Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
J Cell Physiol ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31294463

RESUMO

The long noncoding RNA MEG3 is a significant tumor-suppressive gene in various tumors. But its biological role in bladder cancer remains uninvestigated. Herein, the biological mechanism of MEG3 in bladder cancer pathogenesis was explored. First, the expression of MEG3 in bladder cancer cells was examined, and we found that it was significantly reduced. In addition, in bladder cancer cells, we observed htat miR-494 was increased. Then, MEG3 was overexpressed in UMUC3 and SW780 cells and it could negatively modulate miR-494 expression. Bladder cancer cell proliferation was repressed, cell apoptosis was triggered and meanwhile, the cell cycle was remarkably arrested by the overexpression of MEG3. Moreover, the increase of MEG3 suppressed bladder cancer cell migration and invasion capacity. MEG3 can sponge miR-494 and the binding sites between them were confirmed by carrying out a series of functional assays. Furthermore, PTEN was speculated as a putative target of miR-494. Meanwhile, we found that miR-494 inhibitors induced PTEN. Finally, in vivo assays were conducted to prove that MEG3 can restrain bladder tumor growth by modulating miR-494 and PTEN. In conclusion, it was suggested MEG3 can interact with miR-494 to regulate PTEN in bladder cancer development.

2.
J Surg Res ; 244: 547-557, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31351398

RESUMO

BACKGROUND: Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury. MATERIALS AND METHODS: A CoCl2-stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2-related factor 2 (Nrf2) signaling-related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot. RESULTS: HaCAT cells treated with 40 µM CoCl2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues. CONCLUSIONS: KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling.

3.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31266813

RESUMO

Adipose-derived stem cells (ADSCs) and vascular endothelial growth factor (VEGF) contribute to the healing of wound. The purpose of the present study was to investigate the role of VEGF produced by ADSCs in the protection of fibroblasts and skin of mice from ultraviolet (UV) radiation. ADSCs and fibroblasts were extracted from adipose and skin on the abdomen of mice by enzyme digestion methods. ADSCs surface markers were detected using flow cytometry, and immunofluorescence was used to identify fibroblasts. The expression of VEGF in modified ADSCs with lentivirus was determined. Fibroblasts were injured by UV radiation and co-cultured with ADSCs carrying overexpressed VEGF or normal VEGF. Cell cycle was assessed by flow cytometry. Mice were treated with UV radiation dorsally and injected with ADSCs containing overexpressed VEGF or normal VEGF. mRNA and protein levels of cell senescence-related genes were measured by qPCR and western blot. It was found that ADSCs with overexpressed VEGF not only promoted the effect of ADSCs on down-regulating senescence-associated (SA)-ß-Gal, p21 and matrix metalloproteinase (MMP)-1, the healing of wound injured by UV radiation and up-regulating collagen I expression in fibroblasts and wound, but also on inhibiting cell cycle arrest in fibroblasts injured by UV radiation and preventing the skin from photoaging caused by UV radiation. VEGF expression in ADSCs played a key role in protecting skin fibroblasts from ageing, which further allowed the skin to resist photoaging, thereby promoting the recovery of wound injured by UV radiation.

4.
Int J Biol Macromol ; 133: 156-164, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30986459

RESUMO

Over the recent years, the exploitation of antibacterial performance of lignin and its subsequent usage as bacteriostatic additives has gained increasing interests. However, due to the restriction from structural heterogeneity, the antibacterial activity of lignin is always modest and unstable (especially against Gram-negative bacteria). In this regard, we proposed a facile one-step ethanol fractionation process to decrease the heterogeneity of lignin and, therefore, improve its antibacterial activity. Two fractions (Fs and Fi, 95% ethanol soluble and insoluble fraction, respectively) were obtained from bamboo kraft lignin (BKL) and their antibacterial effectiveness was compared. The results showed that the antibacterial activity of Fs increased significantly compared to that of BKL. On the contrary, Fi barely exhibited inhibitory effect on the growth of two Gram-positive bacteria and even promoted the growth of two Gram-negative bacteria. The much lower phenolic-OH content in Fi was an important reason for the absence of antibacterial activity. Besides, the growth promotion of Gram-negative bacteria by Fi was possibly caused by the formation of insoluble carriers for bacteria growth due to the poor water-solubility of Fi. Accordingly, after the elimination of Fi, the one-step fractionation significantly enhanced the antibacterial activity of lignin against both Gram-positive and Gram-negative bacteria.

