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1.
Science ; 361(6404): 804-806, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30026315

RESUMO

The consequences of global warming for fisheries are not well understood, but the geological record demonstrates that carbon cycle perturbations are frequently associated with ocean deoxygenation. Of particular interest is the Paleocene-Eocene Thermal Maximum (PETM), where the carbon dioxide input into the atmosphere was similar to the IPCC RCP8.5 emission scenario. Here we present sulfur-isotope data that record a positive 1 per mil excursion during the PETM. Modeling suggests that large parts of the ocean must have become sulfidic. The toxicity of hydrogen sulfide will render two of the largest and least explored ecosystems on Earth, the mesopelagic and bathypelagic zones, uninhabitable by multicellular organisms. This will affect many marine species whose ecozones stretch into the deep ocean.


Assuntos
Organismos Aquáticos , Sulfeto de Hidrogênio/toxicidade , Oxigênio/metabolismo , Ciclo do Carbono , Modelos Teóricos , Oceanos e Mares , Oxigênio/análise
2.
Oncotarget ; 8(41): 70707-70726, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050313

RESUMO

Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD), however effective treatments are still elusive. This study aimed to investigate the therapeutic efficacy of human adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and illuminate the role of Sox9, a vital transcription factor in the development of kidney, in this process. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment. We found that hAD-MSC treatment upregulated the expression of tubular Sox9, promoted tubular regeneration, attenuated AKI, and mitigated subsequent renal fibrosis. However, these beneficial effects were abolished by a drug inhibiting the release of exosomes from hAD-MSCs. Similarly, Sox9 inhibitors reversed these protective effects. Further, we verified that hAD-MSCs activated tubular Sox9 and prevented TGF-ß1-induced transformation of TECs into pro-fibrotic phenotype through exosome shuttling in vitro, but the cells did not inhibit TGF-ß1-induced transition of fibroblasts into myofibroblasts. Inhibiting the release of exosomes from hAD-MSCs or the expression of Sox9 in TECs reversed these antifibrotic effects. In conclusion, hAD-MSCs employed exosomes to mitigate AKI-CKD transition through tubular epithelial cell dependent activation of Sox9.

3.
ACS Appl Mater Interfaces ; 9(45): 39371-39379, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28937731

RESUMO

A novel two-dimensional porous sandwich-like Si/carbon nanosheet is designed and successfully fabricated as an anode for superior lithium storage, where a porous Si nanofilm grows on the two sides of reduced graphene oxide (rGO) and is then coated with a carbon layer (denoted as C/Si-rGO-Si/C). The coexistence of micropores and mesopores in C/Si-rGO-Si/C nanosheets offers a rapid Li+ diffusion rate, and the porous Si provides a short pathway for electric transportation. Meanwhile, the coated carbon layer not only can promote to form a stable SEI layer, but also can improve the electric conductivity of nanoscale Si coupled with rGO. Thus, the unique nanostructures offer the resultant C/Si-rGO-Si/C electrode with high reversible capacity (1187 mA h g-1 after 200 cycles at 0.2 A g-1), excellent cycle stability (894 mA h g-1 after 1000 cycles at 1 A g-1), and high rate capability (694 mA h g-1 at 5 A g-1, 447 mA h g-1 at 10 A g-1).

4.
Int J Mol Sci ; 18(4)2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28420144

RESUMO

Retinoids may regulate cell differentiation as ligands of retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein ß (C/EBPß) in the early stages, but blocked adipogenesis at a later stage in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted adipogenesis at all time points in hBMSCs. The effect of RAR agonists was mediated mainly by the RARß subtype. RAR agonists, in contrast to RXR agonists, significantly promoted the expression of RARß. Knockdown of the RARß gene via small hairpin RNA (shRNA) attenuated the inhibition of RAR agonists toward adipogenesis. Furthermore, we found that RAR agonists upregulated the transforming growth factor ß (TGFß)/SMAD pathway and Wnt/ß-catenin pathway on adipogenesis in hBMSCs, and the stimulating effects were noticeably decreased with the RARß gene knockdown. Both RAR agonists and RXR agonists inhibited adipogenesis and blocked the promoter activity of C/EBPß and peroxisome proliferator-activated receptor γ (PPARγ) in SW872 cell. These results indicated the RAR agonists perform dual roles in adipogenesis in hBMSCs, and the TGFß/SMAD pathway and Wnt/ß-catenin pathway may involve the inhibitory effect of RAR agonists. RARß is the main receptor subtype mediating the effect. The roles of RXR agonists in adipogenesis exhibited cell type-specific differences, and may be based on the integration of signals from different RXR dimers.


