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Alpha-synuclein overexpression in the olfactory bulb initiates prodromal symptoms and pathology of Parkinson’s disease

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translational Neurodegeneration 2018年第1期7卷 244-260页

作者： Haichen Niu Lingyu Shen Tongzhou Li Chao Ren Sheng Ding Lei Wang Zhonghai Zhang Xiaoyu Liu Qiang Zhang Deqin Geng Xiujuan Wu Haiying Li Department of Genetics Xuzhou Medical UniversityXuzhou 221004China Department of Epidemiology and Health Statistics Xuzhou Medical UniversityXuzhou 221004China Department of Neurology Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantai 264000China College of Medicine Institute for Behavioral Medicine ResearchThe Ohio State UniversityColumbusOHUSA Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Department of Pathology Xuzhou Medical UniversityXuzhou 221004China

Background:Parkinson’s disease(PD)is a neurodegenerative disease characterized by intraneuronal Lewy Body(LB)aggregates composed of misfolded alpha-synuclein(α-syn).The spread of misfoldedα-syn follows a typical pattern:starting in the olfactory bulb(OB)and the gut,this pathology is followed by the progressive invasion of misfoldedα-syn to the posterior part of the *** is unknown whether the administration of human mutant alpha-synuclein(hm-α-syn,a human mutation which occurs in familial PD)into the OB of rats would trigger similarα-syn propagation and subsequently cause pathological changes in broader brain fields associated to PD and establish an animal model of prodromal ***:hm-α-syn was overexpressed in the OB of rats with an AAV *** motor and non-motor symptoms of the SD rats were tested in different behavioral tasks following the AAV *** follow-up studies,pathological mechanisms ofα-syn spread were explored at the histological,biochemical and micro-structure ***:The experimental results indicated that hm-α-syn was overexpressed in the OB 3 weeks after the AAV injection.1)overexpression of the Hm-α-syn in the OB by the AAV injection could transfer to wider adjacent fields beyond the monosynaptic scope.2)The number of tyrosine hydroxylase positive cells body and fibers was decreased in the substantia nigra(SN)12 weeks after AAV *** was consistent with decreased levels of the DA ***,behavioral dysfunctions were found that included olfactory impairment after 3 weeks,motor ability impairment and decreased muscular coordination on a rotarod 6 weeks after the AAV injection.3)The morphological level studies found that the Golgi staining revealed the number of neuronal branches and synapses in the OB,prefrontal cortex(PFC),hippocampus(Hip)and striatum caudate putamen(CPU)were decreased.4)phosphorylatedα-syn,at Ser-129(pSer129),was found to be increased in hm-α-syn injected animals in compari

关键词： Alpha-synuclein Prodromal animal model Parkinson’s disease Olfactory bulb Autophagy

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Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries

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Journal of Animal Science and Biotechnology 2019年第3期10卷 618-632页

作者： Katarzyna Knapczyk-Stwora Anna Nynca Renata E.Ciereszko Lukasz Paukszto Jan P.Jastrzebski Elzbieta Czaja Patrycja Witek Marek Koziorowski Maria Slomczynska Department of Endocrinology Institute of Zoology and Biomedical ResearchJagiellonian University in KrakowGronostajowa 9 Street30-387 KrakowPoland Laboratory of Molecular Diagnostics Faculty of Biology and BiotechnologyUniversity of Warmia and Mazury in OlsztynOlsztynPoland Department of Animal Anatomy and Physiology Faculty of Biology and BiotechnologyUniversity of Warmia and Mazury in OlsztynOlsztynPoland Department of Plant Physiology Genetics and BiotechnologyFaculty of Biology and BiotechnologyUniversity of Warmia and Mazury in OlsztynOlsztynPoland Department of Physiology and Reproduction of Animals University of RzeszowRzeszowPoland

