochondrial membrane potential, while Seahorse XFp Mito stress assay was used to comprehensively analyze mitochondrial function.

Results: The experimental results showed that high-concentration homocysteine diminished carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone-stimulated oxygen consumption rate and mitochondrial spare respiration capacity in a time- and concentration-dependent manner, and homocysteine also reduced reactive oxygen species in cultured neuron cell lines while no changes in mitochondrial membrane potential were observed.

Conclusion: These results indicate that homocysteine diminished mitochondrial respiration function in neuron cell lines mediated by its reactive oxygen species-reducing effects, which may underlie the association between hyperhomocysteinemia and human diseases.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105109DOI Listing
October 2020

Systematic Modulation of Charge Transport in Molecular Devices through Facile Control of Molecule-Electrode Coupling Using a Double Self-Assembled Monolayer Nanowire Junction.

J Am Chem Soc 2020 May 14;142(21):9708-9717. Epub 2020 May 14.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University & Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.

We report a novel solid-state molecular device structure based on double self-assembled monolayers (D-SAM) incorporated into the suspended nanowire architecture to form a "Au|SAM-1||SAM-2|Au" junction. Using commercially available thiol molecules that are devoid of synthetic difficulty, we constructed a "Au|S-(CH)-ferrocene||SAM-2|Au" junction with various lengths and chemical structures of SAM-2 to tune the coupling between the ferrocene conductive molecular orbital and electrode of the junction. Combining low noise and a wide temperature range measurement, we demonstrated systematically modulated conduction depending on the length and chemical nature of SAM-2. Meanwhile, the transport mechanism transition from tunneling to hopping and the intermediate state accompanied by the current fluctuation due to the coexistence of the hopping and tunneling transport channels were observed. Considering the versatility of this solid-state D-SAM in modulating the electrode-molecule interface and electroactive groups, this strategy thus provides a novel facile strategy for tailorable nanoscale charge transport studies and functional molecular devices.
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http://dx.doi.org/10.1021/jacs.0c02215DOI Listing
May 2020

The association between homocysteine and ischemic stroke subtypes in Chinese: A meta-analysis.

Medicine (Baltimore) 2020 Mar;99(12):e19467

Qinghai University Affiliated Hospital, Xining, Qinghai Province.

Background: The findings on the association between elevated plasma homocysteine levels and the risk of the trial of org 10172 in acute stroke treatment (TOAST) of ischemic stroke have been inconsistent in Chinese. So far, there is no meta-analysis about the association between Hcy and the TOAST subtypes of ischemic stroke in Chinese. This study; therefore, aimed to evaluate whether elevated homocysteine levels are associated with the TOAST subtypes of ischemic stroke using a meta-analysis.

Materials And Methods: A systematic search of electronic databases were conducted for studies reporting homocysteine levels in ischemic stroke and the TOAST of ischemic stroke to April 18, 2018. The data were extracted after the application of inclusion and exclusion criteria. All the data were analyzed using Stata software version 9.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables.

Results: Thirteen studies comprising 3114 participants (2243 patients and 871controls) met the eligibility criteria and were included in the meta-analysis. The meta-analysis revealed that the ischemic stroke group had significantly higher levels of homocysteine than controls (SMD = 1.15, 95% CI = 0.85-1.45, P < .05). The subgroup analyses suggested that the groups of patients with large-artery atherosclerosis, small-vessel occlusion, cardioembolism, stroke of other determined etiology and stroke of undetermined etiology had significantly higher levels of homocysteine compared to those in the control group (large-artery atherosclerosis: SMD = 2.12, 95% CI = 1.40-2.84, P < .05; small-vessel occlusion: SMD = 1.10, 95% CI = 0.72-1.48, P < .05; CE: SMD = 1.17, 95% CI = 0.64-1.71, P < .05; stroke of other determined etiology: SMD = 0.88, 95% CI = 0.53-1.24, P < .05; stroke of undetermined etiology: SMD = 1.50, 95% CI = 0.66-2.33, P < .05, respectively).

Conclusion: This meta-analysis found that ischemic stroke patients and the TOAST of ischemic stroke patients in Chinese had significantly higher homocysteine levels than the controls, suggesting that serum homocysteine levels may be a risk factor for ischemic stroke and the TOAST subtypes of ischemic stroke in Chinese.
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http://dx.doi.org/10.1097/MD.0000000000019467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220264PMC
March 2020

Improvement of Antialveolar Echinococcosis Efficacy of Albendazole by a Novel Nanocrystalline Formulation with Enhanced Oral Bioavailability.

ACS Infect Dis 2020 05 17;6(5):802-810. Epub 2019 Oct 17.

School of Pharmaceutical Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, and Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. China.

Alveolar echinococcosis (AE) is a chronic infectious parasitic disease that is fatal and still being neglected. Currently, the AE treatment recommended by the WHO is complete excision of the lesions, followed by the oral administration of albendazole (ABZ), the only effective first-line anti-AE drug, for two years. Unfortunately, complete excision of AE lesions is impossible in most cases, leaving the long-term use of ABZ as the only alternative. However, only about one-third of patients experience complete remission or cure with such treatments, largely because of the low oral bioavailability of ABZ caused by its very low solubility. To improve the oral bioavailability of ABZ, a novel nanocrystalline (NC) formulation of ABZ was obtained by spray-drying ABZ with a triblock copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Poloxamer 188), and its physical structure was confirmed by scanning electron microscopy (SEM), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXRD), and polarized optical microscopy (POM). The significantly reduced ABZ crystallite size coupled with prolonged ABZ supersaturation significantly improved the drug dissolution performance compared with that of the commercial ABZ oral product (Albenda), and the NC formulation showed an approximately 4.2-fold higher AUC than Albenda in a pharmacokinetic comparison in Beagle dogs as measured by the plasma concentration of albendazole sulfoxide, the active antiparasitic metabolite. Even more encouragingly, after 30 days of once-daily oral administration of the NC and Albenda formulations to SD rats with hepatic alveolar echinococcosis, the NC formulation demonstrated a cyst inhibition effect 3.7-fold greater than that of Albenda. We therefore conclude that the NC formulation could potentially be developed into an improved anti-AE drug therapy.
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http://dx.doi.org/10.1021/acsinfecdis.9b00231DOI Listing
May 2020

Franck-Condon Blockade and Aggregation-Modulated Conductance in Molecular Devices Using Aggregation-Induced Emission-Active Molecules.

Angew Chem Int Ed Engl 2019 Apr 26;58(18):5951-5955. Epub 2019 Mar 26.

Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Physics and Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, P. R. China.

We report an effective modulation of the quantum transport in molecular junctions consisting of aggregation-induced-emission(AIE)-active molecules. Theoretical simulations based on combined density functional theory and rate-equation method calculations show that the low-bias conductance of the junction with a single tetraphenylethylene (TPE) molecule can be completely suppressed by strong electron-vibration couplings, that is, the Franck-Condon blockade effect. It is mainly associated with the low-energy vibration modes, which is also the origin of the fluorescence quenching of the AIE molecule in solution. We further found that the conductance of the junction can be lifted by restraining the internal motion of the TPE molecule by either methyl substitution on the phenyl group or by aggregation, a mechanism similar to the AIE process. The present work demonstrates the correlation between optical processes of molecules and quantum transport in their junction, and thus opens up a new avenue for the application of AIE-type molecules in molecular electronics and functional devices.
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http://dx.doi.org/10.1002/anie.201900731DOI Listing
April 2019
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