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1.
J Neuroinflammation ; 20(1): 172, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481571

RESUMO

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. FINDINGS: In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = - 0.401, p = 0.031). CONCLUSION: Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Barreira Hematoencefálica , Humanos , Metaloproteinase 9 da Matriz , Microglia , Biomarcadores
2.
Photosynth Res ; 153(3): 177-189, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35834037

RESUMO

Iris tectorum Maxim. is an important plant that plays a very crucial role in the ecological welfare of wetlands. In this study, the effects of different intensities of UV-B radiation on the growth, photosynthetic pigment content, chlorophyll fluorescence characteristics, chloroplast ultrastructure, and gas exchange parameters of Iris tectorum Maxim. were studied. The results showed that enhanced UV-B radiation had a significant influence on the above-mentioned parameters of iris. Compared with the control, enhanced UV-B radiation caused certain damage to the leaf appearance. With the increasing intensity of radiation, the apparent damage degree became more serious. Enhanced UV-B radiation significantly decreased leaf chlorophyll contents, and the effect accumulated with the exposure time. Enhanced UV-B radiation increased Fo, significantly increased the non-photochemical quenching coefficient NPQ, reduced PSII and Qp, and significantly decreased the Fm, Fv/Fm, and Fv/Fo in leaves. The effect of UV-B radiation on PSII destruction of Iris tectorum Maxim. increased as the radiation intensity increased and the exposure time prolonged. The chloroplast structure was damaged under the enhanced UV-B radiation. More specifically, thylakoid lamellae were distorted, swelling and even blurred, and a large number of starch granules appeared. The effect of the high intensity of radiation on chloroplast ultrastructure was greater than that of lower intensity. Enhanced UV-B radiation reduced significantly the net photosynthetic rate, stomatal conductance, and transpiration rate, and the degree of degradation increased with the increasing irradiation intensity. However, the intercellular CO2 content increased, which suggests that the main reason for the decrease of photosynthetic rate was the non-stomatal factors.


Assuntos
Gênero Iris , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Gênero Iris/metabolismo , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Amido/metabolismo
3.
Int Urogynecol J ; 33(1): 3-13, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34081163

RESUMO

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy and sacrospinous ligament fixation (SSLF) have been used for the restoration of apical support. Studies comparing sacrocolpopexy and SSLF have reported conflicting results. We aim to assess the current evidence regarding efficiency and the complications of sacrocolpopexy compared with SSLF. METHODS: We searched PubMed, Embase, and Cochrane Library and performed a systematic review meta-analysis to assess the two surgical approaches. RESULTS: 5Five randomized controlled trials, 8 retrospective studies, and 2 prospective studies including 4,120 cases were identified. Compared with abdominal sacrocolpopexy (ASC), SSLF was associated with a lower success rate (88.32% and 91.45%; OR 0.52; 95% CI 0.29-0.95; p = 0.03), higher recurrence (11.58% and 8.32%; OR 1.97; 95% CI 1.04-3.46; p = 0.04), and dyspareunia rate (14.36% and 4.67%; OR 3.10; 95% CI 1.28-7.50; p = 0.01). Patients in this group may benefit from shorter operative time (weighted mean difference -25.08 min; 95% CI -42.29 to -7.88; p = 0.004), lower hemorrhage rate (0.85% and 2.58%; OR 0.45; 95% CI 0.25-0.85; p = 0.009), wound infection rate (3.30% and 5.76%; OR 0.55; 95% CI 0.39-0.77; p = 0.0005), and fewer gastrointestinal complications (1.33% and 6.19%; OR 0.33; 95% CI 0.15-0.76; p = 0.009). CONCLUSION: Both sacrocolpopexy and SSLF offer an efficient alternative to the restoration of apical support. When anatomical durability and sexual function is a priority, ASC may be the preferred option. When considering factors of mesh erosion, operative time, gastrointestinal complications, hemorrhage, and wound infections, SSLF may be the better option.


