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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(7): 704-710, 2021 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34382586

RESUMO

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.


Assuntos
Pacientes Internados , Lúpus Eritematoso Sistêmico , Idoso , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Prednisona , Fatores de Risco
2.
Stem Cell Res ; 53: 102326, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33845242

RESUMO

Skin fibroblasts derived from a 71-year-old healthy woman were reprogrammed into induced pluripotent stem cells (iPSCs) by the transduction of retroviruses expressing OCT4, SOX2, KLF4 and c-MYC, respectively. The generated iPSCs maintained a normal karyotype and expressed various pluripotency markers. Moreover, they could be induced to form embryoid bodies in vitro and teratomas in vivo, indicating the full capacity of differentiating into three germ layers. This iPSC line could be differentiated into multiple cell subtypes for cellular modeling and drug discovery.


Assuntos
Células-Tronco Pluripotentes Induzidas , Idoso , Diferenciação Celular , Corpos Embrioides , Feminino , Fibroblastos , Camadas Germinativas , Humanos
3.
Stem Cell Res ; 53: 102336, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33865102

RESUMO

We established an induced pluripotent stem cell (iPSC) reprogrammed from dermal fibroblasts of a 53-year-old healthy man. Retroviruses expressing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) were employed to initiate the reprogramming and were silenced in iPSCs. The generated iPSCs were pluripotent as determined by immunostaining and expression of pluripotency markers. They were further induced as embryoid bodies in vitro and teratomas in vivo, reminiscent of their full capacity of differentiating into three germ layers. They are with a normal karyotype and genetically identical to donor fibroblasts. This iPSC line provides excellent cell sources for studying and modeling human-specific physiology.


Assuntos
Células-Tronco Pluripotentes Induzidas , Teratoma , Diferenciação Celular , Reprogramação Celular , Corpos Embrioides , Fibroblastos , Humanos , Masculino , Pessoa de Meia-Idade
4.
Stem Cell Res ; 53: 102277, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33706202

RESUMO

Early onset isolated dystonia (DYT1) is a hereditary neurological movement disease caused by a single amino-acid deletion in torsin A (TOR1A), a gene encoding a membrane-embedded ATPase. In this study, we generated an induced pluripotent stem cell (iPSC) line from fibroblasts of a DYT1 patient by the retroviral transduction of Yamanaka factors. The iPSCs retained the heterozygous TOR1A mutation (p.Glu303del), showed a normal karyotype, expressed pluripotency markers and exhibited the potential to differentiate into three germ layers both in vitro and in vivo. This DYT1 patient-specific iPSC will be used for modeling the dystonia pathophysiology and probably drug screening.


Assuntos
Distonia , Células-Tronco Pluripotentes Induzidas , Fibroblastos , Heterozigoto , Humanos , Chaperonas Moleculares , Mutação
5.
Front Neurol ; 11: 566680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178109

RESUMO

As the pandemic of COVID-19 is raging around the world, the mysteriousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) coronavirus is being revealed by the concerted endeavors of scientists. Although fever and pneumonia are typical symptoms, COVID-19 patients exhibit multiple neurological complications. In this interim review, we will summarize the neurological manifestations and their potential causes in COVID-19. Similar to the other two fatal respiratory coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 also shows to be neuroinvasive that may spread from the periphery to brain, probably by the retrograde axonal transport. The invaded viruses may directly disrupt the complex neural circuits, and raise a chronic activation of immune responses. In another hand, multiple organ failure in severe COVID-19 is caused by the systemic acute immune responses, and unsurprisingly caused the brain inflammation and led to encephalitis. However, in the central nervous system (CNS), the activation of resident immune cells including microglia and astrocytes may lead to chronic immune imbalance, which underlies the potential long-term effects in synaptic changes and neuropsychiatric impairments. The neuroinvasive biology also provides a possible link with the Braak staging of neurodegenerative diseases such as Parkinson's disease (PD). Although with considerable advances, the neurotropic potential and chronic neurological effects caused by SARS-CoV-2 infections merit further investigations.

6.
Hypertens Pregnancy ; 39(2): 165-171, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32239976

RESUMO

Objective: This study aimed to investigate the expression and role of ERAP1 in preeclampsia pathogenesis.Methods: ERAP1 expression of placental tissues was analyzed by Real-Time PCR and western blot. The location of ERAP1 was detected by immunohistochemistry. Cellular preeclampsia model was established by hypoxia treatment of HTR-8/SVneo cells (2% oxygen).Results: The present study revealed that ERAP1 expression were significantly elevated in placental tissues of preeclampsia, and hypoxiaincreased ERAP1 expression in trophoblast, suggesting that ERAP-1 may be involved in the development of preeclampsia.Conclusion: These finds highlight the role of ERAP1 in the pathogenesis of preeclampsia.


