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1.
Org Biomol Chem ; 19(35): 7690-7694, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524340

RESUMO

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

2.
Clin Pharmacol Ther ; 110(4): 1119-1126, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34287856

RESUMO

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Anticoagulantes/administração & dosagem , Fondaparinux/administração & dosagem , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Mortalidade Hospitalar , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , China , Terapia Antiplaquetária Dupla , Feminino , Heparina/administração & dosagem , Humanos , Infusões Parenterais , Injeções , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Recidiva
3.
Cell Signal ; 85: 110048, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34015470

RESUMO

Integrated stress response (ISR) contributes to various neuropathological processes and acting as a therapy target in CNS injuries. However, the fundamental role of ISR in regulating microglial polarization remains largely unknown. Currently no proper pharmacological approaches to reverse microglia-driven neuroinflammation in surgical brain injury (SBI) have been reported. Here we found that inhibition of the crucial ISR effector, activating transcription factor 4 (ATF4), using the RNA interference suppressed the lipopolysaccharide (LPS)-stimulated microglial M1 polarization in vitro. Interestingly, counteracting ISR with a small-molecule ISR inhibitor (ISRIB) resulted in a significant microglial M1 towards M2 phenotype switching after LPS treatment. The potential underlying mechanisms may related to downregulate the intracellular NADPH oxidase 4 (NOX4) expression under the neuroinflammatory microenvironment. Notably, ISRIB ameliorated the infiltration of microglia and improved the neurobehavioral outcomes in the SBI rat model. Overall, our findings suggest that targeting ISR exerts a novel anti-inflammatory effect on microglia via regulating M1/M2 phenotype and may represent a potential therapeutic target to overcome neuroinflammation following SBI.

4.
BMC Cardiovasc Disord ; 21(1): 202, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882836

RESUMO

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.


Assuntos
Doença da Artéria Coronariana/terapia , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(27): e21055, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629732

RESUMO

Food allergen and aeroallergen sensitization are common allergic diseases worldwide, with widely varying estimates of prevalence in children. Our study investigated the characteristics of ingestion and inhalation allergy among children from Sichuan province in Southwest China, so as to get public awareness of these disorders.A total of 1722 children between 0 and 14 years' old were enrolled in this study. They were outpatients in the West China Second University Hospital during June 2019 to September 2019. Serum specific IgE specific to 10 types of food allergen and 10 types of aeroallergen were estimated. Nutrition indicators were tested by electrochemical luminescence.59.70% children were allergic to at least 1 allergen, comprising 24.90% to aeroallergen and 38.81% to food allergen, respectively, whereas 36.28% children were allergic to both aeroallergen and food allergen. Milk was the most common food allergen, and egg came in second place. With regard to aeroallergen, house dust mite held the maximum proportion (65.02%), whereas dust mite followed behind. Inhalation allergy was more commonly seen in boys than girls. Bronchitis was the most common symptom of both allergies. In addition, the highest incidence age for children to be sensitive to food allergen and aeroallergen were 0∼2 years' old and 3∼5 years' old, respectively. It is worth mentioning that there was no significant difference in nutritional status between children with or without allergic diseases.Our findings reveal that milk, egg, house dust mite, and dust mite are the most common allergens among children in Sichuan province. Boys are more susceptible to aeroallergen than girls. Furthermore, the prevalence of ingestion and inhalation allergy varies from different age groups, and has no correlation with nutritional status. In brief, the analysis of the pattern of food allergen and aeroallergen sensitization is invaluable to effective diagnosis and treatment of allergic diseases.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/epidemiologia , Imunização/métodos , Adolescente , Alérgenos/efeitos adversos , Animais , Conscientização , Bronquite/epidemiologia , Bronquite/imunologia , Criança , Pré-Escolar , China/epidemiologia , Ingestão de Alimentos/imunologia , Hipersensibilidade a Ovo/epidemiologia , Hipersensibilidade a Ovo/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/sangue , Incidência , Lactente , Recém-Nascido , Inalação/imunologia , Masculino , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/imunologia , Estado Nutricional/imunologia , Prevalência , Pyroglyphidae/imunologia
7.
JAMA Intern Med ; 179(2): 186-194, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30592483