Assuntos
Prolapso de Órgão Pélvico , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Ligamentos/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
4.
J Cell Mol Med ; 24(1): 371-384, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746138

RESUMO

Excessive immune-mediated inflammatory reaction plays a deleterious role in ventricular remodelling after myocardial infarction (MI). Interleukin (IL)-38 is a newly characterized cytokine of the IL-1 family and has been reported to exert a protective effect in some autoimmune diseases. However, its role in cardiac remodelling post-MI remains unknown. In this study, we found that the expression of IL-38 was increased in infarcted heart after MI induced in C57BL/6 mice by permanent ligation of the left anterior descending artery. In addition, our data showed that ventricular remodelling after MI was significantly ameliorated after recombinant IL-38 injection in mice. This amelioration was demonstrated by better cardiac function, restricted inflammatory response, attenuated myocardial injury and decreased myocardial fibrosis. Our results in vitro revealed that IL-38 affects the phenotype of dendritic cells (DCs) and IL-38 plus troponin I (TNI)-treated tolerogenic DCs dampened adaptive immune response when co-cultured with CD4+ T cells. In conclusion, IL-38 plays a protective effect in ventricular remodelling post-MI, one possibility by influencing DCs to attenuate inflammatory response. Therefore, targeting IL-38 may hold a new therapeutic potential in treating MI.


Assuntos
Interleucina-1/metabolismo , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular , Animais , Apoptose/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Fibrose , Tolerância Imunológica/efeitos dos fármacos , Inflamação/patologia , Interleucina-1/genética , Interleucina-1/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Troponina I/metabolismo , Remodelação Ventricular/efeitos dos fármacos
5.
Cell Biochem Funct ; 38(5): 630-641, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390230

RESUMO

Glioblastoma is one of the most malignant tumors and causes the high mortality in cancer patients. Currently, there is no highly efficient therapy against glioblastoma. Therefore, searching for a new molecular target to anti-glioblastoma therapy is urgent and necessary. In this study, we elucidated the role of Signal transducer and activator of transcription 1 (STAT1) in proliferation, migration and apoptosis of glioblastoma cells. We found that STAT1 downregulation could weaken the aggressiveness of glioblastoma cells. Besides, the glioblastoma growth in vivo was also inhibited with the STAT1 downregulation by shRNA as well as by pharmacological stimulation withSTAT1inhibitors. This negative regulation of tumor growth was accompanied by the inhibition in epithelial-mesenchymal transition (EMT), whereas the STAT1 overexpression promoted EMT. Furthermore, the involvement of wnt/ß-catenin was observed in STAT1 downregulation mediated weakness in glioblastoma aggressiveness since application of activator wnt agonist 1 could counteract the inhibitory effect induced by STAT1 downregulation. Collectively, this work provided the evidence to support the conclusion that STAT1 can regulate the glioblastoma growth and migration, potentially serving as a therapeutic target against glioblastoma. SIGNIFICANCE OF THE STUDY: Glioblastoma is one of the most malignant tumors with very high mortality. Until now, there is no efficient therapy against glioblastoma. In this study, we found downregulation of Signal transducer and activator of transcription 1 (STAT1) could weaken the aggressiveness of glioblastoma cells through inhibition in epithelial-mesenchymal transition, mediated through wnt/ß-catenin signalling pathway. Thus, this work supported the regulatory role of STAT1 in glioblastoma growth and migration. This potentially serves as a new therapeutic target against glioblastoma.


Assuntos
Neoplasias do Sistema Nervoso Central/metabolismo , Glioblastoma/metabolismo , Fator de Transcrição STAT1/metabolismo , Animais , Sobrevivência Celular , Neoplasias do Sistema Nervoso Central/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/genética , Células Tumorais Cultivadas , Via de Sinalização Wnt
6.
Mediators Inflamm ; 2019: 9515346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686988

RESUMO

BACKGROUND: Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. RESULTS: Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. CONCLUSION: In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.