Background: Androgens are involved in the regulation of ovarian development during fetal/neonatal *** chemicals displaying anti-androgenic activities may affect multiple signal transduction pathways by blocking endogenous androgen *** aim of the current study was to examine effects of the anti-androgen flutamide on the expression of coding transcripts and long non-coding rnas(lncrnas) in neonatal porcine *** employing rna-Seq technology we aimed to extend our understanding of the role of androgens in neonatal folliculogenesis and examine the impact of the anti-androgen flutamide on ovarian ***: Piglets were subcutaneously injected with flutamide(50 mg/kg BW) or corn oil(controls) between postnatal days 1 and 10(n = 3/group).Ovaries were excised from the 11-day-old piglets and total cellular rnas were isolated and ***: Flutamide-treated piglet ovaries showed 280 differentially expressed genes(DEGs;P-adjusted rnas(DELs;P-adjusted rnas were associated with intracellular transport and cell ***: Our results suggest that neonatal exposure of pigs to flutamide alters the expression of genes involved in ovarian cell proliferation,ovarian steroidogenesis and oocyte fertilization,which in turn may affect female reproduction in adult life.

关键词： Flutamide Lncrna Ovary Pig rna-Seq Transcriptome

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TGF-activated Lncrna LINC00115 is a critical regulator for glioma stem-like cell tumorigenicity

TGF-activated LncRNA LINC00115 is a critical regulator for g...

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2019中国生理学会学术年会暨张锡钧基金第十五届全国青...

作者：唐建明余波李彦欣冯海忠 State Key Laboratory of Oncogenes and Related Genes Renji-Med X Clinical Stem Cell Research CenterShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong University Key Laboratory of Pediatric Hematology and Oncology Ministry of Health Department of Hematology & OncologyShanghai Children's Medical CenterSchool of MedicineShanghai Jiao Tong University

Background: Long non-coding rnas（lncrnas） are critical regulators in ***, the involvement of lncrnas in TGF-regulated tumorigenicity is still *** we identify TGFactivated lncrna LINC00115 as a critical regulator in glioma stem-like cell（GSC） self-renewal and ***: LINC00115 expression was determined by in situ hybridization rnascope and ***-Seq was performed to compare lncrna expression levels treated with or without TGF-1 in *** proliferation and neuro-like sphere formation were *** tumor growth of LINC00115 knockdown in combination with EZH2 inhibitor was assessed in vivo using orthotopic mouse astrocyte and GSC xenograft ***: LINC00115 is upregulated by TGF-, acts as a mirna sponge and upregulates ZEB1 by competitively binding miR-200 s, thereby enhancing ZEB1 signaling and GSC ***00115 also promotes ZNF596 transcription by sequestering miR-200 s from binding to the 5’-UTR of ZNF596, resulting in augmented ZNF596/EZH2/STAT3 signaling and GBM tumor *** of EZH2 by genetic approaches or a small molecular inhibitor markedly suppresses LINC00115-driven GSC self-renewal and ***, LINC00115 is highly expressed in GBM, and LINC00115 expression or co-expression with ZEB1 or ZNF596 are prognostic for clinical GBM ***: Our work defines a critical role of LINC00115 in GSC self-renewal and tumorigenicity, suggesting LINC00115 as a potential target for GBM treatment.

关键词： lncrna LINC00115 glioma stem-like cell ZEB1 ZNF596 EZH2

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Long non-coding rna HOTAIR for Tumor Diagnosis and Pathological Staging

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Advances in Modern Oncology research 2019年第1期5卷 1-5页

作者： Aswir B.Abd.Rashid Zhiming Su Haematology Dept Institute of Medical ResearchJalan PengKuala Lumpur50588Malaysia China Medical Medicine Institute Beijing100000China

