162 results on '"Cao, Huang"'
Search Results
2. Characteristics of HPV integration in cervical adenocarcinoma and squamous carcinoma
- Author
-
Bi, Yuxin, Hu, Junbo, Zeng, Ling, Chen, Gang, Cai, Hongning, Cao, Huang, Ma, Quanfu, and Wu, Xufeng
- Published
- 2023
- Full Text
- View/download PDF
3. Subacute thyroiditis presenting as simple acute headache was misdiagnosed as meningitis: case report and literature review
- Author
-
Cao Huang, Shuang Shen, and Jianping Yao
- Subjects
Subacute thyroiditis ,Thyrotoxicosis ,Headache ,Misdiagnosis ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract Background The relationship between headache and thyrotoxicosis has been occasionally mentioned in case reports, but there are few related reports. Thus, the relationship cannot be determined. Few cases of subacute thyroiditis (SAT) presenting as simple headache have been reported. Case presentation This case report describes a middle-aged male patient who came to our hospital with acute headache for 10 days. He was initially misdiagnosed as meningitis due to headache, fever, and increased C-reactive protein. Routine antibacterial and antiviral therapy did not improve his symptoms. Blood test suggested thyrotoxicosis, and color ultrasound suggested SAT sonography. He was diagnosed with SAT. With the treatment of SAT, the headache was relieved after the thyrotoxicosis improved. Conclusion This patient is the first detailed report of SAT presenting with simple headache, which is helpful for clinicians to differentiate and diagnose atypical SAT.
- Published
- 2023
- Full Text
- View/download PDF
4. PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma
- Author
-
Chen, Tian-rui, Cao, Huang-ming, Wu, Yin, Xie, Jiang-tao, Lan, Hai-feng, and Jin, Li-na
- Published
- 2022
- Full Text
- View/download PDF
5. Protective effects of METRNL overexpression against pathological cardiac remodeling
- Author
-
Cao, Huang, primary, Liao, Yiming, additional, and Hong, Junmou, additional
- Published
- 2024
- Full Text
- View/download PDF
6. Erratum to: PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma
- Author
-
Chen, Tian-rui, Cao, Huang-ming, Wu, Yin, Xie, Jiang-tao, Lan, Hai-feng, and Jin, Li-na
- Published
- 2023
- Full Text
- View/download PDF
7. Inhibition mechanism of theaflavins on matrix metalloproteinase-2: inhibition kinetics, multispectral analysis, molecular docking and molecular dynamics simulation.
- Author
-
Guo, Jing, Hu, Mengna, Yang, Mingqi, Cao, Huang, Li, Hongan, Zhu, Jiayu, Li, Shuang, and Zhang, Jinsheng
- Published
- 2024
- Full Text
- View/download PDF
8. Stability for Sampled-Data Systems with Delay and Applications for Networked Control Systems.
- Author
-
Cao Huang, Huiyu Jin, and Ying Wang 0005
- Published
- 2018
- Full Text
- View/download PDF
9. Mutant UBQLN2P497H in motor neurons leads to ALS-like phenotypes and defective autophagy in rats
- Author
-
Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, and Cao Huang
- Subjects
Amyotrophic lateral sclerosis ,ALS ,UBQLN2 ,P62 ,Motor neuron degeneration ,Autophagy ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes were not observed when mutant UBQLN2P497H was overexpressed in the astrocytes, however, even though the expression of the mutant UBQLN2P497H protein was higher in these rats. Our results suggest that selectively expressing mutant UBQLN2P497H in motor neurons is sufficient to trigger the development of ALS in rats. Our results further indicate that the compromised autophagy-lysosomal pathway plays a critical role in the pathogenesis of UBQLN2-related neurodegenerative diseases.
- Published
- 2018
- Full Text
- View/download PDF
10. Characteristics of HPV Integration in Cervical Adenocarcinoma and Squamous Carcinoma
- Author
-
Bi, Yuxin, primary, Hu, Junbo, additional, Zeng, Ling, additional, Chen, Gang, additional, Cao, Huang, additional, Wu, Xufeng, additional, and Ma, Quanfu, additional
- Published
- 2023
- Full Text
- View/download PDF
11. RNA binding protein 24 regulates the translation and replication of hepatitis C virus
- Author
-
Cao, Huang, Zhao, Kaitao, Yao, Yongxuan, Guo, Jing, Gao, Xiaoxiao, Yang, Qi, Guo, Min, Zhu, Wandi, Wang, Yun, Wu, Chunchen, Chen, Jizheng, Zhou, Yuan, Hu, Xue, Lu, Mengji, Chen, Xinwen, and Pei, Rongjuan
- Published
- 2018
- Full Text
- View/download PDF
12. Research on vehicle lane-changing obstacle avoidance for Internet of Vehicles
- Author
-
Hao Cong, Xueming Li, and Cao Huang
- Published
- 2023
- Full Text
- View/download PDF
13. Research on retrieval algorithm of middle atmospheric temperature using Rayleigh lidar based on Kalman filter
- Author
-
Zheng Ming, Xueming Li, Guofeng Teng, Chonghao Wu, Cao Huang, and Qihai Chang
- Published
- 2023
- Full Text
- View/download PDF
14. Tetramerization of upstream stimulating factor USF2 requires the elongated bent leucine zipper of the bHLH-LZ domain.
