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1.
Medicine (Baltimore) ; 100(37): e27234, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664866

RESUMO

ABSTRACT: Various studies have revealed an association between cigarette smoking and increased risk for multiple sclerosis (MS). However, its role in neuromyelitis optica spectrum disorder (NMOSD) remains elusive. Therefore, in the present case-control study, we aimed to assess the association of active and passive cigarette smoking with the risk of MS and NMOSD.Thirty-six patients with NMOSD, 46 patients with MS, and 122 healthy individuals were included in this study. Standardized questionnaires and telephone interviews were used to collect information regarding the active and passive cigarette smoking behaviors of the patients and normal controls.The risk of MS was significantly higher among smokers than among nonsmokers (odds ratio = 2.166, 95% confidence interval: 1.109-4.170; P = .027). Further analysis of the risk between active and passive smokers, male smokers and nonsmokers showed no statistical difference. However, neither smokers nor active smokers had a greater or lower risk of NMOSD than their nonsmoking counterparts.Our preliminary study showed no significant association between cigarette smoking and the risk of NMOSD, strongly suggesting that, unlike MS, cigarette smoking might not confer NMOSD susceptibility, at least in the Northern Han Chinese population.

2.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3165-3170, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467709

RESUMO

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.


Assuntos
Aptâmeros de Nucleotídeos , Ácidos Nucleicos , Sistemas de Liberação de Medicamentos , Medicina Tradicional Chinesa , RNA Interferente Pequeno
4.
Nucleic Acids Res ; 48(6): 3089-3102, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030426

RESUMO

Long non-coding RNAs (lncRNAs) have emerged as important biological tuners. Here, we reveal the role of an uncharacterized lncRNA we call SENEBLOC that is expressed by both normal and transformed cells under homeostatic conditions. SENEBLOC was shown to block the induction of cellular senescence through dual mechanisms that converge to repress the expression of p21. SENEBLOC facilitates the association of p53 with MDM2 by acting as a scaffold to promote p53 turnover and decrease p21 transactivation. Alternatively, SENEBLOC was shown to affect epigenetic silencing of the p21 gene promoter through regulation of HDAC5. Thus SENEBLOC drives both p53-dependent and p53-independent mechanisms that contribute to p21 repression. Moreover, SENEBLOC was shown to be involved in both oncogenic and replicative senescence, and from the perspective of senolytic agents we show that the antagonistic actions of rapamycin on senescence are dependent on SENEBLOC expression.


Assuntos
Envelhecimento/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Animais , Carcinogênese/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Xenoenxertos , Histona Desacetilases/genética , Humanos , Camundongos , Ligação Proteica/genética , Transdução de Sinais/genética
5.
Nat Commun ; 10(1): 5334, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767869

RESUMO

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA-DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.


Assuntos
Carcinogênese/genética , Elementos Facilitadores Genéticos/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Proteínas Associadas a Pancreatite/genética , RNA Helicases/genética , RNA Longo não Codificante/genética , Transcrição Genética , Biomarcadores Tumorais/genética , Linhagem Celular , Linhagem Celular Tumoral , DNA/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Células HT29 , Humanos , Neoplasias/genética , Neoplasias/patologia , Proteínas Associadas a Pancreatite/metabolismo , Regiões Promotoras Genéticas/genética , RNA Helicases/metabolismo
6.
Org Biomol Chem ; 17(34): 7938-7942, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31417995

RESUMO

A series of C-2' modified cinchonine-derived phase-transfer catalysts were synthesized and used in the enantioselective photo-organocatalytic aerobic oxidation of ß-dicarbonyl compounds with excellent yields (up to 97%) and high enantioselectivities (up to 90% ee). Furthermore, the reaction was carried out in a flow photomicroreactor, in which the heterogeneous gas-liquid-liquid asymmetric photocatalytic oxidation reaction was performed affording good yields (up to 97%) and enantioselectivities (up to 86% ee) within 0.89 min.

7.
Cell Mol Neurobiol ; 39(3): 451-460, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30778712

RESUMO

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.


Assuntos
Ligante 4-1BB/metabolismo , Isquemia Encefálica/metabolismo , Ligante 4-1BB/sangue , Animais , Linfócitos B/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Membrana Celular/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
9.
Proc Natl Acad Sci U S A ; 115(50): E11661-E11670, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30478051

RESUMO

Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.