Lncrna HOTAIR has different expression levels in different stages of tumorigenesis and ***,it has potential application in clinical diagnosing tumor stage as a tumor *** patients with lung cancer and fifty healthy volunteers were selected as lung cancer group and control group *** to T and N stage of cancer,the patients were divided into T1,T2,T3 and N0,N1,N2 *** in situ hybridization(FISH)was used to detect the expression of HOTAIR in lung cancer tissues and paraneoplastic *** expression levels of NSE,CEA and CYFRA21-1 in serum were detected by *** results showed that the expression level of HOTAIR in paraneoplastic tissues(0.98±0.04)were significantly lower than that in lung cancer tissues(3.56±0.15).The serum levels of NSE,CEA and CYFRA21-1 of the lung cancer group were higher than those in the control *** concentrations of HOTAIR,NSE,CEA and CYFRA21-1 increased with the progress of clinical stages,which indicated that the expression of HOTAIR was positively correlated with the expression of SE,CEA and *** results indicate that HOTAIR,NSE,CEA and CYFRA21-1 are associated with the initiation and development of ***,HOTAIR combined with tumor marker can improve the accuracy of detection of pathological stage of lung cancer.

关键词： Lncrna HOTAIR Pathological staging Tumor detection

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Epigenetic regulation of aging:implications for interventions of aging and diseases

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Signal Transduction and Targeted Therapy 2022年第12期7卷 4283-4304页

作者： Kang Wang Huicong Liu Qinchao Hu Lingna Wang Jiaqing Liu Zikai Zheng Weiqi Zhang Jie Ren Fangfang Zhu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina University of Chinese Academy of Sciences 100049 BeijingChina School of Biomedical Engineering Shanghai Jiao Tong University200030 ShanghaiChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for Bioinformation100101 BeijingChina Hospital of Stomatology Sun Yat-sen University510060 GuangzhouChina Guangdong Provincial Key Laboratory of Stomatology Guanghua School of StomatologySun Yat-sen University510060 GuangzhouChina Institute for Stem Cell and Regeneration Chinese Academy of Sciences100101 BeijingChina Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu HospitalCapital Medical University100053 BeijingChina Beijing Institute for Stem Cell and Regenerative Medicine 100101 BeijingChina

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic *** aging-associated epigenetic changes include DNA methylation,histone modification,chromatin remodeling,non-coding rna(ncrna)regulation,and rna modification,all of which participate in the regulation of the aging process,and hence contribute to aging-related ***,understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay ***,aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal *** molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related *** addition,adopting health-promoting activities,such as caloric restriction,exercise,and calibrating circadian rhythm,has been demonstrated to delay ***,various clinical trials for aging intervention are ongoing,providing more evidence of the safety and efficacy of these ***,we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.

关键词： aging prevention hence

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Constipation,deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alphasynucleinopathy

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translational Neurodegeneration 2019年第1期8卷 48-62页

作者： Lucia Rota Carolina Pellegrini Laura Benvenuti Luca Antonioli Matteo Fornai Corrado Blandizzi Antonino Cattaneo Emanuela Colla Bio@SNS Laboratory Scuola Normale SuperiorePiazza dei Cavalieri 756126 PisaItaly Department of Pharmacy University of PisaVia Roma 5556126 PisaItaly Department of Clinical and Experimental Medicine University of PisaVia Roma 5556126 PisaItaly Neurotrophins and Neurodegenerative Diseases Laboratory Rita Levi-Montalcini European Brain Research InstituteViale Regina Elena 295Rome 00161Italy.

