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1.
Int Heart J ; 62(4): 752-755, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276017

RESUMO

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.


Assuntos
Isquemia Miocárdica/sangue , Hormônios Peptídicos/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/classificação
2.
Cell Death Dis ; 12(5): 436, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934111

RESUMO

Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE-/-) mice. Six-week IMD1-53 infusion significantly reduced atherosclerotic lesion size. Of note, IMD1-53 lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD1-53 administration prevented ERS activation in aortic lesions of ApoE-/- mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE-/- mice. IMD1-53 decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD1-53 infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.


Assuntos
Inflamassomos/metabolismo , Macrófagos/metabolismo , Neuropeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Placa Aterosclerótica/metabolismo , Animais , Apoptose/fisiologia , Humanos , Camundongos , Placa Aterosclerótica/patologia
3.
J Geriatr Cardiol ; 18(3): 204-209, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33907550

RESUMO

OBJECTIVE: To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol (LDL-C) and the clinical features of haemorrhagic stroke. METHODS: This study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018. Patients were stratified into three groups according to their baseline LDL-C levels: < 70, 70 to < 100 and ≥ 100 mg/dL. We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits (National Institute Health Stroke Scale [NIHSS] scores ≥ 15) and unfavourable outcomes (modified Rankin Scale [mRS] scores>2) at discharge. RESULTS: Six-hundred and six patients were analysed. Their median age was 58 years. Among the patients, 75 (12%) patients had LDL-C levels < 70 mg/dL, 194 (32%) patients had LDL-C levels between 70 to < 100 mg/dL and the other 337 (56%) patients had LDL-C levels ≥ 100 mg/dL. Patients with higher LDL-C levels were less likely to suffer severe neurological deficits (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted odds ratio [OR]: 0.29, 95% CI: 0.15-0.57; LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.27, 95% CI: 0.15-0.51) and to have unfavourable outcomes at discharge (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted OR = 0.50, 95% CI: 0.29-0.87 and LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.46, 95% CI: 0.28-0.78). CONCLUSIONS: An LDL-C level < 70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.

4.
Infect Immun ; 89(3)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33257536

RESUMO

Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms responsible for the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during S. japonicum infection by RNA transcriptome resequencing. Liver deficiency of phospho-STAT3 alleviated infection-induced liver dysfunction, hepatic granuloma formation, and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress, and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation, and apoptosis are involved in S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Inflamação/genética , Cirrose Hepática/genética , Estresse Oxidativo/genética , Fator de Transcrição STAT3/genética , Esquistossomose Japônica/genética , Animais , Inflamação/parasitologia , Cirrose Hepática/parasitologia , Schistosoma japonicum/genética , Esquistossomose Japônica/patologia
5.
Chin Med J (Engl) ; 131(3): 347-351, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29363651

RESUMO

BACKGROUND: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. METHODS: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. CONCLUSIONS: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820.


Assuntos
Ataque Isquêmico Transitório/prevenção & controle , Precondicionamento Isquêmico , Acidente Vascular Cerebral/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Doenças Cardiovasculares , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Recidiva , Projetos de Pesquisa , Tamanho da Amostra , Prevenção Secundária , Resultado do Tratamento , Adulto Jovem
6.
Chin Med J (Engl) ; 129(17): 2079-84, 2016 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-27569235

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. METHODS: Data including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. RESULTS: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. CONCLUSION: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.


Assuntos
Esclerose Múltipla/patologia , Neuromielite Óptica/patologia , Adolescente , Adulto , Aquaporina 4/sangue , Aquaporina 4/líquido cefalorraquidiano , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Glicoproteína Mielina-Oligodendrócito/sangue , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquidiano , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Estudos Retrospectivos , Adulto Jovem
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(5): 649-54, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27222179

RESUMO

OBJECTIVE: To detect the expression of protein 4.1 family members in mouse melanoma cell lines and evaluate their effect on cell proliferation. METHODS: PCR and Western blot were used to detected to the expression of protein 4.1 family members (4.1R, 4.1B, 4.1G, and 4.1N) at the mRNA and protein levels in B16 and B16-F10 cell lines. The expression plasmid vector pEGFP-N1-EPB41L3 carrying 4.1B gene sequence amplified from genomic RNA of mouse embryo fibroblasts was constructed and transiently transfected into mouse melanoma cells. The change in cell proliferation was assessed using MTT assay. RESULTS: The mRNA and protein expressions of all the protein 4.1 family members, with the exception of 4.1B, were detected in both B16 and B16-F10 cells. Transfection of cells with the eukaryotic expression vector pEGFP-N1-EPB41L3 markedly inhibited cell proliferation as compared with the non-transfected cells. CONCLUSION: The eukaryotic expression vector carrying EPB41L3 sequence is capable of inhibiting the proliferation of mouse melanoma B16 and B16-F10 cells.