Assuntos
Síndrome Coronariana Aguda/metabolismo , Interleucina-1/farmacologia , Angina Estável/metabolismo , Angina Instável/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo
7.
J Transl Med ; 16(1): 79, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29571296

RESUMO

BACKGROUND: Radiotherapy constitutes a standard arm of therapy in the multimodal treatment of patients with glioblastoma (GBM). Ironically, studies have recently revealed that radiation can augment malignant progression, by promoting migration and invasion, which make the disease especially difficult to cure. Here, we investigated the anticancer effects of YM155, a purported radiosensitizer, in GBM cell lines. METHODS: GBM cell lines U251 and U87 were treated with YM155 to assess cytotoxicity and activity of the molecule in vitro. Nude mice were implanted with cells to generate orthotopic xenografts for in vivo studies. Response of cells to treatment was examined using cell viability, immunofluorescence, wound healing, and the Transwell invasion assay. Molecules potentially mediating response were examined through western blot analysis, phospho-kinase arrays, and qPCR. Cells were transfected with siRNA knockdown and gene expression constructs to identify molecular mediators of response. RESULTS: YM155 reduced viability of U251 and U87 cells and enhanced radiosensitivity through inhibition of homologous recombination. Besides, YM155 decreased invasion caused by radiation and led to expression changes in molecular markers associated with EMT. STAT3 was one of 10 molecules identified on a phosphokinase array exhibiting significant change in phosphorylation under YM155 treatment. Transfection with STAT3 siRNAs or expression constructs demonstrated that EMT changes were achieved by inhibiting the phosphorylation of STAT3 and were survivin-independent. Finally, combining YM155 and radiation in orthotopic xenografts reduced growth and prolonged overall survival of animals. CONCLUSIONS: YM155 decreased radiation-induced invasion in GBM cell lines in vitro and in vivo through inhibition of STAT3.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/radioterapia , Imidazóis/farmacologia , Naftoquinonas/farmacologia , Fator de Transcrição STAT3/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioblastoma/patologia , Recombinação Homóloga/genética , Humanos , Camundongos Nus , Invasividade Neoplásica , Survivina/metabolismo
8.
Neuroimmunomodulation ; 25(4): 215-224, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30544111

RESUMO

OBJECTIVE: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. METHODS: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy. Fifteen patients with other noninflammatory neurological diseases (OND) were also included. The serum and CSF levels of interleukin (IL)-6, IL-10, IL-17, IL-21, IL-23, transforming growth factor (TGF)-ß1 and the CSF levels of 3 biomarkers of axonal loss and astrocytic damage were measured using the human cytokine multiplex assay or ELISA. RESULTS: Serum levels of IL-10 and TGF-ß1 and CSF levels of IL-6, IL-10, and TGF-ß1 were significantly increased in first-onset NMOSD compared to in OND patients. In a subgroup analysis, the CSF levels of IL-6, neurofilament light protein (NFL), S100B, and glial fibrillary acidic protein (GFAP) were significantly more elevated in the AQP4-IgG-positive patients than in the AQP4-IgG-negative NMOSD patients. Correlations were found between the CSF cytokines and tissue damage biomarkers and the clinical findings in NMOSD patients. Notably, the CSF IL-6 level had the strongest correlation with the tissue damage biomarkers and it also correlated with CSF white blood cell (WBC) count. CONCLUSIONS: IL-6 plays a role in the pathogenetic process of NMOSD, especially in the AQP4-IgG-positive subtype. Distinct pathogenesis exists between AQP4-IgG-positive and AQP4-IgG-negative NMOSD in the initial phase of the disease.