Background:Gastrointestinal dysfunction can affect Parkinson’s disease(PD)patients long before the onset of motor ***,little is known about the relationship between gastrointestinal abnormalities and the development of *** to other animal models,the human A53T alpha-synuclein(αS)transgenic mice,Line G2–3,developsαS-driven neurological and motor impairments after 9 months of age,displaying a long presymptomatic phase free of central nervous system(CNS)***:To determine whether this line can be suitable to study constipation as it occurs in prodromal PD,gastrointestinal functionality was assessed in young mice through a multidisciplinary approach,based on behavioral and biochemical analysis combined with electrophysiological recordings of mouse intestinal ***:We found that the A53TαS mice display remarkable signs of gastrointestinal dysfunction that precede motor abnormalities andαS pathology in the CNS by at least 6 ***αS mice show a drastic delay in food transit along the gastrointestinal tract,of almost 2 h in 3 months old mice that increased to more than 3 h at 6 *** impairment was associated with abnormal formation of stools that resulted in less abundant but longer pellets excreted,suggesting a deficit in the intestinal *** agreement with this,electrically evoked contractions of the colon,but not of the ileum,showed a reduced motor response in both longitudinal and circular muscle layers inαS mice already at 3 months of age,that was mainly due to an impaired cholinergic transmission of the underlying enteric nervous ***,the presence of insoluble and aggregatedαS was found in enteric neurons in both myenteric and submucosal plexi only in the colon of 3 months oldαS mice,but not in the small intestine,and exacerbated with age,mimicking the increase in transit delay and the contraction deficit showed by behavioral and electrical recordings ***:Gastrointest

关键词： Alpha-synuclein Constipation Gastrointestinal dysfunction Bowel dysmotility non-motor symptoms Parkinson’s disease Enteric nervous system Alpha-synucleinopathy

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Cell signaling during drought and/or cold stress in cassava

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Tropical Plants 2022年第1期1卷 47-53页

作者： Shuxia Li Pingjuan Zhao Xiaoling Yu Wenbin Liao Ming Peng Mengbin Ruan Key Laboratory of Biology and Genetic Resources of Tropical Crops Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikou 571101China Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan Province Hainan Institute for Tropical Agricultural ResourcesHaikou 571101China Sanya research Institute of Chinese Academy of Tropical Agricultural Sciences Sanya 572024China

Cassava(Manihot esculenta Crantz)is a root crop significant in food security and various bio-industrial applications such as animal feed,modified starch,and *** and cold stress are two major factors limiting cassava production qualitatively and quantitatively,for which plants have evolved mechanisms to overcome the impact of these two *** recent years,significant progress has been achieved in understanding the response mechanism of cassava plants to stress signals to tolerate the above *** this review,core stress-signaling pathways,including transcription factor(TF)-related regulatory networks,plant hormone signaling,reactive oxygen species(ROS)scavenging,and non-coding rna(ncrna)and alternative splicing(AS)that modify gene expression levels in response to drought and/or cold stress in cassava,are *** these stress signaling and responses will increase our ability to improve the crops tolerance to multiple stresses for agricultural sustainability and food security for the growing world population.

关键词： crops stress drought

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A novel long non-coding rna NFIA-AS1 is down-regulated in gastric cancer and inhibits proliferation of gastric cancer cells

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The Journal of Biomedical research 2019年第6期33卷 371-381页

作者： Jing Wang Xuezhi He Xiyi Lu Muhammad Amin Karim Dengshun Miao Erbao Zhang Departments of Anatomy Histology and Embryologythe Research Center for Bone and Stem CellsNanjing Medical UniversityNanjingJiangsu 211166China Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210009China Department of Epidemiology and Biostatistics Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in *** an important participant in tumor biology,the abnormal expression of long non-coding rna(lncrnas)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor *** this study,we identified a novel lncrna NFIA antisense rna 1(NFIA-AS1)and explored its role and clinical significance in gastric ***-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer *** lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM ***-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall *** also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 *** conclusion,our results suggest that the lncrna NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.

关键词： gastric cancer long non-coding rna NFIA antisense rna 1(NFIA-AS1) cell proliferation

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Altered neurogenesis and disrupted expression of synaptic proteins in SHANK3 deficient non-human primate prefrontal cortex

Altered neurogenesis and disrupted expression of synaptic pr...

