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Small regulators making big impacts:regulation of neural stem cells by small non-coding RNAs

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Neural Regeneration Research 2017年第3期12卷 397-398页

作者： Zhong Liu Rui Zhao department of biochemistry and Molecular genetics Stem Cell InstituteUniversity of Alabama at BirminghamBirminghamALUSA

Neurodegeneration and traumatic brain injuries are leading causes of disability and present an enormous disease burden both in terms of patient suffering and healthcare *** of brain lesions remains as a major challeng... 详细信息

关键词： NSCs cell Small regulators making big impacts:regulation of neural stem cells by small non-coding RNAs stem

Neuromodulatory effects of ethyl acetate fraction of Zingiber officinale Roscoe extract in rats with lead-induced oxidative stress

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Journal of Integrative Medicine 2019年第2期17卷 125-131页

作者： Mary Abiola Okesola Basiru Olaitan Ajiboye Babatunji Emmanuel Oyinloye Oluwafemi Adeleke Ojo department of biochemistry Covenant University department of biochemistry Afe Babalola University department of biochemistry University of Ilorin

Objective: This study investigated the ameliorative potential of Zingiber officinale Roscoe extract against lead-induced brain damage in ***: Thirty male rats were divided into 5 groups of 6 rats each. Lead-acetate toxicity was induced by intraperitoneal injection(10 mg/kg body weight(b.w.)) in Groups B–E. Group A(control) and Group B(lead-acetate) were left untreated; vitamin C(200 mg/kg b.w.) was administered to Group C; ethyl acetate fraction from Z. officinale extract(200 and 100 mg/kg b.w.) was administered to Group D and E by oral gavage once daily for 7 days. Changes in the content of some key marker enzymes such as acetylcholinesterase(AChE), butyrylcholinesterase(BChE), monoamine oxidase(MAO), epinephrine, dopamine,Na^+/K^+-ATPase, catalase(CAT), superoxide dismutase(SOD) and glutathione peroxidase(GPx) as well as malonaldehyde(MDA) levels were determined in ***: Exposure to lead acetate resulted in a significant decrease(P < 0.05) in the activities of BChE,AChE, Na^+/K^+-ATPase, SOD, CAT and GPx with a corresponding increase in the levels of MDA, xanthine oxidase, epinephrine, dopamine and MAO relative to the control group. Levels of all disrupted parameters were alleviated by co-administration of Z. officinale fraction and by the standard drug, vitamin ***: These results suggest that ethyl acetate fraction of Z. officinale extract attenuates leadinduced brain damage and might have therapeutic potential as a supplement that can be applied in lead poisoning.

关键词： Zingiber officinale Acetylcholinesterase Monoamine oxidase Na^(+)/K^(+)-ATPase Lead acetate Neurodegenerative disorders

The correlation between iron homeostasis and telomere maintenance

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Frontiers in Biology 2014年第5期9卷 347-355页

作者： Caiguo ZHANG department of biochemistry and Molecular genetics University of Colorado School of Medicine Aurora CO 80045 USA

Eukaryotic organisms require iron to sustain genome stability, cell proliferation and development. Chromosomes contain telomeres to ensure complete replications and avoid fusions. Numerous evidences reveal that iron can act directly or indirectly on telomere maintenance. In human, disruption of systemic or cellular iron homeostasis is reportedly to cause serious health problems such as iron overload （hereditary hemochromatosis）, iron deficiency anemia, carcinogenesis and acceleration of aging process. These processes commonly associate with abnormal telomere length. Additionally, cells containing mutations in iron-containing proteins such as DNA polymerases （Pola, g, and ~）, regulator of telomere length 1 （RTEL1） and the small subunit of ribonucleotide reductases （RNRs） have abnormal telomere length. This review briefly summarizes current understandings on iron homeostasis and telomere maintenance in cancer and aging process, followed by discussing their direct and indirect correlation, and the possible regulatory mechanisms.