Assuntos
Senescência Celular/genética , Senescência Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Xenoenxertos , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Camundongos Nus , Estabilidade Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
10.
Cancer Res ; 78(23): 6666-6679, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30301840

RESUMO

: Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. SIGNIFICANCE: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.


Assuntos
Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Senescência Celular/genética , Genes Reporter , Genes cdc , Humanos , Camundongos , Modelos Biológicos , Fosforilação , Interferência de RNA , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo
11.
Clin Transl Sci ; 11(4): 428-434, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29697202

RESUMO

As a proinflammatory cytokine, CD137 (4-1BB, TNFRSF9) is present in membrane-bound and soluble forms. Increased expression of CD137 was recently found in T cells in human atherosclerotic plaques. However, the exact role of CD137 in ischemic stroke is not clear. In this study we analyzed the protein levels of soluble CD137 (sCD137) and the expression of CD137 on CD4+ T cells in the peripheral blood of patients with acute atherothrombotic stroke by using the cytometry beads array (CBA) and flow cytometry. Within 24 hours of onset, the stroke patients showed elevated levels of sCD137 (2.7 pg/ml) and CD137 expression on CD4+ T cells (4.9 ± 3.2%) compared with normal controls (1.1 pg/ml, P < 0.01; 1.3 ± 1.0%, P < 0.01). Alterations in CD137 expression may enhance ischemia-induced inflammatory responses via bidirectional signaling and, consequently, aggravate brain injury in early stages of this disorder.


Assuntos
Aterosclerose/sangue , Linfócitos T CD4-Positivos/metabolismo , Acidente Vascular Cerebral/sangue , Trombose/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Idoso , Aterosclerose/complicações , Aterosclerose/imunologia , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia , Trombose/etiologia , Trombose/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
12.
Cancer Res ; 77(22): 6226-6239, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28947420

RESUMO

MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1 upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment. Cancer Res; 77(22); 6226-39. ©2017 AACR.


Assuntos
Enzimas Reparadoras do DNA/genética , Melanoma/genética , Estresse Oxidativo , Monoéster Fosfórico Hidrolases/genética , Proteínas Quinases Associadas a Fase S/genética , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Enzimas Reparadoras do DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases/genética , Melanoma/metabolismo , Melanoma/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Poliubiquitina/metabolismo , Estabilidade Proteica , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Quinases Associadas a Fase S/metabolismo , Ubiquitinação
13.
Chin Med J (Engl) ; 130(19): 2296-2301, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28937034

RESUMO

BACKGROUND: As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). METHODS: Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35-55to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low-CS group, n = 5), high dosage of CS (high-CS group, n = 5), or the same volume of normal saline (control group, n = 5). All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T-cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin-eosin and luxol fast blue staining. Data were analyzed using the one-way analysis of variance (ANOVA). RESULTS: Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group. CONCLUSIONS: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.


Assuntos
Cordyceps , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Medicina Tradicional Chinesa/métodos , Análise de Variância , Animais , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/tratamento farmacológico , Feminino , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Projetos Piloto , Células Th1/metabolismo , Células Th17/metabolismo
14.
J Huazhong Univ Sci Technolog Med Sci ; 37(1): 93-99, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28224419

RESUMO

The theory of branch atheromatous disease (BAD) has been commonly underused in clinical practice and research since it was proposed in 1989. In this study, we sought to explore clinical characteristics of its substypes and biomarkers for prognosis of BAD. A total of 176 consecutive patients with BAD were classified into two groups: paramedianpontine artery group (PPA group, n=70) and lenticulostriate artery group (LSA group, n=106). Bivariate analyses were used to explore the relationship between white matter hyperintensities (WMHs), National Institutes of Health Stroke Scale (NIHSS) scores and prognosis evaluated by the modified Rank Scale (mRS) at 6th month after stroke. The differences in prevalence of diabetes mellitus and a history of ischemic heart disease were statistically significant between PPA group and LSA group (χ 2=8.255, P=0.004; χ 2=13.402, P<0.001). The bivariate analyses demonstrated a positive correlation between NIHSS and poor prognosis in patients with BAD and in the two subtype groups, and a positive correlation between WMHs and poor prognosis in the PPA group. It is concluded that a significantly higher prevalence of diabetes mellitus and a history of ischemic heart disease exist in the PPA group than in the LSA group. In addition, high grades of NIHSS scores imply poor prognosis in patients with BAD and in the two subtype groups. Moreover, WMHs are a positive predictor for poor prognosis in patients in the PPA group.