Assuntos
Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Interleucina-6/sangue , Interleucina-6/líquido cefalorraquidiano , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Adulto Jovem
9.
Appl Microbiol Biotechnol ; 102(13): 5519-5532, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29725718

RESUMO

In this study, endophytic fungi were isolated from Dioscorea zingiberensis C.H. Wright (DZW), and a novel clean process to prepare diosgenin from DZW was developed. A total of 123 strains of endophytic fungi were isolated from different plant tissues of DZW. Among them, the strain Fusarium sp. (CPCC 400709) showed the best activity of hydrolyzing steroidal saponins in DZW into diosgenin. Thus, this strain was used to prepare diosgenin from DZW by solid-state fermentation. The fermentation parameters were optimized using response surface methodology, and a high yield of diosgenin (2.16%) was obtained at 14.5% ammonium sulfate, an inoculum size of 12.3%, and 22 days of fermentation. Furthermore, the highest diosgenin yield (2.79%) was obtained by co-fermentation with Fusarium sp. (CPCC 400709) and Curvularia lunata (CPCC 400737), which was 98.9% of that obtained by ß-glucosidase pretreated acid hydrolysis (2.82%). This process is acid-free and wastewater-free, and shows promise as an effective and clean way to prepare diosgenin for use in industrial applications from DZW.


Assuntos
Dioscorea/microbiologia , Diosgenina/metabolismo , Fermentação , Fusarium/isolamento & purificação , Fusarium/metabolismo , Microbiologia Industrial , Hidrólise , Saponinas/metabolismo
10.
Immunology ; 151(3): 291-303, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28207945

RESUMO

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4+ T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4+  CD25+  GARP+ regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon-γ (IFN-γ), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-ß1 (TGF-ß1 ) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4+  CD25+  GARP+ Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-ß1 and higher levels of IFN-γ and IL-17 detected using ELISA were found in supernatants of the cultured CD4+  CD25+  GARP+ Treg cells in DCM patients compared with controls. Together, our results indicate that CD4+  CD25+  GARP+ Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.


Assuntos
Imunidade Adaptativa , Cardiomiopatia Dilatada/imunologia , Proliferação de Células , Subunidade alfa de Receptor de Interleucina-2/imunologia , Ativação Linfocitária , Proteínas de Membrana/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Contagem de Linfócito CD4 , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Comunicação Celular , Células Cultivadas , Técnicas de Cocultura , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Fenótipo , Transdução de Sinais , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismo
11.
Cell Physiol Biochem ; 44(5): 1810-1827, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29224017

RESUMO

BACKGROUND/AIMS: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice. METHODS: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-ß1 mAbs, 11) IL-2C+anti-IL-10 mAbs. The following parameters were measured at different time points: infarct area, myocardial apoptosis, splenocytes, the inhibitory function of Tregs, and presence of inflammatory factors. In addition, immunohistochemistry analysis was performed. RESULTS: We observed that Tregs were activated in response to MIRI. IL-2C administered before MIRI induced Treg expansion in both spleen and heart, attenuated Th1 and Th17 cell numbers, improved myocardial function, and attenuated both infiltration of inflammatory cells and apoptosis after MIRI. Furthermore, IL-2C administration reduced expression of inflammatory cytokines in the heart and attenuated proliferation of splenic cells. Depletion of Tregs with anti-CD25 mAb abrogated the beneficial effects of IL-2C. However, IL-2C-mediated myocardial protection was not dependent on either IL-10 or TGF-ß. In addition, IL-2C administration after MIRI did not reduce infarct area, but did improve myocardial function slightly and reduced myocardial fibrosis. CONCLUSION: Our results demonstrate that IL-2C-induced Treg expansion attenuates MIRI and improves myocardial recovery in vivo, suggesting that IL-2C is a promising therapeutic target for myocardial IRI.