关键词： iron homeostasis telomere telomere maintenance cancer aging

Genomic data mining for functional annotation of human long noncoding RNAs

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第6期20卷 476-487页

作者： Brian L.GUDENAS Jun WANG Shu-zhen KUANG An-qi WEI Steven B.COGILL Liang-jiang WANG department of genetics and biochemistry Clemson University

Life may have begun in an RNA world,which is supported by increasing evidence of the vital role that RNAs perform in biological *** the human genome,most genes actually do not encode proteins;they are noncoding RNA *** largest class of noncoding genes is known as long noncoding RNAs(lncRNAs),which are transcripts greater in length than 200 nucleotides,but with no protein-coding *** some lncRNAs have been demonstrated to be key regulators of gene expression and 3D genome organization,most lncRNAs are still *** thus propose several data mining and machine learning approaches for the functional annotation of human lncRNAs by leveraging the vast amount of data from genetic and genomic *** results from our studies and those of other groups indicate that genomic data mining can give insights into lncRNA functions and provide valuable information for experimental studies of candidate lncRNAs associated with human disease.

关键词： Long noncoding RNA Functional annotation Genomic data mining Machine learning

Ribonucleotide reductase metallocofactor： assembly, maintenance and inhibition

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Frontiers in Biology 2014年第2期9卷 104-113页

作者： Caiguo ZHANG Guoqi LIU Mingxia HUANG department of biochemistry and Molecular genetics University of Colorado School of Medicine Aurora CO 80045 USA

Ribonucleotide rcductase （RNR） supplies cellular deoxyribonucleotidc triphosphates （dNTP） pools by converting ribonucleotides to the corresponding deoxy forms using radical-based chemistry. Eukaryotic RNR comprises a and β subunits： u contains the catalytic and ailosteric sites; β houses a diferric-tyrosyl radical cofactor （FeⅢ2-Y· ） that is required to initiates nucleotide reduction in α. Cells have evolved multi-layered mechanisms to regulate RNR level and activity in order to maintain the adequate sizes and ratios of their dNTP pools to ensure high- fidelity DNA replication and repair. The central role of RNR in nucleotide metabolism also makes it a proven target of chemotherapeutics. In this review, we discuss recent progress in understanding the function and regulation of eukaryofic RNRs, with a focus on studies revealing the cellular machineries involved in RNR metaUocofactor biosynthesis and its implication in RNR-targeting therapeutics.

关键词： ribonucleotide reductase (RNR) diferric-tyrosyl radical (FeⅢ2-Y·) iron homeostasis

Ethane dimethylsulphonate selectively destroys Leydig cells in the adult bonnet monkeys (Macaca radiata)

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Asian Journal of Andrology 1999年第3期1卷 115-120页

作者： R.Sumathi V.Sriraman B.S.Kurkalli F.F.G.Rommerts A.JagannadhaRao department of biochemistry Development and genetics Indian Institute of ScienceBangalore 560012India department of biochemistry Erasmus University RotterdamRotterdam 3000 DRThe Netherlands 不详

Aim:To study the effect of intratesticular administration of ethane-1,2-dimethylsulphonate(EDS)which has been exten-sively used to selectively destroy Leydig cells in rats and study the role of gonadotropin in regulation of differentiation ofLeydig cells(LC)in the adult male bonnet *** and Results:In vitro studies with cultured interstitialcells isolated from monkey testis revealed an inhibitory effect of EDS on LC as assessed by decrease in testosterone *** administration of EDS(5,10,20,50 mg/testis)resulted in a dose-dependent rapid decrease inserum testosterone levels,with a 65%decrease with 5 mg of EDS by the 3rd day,which returned to control levels by the45th *** treatment resulted in a significant decrease in testicular *** addition a significant decrease in[(125)~I]hCG binding and phenylesterase activity in the interstitial cells was *** analysis of the testes onthe 5th day after administration of EDS revealed an interstitium devoid of LC indicating the destructive action of ***:The monkey LC are sensitive to destructive action of EDS.