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中国神经科学学会第十二届全国学术会议

作者： Hui Zhao Zhuchi Tu Huijuan Xu Sen Yan Huanhuan Yan Yinghui Zheng Weili Yang Jiezhao Zheng Zhujun Li Rui Tian Youming Lu Xiangyu Guo Yong-hui Jiang Xiao-Jiang Li Yong Q.Zhang State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Guangdong-Hongkong-Macau Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint Laboratory Jinan University The Institute for Brain research Collaborative Innovation Center for Brain Science Huazhong University of Science and Technology Department of Human Genetics Emory University School of Medicine

Mutations in SHANK3 remained one of the best characterized and replicated genetic defects in autism spectrum disorders(ASD) in humans. Genetically modified Shank3 mutant mice have served as valuable tools to dissect the pathophysiology of SHANK3 causing ASD. However, the significant evolutional differences between mouse and human brain and behaviors pose many challenges to assess the translational value of the mouse models to humans and highlight the demand of developing non-human primate models. We found that the SHANK3 expression pattern in sub-regions of early developing brain in cynomolgus monkeys is significantly different from that in mouse brain. Using the CRISPR/Cas9 to target the SHANK3 gene in the embryos of cynomolgus monkeys, we successfully generated three mutant monkey offspring with various deleterious mutations in the SHANK3 gene. Of them, one miscarried close to the end of gestation(SHANK3 ), one lost due to a difficult labor(SHANK3 ), and one was alive(SHANK3 ). SHANK3 showed a complete loss and isoform-specific deficiency of SHANK3 in cerebral cortex and striatum, respectively. SHANK3 complete deficiency resulted in a significant reduction in postsynaptic proteins such as Glu N2 B, PSD95, m Glu R5 and increased cytosolic localization of Homer1 b/c. The number of mature neurons is markedly reduced but activated astrocytes are increased in the prefrontal cortex in SHANK3 monkey. The neuropathology caused by the complete loss of SHANK3 in monkey brain is much more severe than that in patients with heterozygous SHANK3 mutations and is also remarkably distinct from the findings reported from Shank3 knockout mice. Our findings indicate that SHANK3 is essential for the early development of primate brains and support the necessity and value of non-human primate model for SHANK3 and other genetic causing ASD in future studies.

关键词： autism non-human primate SHANK3

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人胰岛素基因的合成——Ⅷ.表达型质粒的构建和在大肠杆菌内生产含有胰岛素原的融合蛋白

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生物工程学报 1985年第2期 14-33页

作者：郭礼和 Piotr P.Stepien 曹仲欣 Roland Brousseau Saran Narang David Y.Thomas 吴瑞中国科学院上海细胞生物学研究所 Division of Biological Sciences National research Council of Canada Section of Biochemistry Molecular and Cell Biology Cornell University Ithaca NY 14853 U.S.A.

我们已构建两组质粒,适合于在大肠杆菌内克隆基因和直接大量合成融合蛋白。这些质粒含有***的lac启动基因和部分编码β-半乳糖苷酶的序列,编码的蛋白长度约590或450个氨基酸残基(原基因编码1023个氨基酸残基)。被缩短的β-半乳糖苷酶基... 详细信息

我们已构建两组质粒,适合于在大肠杆菌内克隆基因和直接大量合成融合蛋白。这些质粒含有***的lac启动基因和部分编码β-半乳糖苷酶的序列,编码的蛋白长度约590或450个氨基酸残基(原基因编码1023个氨基酸残基)。被缩短的β-半乳糖苷酶基因的末端跟随一个多种限制性酶的接头序列;这个序列可被八种限制性酶中的任一种切断,然后插入任何蛋白基因。每组质粒有三种,可以满足所有三种不同的翻译读框。我们克隆了人工合成的人胰岛素原基因到这些质粒上去,在大肠杆菌内可以生产大量β-半乳糖苷酶残基——人胰岛素原融合蛋白。

关键词： BCA gene 大肠杆菌大肠埃希氏菌埃希氏杆菌属融合蛋白蛋白质质粒基因载体

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