Assuntos
Infarto Encefálico/classificação , Infarto Encefálico/patologia , Diabetes Mellitus/epidemiologia , Isquemia Miocárdica/epidemiologia , Acidente Vascular Cerebral/complicações , Substância Branca/patologia , Idoso , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/etiologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Substância Branca/diagnóstico por imagem
15.
Transl Neurosci ; 7(1): 76-83, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28123825

RESUMO

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system (CNS). Various genetic and environmental factors have been identified to contribute to etiology of MS and NMO. Aquaporin 4 (AQP4), is the most abundant water channel in CNS. AQP4 is expressed in astrocytes of the brain, spinal cord, optic nerve and supportive cells in sensory organs. In contrast to MS, immunoreactivity of AQP4 is abolished in NMO lesions. However, conflicting results have been reported regarding the association between AQP4 polymorphisms and demyelinating disorders. Considering the ethnic differences of genetic variations, replications in other cohorts are required. In this study, single nucleotide polymorphisms (SNPs) of AQP4 gene in patients with NMO/neuromyelitis optica spectrum disorders (NMOSD), and MS in the Northern Han Chinese population were examined. Six selected AQP4 SNPs were genotyped by high-resolution melting (HRM) method. Compared with healthy control (HC), there was no significant difference of AQP4 allele and genotype frequency in MS or NMO/NMOSD group. This study showed no significant association of common AQP4 SNPs with MS or NMO/NMOSD, strongly suggesting that polymorphisms of AQP4 gene are unlikely to confer MS or NMO/NMOSD susceptibility, at least in Northern Han Chinese population.

16.
J Huazhong Univ Sci Technolog Med Sci ; 35(6): 885-890, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26670441

RESUMO

Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non-BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed.


Assuntos
Isquemia Encefálica/patologia , Acidente Vascular Cerebral/patologia , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Gene ; 550(1): 27-32, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25106857

RESUMO

To investigate the role of TLR3/PI3K signals in the occurrence and development of cervical cancer disease, TLR3-siRNA was used to block key signaling pathways involved in cervical cancer metastasis that are pivotal to metastatic tumor cells but not to normal cells under ordinary physiologic conditions. Results show that tumor U14 cell growth, migration and invasion in TLR3-siRNA treatment group were significantly decreased. Through LY294002 suppressing targeted gene, the LY294002 treatment specifically and significantly knocked down the expressions of tumor TLR3 and PI3K proteins in cervical cancer mice. Furthermore, expressions of tumor Survivin and FasL proteins were markedly suppressed, whereas expressions of Fas protein were upregulated in LY294002 treatment group mice. LY294002 treatment suppressed tumor growth and increased the thymus and spleen indeces and survival days of cervical cancer mice. This study demonstrates that TLR3-siRNA and LY294002 treatments can markedly suppress cervical cancer cell invasion and tumor growth and increase survival life by silencing targeted genes.


Assuntos
Proteína Ligante Fas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Repressoras/metabolismo , Receptor 3 Toll-Like/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína Ligante Fas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/genética , Camundongos , Camundongos Endogâmicos BALB C , Morfolinas/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Interferência de RNA , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Baço/efeitos dos fármacos , Baço/patologia , Survivina , Timo/efeitos dos fármacos , Timo/patologia , Receptor 3 Toll-Like/genética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controle , Receptor fas
18.
PM R ; 4(2): 123-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22192459