RESUMO

Importance: The association of parenteral anticoagulation therapy with improved outcomes in patients with non-ST-segment elevation acute coronary syndrome was previously established. This benefit has not been evaluated in the era of dual antiplatelet therapy and percutaneous coronary intervention. Objective: To evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. Design, Setting, and Participants: This cohort study included 8197 adults who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome from January 1, 2010, to December 31, 2014, at 5 medical centers in China. Patients receiving parenteral anticoagulation therapy only after percutaneous coronary intervention were excluded. Exposures: Parenteral anticoagulation therapy. Main Outcomes and Measures: The primary outcome was in-hospital all-cause death and in-hospital major bleeding as defined by the Bleeding Academic Research Consortium definition (grades 3-5). Results: Of 6804 patients who met the final criteria, 5104 (75.0%) were male, with a mean (SD) age of 64.2 (10.4) years. The incidence of in-hospital death was not significantly different between the patients who received and did not receive parenteral anticoagulation therapy (0.3% vs 0.1%; P = .13) (adjusted odds ratio, 1.27; 95% CI, 0.38-4.27; P = .70). A similar result was found for myocardial infarction (0.3% vs 0.3%; P = .82) (adjusted odds ratio, 0.77; 95% CI, 0.29-2.07; P = .61). In-hospital major bleeding was more frequent in the parenteral anticoagulation group (2.5% vs 1.0%; P < .001) (adjusted odds ratio, 1.94; 95% CI, 1.24-3.03; P = .004). At a median (interquartile range) follow-up of 2.96 years (1.93-4.46 years), all-cause death was not significantly different between the 2 groups (adjusted hazards ratio, 0.87; 95% CI, 0.71-1.07; P = .19), but the incidence of major bleeding was higher in the parenteral anticoagulation group (adjusted hazards ratio, 1.43; 95% CI, 1.01-2.02; P = .04). The propensity score analysis confirmed these primary analyses. Conclusions and Relevance: In the patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome, parenteral anticoagulation therapy was not associated with a lower risk of all-cause death or myocardial infarction but was significantly associated with a higher risk of major bleeding. These findings raise important safety questions about the current practice of routine parenteral anticoagulation therapy while we await randomized trials of this practice.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Anticoagulantes/administração & dosagem , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/mortalidade , Anticoagulantes/efeitos adversos , China/epidemiologia , Terapia Combinada , Feminino , Hemorragia/epidemiologia , Mortalidade Hospitalar , Humanos , Incidência , Infusões Parenterais , Masculino , Pessoa de Meia-Idade
8.
Int J Ophthalmol ; 10(4): 507-514, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28503420

RESUMO

AIM: To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial (RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2). Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay. EGFR/AKT signaling was detected by Western blot. EGFR localization was also detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK-2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through alleviating reduction of EGFR, and phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.

9.
World Neurosurg ; 100: 280-287, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28093349

RESUMO

OBJECTIVE: We summarize the treatment effectiveness and experience of 4 patients who underwent internal carotid ligation combined with low-flow bypass as a treatment for large-giant cavernous sinus segment (CS ICA) aneurysms. METHODS: Surgery-suitable patients with large-giant CS ICA aneurysms received internal carotid ligation combined with low-flow superficial temporal artery-middle cerebral artery bypass surgery. All the patients were followed up for aneurysm prognosis, anastomosis patency, and occurrences of low-flow-related ischemic complications. RESULTS: Four suitable cases between 2012 and 2015 were studied. They consisted of 1 man and 3 women, with the mean age of 56.3 ± 11.9 years. Maximum and minimum aneurysm diameter were 26 mm and 20 mm, respectively, with an average of 22.3 ± 2.6 mm. During surgery, the mean blockage time of the middle cerebral artery was 19.3 ± 1.3 minutes. Postoperative computed tomography angiography examination indicated that thrombosis could be found in the aneurysm lumen. No patient was found with low-flow-related ischemic complications after surgery. The mean postoperative follow-up time was 25.0 ± 10.4 months. During the follow-up period, no patient showed low-flow-related ischemic complications or aneurysm recurrence. CONCLUSIONS: For patients with large-giant CS ICA aneurysms, treatment of internal carotid ligation combined with low-flow superficial temporal artery-middle cerebral artery bypass surgery was an effective and safe surgical strategy. To improve surgery safety and for appropriate selection of surgery cases, the details, risks, and benefits associated with the surgery should be considered by the surgeon.