Assuntos
Adipogenia/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Retinoides/farmacologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt , Adipogenia/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células-Tronco Mesenquimais/citologia , PPAR gama/metabolismo , Receptores do Ácido Retinoico/metabolismo , Receptores X Retinoide/metabolismo , Ativação Transcricional/efeitos dos fármacos
5.
Oncol Lett ; 14(6): 7917-7922, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29344236

RESUMO

The present study aimed at investigating the underlying molecular mechanisms for patients following cytokine-induced killer (CIK) therapy, particularly involving the alterations in p53-associated signaling pathways, to elucidate whether CIK therapy serves a function in cancer treatment. Samples of blood were collected from patients with breast cancer prior to and following CIK therapy. Two group samples were used for RNA sequencing (RNA-Seq) to determine the alterations in gene expression levels following CIK therapy and one for the quantitative polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results. The genes that may encode proteins associated with p53 pathways were selected and analyzed. The expression levels of 8 genes were analyzed, including tumor suppressor protein 53 (TP53), murine double minute homolog 2 (MDM2), ribosomal protein L11 (RPL11), ribosomal protein S23 (RPS23), sirtuin 1, histone deacetylase 1, tuberous sclerosis complex 1 (TSC1) and mechanistic target of rapamycin (mTOR), and alterations in expression levels following CIK therapy were determined. However, only RPL11 and RPS23 were identified to exhibit marked alterations in expression levels (FDR <0.05), which was considered to be due to individual distinctions. qPCR analysis revealed that the expression levels of the RPL11, TP53 and TSC1 genes were downregulated, and those of the RPS23 and MDM2 genes were upregulated following CIK therapy. Only MDM2 exhibited a marked alteration in the gene expression level following CIK therapy. Alterations in the expression levels of TP53, RPL11 and TSC1 were associated with those of MDM2, RPS23 and mTOR, respectively.

6.
PLoS One ; 11(2): e0149926, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900858

RESUMO

AMD3100 is a small molecule inhibitor of chemokine receptor type 4 (CXCR4), which is located in the cell membranes of CD34+ cells and a variety of inflammatory cells and has been reported to reduce organ fibrosis in the lung, liver and myocardium. However, the effect of AMD3100 on renal fibrosis is unknown. This study investigated the impact of AMD3100 on renal fibrosis. C57bl/6 mice were subjected to unilateral ureteral obstruction (UUO) surgery with or without AMD3100 administration. Tubular injury, collagen deposition and fibrosis were detected and analyzed by histological staining, immunocytochemistry and Western Blot. Bone marrow derived pro-angiogenic cells (CD45+, CD34+ and CD309+ cells) and capillary density (CD31+) were measured by flow cytometry (FACS) and immunofluorescence (IF). Inflammatory cells, chemotactic factors and T cell proliferation were characterized. We found that AMD3100 treatment did not alleviate renal fibrosis but, rather, increased tissue damage and renal fibrosis. Continuous AMD3100 administration did not improve bone marrow derived pro-angiogenic cells mobilization but, rather, inhibited the migration of bone marrow derived pro-angiogenic cells into the fibrotic kidney. Additionally, T cell infiltration was significantly increased in AMD3100-treated kidneys compared to un-treated kidneys. Thus, treatment of UUO mice with AMD3100 led to an increase in T cell infiltration, suggesting that AMD3100 aggravated renal fibrosis.


Assuntos
Medula Óssea/patologia , Compostos Heterocíclicos/farmacologia , Inflamação/patologia , Rim/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Linfócitos T/patologia , Animais , Complexo CD3/metabolismo , Proliferação de Células/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Colágeno Tipo IV/metabolismo , Citocinas/metabolismo , Fibrose , Hipóxia/complicações , Hipóxia/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Masculino , Camundongos Endogâmicos C57BL , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Linfócitos T/efeitos dos fármacos , Obstrução Ureteral/complicações
7.
Exp Ther Med ; 10(2): 468-476, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26622339

