Publications by authors named "Guobin Huang"

7 Publications

  • Page 1 of 1

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

Biochem Biophys Res Commun 2021 Aug 12;567:9-16. Epub 2021 Jun 12.

State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.015DOI Listing
August 2021

Quantitative Fluorescent Hybridization Reveals Differential Transcription Profile Sharpening of Endocytic Proteins in Cochlear Hair Cells Upon Maturation.

Front Cell Neurosci 2021 26;15:643517. Epub 2021 Feb 26.

Center for Integrative Physiology and Molecular Medicine, School of Medicine, Department of Biophysics, Saarland University, Homburg, Germany.

The organ of Corti (OC) comprises two types of sensory cells: outer hair cells (OHCs) and inner hair cells (IHCs). While both are mechanotransducers, OHCs serve as cochlear amplifiers, whereas IHCs transform sound into transmitter release. Reliable sound encoding is ensured by indefatigable exocytosis of synaptic vesicles associated with efficient replenishment of the vesicle pool. Vesicle reformation requires retrieval of vesicle membrane from the hair cell's membrane via endocytosis. So far, the protein machinery for endocytosis in pre-mature and terminally differentiated hair cells has only partially been deciphered. Here, we studied three endocytic proteins, dynamin-1, dynamin-3, and endophilin-A1, by assessing their transcription profiles in pre-mature and mature mouse OCs. State-of-the-art RNAscope fluorescent hybridization () of whole-mount OCs was used for quantification of target mRNAs on single-cell level. We found that pre-mature IHCs contained more mRNA transcripts of (encoding dynamin-1) and (endophilin-A1), but less of (dynamin-3) than OHCs. These differential transcription profiles between OHCs and IHCs were sharpened upon maturation. It is noteworthy that low but heterogeneous signal numbers were found between individual negative controls, which highlights the importance of corresponding analyses in RNAscope assays. Complementary immunolabeling revealed strong expression of dynamin-1 in the soma of mature IHCs, which was much weaker in pre-mature IHCs. By contrast, dynamin-3 was predominantly found in the soma and at the border of the cuticular plates of pre-mature and mature OHCs. In summary, using quantitative RNAscope FISH and immunohistochemistry on whole-mount tissue of both pre-mature and mature OCs, we disclosed the cellular upregulation of endocytic proteins at the level of transcription/translation during terminal differentiation of the OC. Dynamin-1 and endophilin-A1 likely contribute to the strengthening of the endocytic machinery in IHCs after the onset of hearing, whereas expression of dynamin-3 at the cuticular plate of pre-mature and mature OHCs suggests its possible involvement in activity-independent apical endocytosis.
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http://dx.doi.org/10.3389/fncel.2021.643517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952526PMC
February 2021

Generation of Chicken IgY against SARS-COV-2 Spike Protein and Epitope Mapping.

J Immunol Res 2020 17;2020:9465398. Epub 2020 Oct 17.

Huamin Medicine Co Ltd., Zhuhai, China.

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.
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http://dx.doi.org/10.1155/2020/9465398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568776PMC
November 2020

Role of Chromatin Remodeling Genes and TETs in the Development of Human Midbrain Dopaminergic Neurons.

Stem Cell Rev Rep 2020 08;16(4):718-729

Center for Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, No.9, Tujialing, Wuchang District, Wuhan, 430064, Hubei, China.

Understanding epigenetic regulation in the differentiation and maturation of dopaminergic neurons is critical to improve and develop new medications for Parkinson's disease (PD). To explore the role of ten-eleven translocation (TETs) family of dioxygenases and chromatin remodeling genes in the development of human midbrain dopaminergic (mDA) neurons, we globally analyze the epigenetic regulation of gene expression in human induced pluripotent stem cells (iPSCs) and iPSCs-derived mDA neurons. During the conversion of iPSCs into neuronal lineages of dopaminergic progenitors and mDA neurons, the expression patterns of epigenetic genes in multiple sets alter significantly. Vitamin C, an activator of TET enzymes, increases hydroxymethylcytosine (5hmC) level along with a higher yield of mDA neurons. Additionally, vitamin C treatment elevates gene expressions of TET2/3 and vitamin C transporters. Importantly, functional arrays indicate that vitamin C can promote neuronal maturation, synaptic activity, and dopamine release. Collectively, our study demonstrates that chromatin remodeling genes and the TET-5hmC pathway, which is regulated by vitamin C, are critical for the vital developmental stages of human mDA neurons.
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http://dx.doi.org/10.1007/s12015-020-09972-xDOI Listing
August 2020

The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex.

Sci Rep 2015 Aug 26;5:13403. Epub 2015 Aug 26.

State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.

The exosome is a complex with exoribonuclease activity that regulates RNA surveillance and turnover. The exosome also plays a role in regulating the degradation of precursor mRNAs to maintain the expression of splicing variants. In Neurospora, the silencing of rrp44, which encodes the catalytic subunit of the exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and SR protein related genes. The knockdown of rrp44 also affected the assembly of the spliceosome. RNA-seq analysis revealed a global change in bulk splicing events. Exosome-mediated splicing may regulate alternative splicing of NCU05290, NCU07421 and the circadian clock gene frequency (frq). The knockdown of rrp44 led to an increased ratio of splicing variants without intron 6 (I-6) and shorter protein isoform small FRQ (s-FRQ) as a consequence. These findings suggest that the exosome controls splicing events by regulating the degradation of precursor mRNAs and the gene expression, assembly and function of the spliceosome.
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http://dx.doi.org/10.1038/srep13403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549623PMC
August 2015

Total synthesis of N-malayamycin A and related bicyclic purine and pyrimidine nucleosides.

J Org Chem 2005 Aug;70(17):6721-34

Department of Chemistry, Université de Montréal, C. P. 6128, Succ. Centre-Ville, Montréal, P. Q., Canada H3C 3J7.

Methods are described for the total synthesis of bicyclic perhydrofuropyran nucleosides as N-analogues of the naturally occurring malayamycin A. Formation of the N-nucleosides relied on the activation of thioglycosides, proceeding via sulfonium intermediates. Ring closure metathesis was used in two approaches to build the bicyclic dioxa heterocycle. Another approach relied on the use of a sugar precursor and cyclization to the bicyclic thioglycoside.
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http://dx.doi.org/10.1021/jo050727bDOI Listing
August 2005

Total synthesis and structural confirmation of malayamycin A: a novel bicyclic C-nucleoside from Streptomyces malaysiensis.

Org Lett 2003 Nov;5(23):4277-80

Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, Quebec H3C 3J7, Canada.

[reaction: see text] The stereocontrolled synthesis of malayamycin A, a novel naturally occurring bicyclic C-nucleoside of the perhydrofuropyran type, is described.
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http://dx.doi.org/10.1021/ol030095kDOI Listing
November 2003
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