Assuntos
Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Interna/cirurgia , Seio Cavernoso/cirurgia , Revascularização Cerebral/métodos , Terapia Combinada/métodos , Aneurisma Intracraniano/cirurgia , Adulto , Idoso , Feminino , Humanos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/cirurgia , Técnicas de Sutura , Resultado do Tratamento
10.
Oncol Lett ; 11(5): 3091-3096, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27123069

RESUMO

The current study presents a case of cluster of differentiation (CD)56+ myeloid sarcoma in a patient that initially presented with skin lesions, and provides evidence for the clinical and differential diagnosis of myeloid sarcoma. The patient of the present case report was a 65-year-old man who was admitted to hospital with a six-month history of bilateral purple-red papules and nodules, which were present on the upper limbs of the patient and had spread over his whole body one month prior to admission to the hospital. Pathological examination demonstrated a diffuse infusion of primitive round cells at the papillary dermis and subcutaneous tissues. The infiltrated cells were 40-60 µm in diameter and morphologically identical. Immunohistochemical examination revealed that the cells expressed myeloperoxidase, CD56, CD43 and T-cell intracytoplasmic antigen. In addition, several cells expressed CD34, and 90% of the cells expressed Ki67. While the majority of cells in myeloid sarcoma do not express CD56, the present case was a myeloid sarcoma that expressed CD56, which is extremely rare. The sarcoma in the present patient progressed rapidly, and the patient died eight months following the onset of disease. Clinicians should be aware of CD56+ myeloid sarcoma, which is easily misdiagnosed and inappropriately treated. Consequently, myeloid sarcoma may have a high malignancy and poor outcome for patients.

11.
Mol Cancer ; 14: 2, 2015 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-25971746

RESUMO

BACKGROUND: Inflammatory cytokines and transforming growth factor-ß (TGF-ß) are mutually inhibitory. However, hyperactivation of nuclear factor-κB (NF-κB) and TGF-ß signaling both emerge in glioblastoma. Here, we report microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a directly suppressed Quaking (QKI), a negative regulator of TGF-ß signaling. METHODS: We determined NF-κB and TGF-ß/Smad signaling activity using pNF-κB-luc, pSMAD-luc, and control plasmids. The association between an RNA-induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase kinase-associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real-time PCR. Xenograft tumors were established in the brains of nude mice. RESULTS: QKI suppression induced an aggressive phenotype of glioblastoma cells both in vitro and in vivo. Interestingly, we found that NF-κB induced miR-148a expression, leading to enhanced-strength and prolonged-duration TGF-ß/Smad signaling. Notably, these findings were consistent with the significant correlation between miR-148a levels with NF-κB hyperactivation and activated TGF-ß/Smad signaling in a cohort of human glioblastoma specimens. CONCLUSIONS: These findings uncover a plausible mechanism for NF-κB-sustained TGF-ß/Smad activation via miR-148a in glioblastoma, and may suggest a new target for clinical intervention in human cancer.


Assuntos
Glioblastoma/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Sequência de Bases , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Progressão da Doença , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Camundongos Nus , MicroRNAs/genética , Dados de Sequência Molecular , Invasividade Neoplásica , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Fenótipo , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Regulação para Cima
12.
Dev Comp Immunol ; 51(1): 134-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25819083

RESUMO

The transforming growth factor ß (TGF-ß) superfamily plays critical roles in tumor suppression, cell proliferation and differentiation, tissue morphogenesis, lineage determination, cell migration and apoptosis. Recently, TGF-ß1, one important member of TGF-ß superfamily, is suggested as an immune regulator in the teleost. In this study, we cloned the cDNAs of TGF-ß1 and its receptors, TßR I and TßR II (including three isoforms) from tilapia (Genbank accession numbers: KP754231- KP754235). A tissue distribution profile analysis indicated that TGF-ß1 was highly expressed in the head kidney, gill, spleen, kidney and PBLs (peripheral blood leukocytes); TßR I only showed considerable expression in the liver; and TßR II-2 was highly expressed in the kidney, gill, liver, head kidney and heart. We determined that the mRNA expressions of TGF-ß and TßR I /TßR II-2 were significantly increased in tilapia head kidney and spleen leukocytes by the stimulation of Lipopolysaccharide (LPS) or Poly I: C. We also examined their expressions in the spleen and head kidney of tilapia after IP injection of streptococcus agalactiae. The results showed that the mRNA expressions of these three genes all increased in the head kidney as early as 6 h post infection, and in the spleen 3 d post infection. In addition, the protein level of TGF-ß1 was also up-regulated in the head kidney and the spleen after infection. Taken together, our data indicate that the TGF-ß1-TßR I /TßR II-2 system functions potentially in tilapia immune system.