RESUMO

Cisplatin has been hypothesized to induce nephrotoxicity through triggering the apoptosis of tubular cells; however, the drug remains widely administered for the treatment of tumors. Recently, mesenchymal stem cells (MSCs) have been demonstrated to protect the kidney from the adverse effects induced by cisplatin. The aim of the present study was to investigate the mechanisms underlying the protective effects of human adipose-derived MSCs (AD-MSCs) on kidney function and tubular cells. Sprague-Dawley rats were divided into three groups, which included the healthy controls, those subjected to cisplatin-induced acute kidney injury (AKI) for 24 h without subsequent treatment and those subjected to cisplatin-induced AKI for 24 h, followed by AD-MSC engraftment. The rats were sacrificed at day 5 and the effects were analyzed using various methods, including biochemical analysis, structural examination and cell tracking experiments. In addition, an in vitro experiment with NRK-52E cells was performed. The cells were divided into three groups, including the healthy control, cisplatin induction and cisplatin induction with co-culture of AD-MSCs, and were subsequently assessed with a Transwell assay. After culture for four days, the cells were lysed and the total protein extract was subjected to western blot analysis. Cisplatin-induced renal dysfunction and tissue damage was shown to recover following AD-MSC infusion, although there were few AD-MSCs observed around the injured kidney tubules in the kidney. When the cisplatin-treated NRK-52E cells were co-cultured with AD-MSCs, the activation of p38 and BAX were inhibited, while the expression of Bcl-2 was upregulated, as compared with the cisplatin-treated NRK-52E cells that were not co-cultured. Therefore, AD-MSCs were shown to markedly improve cisplatin-induced renal failure and tubular cells necrosis through the secretion of certain factors, which subsequently inhibited the apoptosis pathway in vitro. It was hypothesized that AD-MSC secretion was triggered by the injured tubular cells. Thus, AD-MSCs may be important for the therapy of patients with renal injury due to their antiapoptotic capacity.

8.
Int J Clin Exp Pathol ; 8(10): 13719-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26722600

RESUMO

OBJECTIVE: This study aimed to understand the relationship between tissue factor (TF) and laryngeal carcinoma. METHODS: Differences in TF expression between pericarcinomatous and carcinomatous tissues were studied in patients with laryngeal carcinoma; the potential clinical significance of the observed differences is discussed. Immunohistochemical, western blot, and RT-PCR analyses were performed to assess the expression of TF at the protein and mRNA levels, and differences between pericarcinomatous and carcinomatous tissues in patients (n = 20) with laryngeal carcinoma were analyzed. RESULTS: Expression of TF was significantly higher in pericarcinomatous tissues than in carcinomatous tissues (P < 0.01); furthermore, the intensity of TF mRNA expression was also significantly stronger in pericarcinomatous than in carcinomatous tissue (P < 0.001). Robust expression of TF was observed in pericarcinomatous tissues but not in carcinomatous tissues. CONCLUSION: TF may contribute to the carcinogenesis and development of laryngeal carcinoma and may provide a marker for assessment of the degree of malignancy and the progression of laryngeal carcinoma. TF may also provide a new target for therapeutics for human head and neck cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Laríngeas/patologia , Tromboplastina/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Neoplasias Laríngeas/metabolismo , Masculino , Pessoa de Meia-Idade , Tromboplastina/genética
9.
Exp Ther Med ; 6(1): 140-146, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23935735

RESUMO

Spinal cord injury (SCI) is a severe neurological disease. An effective strategy for the treatment of SCI is urgently required. Stem cell transplantation has emerged as a viable therapeutic option with great potential for restoring neurological function lost following SCI. From 2009 to 2010, a total of 20 SCI patients were enrolled in a clinical trial by Wuhan Hongqiao Brain Hospital; all patients completed and signed informed consent prior to autologous bone marrow-derived mesenchymal stem cell transplantation. Analysis of subsequent treatment results indicated significant improvements in sensory, motor and autonomic nerve function as assessed by the American Spinal Injury Association's impairment scale. Thirty days after transplantation, a total of 15 patients (75%) demonstrated improvement, including four of the eight patients (50%) with grade A SCI, three of the four patients (75%) with grade B injury and all eight patients (100%) with grade C injury. The most common adverse events, fever and headache, disappeared within 24-48 h without treatment.

10.
Mol Cell Biochem ; 357(1-2): 415-22, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21660463

RESUMO

In this study, in order to investigate the p53-independent function of p14ARF, we established p14ARF-inducible clones in the p53-deficient HCT cell line using the doxycycline-inducible expression system. A strong cell growth inhibition and G1/S arrest were observed after doxycycline induction in p53-/-HCT cells, and the cells also exhibited an obvious decrease of DNA synthesis. We further examined if the MEK/ERK pathway is involved in the G1 arrest induced by p14ARF in p53-/-HCT cells. The results indicate that ERK1/2 and p21 were activated upon p14ARF induction. Totally, the functional roles of ERK and p21 for ARF in p53-independent tumor suppression were demonstrated.


Assuntos
Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Sistema de Sinalização das MAP Quinases/genética , Proteína Supressora de Tumor p14ARF/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Bromodesoxiuridina/farmacologia , Butadienos/farmacologia , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Células HCT116 , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nitrilos/farmacologia , Fosforilação , Proteína Supressora de Tumor p14ARF/genética , Proteína Supressora de Tumor p53/genética , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
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