Assuntos
Complexo Antígeno-Anticorpo/farmacologia , Interleucina-2/imunologia , Traumatismo por Reperfusão Miocárdica/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Complexo Antígeno-Anticorpo/uso terapêutico , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/citologia , Miocárdio/imunologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/citologia , Células Th1/imunologia , Células Th17/citologia , Células Th17/imunologia , Fator de Crescimento Transformador beta1/imunologia
12.
J Transl Med ; 15(1): 165, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754121

RESUMO

BACKGROUND: The coiled-coil domain is a structural motif found in proteins that participate in a variety of biological processes. Aberrant expression of such proteins has been shown to be associated with the malignant behavior of human cancers. In this study, we investigated the role of a specific family member, coiled-coil domain containing 109B (CCDC109B), in human gliomas. METHODS AND RESULTS: We confirmed that CCDC109B was highly expressed in high grade gliomas (HGG; WHO III-IV) using immunofluorescence, western blot analysis, immunohistochemistry (IHC) and open databases. Through Cox regression analysis of The Cancer Genome Atlas (TCGA) database, we found that the expression levels of CCDC109B were inversely correlated with patient overall survival and it could serve as a prognostic marker. Then, a serious of cell functional assays were performed in human glioma cell lines, U87MG and U251, which indicated that silencing of CCDC109B attenuated glioma proliferation and migration/invasion both in vitro and in vivo. Notably, IHC staining in primary glioma samples interestingly revealed localization of elevated CCDC109B expression in necrotic areas which are typically hypoxic. Moreover, small interfering RNA (siRNA) and specific inhibiters of HIF1α led to decreased expression of CCDC109B in vitro and in vivo. Transwell assay further showed that CCDC109B is a critical factor in mediating HIF1α-induced glioma cell migration and invasion. CONCLUSION: Our study elucidated a role for CCDC109B as an oncogene and a prognostic marker in human gliomas. CCDC109B may provide a novel therapeutic target for the treatment of human glioma.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Hipóxia Celular/genética , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Glioma/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida
13.
J Nat Prod ; 80(2): 371-376, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28117586

RESUMO

A new griseofulvin derivative, 4'-demethoxy-4'-N-isopentylisogriseofulvin (1), three new indole alkaloids, 2-demethylcyclopiamide E (2), 2-demethylsperadine F (3), and clopiamine C (4), and five known metabolites (5-9) were isolated from Penicillium griseofulvum CPCC 400528. Compound 1 is the first reported griseofulvin analogue with an N-isopentane group and the first example of a naturally occurring N-containing griseofulvin analogue. Their structures and absolute configurations were elucidated through extensive spectroscopic analyses, calculated ECD, and single-crystal X-ray diffraction (Cu Kα). The possible biogenetic pathway of 1-3 was proposed. Compounds 1, 2, and 5 exhibited anti-HIV activities with IC50 values of 33.2, 20.5, and 12.6 µM, respectively.


Assuntos
Griseofulvina/isolamento & purificação , Griseofulvina/farmacologia , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Penicillium/química , China , Cristalografia por Raios X , Griseofulvina/análogos & derivados , Griseofulvina/química , Alcaloides Indólicos/química , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
14.
Biotechnol Lett ; 39(2): 197-205, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27837373

RESUMO

OBJECTIVE: To elucidate the molecular mechanism of microRNA-215 (miR-215) in the migration and invasion of high grade glioma. RESULTS: 42 Patients were analysed for clinicopathological characteristics. qRT-PCR showed that miR-215 was up-regulated in glioma tissues compared with non-neoplastic brain tissues (P < 0.05). The up-regulated miR-215 was closely associated with high grade glioma (P < 0.01) and poor overall survival (P < 0.01). Transwell assay showed that re-expression of miR-215 enhanced migration and invasion of glioma cells. miR-215 also down-regulated retinoblastoma tumor suppressor gene 1 (RB1) expression by targeting its 3'-UTR. Reversely, re-expression of RB1 inhibited partial effect of miR-215 on migration and invasion in vitro. CONCLUSIONS: Re-expression of miR-215 promoted cell migration and invasion of glioma by targeting RB1. miR-215 can thus be used as a biomarker for tumor progression and prognosis in human high grade glioma.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Movimento Celular/fisiologia , Glioma/genética , Glioma/patologia , MicroRNAs/genética , Adulto , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Técnicas In Vitro , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade
16.
Cell Physiol Biochem ; 38(6): 2219-29, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27184135