- Author
-
Cao Huang, Mingyu Xia, Hang Qiao, Zaizhou Liu, Yuqi Lin, Hanyin Sun, Biao Yu, Pengfei Fang, and Jing Wang
- Subjects
- *
LEUCINE zippers , *TRANSCRIPTION factors , *CRYSTAL structure , *DNA - Abstract
Upstream stimulating factors (USFs), including USF1 and USF2, are key components of the transcription machinery that recruit coactivators and histone-modifying enzymes. Using the classic basic helix-loop-helix leucine zipper (bHLH-LZ) domain, USFs bind the E-box DNA and form tetramers that promote DNA looping for transcription initiation. The structural basis by which USFs tetramerize and bind DNA, however, remains unknown. Here, we report the crystal structure of the complete bHLH-LZ domain of USF2 in complex with E-box DNA. We observed that the leucine zipper (LZ) of USF2 is longer than that of other bHLH-LZ family transcription factors and that the C-terminus of USF2 forms an additional β-helix following the LZ region (denoted as LZ-Ext). We also found the elongated LZ-Ext facilitates compact tetramer formation. In addition to the classic interactions between the basic region and DNA, we show a highly conserved basic residue in the loop region, Lys271, participates in DNA interaction. Together, these findings suggest that USF2 forms a tetramer structure with a bent elongated LZ-Ext region, providing a molecular basis for its role as a key component of the transcription machinery. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
15. Mimecan, a Hormone Abundantly Expressed in Adipose Tissue, Reduced Food Intake Independently of Leptin Signaling
- Author
-
Cao, Huang-Ming, Ye, Xiao-Ping, Ma, Jun-Hua, Jiang, He, Li, Sheng-Xian, Li, Rong-Ying, Li, Xue-Song, Guo, Cui-Cui, Wang, Zhi-Quan, Zhan, Ming, Zuo, Chun-Lin, Pan, Chun-Ming, Zhao, Shuang-Xia, Zheng, Cui-Xia, and Song, Huai-Dong
- Published
- 2015
- Full Text
- View/download PDF
16. UBQLN2 Promotes the Production of Type I Interferon via the TBK1-IRF3 Pathway
- Author
-
Tianhong Chen, Wenjuan Zhang, Bo Huang, Xuan Chen, and Cao Huang
- Subjects
ALS ,FTD ,UBQLN2 ,TBK1 ,IFN1 ,IRF3 ,Cytology ,QH573-671 - Abstract
Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR–Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration.
- Published
- 2020
- Full Text
- View/download PDF
17. A distributed class-based alternative routing under a congestion control architecture for LEO satellite networks.
- Author
-
Cao Huang and Falin Liu
- Published
- 2010
- Full Text
- View/download PDF
18. RBM24 stabilizes hepatitis B virus pregenomic RNA but inhibits core protein translation by targeting the terminal redundancy sequence
- Author
-
Yao, Yongxuan, Yang, Bo, Cao, Huang, Zhao, Kaitao, Yuan, Yifei, Chen, Yingshan, Zhang, Zhenhua, Wang, Yun, Pei, Rongjuan, Chen, Jizheng, Hu, Xue, Zhou, Yuan, Lu, Mengji, Wu, Chunchen, and Chen, Xinwen
- Published
- 2018
- Full Text
- View/download PDF
19. Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
- Author
-
Hongxia Zhou, Cao Huang, Jianbin Tong, Xu-Gang Xia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by constitutive gene silencing. Moreover, early exposure to paraquat sensitized dopaminergic neurons to subsequent silencing of PINK1 gene expression, leading to a significant loss of dopaminergic neurons. Our findings suggest a novel pathogenesis of PD: exposure to environmental toxicants early in the life reduces the threshold of developing PD and partial dysfunction of neuron-protective genes later in the life initiates a process of progressive neurodegeneration to cross the reduced threshold of disease onset.
- Published
- 2011
20. TDP-43 Potentiates Alpha-synuclein Toxicity to Dopaminergic Neurons in Transgenic Mice
- Author
-
Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xu-Gang Xia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in the transgenic mice at advanced ages. Interestingly, concomitant overexpression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopaminergic neurons in the double transgenic mice as compared to single-gene transgenic mice. TDP-43 potentiated α-synuclein toxicity to dopaminergic neurons in living animals. Our finding provides in vivo evidence suggesting that disease proteins such as TDP-43 and α-synuclein may play a synergistic role in disease induction in neurodegenerative diseases.
- Published
- 2011
21. Temporal Expression of Mutant LRRK2 in Adult Rats Impairs Dopamine Reuptake
- Author
-
Hongxia Zhou, Cao Huang, Jianbin Tong, Weimin C Hong, Yong-Jian Liu, Xu-Gang Xia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Parkinson's disease (PD) results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2G2019S in adult rats impaired dopamine reuptake by dopamine transporter (DAT) and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in asymptomatic subjects carrying pathogenic mutation in LRRK2. Our transgenic rats recapitulated the initiation process of dopaminergic dysfunction caused by pathogenic mutation in LRRK2. Inducible transgenic approach uncovered phenotypes that may be obscured by developmental compensation in constitutive transgenic rats. Finding in inducible LRRK2 transgenic rats would guide developing effective strategy in transgenic studies: Inducible expression of transgene may induce greater phenotypes than constitutive gene expression, particularly in rodents with short life time.
- Published
- 2011
22. Sustained Expression of TDP-43 and FUS in Motor Neurons in Rodent's Lifetime
- Author
-
Cao Huang, Pedro Yuxing Xia, Hongxia Zhou
- Subjects
Biology (General) ,QH301-705.5 - Abstract
TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, TDP-43 and FUS proteins were even undetectable in peripheral organs including skeletal muscles, liver, and kidney, but were constantly expressed at substantial levels in the central nervous system. Motor neurons expressed the TDP-43 and the FUS genes at robust levels throughout rodent's lifetime. Moreover, TDP-43 and FUS were accumulated in the cytoplasm of motor neurons in aged animals. Our findings suggest that TDP-43 and FUS play an important role in development and that constant and robust expression of the genes in motor neurons may render the neurons vulnerable to pathogenic mutation of the TDP-43 or the FUS gene. To faithfully model the pathology of TDP-43- or FUS gene mutations in rodents, we must replicate the expression patterns of the TDP-43 and the FUS gene in animals.