Assuntos
Aminopeptidases/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Adulto , Aminopeptidases/genética , Linhagem Celular , Feminino , Humanos , Antígenos de Histocompatibilidade Menor/genética , Pré-Eclâmpsia/genética , Gravidez , Trofoblastos/metabolismo
7.
Theranostics ; 10(7): 3118-3137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194858

RESUMO

The CRISPR-based genome editing holds immense potential to fix disease-causing mutations, however, must also handle substantial natural genetic variations between individuals. Previous studies have shown that mismatches between the single guide RNA (sgRNA) and genomic DNA may negatively impact sgRNA efficiencies and lead to imprecise specificity prediction. Hence, the genetic variations bring about a great challenge for designing platinum sgRNAs in large human populations. However, they also provide a promising entry for designing allele-specific sgRNAs for the treatment of each individual. The CRISPR system is rather specific, with the potential ability to discriminate between similar alleles, even based on a single nucleotide difference. Genetic variants contribute to the discrimination capabilities, once they generate a novel protospacer adjacent motif (PAM) site or locate in the seed region near an available PAM. Therefore, it can be leveraged to establish allele-specific targeting in numerous dominant human disorders, by selectively ablating the deleterious alleles. So far, allele-specific CRISPR has been increasingly implemented not only in treating dominantly inherited diseases, but also in research areas such as genome imprinting, haploinsufficiency, spatiotemporal loci imaging and immunocompatible manipulations. In this review, we will describe the working principles of allele-specific genome manipulations by virtue of expanding engineering tools of CRISPR. And then we will review new advances in the versatile applications of allele-specific CRISPR targeting in treating human genetic diseases, as well as in a series of other interesting research areas. Lastly, we will discuss their potential therapeutic utilities and considerations in the era of precision medicine.

8.
Biomed Res Int ; 2019: 1039623, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828084

RESUMO

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder, caused by a CAG/polyglutamine (polyQ) repeat expansion in the Huntingtin (HTT) gene. The polyQ tract is located in and transcribed from N-terminal HTT of exon 1. HTT is a large multifaceted protein, which participates in a range of cellular functions. Previous studies have shown that truncated HTT, which lacks N-terminus, retains specific functions that can produce neuroprotective benefits. It gives an insight that it is possible to repair HD by removing deleterious N-terminal HTT with CRISPR/Cas9, without compromising functions of remaining HTT peptides. To successfully generate functional truncated HTT proteins, an alternative downstream ATG start codon that is capable of initiating truncated HTT expression is required. In this study, we searched all possible in-frame ATGs before exon 7 and demonstrated that one of them can indeed initiate the downstream GFP expression in plasmids. We then tried to remove endogenous N-terminal HTT with an optimized dual-sgRNA strategy by CRISPR/Cas9; however, we cannot detect obvious traits of truncated HTT expression. Our results suggest that noncanonical ATGs of N-terminal HTT may not be effective in the genomic context, as in the construct context. Nevertheless, our study examined the therapeutic efficacy of downstream noncanonical ATGs for protein translation and also provided an optimized dual-sgRNA strategy for further genome manipulation of the HTT gene.


Assuntos
Sistemas CRISPR-Cas/genética , Proteína Huntingtina/genética , RNA/genética , Sequência de Aminoácidos , Linhagem Celular , Expressão Gênica/genética , Células HEK293 , Humanos , Doença de Huntington/genética , Degeneração Neural/genética , Biossíntese de Proteínas/genética , Alinhamento de Sequência
9.
Front Mol Neurosci ; 9: 89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27708561

RESUMO

Microglia-mediated neuroinflammation is a hallmark of Parkinson's disease (PD). In the brains of patients with PD, microglia have both neurotoxic and neuroprotective effects, depending on their activation state. In this review, we focus on recent research demonstrating the neuroprotective role of microglia in PD. Accumulating evidence indicates that the protective mechanisms of microglia may result from their regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification, and microRNA regulation. All of these mechanisms work together to suppress the production of neurotoxic inflammatory components. However, during the progression of PD, the detrimental effects of inflammation overpower the protective actions of microglia. Therefore, an in-depth exploration of the mechanisms underlying microglial neuroprotection, and a means of promoting the transformation of microglia to the protective phenotype, are urgently needed for the treatment of PD.

10.
Asian Pac J Cancer Prev ; 12(10): 2801-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22320996

RESUMO

OBJECTIVE: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening. METHODS: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire. RESULTS: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge. CONCLUSION: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.


Assuntos
Detecção Precoce de Câncer , Educação de Pós-Graduação em Medicina , Avaliação Educacional , Conhecimentos, Atitudes e Prática em Saúde , China , Competência Clínica , Feminino , Humanos , Internato e Residência , Masculino , Programas de Rastreamento , Neoplasias/diagnóstico , Padrões de Prática Médica , Faculdades de Medicina , Inquéritos e Questionários
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