Assuntos
Rim Cefálico/fisiologia , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Baço/fisiologia , Infecções Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Tilápia/imunologia , Fator de Crescimento Transformador beta1/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica , Rim Cefálico/microbiologia , Imunidade , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Baço/microbiologia , Transcriptoma
13.
Int J Clin Exp Med ; 8(11): 21114-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885043

RESUMO

OBJECTIVE: To evaluate the application of eyebrow-lateral keyhole approach in clipping of anterior communicating artery aneurysm (ACAA) through observing the therapeutic effect of eyebrow-lateral keyhole approach on ACAA. METHODS: In 37 patients with ACAA, cisterns were exposed via the eyebrow-lateral keyhole approach to reveal ACAA complex followed by clipping of ACAA. Of the 37 patients, external ventricular drainage was performed on 5 patients before microsurgery. All patients underwent head CT angiography on the second day after operation. RESULTS: Clipping of ACAA was successful in all patients at the first time. In 3 patients, ruptured aneurysm occurred during operation. Three patients underwent ventriculoperitoneal shunt because of postoperative hydrocephalus. Two patients had one-sided anterior cerebral artery infarction after operation. No patient died during operation. Follow-up after the operation indicated that 26 patients returned to normal life and work, 6 patients were able to look after themselves, 4 patients required care in their daily life and one patient died. CONCLUSION: The eyebrow-lateral keyhole approach is a preferred choice for surgical treatment of ACAA because it can cope with brain swelling and intraoperative ruptured aneurysm. However, it has a certain range of application, so we must strictly follow its indications.

15.
Hum Gene Ther Methods ; 25(6): 339-44, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25420185

RESUMO

The objective of this study was to construct stable rhesus monkey Schwann cells (SCs) modified with the human glial cell-derived neurotrophic factor (hGDNF) gene. hGDNF gene amplification was performed with pUC19-hGDNF as templates, and then the coding sequence of hGDNF was inserted into the eukaryotic expression vector pBABE-puro to obtain the recombinant vector pBABE-puro-hGDNF. The recombinant vector pBABE-puro-hGDNF was identified with restriction enzyme, and then underwent DNA sequencing. SCs from rhesus monkeys were transfected with the recombinant vector pBABE-puro-hGDNF, and then the expression levels of mRNA and protein of the hGDNF gene were determined with real-time fluorescence quantitative PCR and Western blot, respectively, in the transfected SCs. The biological activity of GDNF gene-modified SCs (GDNF-SCs) was assessed by MTT assay. The length of the hGDNF coding sequence of PCR products was 569 bp. After the recombinant eukaryotic expression vectors were digested with restriction enzyme, there was a specific segment of 596 bp. The results of DNA sequencing of the specific segment of 596 bp were the same as that of hGDNF in GenBank, suggesting that the hGDNF gene was successfully inserted into the recombinant retrovirus vectors. The expression levels of mRNA and protein were significantly higher in transfected SCs as compared to nontransfected SCs (p<0.05). MTT assay indicated that the OD value was significantly higher in GDNF-SCs group than in SCs and DMEM groups (p<0.05). hGDNF-SCs can steadily and efficiently release hGDNF. This study provides a basis for cell therapy of nerve injury.


Assuntos
Vetores Genéticos/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Células de Schwann/metabolismo , Animais , DNA Recombinante/genética , Terapia Genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/biossíntese , Humanos , Macaca mulatta , Traumatismos dos Nervos Periféricos/terapia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Análise de Sequência de DNA , Transfecção , Transgenes
16.
Hum Immunol ; 75(11): 1104-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25300997

RESUMO

Human alpha-defensins are natural antimicrobial peptides of neutrophils evolved in host defense reactions and circulating nonstressed alpha-defensins may be associated with serum lipid levels. The aim of this work was to examine whether the expression of alpha-defensins 1, 2 and 3 genes are changed and whether this changes are reversed following treatment in patients with hypercholesteremia. A total of 40 individuals of hypercholesteremia group were studied, compared with 40 individuals of normal control group. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were significantly higher in patients with hypercholesteremia compared with subjects in normal control group. In patients with hypercholesteremia, protein levels of alpha-defensins 1, 2 and 3 correlated positively with the levels of total cholesterol and low-density lipoprotein cholesterol. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were decreased significantly after a treatment with atorvastatin calcium 20mg daily compared with the patients before the treatment. Our results suggest that the expression of alpha-defensins 1, 2 and 3 genes is involved in dyslipidemia in patients with hypercholesteremia.