RESUMO

BACKGROUND/AIMS: Myocarditis is an important inflammatory disease of the heart which causes life-threatening conditions. 1, 25(OH)2 D3 has effects on multiple systems and diseases. The present study was aimed to investigate the effect of 1, 25(OH)2 D3 on experimental autoimmune myocarditis (EAM), and explored the underlying mechanisms involved. METHODS: EAM was induced by immunizing BALB/c mice with cardiac α-myosin heavy chain peptides (MyHC-α). 1, 25(OH)2 D3 (1,000 ng/kg once) or vehicle was administered intraperitoneally every other day during the entire experiment. On day 21, transthoracic echocardiography was performed and cardiac inflammatory infiltration was detected by hematoxylin and eosin (HE). The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, and Western blots for the expression of protein caspase-3 and cleaved-caspase3 were used to evaluate apoptosis. Transmission electron microscopy and Western blots for the expression of protein Beclin-1, LC3B, and P62 were used to evaluate autophagy. RESULTS: The ratio of heart weight/body weight was significantly reduced in 1, 25(OH)2 D3 -treated EAM mice, compared with vehicle -treated ones. 1, 25(OH)2 D3 treatment improved cardiac function, diminished cell infiltration in cardiac, suppressed myocardial apoptosis, decreased the number of autophagosomes, and decreased the protein expression of Beclin-1, LC3-II and p62. CONCLUSIONS: The present results demonstrated that administration of 1, 25(OH)2 D3 decreased EAM severity. 1, 25(OH)2 D3 treatment may be a feasible therapeutic approach for EAM.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Coração/efeitos dos fármacos , Miocardite/tratamento farmacológico , Vitamina D/análogos & derivados , Vitaminas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Coração/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Miocardite/patologia , Miocardite/fisiopatologia , Miocárdio/patologia , Vitamina D/uso terapêutico
18.
Extremophiles ; 20(4): 461-70, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27240672

RESUMO

Endolichenic fungi within 17 lichen species in the area near Ny-Ålesund (Svalbard, High Arctic) were studied by a culture-based method. The 247 fungal isolates were obtained from 2712 lichen thallus segments. The colonization rate of endolichenic fungi ranged from 1.6 to 26.5 %, respectively. These isolates were identified to 40 fungal taxa, including 35 Ascomycota (10 orders), 4 Basidiomycota (3 orders), and 1 unidentified fungus. Thelebolales was the most abundant order, while Sordariales were the most diverse order. The common fungal taxa shared by more than 3 lichen species were Thelebolus microsporus (93 isolates), Coniochaeta hoffmannii (7 isolates), Sarocladium kiliense (33 isolates), Coniochaeta sp. 1 (5 isolates), Coniochaeta sp. 4 (28 isolates), and Coniochaeta sp. 2 (5 isolates). Low Sorenson's similarity coefficients were observed among different lichen species, indicating that host-related factor may shape the endolichenic fungal communities in this region. In addition, no endolichenic fungal taxa were previously found in the Antarctica and Austrian Alps, suggesting endolichenic fungal communities in this region might be also shaped by the Arctic climate. The results demonstrate the existence of specific cultured endolichenic fungal species, which may be suitable objects for further study of their possible functional roles in the lichen thalli.