Assuntos
Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Melanoma Experimental/metabolismo , Proteínas de Membrana/metabolismo , Neuropeptídeos/metabolismo , Animais , Linhagem Celular Tumoral , Vetores Genéticos , Camundongos , Proteínas dos Microfilamentos , Plasmídeos , Transfecção
8.
Sheng Li Xue Bao ; 67(1): 48-58, 2015 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-25672626

RESUMO

The p26, a multifunctional ubiquitin-binding protein, has been proposed to be involved in protein degradation as a component within the ubiquitin-proteasome and autophagy-lysosome systems. As a scaffolding protein with several different kinds of protein-protein interaction domains, p62 mediates various cellular functions. Importantly, p62 plays a critical role in cell's selective autophagy and oxidative stress response, which are associated with the pathogenesis of several human diseases. In this review, we describe the structure of p62 and the mechanism of connection between p62 and ubiquitin-proteasome system/autophagy, so as to provide some perspectives on p62 research.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteólise , Autofagia , Humanos , Estresse Oxidativo , Complexo de Endopeptidases do Proteassoma , Domínios e Motivos de Interação entre Proteínas , Ubiquitina
9.
Proc Natl Acad Sci U S A ; 111(4): 1509-14, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24434549

RESUMO

TNFα and IL-1ß are two proinflammatory cytokines that play critical roles in many diseases, including rheumatoid arthritis and infectious diseases. How TNFα- and IL-1ß-mediated signaling is finely tuned is not fully elucidated. Here, we identify tripartite-motif protein 38 (TRIM38) as a critical negative regulator of TNFα- and IL-1ß-triggered signaling. Overexpression of TRIM38 inhibited activation of NF-κB and induction of downstream cytokines following TNFα and IL-1ß stimulation, whereas knockdown or knockout of TRIM38 had the opposite effects. TRIM38 constitutively interacted with critical components TGF-ß-activated kinase 1 (TAK1)-binding protein 2/3 (TAB2/3) and promoted lysosome-dependent degradation of TAB2/3 independent of its E3 ubiquitin ligase activity. Consistently, deficiency of TRIM38 resulted in abolished translocation of TAB2 to the lysosome, increased level of TAB2 in cells, and enhanced activation of TAK1 after TNFα and IL-1ß stimulation. We conclude that TRIM38 negatively regulates TNFα- and IL-1ß-induced signaling by mediating lysosome-dependent degradation of TAB2/3, two critical components in TNFα- and IL-1ß-induced signaling pathways. Our findings reveal a previously undiscovered mechanism by which cells keep the inflammatory response in check to avoid excessive harmful immune response triggered by TNFα and IL-1ß.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/fisiologia , Interleucina-1beta/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Sequência de Bases , Proteínas de Transporte/genética , Primers do DNA , Humanos , Proteólise , Interferência de RNA , Transdução de Sinais/fisiologia , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
10.
Cancer Cell Int ; 13(1): 67, 2013 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-23819802

RESUMO

BACKGROUND: In order to search for new structural modification strategies on fluoroquinolones, we have designed and synthesized a series of fluoroquinolone derivatives by linking various hydrazine compounds to the C-3 carboxyl group of levofloxacin and assessed their anticancer activities. Several novel levofloxacin derivatives displayed potent cytotoxicity against the tested cancer cell lines in vitro. In the present study, we investigated the effect of 1-Cyclopropyl-6-fluoro-4-oxo-7- piperazin-1, 4-dihydro- quinoline- 3-carboxylic acid benzo [1,3] dioxol-5- ylmethylene- hydrazide (QNT11) on the apoptosis of human hepatocarcinoma cells in vitro. METHODS: The inhibition effects of QNT11 on cell proliferation were examined by MTT assay. Cell apoptosis was determined by TUNEL and DNA agarose gel electrophoresis method. The topoisomerase ΙΙ activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Cell cycle progression was analyzed using flow cytometry in conjunction with ethanol fixation and propidium iodide staining. Mitochondrial membrane potential (△ψm) was measured by high content screening image system. The caspase-9, caspase-8, caspase-3, Bcl-2, Bax, CDK1, Cyclin B1and cytochrome c protein expressions were detected by Western blot analysis. RESULTS: QNT11 showed selective cytotoxicity against Hep3B, SMMC-7721, MCF-7 and HCT-8 cell lines with IC50 values of 2.21 µM, 2.38 µM, 3.17 µM and 2.79 µM, respectively. In contrast, QNT11 had weak cytotoxicity against mouse bone marrow mesenchymal stem cells (BMSCs) with IC50 value of 7.46 µM. Treatment of Hep3B cells with different concentrations of QNT11 increased the percentage of the apoptosis cells significantly, and agarose gel electrophoresis revealed the ladder DNA bands typical of apoptotic cells, with a decrease in the mitochondrial membrane potential. Compared to the control group, QNT11 could influence the DNA topoisomerase IIactivity and inhibit the religation of DNA strands, thus keeping the DNA in fragments. There was a significant increase of cytochrome c in the cytosol after 24 h of treatment with QNT11 and a decrease in the mitochondrial compartment. Observed changes in cell cycle distribution by QNT11 treated might be caused by insufficient preparation for G2/M transition. In addition, QNT11 increased the protein expression of Bax, caspase-9, caspase-8, caspase-3, as well as the cleaved activated forms of caspase-9, caspase-8 and caspase-3 significantly, whereas the expression of Bcl-2 decreased. CONCLUSIONS: Our results showed that QNT11 as a fluoroquinolone derivative exerted potent and selectively anticancer activity through the mechanism of eukaryotic topoisomerase II poisoning. The growth inhibition was in large part mediated via apoptosis-associated mitochondrial dysfunction and regulation of Bcl-2 signaling pathways.

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