关键词： Macaca radiata ethane dimethylsulphonate Leydig cells testosterone

Wilson's disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

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World Journal of Gastroenterology 2017年第36期23卷 6715-6725页

作者： Kassem Barada Aline El Haddad Meghri Katerji Mustapha Jomaa Julnar Usta department of Internal Medicine American University of Beirut Medical Center department of biochemistry and Molecular genetics Faculty of Medicine American University of Beirut

AIM To determine the phenotypes and predominant diseasecausing mutations in Lebanese patients with Wilson's disease,as compared to regional non-European *** The clinical profile of 36 patients diagnosed in Lebanon was studied and their mutations were determined by molecular *** patients underwent full physical exam,including ophthalmologic slit-lamp examination ultrasound imaging of the liver,as well as measurement of serum ceruloplasmin and 24-h urinaryCu *** addition,genetic screening using PCR followed by sequencing to determine disease-causing mutations and polymorphisms in the ATP7B gene was carried on extracted DNA from patients and immediate family *** phenotypic-genotypic findings were then compared to reported mutations in Wilson's disease patients from regional Arab and non-European countries. RESULTS Patients belonged to extended consanguineous *** majority were homozygous for the disease-causing mutation,with no predominant mutation identified. The most common mutation,detected in 4 out of 13families,involved the ATP hinge region and was present in patients from Lebanon,Egypt,Iran and ***,mutations in Lebanese patients and those of the region were scattered over 17 exons of *** the homozygous exon 12 mutation Trp939Cys was only detected in patients from Lebanon but none from the regional countries,the worldwide common mutation H1069Q was not present in the Lebanese and was rare in the *** hepatic phenotype was predominant in patients from both Lebanon and the region(25%-65%).Furthermore,the majority of patients,including those who were asymptomatic,had evidence of some hepatic *** neurologic phenotype was rare. CONCLUSION Findings do not support presence of a founder *** and genetic screening is recommended for family members with index patients and unexplained hepatic dysfunction.

关键词： Wilson Disease Cu-metabolism Phenotype Genotype ATP7B Hepatic manifestations

Recombinant adenovirus-mediated overexpression of 3β-hydroxysteroid-Δ24 reductase

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Neural Regeneration Research 2014年第5期9卷 504-512页

作者： Xiuli Lu Dan Jia Chenguang Zhao Weiqi Wang Ting Liu Shuchao Chen Xiaoping Quan Deliang Sun Bing Gao department of biochemistry and Cell Biology School of Life ScienceLiaoning University department of Cell Biology and genetics School of Basic Medical Sciences Shenyang Medical College

3β-Hydroxysteroid-△24 reductase （DHCR24） is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid β deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human （h） and rat （r）. Recombinant Ad-r（h）SYN1-DHCR24 was transfected into AD-293, N2A （mouse neuroblastoma）, and MIN6 （mouse pancreatic carcinoma） cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunoflu- orescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer＇s disease.

关键词： nerve degeneration 3β-hydroxysteroid-△ 2 4 reductase recombinant adenovirus neuron oxidative stress synapsin-1 gene therapy neuroprotection NSFC grant neural regeneration

Immunity Genes and Susceptibility to Otitis Media:A Comprehensive Review

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Journal of genetics and Genomics 2014年第11期41卷 567-581页

作者： Rahul Mittal Giannina Robalino Robert Gerring Brandon Chan Denise Yan M'hamed Grati Xue-Zhong Liu department of Otolaryngology University of Miami Miller School of Medicine department of Human genetics University of Miami Miller School of Medicine department of biochemistry University of Miami Miller School of Medicine

Otitis media （OM） is a middle ear infection associated with inflammation and pain. This disease frequently afflicts humans and is the major cause of hearing loss worldwide. OM continues to be one of the most challenging diseases in the medical field due to its diverse host targets and wide range of clinical manifestations. Substantial morbidity associated with OM is further exacerbated by high frequency of recurrent infections leading to chronic suppurative otitis media （CSOM）. Children have greater susceptibility to, and thus, suffer most frequently from OM, which can cause significant deterioration in quality of life. Genetic factors have been demonstrated, in large part by twin and family studies, to be key determinants of OM susceptibility. In this review, we summarize the current knowledge on immunity genes and selected variants that have been associated with predisposition to OM. In particular, polymorphisms in innate immunity and cytokine genes have been strongly linked with the risk of developing OM. Future studies employing state-of-the-art technologies, including next-generation sequencing （NGS）, will aid in the identification of novel genes associated with susceptibility to OM. This, in turn, will open up avenues for identifying high-risk individuals and designing novel therapeutic strategies based on precise targeting of these genes.

关键词： Otitis media genetics Innate immunity Cytokines