5.
Int Immunopharmacol ; 72: 454-458, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035087

RESUMO

Ulcerative colitis, one of the most important inflammatory bowel diseases, affects millions of people worldwide. The aim of this study was to investigate the effects of Saikosaponin A on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were treated with 2.5% DSS for 5 d to induce acute colitis. Saikosaponin A was given 3 d before and during DSS treatment by intragastric administration. The results showed that Saikosaponin A significantly inhibited DSS-induced body weight loss and shortening of colon length. DSS-induced colonic histological changes and MPO activity were also prevented by treatment of Saikosaponin A. The levels of TNF-α and IL-1ß were increased by DSS and dose-dependently inhibited by Saikosaponin A. Furthermore, Saikosaponin A significantly inhibited DSS-induced NF-κB activation and up-regulated the expression of LXRα. Taken together, our results indicated that Saikosaponin A had protective effects against DSS-induced colitis. Saikosaponin A protected DSS-induced colitis through inhibiting inflammatory response.

6.
Anal Chim Acta ; 1059: 49-58, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30876632

RESUMO

For fabrication of composite electrode, one-pot strategy is highly attractive for convenience and efficiency. Here, a self-supporting Co3O4/nanoporous gold (NPG) composite electrode was one-pot prepared via one-step in situ anodization of a smooth gold electrode in a CoCl2 solution within 100 s. It worked as a bifunctional electrocatalyst for glucose oxidation and H2O2 reduction in NaOH solution. Under optimized conditions, the electrocatalytic oxidation of glucose exhibits a wide linear range from 2 µM to 2.11 mM with a limit of detection as low as 0.085 µM (S/N = 3) and an ultrahigh sensitivity of 4470.4 µA mM-1 cm-2. Detection of glucose in human serum samples are also realized with results comparable to those from local hospital. The electrocatalytic reduction of H2O2 shows a linear response range from 20 µM to 19.1 mM and a high sensitivity of 1338.7 µA mM-1 cm-2. The present results demonstrate that the facilely prepared Co3O4/NPG is a promising nonenzymatic sensor for rapid amperometric detection of glucose and H2O2 with ultrasensitivity, high selectivity, satisfactory reproducibility, good stability and long duration.


Assuntos
Glicemia/análise , Cobalto/química , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Peróxido de Hidrogênio/análise , Óxidos/química , Glicemia/química , Técnicas Eletroquímicas/instrumentação , Humanos , Limite de Detecção , Oxirredução , Porosidade , Reprodutibilidade dos Testes
8.
Transpl Immunol ; 54: 20-28, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30682409

RESUMO

BACKGROUND: Chronic renal allograft dysfunction (CRAD) is the main condition affecting the long-term survival of renal allografts. Rosiglitazone, which is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been shown to exert antifibrotic and anti-inflammatory effects on some renal diseases. The present paper investigates the effect of rosiglitazone on CRAD using a murine model. METHODS: The CRAD group received classical orthotopic F344-Lewis kidney transplantation. The treatment group was treated with rosiglitazone for 12 weeks following renal transplantation. The control subjects were uninephrectomized F344 and Lewis rats. Twelve weeks after the operation, the rats were harvested for renal function, histological, immunohistochemical and molecular biological analyses. RESULTS: Rosiglitazone treatment effectively decreased urine protein excretion and preserved renal function in the CRAD rats. Administration of rosiglitazone also inhibited interstitial fibrosis and macrophage infiltration in the CRAD rat kidneys. Furthermore, rosiglitazone treatment inhibited TGF-ß and NF-κB pathway activation, decreased collagen I, collagen IV, α-SMA, MCP-1, ICAM-1, TNF-α, and IL-1ß expression, and increased E-cadherin expression in renal allograft tissues from the CRAD rats. CONCLUSIONS: Rosiglitazone successfully attenuates the development of CRAD via inhibition of TGF-ß signaling, the renal tubular epithelial-to-mesenchymal transition (EMT), and inflammation.