Assuntos
Hipercolesterolemia/genética , alfa-Defensinas/genética , Idoso , Anticolesterolemiantes/uso terapêutico , Atorvastatina , Estudos de Casos e Controles , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ácidos Heptanoicos/uso terapêutico , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pirróis/uso terapêutico , alfa-Defensinas/antagonistas & inibidores , alfa-Defensinas/sangue
17.
PLoS One ; 9(8): e105350, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25127032

RESUMO

CD8+ T cells play an important role in the anti-tumor activities of the body. The dysfunction of CD8+ T cells in glioma is unclear. This study aims to elucidate the glioma cell-derived ADAM10 (A Disintegrin and metalloproteinase domain-containing protein 10) in the suppression of CD8+ effector T cells by the induction of regulatory B cells. In this study, glioma cells were isolated from surgically removed glioma tissue and stimulated by Phorbol myristate acetage (PMA) in the culture. The levels of ADAM10 in the culture were determined by enzyme-linked immunosorbent assay. Immune cells were assessed by flow cytometry. The results showed that the isolated glioma cells express ADAM10, which was markedly up regulated after stimulated with PMA. The glioma-derived ADAM10 induced activated B cells to differentiate into regulatory B cells, the later suppressed CD8+ T cell proliferation as well as the induced regulatory T cells, which also showed the immune suppressor effect on CD8+ effector T cell proliferation. In conclusion, glioma cells produce ADAM10 to induce Bregs; the latter suppresses CD8+ T cells and induces Tregs.


Assuntos
Proteínas ADAM/fisiologia , Secretases da Proteína Precursora do Amiloide/fisiologia , Linfócitos B/fisiologia , Linfócitos T CD8-Positivos/imunologia , Glioma/enzimologia , Proteínas de Membrana/fisiologia , Proteína ADAM10 , Linfócitos B Reguladores/imunologia , Glioma/imunologia , Humanos , Tolerância Imunológica , Ativação Linfocitária , Linfócitos T Reguladores/imunologia , Células Tumorais Cultivadas
18.
Mol Med Rep ; 10(4): 1813-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25109509

RESUMO

Severe acute pancreatitis (SAP) is an acute inflammatory disease of the pancreas that involves various distant tissues and organs. This study aimed to investigate post-tissue injury repair by mesenchymal stem cells (MSCs) in a rat model of SAP. A total of 54 pathogen-free adult male SD rats were randomly assigned to the groups SAP, SAP + MSCs and sham-operated (SO). SAP was induced by 4% sodium taurocholate, and MSCs were injected via the dorsal penile vein 1 h later. The amylase activity, and tumor necrosis factor (TNF)-α and diamine oxidase (DAO) levels were measured with an enzyme-linked immunosorbent assay (ELISA), while the expression of aquaporin (AQP)-1 was evaluated by immunohistochemical staining. The pathological score of intestinal tissues was also compared among groups. Marked improvement in intestinal necrosis, villi shedding and infiltration of inflammatory cells was observed in the SAP + MSCs group compared to the SAP and SO groups. Amylase, TNF-α, and DAO levels were significantly increased in the SAP + MSCs group. The intestinal expression of AQP-1 was increased at 12 and 24 h post-MSC transplantation compared to the SO group. Rats of the SAP + MSCs group displayed higher pathological scores compared to the SAP group at all time points. Overall, these data showed that MSCs can inhibit systemic inflammation and reduce TNF-α release in a rat model of SAP-induced intestinal injury, suggesting that MSCs exert protective effects on the intestinal barrier during SAP.


