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1.
Lab Invest ; 102(1): 25-37, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725437

RESUMO

Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)-a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE-/- mice.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Homocisteína/farmacologia , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Proteínas/genética , Transdução de Sinais/genética , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas/metabolismo , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Células THP-1 , Proteínas rap1 de Ligação ao GTP/genética , Proteínas rap1 de Ligação ao GTP/metabolismo
2.
Nanotechnology ; 33(13)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34808604

RESUMO

The catalyst of nanoporous Cu (NP-Cu) powders, with the chemical composition of Cu79.63Ni6.85O13.53(at%), was successfully fabricated by dealloying of Zr-Cu-Ni-Al metallic glassy precursors. The as-prepared NP-Cu powders, co-existing with Cu2O phase on Cu ligament surface, had a three-dimensional network porous structure. The NP-Cu powders/H2O2system showed superior catalytic degradation efficiency toward azo dyes in both acidic (pH 2) and neutral (pH 7) environments. Moreover, the cyclic tests indicated that this powder catalyst also exhibited good durability. A novel degradation mechanism of NP-Cu powders/H2O2was proposed: the high degradation performance in acidic environment was mainly derived from heterogeneous reaction involved with a specific pathway related to Cu3+to produce HO·, while in neutral environment it was primarily resulted from homogeneous reaction with the generation of HO· from the classical Cu-based Fenton-like process. This work indicates that the NP-Cu powders have great potential applications as catalysts for wastewater treatments.

3.
Appl Intell (Dordr) ; 52(11): 12191-12205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35125656

RESUMO

Aiming to tackle the most intractable problems of scale variation and complex backgrounds in crowd counting, we present an innovative framework called Hierarchical Region-Aware Network (HRANet) for crowd counting in this paper, which can better focus on crowd regions to accurately predict crowd density. In our implementation, first, we design a Region-Aware Module (RAM) to capture the internal differences within different regions of the feature map, thus adaptively extracting contextual features within different regions. Furthermore, we propose a Region Recalibration Module (RRM) which adopts a novel region-aware attention mechanism (RAAM) to further recalibrate the feature weights of different regions. By the integration of the above two modules, the influence of background regions can be effectively suppressed. Besides, considering the local correlations within different regions of the crowd density map, a Region Awareness Loss (RAL) is designed to reduce false identification while producing the locally consistent density map. Extensive experiments on five challenging datasets demonstrate that the proposed method significantly outperforms existing methods in terms of counting accuracy and quality of the generated density map. In addition, a series of specific experiments in crowd gathering scenes indicate that our method can be practically applied to crowd localization.

4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(3): 240-245, 2021 Mar.
Artigo em Zh | MEDLINE | ID: mdl-33766232

RESUMO

Objective To study the role of long non-coding RNA growth arrest specific transcript 5 (lncGAS5) in the autophagy of hepatocytes induced by homocysteine (Hcy). Methods HL7702 human hepatocyte cells were cultured in vitro and divided into control group and Hcy group. Western blotting was used to detect the expression levels of microtubule-associated protein 1 light chain 3B (LC3B) and P62. The cells were transfected with mRFP-GFP-LC3 adenovirus to observe the autophagy flow with laser scanning confocal microscope. Real-time quantitative PCR was performed to detect the expression level of lncGAS5. lncGAS5 small interfering RNA (si-lncGAS5) and negative control small interfering RNA (si-NC) were transfected into the cells. After the transfected cells were treated with Hcy, the changes of LC3B, P62 and autophagy flow were analyzed with the above methods. Results Compared with the control group, the LC3BII/LC3BI ratio increased and the expression of P62 protein decreased in the Hcy group. When the lever of Hcy lifted, the number of autophagosomes and autolysosomes and the expression of lncGAS5 increased in the cells. After knock-down of lncGAS5, the ratio of LC3BII/LC3BI decreased and the expression of P62 increased. Moreover, the number of autophagosomes and autolysosomes were reduced in the cells. Conclusion lncGAS5 can promote the autophagy of hepatocytes induced by Hcy.


Assuntos
RNA Longo não Codificante , Autofagia/genética , Hepatócitos , Homocisteína/farmacologia , Humanos , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno
5.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33880587

RESUMO

Our previous study reported that microRNA (miR)­30a­5p upregulation under hypoxia postconditioning (HPostC) exert a protective effect on aged H9C2 cells against hypoxia/reoxygenation injury via DNA methyltransferase 3B­induced DNA hypomethylation at the miR­30a­5p gene promoter. This suggests that miR­30a­5p may be a potential preventative and therapeutic target for ischemic heart disease in aged myocardium. The present study aimed to investigate the underlying mechanisms of miR­30a­5p transcription in aged myocardium in ischemic heart disease. Cardiomyocytes were treated with 8 mg/ml D­galactose for 9 days, and then exposed to hypoxic conditions. Cell viability was determined using a cell viability assay. Expression levels of histone deacetylase 2 (HDAC2), LC3B­II/I, beclin­1 and p62 were detected via reverse transcription­quantitative PCR and western blotting. Chromatin immunoprecipitation­PCR and luciferase reporter assays were performed to evaluate the effect of c­Myc binding and activity on the miR­30a­5p promoter in senescent cardiomyocytes following HPostC. It was found that HPostC enhanced the acetylation levels of H3K14 at the miR­30a­5p gene promoter in senescent cardiomyocytes, which attributed to the decreased expression of HDAC2. In addition, c­Myc could positively regulate miR­30a­5p transcription to inhibit senescent cardiomyocyte autophagy. Mechanically, it was observed that increased H3K14 acetylation level exposed to romidepsin facilitated c­Myc binding to the miR­30a­5p gene promoter region, which led to the increased transcription of miR­30a­5p. Taken together, these results demonstrated that HDAC2­mediated H3K14 hyperacetylation promoted c­Myc binding to the miR­30a­5p gene promoter, which contributed to HPostC senescent cardioprotection.


Assuntos
Histonas/metabolismo , Hipóxia/metabolismo , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Autofagia , Proteína Beclina-1 , Sobrevivência Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , MicroRNAs/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Regulação para Cima , DNA Metiltransferase 3B
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