9.
Int J Mol Med ; 43(3): 1217-1228, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664165

RESUMO

Mechanical ventilation may cause ventilator­induced lung injury (VILI). Canonical Wnt signaling has been reported to serve an important role in the pathogenesis of VILI. Bioinformatics analysis revealed that canonical and non­canonical Wnt signaling pathways were activated in VILI. However, the role of non­canonical Wnt signaling in the pathogenesis of VILI remains unclear. The present study aimed to analyze the potential role of non­canonical Wnt signaling in VILI pathogenesis. Lung injury was assessed via Evans blue albumin permeability and histological scoring, as well as by inflammatory cytokine expression and total protein concentration in bronchoalveolar lavage fluid. The relative protein expression of canonical and non­canonical Wnt signaling pathway components were examined via western blotting and immunohistochemistry. The results demonstrated that 6 h of mechanical ventilation at low tidal volume (LTV; 6 ml/kg) or moderate tidal volume (MTV; 12 ml/kg) induced lung injury in sensitive A/J mice. Ventilation with MTV increased the protein levels of Wnt­induced secreted protein 1 (WISP1), Rho­associated protein kinase 1 (ROCK1), phosphorylated (p)­Ras homolog gene family, member A and p­C­Jun N­terminal kinase (JNK). Inhibition of ROCK1 by Y27632 and JNK by SP600125 attenuated MTV­induced lung injury and decreased the expression of proteins involved in non­canonical Wnt signaling, including WISP1. In conclusion, non­canonical Wnt signaling participates in VILI by modulating WISP1 expression, which has been previously noted as critical for VILI development. Therefore, the non­canonical Wnt signaling pathway may provide a preventive and therapeutic target in VILI.


Assuntos
Proteínas de Sinalização Intercelular CCN/genética , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Via de Sinalização Wnt , Animais , Biomarcadores , Proteínas de Sinalização Intercelular CCN/metabolismo , Citocinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Transcriptoma , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
10.
Int J Biol Macromol ; 128: 107-113, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30682470

RESUMO

Valorization of lignin based on its biological activities is always suffering the restriction from lignin heterogeneity, including wide molecular weight distributions and variable functional group contents. In this work, organosolv ethanol lignin (OEL) from corn stalk was divided into four fractions by multiple organic solvent successive extraction and the anti-tyrosinase activities of four obtained fractions were compared to evaluate the effect of lignin heterogeneity on the anti-tyrosinase activity. The characterization revealed that the successive extraction realized the fractionation of the heterogeneous OEL into four relatively homogeneous parts with gradually increasing molecular weight and decreasing phenolic OH content. The enzymatic inhibition study showed that the four fractions exhibited obviously different anti-tyrosinase activities and the dichloromethane fraction had the highest tyrosinase inhibition rate (75.12%, 0.5 mg/mL), whose value was comparable to the positive control p-hydroxybenzaldehyde. Besides, the relationships between the anti-tyrosinase activity and the lignin properties (purity, molecular weight and phenolic OH) were discussed to elucidate the possible formation mechanism of differences among the four lignin fractions in anti-tyrosinase activity. Consequently, these results suggest that lignin heterogeneity has a significant effect on the tyrosinase inhibition rate, and lignin fractionation is an effective way to screen lignin fractions with high anti-tyrosinase activity.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lignina/química , Lignina/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fracionamento Químico , Ativação Enzimática/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Redes e Vias Metabólicas , Peso Molecular , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Cutan Ocul Toxicol ; : 1-21, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30173582

RESUMO

BACKGROUND: Topical drugs for mild to moderate acne include adapalene(ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic schemes. OBJECTIVES: To compare the safety and efficacy of 2% supramolecular SA (2%SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO+0.1%ADA)for treatment of facial acne. MATERIALS AND METHODS: This was an open-label, split face, randomized and single center clinical trial .Subjects with mild to moderate acne were enrolled. 2% SSA cream were randomly applied on one side of the face while 5%BPO+0.1%ADA gel was applied on opposite side for 28 days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14 and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time. RESULTS: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO+0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all P>0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L*-value) and erythema (a*-values) indicators showed no statistically differences in the left and right sides of the face (P>0.05). CONCLUSION: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO+0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.

12.
Biosens Bioelectron ; 117: 758-765, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30029197

RESUMO

Using one-step anodization strategy, a nanoporous gold film (HNPG) with large surface area was rapidly fabricated on Au80Sn20 (wt%) alloy in just 80 s. The formation of highly surface-roughened nanoporous structures results from a complex process of electrochemical dealloying of Sn component from AuSn alloy, anodic electrodissolution, disproportion and deposition of Au component, and spontaneous redox reaction between electrodissolved Sn2+ and AuCl4-species at the applied anodic potential. As-prepared HNPG/AuSn shows enhanced electrochemical performance for glucose oxidation in alkaline electrolyte. At a low potential of 0.1 V (vs. SCE), it offers a short response time of 4 s, a wide linear detection range of 2 µM to 8.11 mM, an ultralow detection limit of 0.36 µM (S/N = 3), an ultrahigh sensitivity of 4374.6 µA cm-2 mM-1, and satisfactory selectivity and reproducibility. Specifically, after 6 weeks, no obvious loss of glucose amperometric signal was observed on HNPG/AuSn. The facile preparation and excellent sensing performance of HNPG/AuSn electrode make sure that it is a promising candidate for advanced enzyme-free glucose sensors.

