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1.
Cell Mol Life Sci ; 79(10): 538, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190571

RESUMO

Early apoptosis of grafted islets is one of the main factors affecting the efficacy of islet transplantation. The combined transplantation of islet cells and bone marrow mesenchymal stem cells (BMSCs) can significantly improve the survival rate of grafted islets. Transcription factor insulin gene enhancer binding protein 1 (ISL1) is shown to promote the angiogenesis of grafted islets and the paracrine function of mesenchymal stem cells during the co-transplantation, yet the regulatory mechanism remains unclear. By using ISL1-overexpressing BMSCs and the subtherapeutic doses of islets for co-transplantation, we managed to reduce the apoptosis and improve the survival rate of the grafts. Our metabolomics and proteomics data suggested that ISL1 upregulates aniline (ANLN) and Inhibin beta A chain (INHBA), and stimulated the release of caffeine in the BMSCs. We then demonstrated that the upregulation of ANLN and INHBA was achieved by the binding of ISL1 to the promoter regions of the two genes. In addition, ISL1 could also promote BMSCs to release exosomes with high expression of ANLN, secrete INHBA and caffeine, and reduce streptozocin (STZ)-induced islets apoptosis. Thus, our study provides mechanical insight into the islet/BMSCs co-transplantation and paves the foundation for using conditioned medium to mimic the ISL1-overexpressing BMSCs co-transplantation.


Assuntos
Exossomos , Insulinas , Ilhotas Pancreáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Compostos de Anilina/metabolismo , Apoptose/genética , Cafeína/metabolismo , Cafeína/farmacologia , Meios de Cultivo Condicionados , Subunidades beta de Inibinas , Insulinas/metabolismo , Ilhotas Pancreáticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Estreptozocina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Stem Cells ; 39(8): 1033-1048, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33754392

RESUMO

Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Células-Tronco Mesenquimais , Animais , Medula Óssea/metabolismo , Humanos , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas/métodos , Células-Tronco Mesenquimais/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 238: 118443, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32403077

RESUMO

A series of fluorescent coordination polymers (CPs) {[Cd2(CH3-bpeb)2(BDC)2] CP1, (BDC)0.5/(NH2-BDC)0.5-CP1, (BDC)0.34/(NH2-BDC)0.66-CP1, (BDC)0.25/(NH2-BDC)0.75-CP1, (BDC)0.2/(NH2-BDC)0.8-CP1, (NH2-BDC)-CP1} were prepared from conjugated ligand 4,4'-((2-methyl-1,4-phenylene)bis(ethene-2,1-diyl))bipyridine (CH3-bpeb), terephthalic acid (BDC), aminoterephthalic acid (NH2-BDC) and CdSO4 under solvothermal conditions. The fluorescence of aqueous suspensions of these CPs was quenched by folic acid (FA) in a concentration dependent manner. The efficiency of quenching increasing with an increased proportion of NH2-BDC ligand in the CP with (NH2-BDC)-CP1 exhibiting a low detection limit of 1.7 × 10-7 M.

4.
Huan Jing Ke Xue ; 34(7): 2906-11, 2013 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-24028031

RESUMO

Extraction and identification of surface active substance of Alcaligenes sp. S-XJ-1, as well as description of its emulsion breaking process were conducted to reveal the demulsifying characteristics of this demulsifying strain. Alkali solvent was adopted in the extraction process with conditions optimized as 35 degrees C, 0.08 mol x L(-1) of alkali concentration, 12 g x L(-1) of sample to solution ratio, and 4 h of extraction time by launching both single-factor and orthogonal tests. Under this optimal condition, the extracted surface active substance (the extraction ratio was 36.1%) achieved 77% emulsion breaking ratio for 500 mg x L(-1) within 48 h. FT-IR showed the existence of glycolipids, lipids and proteins in the surface active substance, the molecular weight of which mainly scattered between 55 and 61 256. Saccharides, lipids and proteins were identified as the three chief components in surface active substance with the content of 22.2%, 7.5% and 13.4%, respectively. The proteins were further proved to take the most responsibility for the emulsion breaking ability. Moreover, obvious difference in the emulsion breaking process was demonstrated between the original demulsifying strain S-XJ-1 and the extracted surface active substance by real time observation of Turbiscan Lab Expert. The results suggested that the demulsifying efficiency of the strain was jointly contributed by its surface active substance and demulsifying cell morphology, and the former possessed higher functional priority than the latter.


Assuntos
Alcaligenes/química , Emulsificantes/isolamento & purificação , Emulsões/química , Petróleo/metabolismo , Tensoativos/isolamento & purificação , Emulsificantes/química , Tensão Superficial , Tensoativos/química
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