RESUMO

OBJECTIVE: To apply and examine the performance of 2 acute stroke outcome prediction models, the Six Simple Variable Model (SSV model) and the One-Year Mortality Model (OYM model), in patients in China who had either a cerebral infarction or a cerebral hemorrhage. DESIGN: An observational study that used both retrospective and prospective study methods. SETTING: A regional acute care facility in China. PARTICIPANTS: Two hundred and forty-eight consecutive patients who had an acute stroke who were admitted to the hospital between October 2007 and March 2009. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survival and daily activity independence 6 months after a stroke and 1-year mortality. RESULTS: The study sample had a mean age of 68.6 years (standard deviation, 11.1); 52.8% of the subjects were men, 66.5% had a cerebral infarction, and 33.5% had a cerebral hemorrhage. In the cohort, 107 patients (43.1%) achieved daily activity independence at 6-month follow-up, and 52 patients (21.0%) had died within 1 year. The area under the receiver operating characteristic curve (ROC) was 0.966 (0.935-0.998) for patients who had a cerebral infarction and 0.859 (0.766-0.952) for patients who had a cerebral hemorrhage in the prediction of 6-month survival and daily activity independence with use of the SSV model. The area under the ROC curve was 0.894 (0.846-0.965) for patients who had a cerebral infarction and 0.937 (0.904-0.988) for patients who had a cerebral hemorrhage in the prediction of 1-year mortality when the OYM model was used. CONCLUSIONS: Both the SSV and OYM prognostic models can be used for function and mortality outcome prediction for patients in China who have had a stroke. Variation existed in the precision of prediction between patients who had a cerebral infarction and those who had a cerebral hemorrhage. Other potential factors influencing functional recovery and mortality after stroke must be considered in outcome prediction.


Assuntos
Acidente Vascular Cerebral/mortalidade , Atividades Cotidianas , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Reabilitação do Acidente Vascular Cerebral , Taxa de Sobrevida
19.
Mult Scler ; 13(2): 149-55, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17439879

RESUMO

A T-cell-mediated autoimmune process against central nervous system myelin is believed to underlie the pathogenesis of multiple sclerosis (MS). Formation of immunological memory is based on the differentiation of naïve T cells to memory T cells after exposure to antigens and specific cytokines. The aim of this study was to analyse peripheral blood mononuclear cells in patients with MS for different T-cell subsets including naïve and memory T cells. Flow cytometry and enzyme-linked immunosorbent assay were used to analyse memory T-cell subsets and plasma concentration of interleukin-15 (IL-15) in peripheral blood of MS patients, patients with other neurological disorders and healthy controls. MS patients had a skewed distribution of T cells with an increased level of CD8+/CCR7+/CD45RA - central memory T cells (TCM) compared to healthy controls. In addition, MS patients showed significantly higher levels of plasma IL-15 than healthy controls did. Upregulated CD8+ TCM in MS patients may reflect a persistent chronic inflammatory response that may have been induced during early stages of the disease. This derangement may be important for maintaining chronic inflammation in MS.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Esclerose Múltipla Crônica Progressiva/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Feminino , Humanos , Interleucina-15/sangue , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores CCR7 , Receptores de Quimiocinas/metabolismo , Subpopulações de Linfócitos T/imunologia
20.
Zhonghua Yi Xue Za Zhi ; 87(39): 2750-2, 2007 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-18167264

RESUMO

OBJECTIVE: To investigate the phenotypes of memory T cell subsets in the patients with multiple sclerosis (MS) and further explore the mechanisms that lead to the changes of the memory T cell subsets. METHODS: Peripheral blood samples were collected from 20 MS patients, 9 with relapsing-remitting MS (RRMS) and 11 with secondary progressive multiple sclerosis (SPMS), 20 patients with cerebral infarction (disease control group), and 22 healthy persons (healthy control group). Flow cytometry and ELISA were used to detect the phenotypes of the memory T cell subsets and plasma concentration of interleukin-15 (IL-15). RESULTS: The level of CD8+ TCM of the MS group was 20% +/- 11%%, significantly higher than that of the healthy control group (13% +/- 6%, P < 0.05). The level of the CD8+ terminal effector memory T cells of the MS group was 24% +/- 15%, significantly lower than that of the healthy control group (39% +/- 19%, P < 0.05). The plasma IL-15 level of the MS group was 36.01 pg/m, significantly higher than that of the healthy control group (9.53 pg/ml, P < 0.05). CONCLUSION: The upregulation of CD8+ TCM in the MS patients may reflect a persistent chronic inflammatory response that may have been induced during early stages of the disease, while IL-15 may participate in the immunoregulatory process of promoting TCM differentiation.


Assuntos
Interleucina-15/sangue , Esclerose Múltipla/sangue , Subpopulações de Linfócitos T/metabolismo , Adulto , Idoso , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos/metabolismo , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia
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