Assuntos
Células-Tronco Mesenquimais/citologia , Pancreatite/patologia , Doença Aguda , Amina Oxidase (contendo Cobre)/metabolismo , Amilases/metabolismo , Animais , Aquaporina 1/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Mucosa Intestinal/patologia , Masculino , Transplante de Células-Tronco Mesenquimais , Pancreatite/induzido quimicamente , Pancreatite/terapia , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/toxicidade , Transplante Homólogo , Fator de Necrose Tumoral alfa/metabolismo
19.
Dev Comp Immunol ; 46(2): 448-60, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24950416

RESUMO

FasL is the most extensively studied apoptosis ligand. In 2000, tilapia FasL was identified using anti-human FasL monoclonal antibody by Evans's research group. Recently, a tilapia FasL-like protein of smaller molecule weight was predicted in Genbank (XM_003445156.2). Based on several clues drawn from previous studies, we cast doubt on the authenticity of the formerly identified tilapia FasL. Conversely, using reverse transcription polymerase chain reaction (RT-PCR), the existence of the predicted FasL-like was verified at the mRNA level (The Genbank accession number of the FasL mRNA sequence we cloned is KM008610). Through multiple alignments, this FasL-like protein was found to be highly similar to the FasL of the Japanese flounder. Moreover, we artificially expressed the functional region of the predicted protein and later confirmed its apoptosis-inducing activity using a methyl thiazolyl tetrazolium (MTT) assay, Annexin-V/Propidium iodide (PI) double staining, and DNA fragment detection. Supported by these evidences, we suggest that the predicted protein is the authentic tilapia FasL. To advance this research further, tilapia FasL mRNA and its protein across different tissues were quantified. High expression levels were identified in the tilapia immune system and sites where active cell turnover conservatively occurs. In this regard, FasL may assume an active role in the immune system and cell homeostasis maintenance in tilapia, similar to that shown in other species. In addition, because the distribution pattern of FasL mRNA did not synchronize with that of the protein, post-transcriptional expression regulation is suggested. Such regulation may be dominated by potential adenylate- and uridylate-rich elements (AREs) featuring AUUUA repeats found in the 3' untranslated region (UTR) of tilapia FasL mRNA.


Assuntos
Proteína Ligante Fas/genética , Proteínas de Peixes/genética , Tilápia/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sequência Conservada , Proteína Ligante Fas/biossíntese , Proteínas de Peixes/biossíntese , Expressão Gênica , Células HeLa , Humanos , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , Tilápia/imunologia , Tilápia/metabolismo
20.
Int J Cancer ; 134(11): 2626-32, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24254881

RESUMO

Helicobacter pylori (H. pylori), a common pathogen residing in the gastrointestinal tract, has been well characterized in stomach cancer,while its correlation with esophageal cancer remains poorly understood. In this study, we aim to assess the relationship between esophageal intraepithelial H. pylori invasion and inflammation as well as atypical hyperplasia in esophageal squamous epithelial tissues. Esophageal squamous cell carcinoma (ESCC) tissue samples from 196 individuals from both southern and northern esophageal carcinoma high-risk areas in China were examined (125 from northern high-risk areas, 71 from southern high-risk area), while additional 30 samples were collected adjacent to the esophageal squamous cell carcinoma (A-ESCC). H. pylori infection was identified by Giemsa staining, immuno-histochemical staining, and H. pylori 16S rRNA-based PCR. A significant increase of H. pylori infection was found in tumor tissues (including ESCC and A-ESCC samples) compared to that of non-tumor tissues (p < 0.05). The positive rate of H. pylori 16S rRNA in ESCC, A-ESCC, and normal groups were 62.5, 74.1, and 26.7%, respectively. The PCR results showed that the positive incidence of the H. pylori virulence factor CagA gene in tumor (ESCC and A-ESCC) and normal groups was 54.9 and 20%, respectively (p < 0.05). To explore the possible causes of CagA+ H. pylori infection leading to carcinogenesis, we found that CagA+ H. pylori filtrate induced DNA strand breaks in esophageal epithelial NE3 cells, suggesting that H. pylori infection may be an original cause leading to atypical hyperplasia of esophageal squamous epithelial tissues and contributed to pathological carcinogenesis of ESCC.


Assuntos
Carcinoma in Situ/microbiologia , Carcinoma de Células Escamosas/microbiologia , Neoplasias Esofágicas/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Células Cultivadas , DNA Viral/genética , Neoplasias Esofágicas/patologia , Seguimentos , Instabilidade Genômica , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Hiperplasia , Técnicas Imunoenzimáticas , Inflamação/etiologia , Inflamação/patologia , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Prognóstico , RNA Ribossômico 16S/genética , Fatores de Risco
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