- Published
- 2010
23. Developing tTA Transgenic Rats for Inducible and Reversible Gene Expression
- Author
-
Hongxia Zhou, Cao Huang, Min Yang, Carlisle P Landel, Pedro Yuxing Xia, Yong-Jian Liu, Xu Gang Xia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 μg/ml in drinking water) for two days to reach the effective concentration, and then was given at a low dose (20 μg/ml) to maintain effectiveness. This regimen of Dox administration can achieve a quick switch between ON and OFF statuses of tTA-activated gene expression. In addition, administration of Dox to pregnant rats fully suppressed postnatal tTA-activated gene expression in their offspring. Sufficient levels of Dox are present in mother's milk to produce maximal efficacy in nursing neonates. Administration of Dox to pregnant or nursing rats can provide a continual suppression of tTA-dependent gene expression during embryonic and postnatal development. The tTA transgenic rat allows for inducible and reversible gene expression in the rat; this important tool will be valuable in the development of genetic rat models of human diseases.
- Published
- 2009
24. Construction of a chimeric hepatitis C virus replicon based on a strain isolated from a chronic hepatitis C patient
- Author
-
Cao, Huang, Zhu, Wandi, Han, Qingxia, Pei, Rongjuan, and Chen, Xinwen
- Published
- 2014
- Full Text
- View/download PDF
25. Safety and efficacy of TACE and gamma knife on hepatocellular carcinoma with portal vein invasion
- Author
-
Lu, Xiao-Jie, Dong, Jing, Ji, Li-Juan, Luo, Jin-Hong, Cao, Huang-Ming, Xiao, Li-Xin, Zhou, Jun, and Ling, Chang-Quan
- Published
- 2016
- Full Text
- View/download PDF
26. Glucocorticoid up-regulates mimecan expression in corticotroph cells
- Author
-
Ma, Qin-Yun, Zuo, Chun-Lin, Ma, Jun-Hua, Zhang, Xiao-Na, Ru, Ying, Li, Ping, Pan, Chun-Ming, Liu, Zhi, Cao, Huang-Ming, Chen, Ming-Dao, and Song, Huai-Dong
- Published
- 2010
- Full Text
- View/download PDF
27. An Adaptive Conservative Finite Volume Method for Poisson-Nernst-Planck Equations on a Moving Mesh
- Author
-
Xiulei Cao Huang and Huaxiong
- Subjects
Physics ,symbols.namesake ,Finite volume method ,Physics and Astronomy (miscellaneous) ,Mathematical analysis ,symbols ,Nernst equation ,Planck ,Poisson distribution - Published
- 2019
- Full Text
- View/download PDF
28. Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats
- Author
-
Wenjuan Zhang, Cao Huang, Limo Gao, and Bo Huang
- Subjects
0301 basic medicine ,Mutant ,medicine.disease_cause ,UBQLN2 ,0302 clinical medicine ,rat ,Biology (General) ,Amyotrophic lateral sclerosis ,Spectroscopy ,Neurons ,Mutation ,biology ,Chemistry ,Neurodegeneration ,FTD ,General Medicine ,Computer Science Applications ,Cell biology ,Cysteine Endopeptidases ,Frontotemporal Dementia ,Rats, Transgenic ,Proteasome Endopeptidase Complex ,QH301-705.5 ,Protein subunit ,Protein Aggregation, Pathological ,Catalysis ,Article ,protein aggregation ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Ubiquitins ,Organic Chemistry ,Amyotrophic Lateral Sclerosis ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,proteasome ,Proteasome ,Proteasome assembly ,biology.protein ,ALS ,030217 neurology & neurosurgery - Abstract
Proteasomal dysfunction is known to be associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). Our previous reports have shown that a mutant form of ubiquilin-2 (UBQLN2) linked to ALS/FTD leads to neurodegeneration accompanied by accumulations of the proteasome subunit Rpt1 in transgenic rats, but the precise pathogenic mechanisms of how this mutation impairs the proteasome remains to be elucidated. Here, we reveal that this UBQLN2 mutation in rats disrupted the proteasome integrity prior to neurodegeneration, that it dissociated the 26S proteasome in vitro, and that its depletion did not affect 26S proteasome assembly. During both disease progression and in an age-dependent manner, we found that proteasome subunits were translocated to the nucleus, including both of the 20S core particles (PSMA1 and PSMB7) and the 19S regulatory particles (Rpt1 and Rpn1), suggesting that defective proteasome function may result from the proteasome-subunit mislocalization. Taken together, the present data demonstrate that impaired proteasome assembly is an early event in the pathogenesis of UBQLN2-associated neurodegeneration in mutant UBQLN2 rats.