13.
Mol Clin Oncol ; 8(5): 631-636, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29732152

RESUMO

Bufalin is a monomer compound extract from Chansu, which is a traditional Chinese medicine obtained from the skin and parotid venom glands of toads, such as Bufo bufo gargarizans Cantor and Bufo melanostictus Schneider. Chansu had been used in traditional Chinese medicine for >1,000 years due to its cardiac, anti-inflammatory and anticancer properties. Previous studies identified bufalin as the main anticancer compound of Chansu, and recent evidence has corroborated its anticancer properties. Bufalin inhibits cancer cell proliferation, induces cell cycle arrest, induces cancer cell apoptosis, inhibits neovascularization, induces cell differentiation, inhibits cancer metastasis and invasion, and enhances chemotherapeutic drug sensitivity. However, the function and mechanism of bufalin in metastatic cancer cells have not yet been expounded. The aim of the present review was to discuss the recent progress and prospects of bufalin in the prevention of cancer metastasis, particularly in inhibiting epithelial-to-mesenchymal transition.

14.
Oncotarget ; 9(34): 23320-23333, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29805736

RESUMO

Achaete-scute-like 2 (ASCL2) is a transcription factor containing a basic helix-loop-helix (bHLH) domain and is a downstream target of Wnt signaling in intestinal stem cells. Bufalin is the primary active ingredient in Chan Su, a traditional Chinese medicine obtained from the skin and parotid venom glands of toads. The purpose of this study was to research the anti-invasion and anti-metastasis activity of bufalin in gastric cancer and to identify the potential mechanism. Bufalin inhibited gastric cancer cell invasion and metastasis, suppressed cancer cell colony formation, and inhibited the growth of subcutaneous xenografted tumors in nude mice. Furthermore, bufalin inhibited ASCL2 expression and down-regulated the expression of invasion-related genes such as MMP2, MMP9, and vimentin, thereby suppressing epithelial-mesenchymal transition (EMT) in gastric cancer. A Wnt signaling inhibitor (XAV939) down-regulated invasion and the expression of ASCL2, ß-catenin, and vimentin but up-regulated E-cadherin expression. In nude mice, bufalin inhibited the tumorigenic behavior of gastric cancer cells, induced cancer cell apoptosis, and regulated invasion-related gene expression. Together, our results suggest that bufalin arrests invasion and metastasis and that its mechanism of action may involve down-regulating Wnt/ASCL2 expression.

15.
Exp Ther Med ; 15(4): 3725-3732, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29581733

RESUMO

Chronic renal allograft dysfunction (CRAD) is the primary factor affecting the long-term survival of patients who have undergone renal transplantation. Oxidative stress and inflammation serve an important role in the pathological damage caused by CRAD in the early post-transplantation phase. Previous studies have demonstrated that sirtuin 3 (sirt3) protects cells from oxidative stress and inflammation. A model of renal orthotopic transplantation was established in the current study and kidney samples were harvested from the rats 12 weeks following surgery. Compared with the control groups, there were significantly increased levels of serum creatinine, blood urea nitrogen and 24 h urinary protein in the allograft group (P<0.05). Pathological examinations indicated mononuclear cell infiltration and intimal proliferation in the allograft group, which had a higher Banff score compared with the control groups. There were increased levels of malondialdehyde, decreased sirt3 protein expression and decreased superoxide dismutase enzyme activity in the allograft group compared with the control groups (P<0.05). In addition, there was a negative correlation between the expression of sirt3 and 24 h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cell infiltration, smooth muscle cell migration in the vascular wall and Banff scores. Thus, sirt3 may serve an important protective role in the early stage of CRAD.