Assuntos
Líquens/classificação , Microbiota , Regiões Antárticas , Líquens/genética , Líquens/isolamento & purificação
19.
Phys Chem Chem Phys ; 18(44): 30630-30642, 2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27790651

RESUMO

A simple route for the preparation of ZnS nanocrystal/reduced graphene oxide (ZnS/RGO) by a hydrothermal synthesis process was achieved. The chemical composition, morphology, and structural characterization reveal that the ZnS/RGO composite is composed of sphalerite-phased ZnS nanocrystals uniformly dispersed on functional RGO sheets with a high specific surface area. The ZnS/RGO composite was utilized as an anode in the construction of a high-performance lithium-ion battery. The ZnS/RGO composite with appropriate RGO content exhibits a high reversible specific capacity (780 mA h g-1), excellent cycle stability over 100 cycles (71.3% retention), and good rate performance at 2C (51.2% of its capacity when measured at a 0.1C rate). To further investigate this ZnS/RGO anode for practical use in full Li-ion cells, we tested the electrochemical performance of the ZnS/RGO anode at different cut-off voltages for the first time. The presence of RGO plays an important role in providing high conductivity as well as a substrate with a high surface area. This helps alleviate the typically problems associated with volume expansion and shrinkage during prolonged cycling. Additionally, the RGO provides multiple nucleation points that result in a uniformly dispersed film of nanosized ZnS that covers its surface. Thus, the high surface area RGO enables high electronic conductivity and fast charge transfer kinetics for ZnS lithiation/delithiation.

20.
Wei Sheng Wu Xue Bao ; 56(4): 614-28, 2016 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-29717852

RESUMO

Objective: To explore the diversity of species and biological activities of the endophytes from Huperzia serrata that is a wild medicinal plant under state protection (category ii), and to discover and collect endophytic bacteria from medicinal plants. Methods: Huperzia serrata samples were collected from Sichuan and Fujian Provinces. Culture-dependent method was used to obtain endophytes from the surface-sterilized plant samples. The diversity of the isolates was analyzed according to the 16S rRNA gene sequences information. Jaccard index, Shannon-wiener Index, Simpson Index and Pielou Index were calculated. Then six screening models were followed to study the physiological activities of the isolates, based on which we evaluated the diversity of biological activities of the endophytes from Huperzia serrata and their potential medicinal value. Results: A total of 356 endophytic bacteria were purified from Huperzia serrata, and the analysis results of their 16S rRNA gene sequences showed that they affiliated to 41 genera of 26 families in the phyla Actinobacteria, Firmicutes and Proteobacteria. The numbers and biodiversity indexes of endophytes from the aboveground part and belowground part of Huperzia serrata were approximately equivalent. Among them 11 potential novel species belonged to the genera Amycolatopsis, Angustibacter, Arthrobacter, Curtobacterium, Frondihabitans, Glaciihabitans, Jatrophihabitans, Luteimicrobium, Massilia, Naumannella and Tardiphaga, and 1 novel genus of the family Dermacoccaceae was discovered. The screening for anti-microbial results from these 356 isolates were as follows: the activity rates of against Enterococcus faecalis, Klebsiella pneumonia, Mycobacterium smegmatis and Xanthomonas campestris were 9.0%, 1.4%, 2.2% and 0.8% respectively. Of them 4.5% exhibited activities on the screening model of statins-like antihyperlipidemics showing inhibition of Sporobolomyces salmonicolor SS04; 8.6% of them had the activities of against HIV-1. In total, the fermentation broths from 74 strains exhibited activities on at least one screening model, the positive rate among the isolates was 20.8%. Conclusion: This study demonstrated that the endophytic bacteria from Huperzia serrata were of great significant bio-diversity and antibiotic diversity, therefore, they could be an ideal microbial resource for further discovery of new natural products.


Assuntos
Bactérias/isolamento & purificação , Biodiversidade , Endófitos/isolamento & purificação , Huperzia/microbiologia , Bactérias/classificação , Bactérias/genética , DNA Bacteriano/genética , Endófitos/classificação , Endófitos/genética , Filogenia , RNA Ribossômico 16S/genética
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