- Published
- 2021
29. The Landscape of Iron metabolism-related Genes for Overall survival prediction in Patients with Hepatocellular carcinoma
- Author
-
Zhu, Zhipeng, primary, Cao, Huang, additional, Sun, Anran, additional, zhan, Hongliang, additional, Liu, Zhengsheng, additional, Lu, Kaihong, additional, Zhang, Ting, additional, Miao, Chaohao, additional, and Wu, Zhun, additional
- Published
- 2021
- Full Text
- View/download PDF
30. The expression of mimecan in adrenal tissue plays a role in an organism’s responses to stress
- Author
-
Su, Bin, primary, Zhang, Qian-Yue, additional, Li, Xue-Song, additional, Yu, Hui-Min, additional, Li, Ping, additional, Ma, Jun-Hua, additional, Cao, Huang-Ming, additional, Sun, Fei, additional, Zhao, Shuang-Xia, additional, Zheng, Cui-Xia, additional, Ru, Ying, additional, and Song, Huai-Dong, additional
- Published
- 2021
- Full Text
- View/download PDF
31. Nephrogenic rests in adult: A case report
- Author
-
Liu, Zhengsheng, primary, Cao, Huang, additional, Zhang, Kaiyan, additional, and Xing, Jinchun, additional
- Published
- 2021
- Full Text
- View/download PDF
32. UBQLN2 Promotes the Production of Type I Interferon via the TBK1-IRF3 Pathway
- Author
-
Xuan Chen, Cao Huang, Wenjuan Zhang, Tianhong Chen, and Bo Huang
- Subjects
TBK1 ,Mutant ,Autophagy-Related Proteins ,Protein Serine-Threonine Kinases ,Article ,TANK-binding kinase 1 ,Protein Domains ,Interferon ,mental disorders ,medicine ,Humans ,Phosphorylation ,lcsh:QH301-705.5 ,Optineurin ,Adaptor Proteins, Signal Transducing ,Chemistry ,Kinase ,Neurodegeneration ,FTD ,General Medicine ,IRF3 ,medicine.disease ,Cell biology ,HEK293 Cells ,lcsh:Biology (General) ,Interferon Type I ,Interferon Regulatory Factor-3 ,Mutant Proteins ,ALS ,IFN1 ,UBQLN2 ,medicine.drug ,Protein Binding ,Signal Transduction - Abstract
Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR&ndash, Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration.
- Published
- 2020
33. Chidamide plus decitabine synergistically induces apoptosis of acute myeloid leukemia cells by upregulating
- Author
-
Qing, Li, Jing-Cao, Huang, Dian-Ying, Liao, and Yu, Wu
- Subjects
Original Article - Abstract
Acute myeloid leukemia (AML) is a malignant clonal disease that originates from hematopoietic stem cells. Because AML has a generally unsatisfactory long-term prognosis, new therapeutic options are required. To this end, we explored the effects of chidamide and decitabine alone or in combination on the AML cell lines THP-1, MV4-11, HL60, and Kasumi-1. Notably, the two drugs exhibited a synergistic effect against these cell lines. Similarly, we also found potential synergistic effects in primary cells of relapsed/refractory (r/r) AML. A transcriptome sequencing analysis performed to elucidate the underlying molecular mechanism revealed differentially expressed genes and regulatory pathways, particularly with regard to apoptosis, when comparing cells subjected to single and combination treatments. We identified PERP as a downstream target gene of the transcription factors P53 and P63, and it was expressed at considerably higher levels in combination-treated cells relative to monotherapy-treated cells. We further used a lentivirus-mediated small interfering RNA to inhibit the endogenous expression of PERP in AML cell lines and observed a significant increase in cell proliferation. Collectively, our results demonstrate, for the first time, the role of PERP in the response of AML to a combination drug regimen, providing a new potential treatment protocol and target in this context.
- Published
- 2020
34. Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis
- Author
-
Jinxia Zhou, Qiao Liao, Cao Huang, Ke Lu, Si Chen, and Fangfang Bi
- Subjects
0301 basic medicine ,Genetically modified mouse ,Neurofilament ,Transgene ,Neurological disorder ,Pharmacology ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Developmental Neuroscience ,medicine ,Animals ,Humans ,Amyotrophic lateral sclerosis ,Riluzole ,business.industry ,Amyotrophic Lateral Sclerosis ,medicine.disease ,Spinal cord ,Choline acetyltransferase ,Rats ,DNA-Binding Proteins ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neuroprotective Agents ,Treatment Outcome ,Neurology ,Rats, Transgenic ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.
- Published
- 2020
35. Temporal Expression of Mutant TDP-43 Correlates with Early Amyotrophic Lateral Sclerosis Phenotype and Motor Weakness
- Author
-
Fangfang Bi, Hongxia Zhou, Bo Xiao, Jinxia Zhou, Qihua Chen, Cao Huang, and Bo Huang
- Subjects
0301 basic medicine ,TAR DNA-binding protein 43 ,Time Factors ,Transgene ,Mutant ,Gene Expression ,Biology ,medicine.disease_cause ,DNA-binding protein ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Gene expression ,mental disorders ,medicine ,motor neurons ,Animals ,Humans ,transgenic rats ,Amyotrophic lateral sclerosis ,Mutation ,Tet-responsive transactivator ,Muscle Weakness ,CAG ,Amyotrophic Lateral Sclerosis ,Muscle weakness ,nutritional and metabolic diseases ,medicine.disease ,Phenotype ,Cell biology ,nervous system diseases ,Rats ,DNA-Binding Proteins ,030104 developmental biology ,Neurology ,medicine.symptom ,Amyotrophic Lateral Sclerosis (ALS) ,Rats, Transgenic - Abstract
Background Mutant transactive response DNA-binding protein (TDP-43) is closely correlated to the inherited form of amyotrophic lateral sclerosis (ALS). TDP-43 transgenic rats can reproduce the core phenotype of ALS and constitutive expression of TDP-43 caused postnatal death. Objective The study aimed to understand whether neurologic deficiency caused by mutant TDP- 43 is dependent on its temporal expression. Method Transgenic rats were established that express mutant human TDP-43 (M337V substitution) in neurons, then a Tet-off system was used to regulate its expression. Results TDP-43 mutant transgenic rats developed significant weakness after the transgene was activated. Rats with expression of mutant TDP-43 at 30 days showed a more aggressive phenotype. More severe pathological changes in neurogenic atrophy were observed in these rats. Conclusion Temporal expression of mutant TDP-43 in neurons promoted serious phenotype in rats. The dysfunction of TDP-43 had a profound impact on the development of motor neurons and skeletal muscles.
- Published
- 2018
36. FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
- Author
-
Cao Huang, Hongxia Zhou, Jianbin Tong, Han Chen, Yong-Jian Liu, Dian Wang, Xiaotao Wei, and Xu-Gang Xia
- Subjects
Genetics ,QH426-470 - Abstract
Fused in Sarcoma (FUS) proteinopathy is a feature of frontotemporal lobar dementia (FTLD), and mutation of the fus gene segregates with FTLD and amyotrophic lateral sclerosis (ALS). To study the consequences of mutation in the fus gene, we created transgenic rats expressing the human fus gene with or without mutation. Overexpression of a mutant (R521C substitution), but not normal, human FUS induced progressive paralysis resembling ALS. Mutant FUS transgenic rats developed progressive paralysis secondary to degeneration of motor axons and displayed a substantial loss of neurons in the cortex and hippocampus. This neuronal loss was accompanied by ubiquitin aggregation and glial reaction. While transgenic rats that overexpressed the wild-type human FUS were asymptomatic at young ages, they showed a deficit in spatial learning and memory and a significant loss of cortical and hippocampal neurons at advanced ages. These results suggest that mutant FUS is more toxic to neurons than normal FUS and that increased expression of normal FUS is sufficient to induce neuron death. Our FUS transgenic rats reproduced some phenotypes of ALS and FTLD and will provide a useful model for mechanistic studies of FUS-related diseases.
- Published
- 2011
- Full Text
- View/download PDF
37. Transgenic rat model of neurodegeneration caused by mutation in the TDP gene.
- Author
-
Hongxia Zhou, Cao Huang, Han Chen, Dian Wang, Carlisle P Landel, Pedro Yuxing Xia, Robert Bowser, Yong-Jian Liu, and Xu Gang Xia
- Subjects
Genetics ,QH426-470 - Abstract
TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43-related neurodegenerative diseases.
- Published
- 2010
- Full Text
- View/download PDF
38. Dense mapping of IL2RA shows no association with Gravesʼ disease in Chinese Han population
- Author
-
Song, Zhi-Yi, Liu, Wei, Xue, Li-Qiong, Pan, Chun-Ming, Wang, Hai-Ning, Gu, Zhao-Hui, Yang, Shao-Ying, Cao, Huang-Ming, Zuo, Chun-Lin, Zhang, Xiao-Na, Jiang, He, Liu, Bing-Li, Bi, Ya-Xin, Zhang, Xiao-Mei, Zhao, Shuang-Xia, and Song, Huai-Dong
- Published
- 2013
- Full Text
- View/download PDF
39. RBM24 stabilizes hepatitis B virus pregenomic RNA but inhibits core protein translation by targeting the terminal redundancy sequence
- Author
-
Yongxuan Yao, Yang, Bo, Cao, Huang, Kaitao Zhao, Yifei Yuan, Yingshan Chen, Zhenhua Zhang, Wang, Yun, Rongjuan Pei, Jizheng Chen, Hu, Xue, Zhou, Yuan, Mengji Lu, Chunchen Wu, and Xinwen Chen
- Subjects
virus diseases ,digestive system diseases - Abstract
The terminal redundancy (TR) sequence of the 3.5-kb hepatitis B virus (HBV) RNA contains sites that govern many crucial functions in the viral life cycle, including polyadenylation, translation, RNA packaging, and DNA synthesis. In the present study, RNA-binding motif protein 24 (RBM24) is shown to be involved in the modulation of HBV replication by targeting the TR of HBV RNA. In HBV-transfected hepatoma cell lines, both knockdown and overexpression of RBM24 led to decreased HBV replication and transcription. Ectopic expression of RBM24 inhibited HBV replication, which was partly restored by knockdown of RBM24, indicating that a proper level of RBM24 was required for HBV replication. The regulation of RBM24 of HBV replication and translation was achieved by the interaction between the RNA-binding domains of RBM24 and both the 5′ and 3′ TR of 3.5-kb RNA. RBM24 interacted with the 5′ TR of HBV pregenomic RNA (pgRNA) to block 80S ribosome assembly on HBV pgRNA and thus inhibited core protein translation, whereas the interaction between RBM24 and the 3′ TR enhanced the stability of HBV RNA. Finally, the regulatory function of RBM24 on HBV replication was further confirmed in a HBV infection model. In conclusion, the present study demonstrates the dual functions of RBM24 by interacting with different TRs of viral RNA and reveals that RBM24 is an important host gene for HBV replication.
- Published
- 2019
- Full Text
- View/download PDF
40. Increased Ubqln2 expression causes neuron death in transgenic rats
- Author
-
Xu-Gang Xia, Cao Huang, Qinxue Wu, Hongxia Zhou, and Bo Huang
- Subjects
0301 basic medicine ,Proteasome Endopeptidase Complex ,Mutant ,Spatial Learning ,Autophagy-Related Proteins ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Biochemistry ,Article ,UBQLN2 ,Rats, Sprague-Dawley ,Pathogenesis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Sequestosome-1 Protein ,Autophagy ,medicine ,Animals ,Humans ,Ubiquitins ,Adaptor Proteins, Signal Transducing ,Neurons ,Mutation ,Cell Death ,Learning Disabilities ,Neurodegeneration ,Brain ,medicine.disease ,Rats ,Cell biology ,030104 developmental biology ,Proteasome ,biology.protein ,Rats, Transgenic ,Neuron death ,030217 neurology & neurosurgery - Abstract
Pathogenic mutation of ubiquilin 2 (UBQLN2) causes neurodegeneration in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. How UBQLN2 mutations cause the diseases is not clear. While over-expression of UBQLN2 with pathogenic mutation causes neuron death in rodent models, deletion of the Ubqln2 in rats has no effect on neuronal function. Previous findings in animal models suggest that UBQLN2 mutations cause the diseases mainly through a gain rather than a loss of functions. To examine whether the toxic gain in UBQLN2 mutation is related to the enhancement of UBQLN2 functions, we created new transgenic rats over-expressing wild-type human UBQLN2. Considering that human UBQLN2 may not function properly in the rat genome, we also created transgenic rats over-expressing rat's own Ubqln2. When over-expressed in rats, both human and rat wild-type Ubqln2 caused neuronal death and spatial learning deficits, the pathologies that were indistinguishable from those observed in mutant UBQLN2 transgenic rats. Over-expressed wild-type UBQLN2 formed protein inclusions attracting the autophagy substrate sequestosome-1 and the proteasome component 26S proteasome regulatory subunit 7. These findings suggest that excess UBQLN2 is toxic rather than protective to neurons and that the enhancement of UBQLN2 functions is involved in UBQLN2 pathogenesis. Pathogenic mutation in ubiquilin 2 (UBQLN2) causes neurodegeneration in ALS and FTLD. Studies in rodent models suggest a gain of toxic function in mutant UBQLN2. We created new transgenic rats as a relevant model and examined whether enhancing wild-type UBQLN2 expression is implicated in the pathogenesis of mutant UBQLN2. We observed that over-expression of human or rat wild-type Ubqln2 caused protein aggregation and neuronal death in transgenic rats. Our findings suggest that excess UBQLN2 is toxic rather than protective to neurons and that uncontrolled enhancement of UBQLN2 function is involved in UBQLN2 pathogenesis. Read the Editorial Highlight for this article on page 159.
- Published
- 2016
- Full Text
- View/download PDF
41. Integrated wireless communication system using MANET for remote pastoral areas of Tibet
- Author
-
Qing Zhou, Dongchen Zhang, and Cao Huang
- Subjects
Adaptive quality of service multi-hop routing ,Computer Networks and Communications ,business.industry ,Computer science ,Wireless ad hoc network ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Mobile computing ,Wireless Routing Protocol ,020206 networking & telecommunications ,02 engineering and technology ,Mobile ad hoc network ,Optimized Link State Routing Protocol ,0202 electrical engineering, electronic engineering, information engineering ,Mobile wireless sensor network ,020201 artificial intelligence & image processing ,Electrical and Electronic Engineering ,business ,Computer network ,Triangular routing - Abstract
To reduce the network deployment cost and provide voice, message and low rate data services in remote pastoral areas of Tibet effectively, an integrated wireless communication system utilizing MANET (Mobile Ad hoc Network) is proposed. The sparse mobile devices, assisted with the solar-powered multi-functional standing stations mainly on networking maintenance and routing arrangement, self-organize into a MANET. The topology of the standing stations is designed for networking robust and to simplify the routing method and energy strategy. Then in the OMNeT++ (Objective Modular Network Test bed in C++) simulation, the energy consumption is analysis while adjusting routing with the different energy status of the standing stations. The result shows that the standing stations should adjust routing as well as control the mobile devices' activity level according to the energy states of the standing stations and their adjacent mobile devices.
- Published
- 2016
- Full Text
- View/download PDF
42. Inflammatory and immuno-reactivity in mice induced by intramuscular implants of HSNGLPL peptide grafted-polyurethane
- Author
-
Gang Wu, Cao Huang, Dandan Shi, Huan Wang, Hua Liao, Rong Zhu, Ruicai Gu, and Jiangwei Xiao
- Subjects
0301 basic medicine ,Materials science ,Necrosis ,Biomedical Engineering ,Peptide ,Inflammation ,02 engineering and technology ,03 medical and health sciences ,Gastrocnemius muscle ,In vivo ,medicine ,Myocyte ,General Materials Science ,chemistry.chemical_classification ,Monocyte ,General Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,Acquired immune system ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Immunology ,medicine.symptom ,0210 nano-technology - Abstract
Synthetic peptide-based polyurethanes (PUs), introduced as bioactive agents and possessing impressive properties, have emerged as attractive functional biomaterials for tissue regeneration. In this study, we developed a PU with a pendent HSNGLPL group through click reaction, which has strong affinity to TGF-β1. The peptide grafted-PUs, or PUs with BDO as the chain extender (control), were implanted into the gastrocnemius muscle (GN) of C57BL/6 mice, for evaluating their inflammatory and immuno-reactivity in vivo. We show herein that, after muscle implantation, BDO-PU induced a conspicuous monocyte/macrophage infiltration and myofiber degeneration. The inflammatory invasion and myofiber necrosis were mainly detected in the site around, but not far from, the implants, suggesting that the degraded PU matrix only triggers a local and limited inflammation in vivo. In contrast, peptide grafted-PU induced intramuscular inflammation was more complex and was sustained for more than 2 months. Apart from nonspecific monocyte/macrophage infiltration as in the case of BDO-PU, CD4+ T cells and dendritic cells (DCs), the members of the adaptive immune system, can be detected within the inflammatory site around peptide grafted-PU implants. The number of apoptotic macrophages in muscle containing peptide-PU was significantly lower compared to that in muscle containing BDO-PU. Thus, our present results suggest that, the PU matrix degradation-produced local environment is toxic to muscle cells and induces muscle degeneration. Moreover, highly aggregated peptide on PU might act as an immunogen to trigger intramuscular inflammation and lead to the delayed inflammatory response.
- Published
- 2016
- Full Text
- View/download PDF
43. Mutant UBQLN2P497H in motor neurons leads to ALS-like phenotypes and defective autophagy in rats
- Author
-
Limo Gao, Bo Huang, Tianhong Chen, Cao Huang, and Xinglong Shi
- Subjects
0301 basic medicine ,Mutant ,P62 ,Protein aggregation ,Biology ,lcsh:RC346-429 ,Pathology and Forensic Medicine ,UBQLN2 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Gene expression ,Autophagy ,medicine ,Amyotrophic lateral sclerosis ,lcsh:Neurology. Diseases of the nervous system ,Denervation ,medicine.disease ,Phenotype ,Cell biology ,030104 developmental biology ,Motor neuron degeneration ,biology.protein ,Neurology (clinical) ,ALS - Abstract
Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes were not observed when mutant UBQLN2P497H was overexpressed in the astrocytes, however, even though the expression of the mutant UBQLN2P497H protein was higher in these rats. Our results suggest that selectively expressing mutant UBQLN2P497H in motor neurons is sufficient to trigger the development of ALS in rats. Our results further indicate that the compromised autophagy-lysosomal pathway plays a critical role in the pathogenesis of UBQLN2-related neurodegenerative diseases.
- Published
- 2018
- Full Text
- View/download PDF
44. [Molecular Characteristics and Clinical Features of Adults with
- Author
-
Yan, Lun, Jing-Cao, Huang, Dan, Long, Fang-Fang, Wang, Yang, Dai, Yan, Yang, Ting-Ting, Zhao, Qing, Li, and Yu, Wu
- Subjects
Adult ,Nuclear Pore Complex Proteins ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,Gene Duplication ,Mutation ,Humans ,Gene Fusion ,Prognosis - Abstract
To determine the molecular characteristics and clinical features of patients with nucleoporin 98 (NUP98) fusion gene positive acute myeloid leukemia (AML) and the impact of coexistence ofSamples of bone marrow or peripheral blood were collected from the adult patients with de novo AML and myelodysplastic syndrome (MDS) in our hospital from July 1st, 2014 to March 1st, 2017.A total of 197 AML patients participated in this study, including 16 (8.1%) having
- Published
- 2018
45. Stability for Sampled-Data Systems with Delay and Applications for Networked Control Systems
- Author
-
Ying Wang, Cao Huang, and Huiyu Jin
- Subjects
Nonlinear system ,Stability conditions ,Control theory ,Computer science ,Network packet ,Control system ,Stability (learning theory) ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,Computer Science::Databases ,Dropout (neural networks) ,Software configuration management - Abstract
Stability1 of networked control systems with nonlinear plant is a challenge problem and this problem is investigated with approximate discrete-time design approach in this paper. The stability conditions for nonlinear sampled-data systems are extended to the time-delay situations, which can guarantee stability of networked control systems when delay and data packet dropout may take place. For these systems, the controller can be designed based on Euler approximation, while the stability can be guaranteed with fast sampling and suitable hardware and software configuration, which control the delay time and data packet dropout.
- Published
- 2018
- Full Text
- View/download PDF
46. Mutant UBQLN2
- Author
-
Tianhong, Chen, Bo, Huang, Xinglong, Shi, Limo, Gao, and Cao, Huang
- Subjects
Proline ,Motor Disorders ,P62 ,Administration, Oral ,Choline O-Acetyltransferase ,Lysosomal-Associated Membrane Protein 2 ,Autophagy ,Animals ,Histidine ,Muscle, Skeletal ,Ubiquitins ,Motor Neurons ,Research ,Amyotrophic Lateral Sclerosis ,Rats ,DNA-Binding Proteins ,Disease Models, Animal ,Gene Expression Regulation ,Spinal Cord ,Doxycycline ,Motor neuron degeneration ,Mutation ,Rats, Transgenic ,ALS ,Protein aggregation ,Psychomotor Performance ,UBQLN2 - Abstract
Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes were not observed when mutant UBQLN2P497H was overexpressed in the astrocytes, however, even though the expression of the mutant UBQLN2P497H protein was higher in these rats. Our results suggest that selectively expressing mutant UBQLN2P497H in motor neurons is sufficient to trigger the development of ALS in rats. Our results further indicate that the compromised autophagy-lysosomal pathway plays a critical role in the pathogenesis of UBQLN2-related neurodegenerative diseases. Electronic supplementary material The online version of this article (10.1186/s40478-018-0627-9) contains supplementary material, which is available to authorized users.
- Published
- 2018
47. [Mutations of G38R and D40G cause amyotrophic lateral sclerosis by reducing Annexin A11 protein stability]
- Author
-
Di, Liao, Qiao, Liao, Cao, Huang, and Fangfang, Bi
- Subjects
HEK293 Cells ,Solubility ,Annexins ,Protein Stability ,Amyotrophic Lateral Sclerosis ,Mutation ,Humans ,Transfection ,Plasmids - Abstract
To explore the role of the mutations G38R and D40G of Annexin A11 (ANXA11) in the onset of amyotrophic lateral sclerosis (ALS). Methods: The plasmids expressing ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein were constructed, respectively. The recombinant plasmids were then transfected into HEK293 cells respectively followed by cycloheximide (CHX) treatment for 0, 2, 4 and 8 h. The protein expressions of ANXA11 wild type, ANXA11 G38R and ANXA11 D40G mutations were determined by Western blot. Gray analysis by Image J was performed to compare the half-life of each protein. The NSC-34 cell lines constantly expressing ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein were established. The cells were treated with NP-40 lysis buffer to examine the protein solubility by Western blot. Results: Both ANXA11 G38R protein and ANXA11 D40G protein showed a shorter half-life than ANXA11 wild type protein (P0.05), while there was no difference between ANXA11 G38R protein and ANXA11 D40G protein (P0.05). There was no visible insoluble substance in the NP-40 lysates for ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein. Conclusion: G38R and D40G mutations reduce the stability of ANXA11 protein. G38R and D40G mutations do not alter ANXA11 solubility.目的:探讨Annexin A11(ANXA11) G38R及D40G突变引起肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)的发病机制。方法:构建编码ANXA11 G38R,ANXA11 D40G突变蛋白及ANXA11野生型蛋白真核表达载体pANXA11-G38R-Flag,pANXA11-D40G-Flag和pANXA11-Flag;将其转染至HEK293细胞后,用放线菌酮分别处理0,2,4,8 h;收集蛋白采用Western印迹检测3种蛋白的含量变化情况,比较目标蛋白的半衰期;构建稳定表达ANXA11 G38R,ANXA11 D40G突变蛋白及ANXA11野生型蛋白的NSC-34细胞系,用Western印迹检测上述蛋白在NP-40裂解液中的溶解情况。结果:ANXA11 G38R,ANXA11 D40G突变蛋白的半衰期较野生型蛋白缩短(P0.05),ANXA11 G38R蛋白和ANXA11 D40G蛋白半衰期无明显差异(P0.05);ANXA11 G38R,ANXA11 D40G突变蛋白与ANXA11野生型蛋白在NP-40裂解液中均未发现不可溶成分。结论:G38R和D40G突变降低了ANXA11蛋白的稳定性;G38R和D40G突变不影响ANXA11蛋白在NP-40裂解液中的可溶性。.
- Published
- 2018
48. Research on Investor Protection System of Chinese Depositary Receipts
- Author
-
Cao Huang
- Subjects
business.industry ,Information disclosure ,Accounting ,Business ,Investor protection - Published
- 2018
- Full Text
- View/download PDF
49. Linear active disturbance rejection control of quadrotor's altitude and attitude
- Author
-
Cao Huang, Bo Ye, Huiyu Jin, and Weiyao Lan
- Subjects
Coupling ,020301 aerospace & aeronautics ,0209 industrial biotechnology ,Engineering ,business.industry ,Control engineering ,Angular velocity ,02 engineering and technology ,Active disturbance rejection control ,Stability (probability) ,Computer Science::Robotics ,Attitude control ,020901 industrial engineering & automation ,Altitude ,0203 mechanical engineering ,Computer Science::Systems and Control ,Control theory ,Torque ,Robust control ,business - Abstract
The problem of how to control a quadrotor is investigated. A nonlinear model of the quadrotor is derived with Newton-Euler formulation and then simplified. With the simplified model, Linear Active Disturbance Rejection Control (LADRC) is used to control the altitude and attitude of the quadrotor. Simulations show LADRC can deal with the model uncertainty and coupling, guarantee stability, and have a good performance in tracking a step signal.
- Published
- 2017
- Full Text
- View/download PDF
50. Profiling the genes affected by pathogenic TDP-43 in astrocytes
- Author
-
Xu-Gang Xia, Cao Huang, Hongxia Zhou, Fangfang Bi, Linda H. Yan, Bo Huang, Jufang Huang, and Jianbin Tong
- Subjects
Programmed cell death ,Cell Survival ,Molecular Sequence Data ,Primary Cell Culture ,Fluorescent Antibody Technique ,Polymerase Chain Reaction ,Biochemistry ,Article ,CHI3L1 ,Cellular and Molecular Neuroscience ,mental disorders ,Gene expression ,medicine ,Animals ,Chitinase-3-Like Protein 1 ,Nerve Growth Factors ,Glycoproteins ,Neurons ,Extracellular Matrix Proteins ,Cell Death ,biology ,Microarray analysis techniques ,Gene Expression Profiling ,Amyotrophic Lateral Sclerosis ,Neurodegeneration ,nutritional and metabolic diseases ,Microarray Analysis ,medicine.disease ,Molecular biology ,Rats ,nervous system diseases ,DNA-Binding Proteins ,Gene expression profiling ,Astrocytes ,Mutation ,biology.protein ,Rats, Transgenic ,Neuron death ,Neurotrophin - Abstract
Mutation in TAR DNA binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neurodegeneration may not require the presence of pathogenic TDP-43 in all types of relevant cells. Rather, expression of pathogenic TDP-43 in neurons or astrocytes alone is sufficient to cause cell-autonomous or non-cell-autonomous neuron death in transgenic rats. How pathogenic TDP-43 in astrocytes causes non-cell-autonomous neuron death, however, is not clear. Here, we examined the effect of pathogenic TDP-43 on gene expression in astrocytes. Microarray assay revealed that pathogenic TDP-43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down-regulated, neurotoxic genes were up-regulated. Representative genes Lcn2 and chitinase-3-like protein 1 were markedly up-regulated in astrocytes from primary culture and intact transgenic rats. Furthermore, synthetic chitinase-3-like protein 1 induced neuron death in a dose-dependent manner. Our results suggest that TDP-43 pathogenesis is associated with the simultaneous induction of multiple neurotoxic genes in astrocytes, which may synergistically produce adverse effects on neuronal survival and contribute to non-cell-autonomous neuron death. Restricted expression of pathogenic TDP-43 in astrocytes causes non-cell-autonomous motor neuron death in transgenic rats. As revealed by microarray assay, pathogenic TDP-43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down-regulated, neurotoxic genes were up-regulated. Therefore, TDP-43 pathogenesis is associated with simultaneous induction of neurotoxic genes and repression of neurotrophic genes in astrocytes.
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.