16.
Cancer Immunol Immunother ; 67(5): 797-803, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29478100

RESUMO

A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4+ T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4+ T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics. Those patients with high IFN-γ and IL-21 expression in CD4+ T cells presented significantly better prognosis than patients with low cytokine secretion in CD4+ T cells. Tumor-infiltrating CD4+ T cells were significantly less potent in expressing IFN-γ, IL-4, and IL-17, and more potent in expressing IL-10 than circulating CD4+ T cells. In addition, we found no difference in CD80, CD86, or MHC II expression by macrophages from patients with different IFN-γ and IL-21 levels. However, the secretion of IL-12, a Th1-skewing cytokine, was released at significantly higher level by macrophages from patients with high IFN-γ or high IL-21 secretion. We also identified that modulating monocytes/macrophages by GM-CSF-mediated polarization resulted in significantly elevated expression of IFN-γ and IL-21 from CD4+ T cells. Overall, these results suggested that the specific types of responses mounted by CD4+ T cells were critical to the final outcome of bladder cancer patients and can be influenced by monocyte/macrophage polarization.


Assuntos
Vacina BCG/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Interleucinas/imunologia , Macrófagos/imunologia , Neoplasias da Bexiga Urinária/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Células Cultivadas , Humanos , Interferon gama/metabolismo , Interleucinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Kidney Blood Press Res ; 43(1): 191-205, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466800

RESUMO

BACKGROUND/AIMS: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. METHODS: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2'-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. RESULTS: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. CONCLUSION: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD.


Assuntos
Isotiocianatos/farmacologia , Transplante de Rim/normas , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Aloenxertos , Animais , Heme Oxigenase (Desciclizante)/metabolismo , NAD(P)H Desidrogenase (Quinona) , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew
18.
Transpl Immunol ; 48: 18-25, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29452170

RESUMO

OBJECTIVE: To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD). METHODS: CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twelve weeks after the operation, the rats were sacrificed for renal function, histological, immunohistochemistry and molecular biological analyses. RESULTS: The 24-h urinary protein excretion and serum creatinine levels, urine microalbumin/creatinine ratios, and Banff score sums were significantly increased in the CRAD group compared with those in the F344 and Lewis control groups. The degree of mononuclear cell infiltration and interstitial fibrosis (IF) was higher in the CRAD group than in the control groups. Sirt1, TGF-ß1, MCP-1, ICAM-1 expression was up-regulated in CRAD. Furthermore, Sirt1 expression was negatively correlated with the 24-h urinary protein excretion and serum creatinine levels, Banff score sums, mononuclear cell infiltration and IF severity, and TGF-ß1, MCP-1 and ICAM-1 expression levels. CONCLUSION: Sirt1 might be involved in the pathogenic process of IF and inflammation at the early stage of CRAD. Thus, Sirt1 represents a novel therapeutic strategy and target for the early prevention and treatment of CRAD.


Assuntos
Aloenxertos/metabolismo , Rejeição de Enxerto/imunologia , Inflamação/imunologia , Transplante de Rim , Rim/metabolismo , Leucócitos Mononucleares/imunologia , Sirtuína 1/metabolismo , Aloenxertos/patologia , Animais , Quimiocina CCL2/metabolismo , Doença Crônica , Creatinina/sangue , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica , Humanos , Rim/patologia , Ratos , Ratos Endogâmicos Lew , Sirtuína 1/genética , Fator de Crescimento Transformador beta1/metabolismo , Transplante Homólogo
19.
J Cell Physiol ; 233(7): 5112-5118, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29215717

RESUMO

Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling. Moreover, lamin A/C is the essential core module regulating stem cell differentiation. The cells with higher migration ability tend to have enhanced differentiation potential, while the optimum amount of lamin A/C in migration and differentiation of MSCs is in conflict. This contrary phenomenon may be the result of mechanical microenvironment modulation.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(11): 1540-1544, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29180338

RESUMO

OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and insulin resistance(IR) in non-diabetic normal-weight individuals and investigate how this association differs between male and femalesubjects. METHODS: From June to October, 2012, we performed a cross-sectional survey among 2142 community-based non-diabetic Chinese participants, who were divided into 4 groups according to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin resistance (HOMA-IR), calculated as the product of fasting plasma glucose (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of insulin resistance. Logistic regression models were used to explore the association of WHR with IR in these subjects. RESULTS: In the unadjusted model, WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26, P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04, P=0.009) after adjustment for the potential confounders including the history of hypertension, coronary heartdisease, current smoker, physical inactivity, and body mass index. CONCLUSION: WHR is independently associated with IR in non-diabetic Chinese women with normal body weight.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA