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1.
Stem Cell Res ; 43: 101718, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32050117

RESUMO

X-linked retinoschisis (XLRS) is a one of most common retinal genetic diseases of juvenile progressive vitreoretinal degeneration in males, which caused by the mutation of RS1 gene. In this study, an induced pluripotent stem cell (iPSC) line was generated from human peripheral blood mononuclear cells (PBMC) of a 13-year-old male patient with X-linked juvenile retinoschisis carrying a novel mutation in RS1 gene. The iPSCs exhibited iPSC morphology, expression of the pluripotency markers and in vitro differentiation potential, and the CSUASOi005-A iPSC line retained the original mutation (c.527T > A) of RS1 with a normal karyotype.

2.
Pediatr Transplant ; : e13635, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011062

RESUMO

XLP-2 is known as a rare primary immunodeficiency disease, which is characterized by the susceptibility to EBV infection and potential development into the pHLH. The existing studies believe that the dysfunction of XIAP represents one of the most significant pathogenic mechanisms of XLP-2, and allo-HSCT is regarded as a crucial treatment for the long-term survival in XLP-2 patients. In our present study, a 2-year-old male patient was diagnosed with XLP-2. After receiving chemotherapy by using HLH-2004 without allo-HSCT, he reached a complete remission, and his EBV load was brought under control. Our family survey revealed a novel frameshift mutation in the XIAP gene in this patient, as well as in his cousin and grandfather. Until now, the patient has been followed up for 22 months with no recurrence reported yet. Based on these findings, it is believed that for child pHLH patients with XLP-2, the treatment by controlling symptoms alone without allo-HSCT and with regular monitoring of EBV load could be conducive to a long-term survival.

4.
J Proteome Res ; 19(2): 819-831, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31887055

RESUMO

The lead compound acridone derivative 8a showed potent antiproliferative activity by inducing DNA damage through direct stacking with DNA bases and triggering ROS in CCRF-CEM cells. To define the chromatin alterations during DNA damage sensing and repair, a detailed quantitative map of single and coexisting histone post-translational modifications (PTMs) in CCRF-CEM cells affected by 8a was performed by the Data Independent Acquisition (DIA) method on QE-plus. A total of 79 distinct and 164 coexisting histone PTMs were quantified, of which 16 distinct histone PTMs were significantly altered when comparing 8a-treated cells with vehicle control cells. The changes in histone PTMs were confirmed by Western blotting analysis for three H3 and one H4 histone markers. The up-regulated dimethylation on H3K9, H3K36, and H4K20 implied that CCRF-CEM cells might accelerate DNA damage repair to counteract the DNA lesion induced by 8a, which was verified by an increment in the 53BP1 foci localization at the damaged DNA. Most of the significantly altered PTMs were involved in transcriptional regulation, including down-regulated acetylation on H3K18, H3K27, and H3K122, and up-regulated di- and trimethylation on H3K9 and H3K27. This transcription-silencing phenomenon was associated with G2/M cell cycle arrest after 8a treatment by flow cytometry. This study shows that the DIA proteomics strategy provides a sensitive and accurate way to characterize the coexisting histone PTMs changes and their cross-talk in CCRF-CEM cells after 8a treatment. Specifically, histone PTMs rearrange transcription-silencing, and cell cycle arrest DNA damage repair may contribute to the mechanism of epigenetic response affected by 8a.

5.
Ann Hematol ; 99(2): 343-349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879790

RESUMO

Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Pirazóis/administração & dosagem , Dermatopatias , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Resistência a Medicamentos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/mortalidade , Esteroides/administração & dosagem , Taxa de Sobrevida
7.
Nat Commun ; 10(1): 4157, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519887

RESUMO

Receptor-interacting protein kinase 1 (RIPK1) is a critical regulator of cell death through its kinase activity. However, how its kinase activity is regulated remains poorly understood. Here, we generate Ripk1K376R/K376R knock-in mice in which the Lys(K)63-linked ubiquitination of RIPK1 is impaired. The knock-in mice display an early embryonic lethality due to massive cell death that is resulted from reduced TAK1-mediated suppression on RIPK1 kinase activity and forming more TNFR1 complex II in Ripk1K376R/K376R cells in response to TNFα. Although TNFR1 deficiency delays the lethality, concomitant deletion of RIPK3 and Caspase8 fully prevents embryonic lethality of Ripk1K376R/K376R mice. Notably, Ripk1K376R/- mice are viable but develop severe systemic inflammation that is mainly driven by RIPK3-dependent signaling pathway, indicating that K63-linked ubiquitination on Lys376 residue of RIPK1 also contributes to inflammation process. Together, our study reveals the mechanism by which K63-linked ubiquitination on K376 regulates RIPK1 kinase activity to control cell death programs.


Assuntos
Morte Celular/fisiologia , Desenvolvimento Embrionário/fisiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Ubiquitinação/fisiologia , Animais , Morte Celular/genética , Desenvolvimento Embrionário/genética , Citometria de Fluxo , Células HEK293 , Humanos , Imunoprecipitação , Inflamação/genética , Inflamação/metabolismo , Camundongos , Biologia Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Ubiquitinação/genética
9.
Med Sci Monit ; 25: 7016-7025, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532760

RESUMO

BACKGROUND Oxidative stress in myocardial ischemia results in cardiomyocyte apoptosis. The expression of microRNA-141-3p (miR-141-3p) and the 105 kD toll-like receptor protein (TLR), RP105, have been identified in cardiomyocytes in vitro. This study aimed to investigate the effects of hypoxia in H9c2 rat cardiomyoblasts with and without the inhibition of miR-141-3p and to investigate the expression of RP105 and the PI3K/AKT signaling pathway. MATERIAL AND METHODS H9c2 rat cardiomyoblasts were cultured in conditions of hypoxia and treated with a specific miR-141-3p-inhibitor. RP105 short-interfering RNA (siRNA) was constructed, and LY294002 was used to inhibit the PI3KA/AKT pathway. The fluorescent probe, dihydroethidium (DHE), was used to detect reactive oxygen species (ROS). Flow cytometry evaluated ROS and apoptosis. Quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot studied the expression of the PI3K/AKT pathway genes and proteins. Bioinformatics and dual-luciferase reporter assays were used to identify the targets for miR-141-3p. RESULTS A predictive TargetScan algorithm showed that the RP105 gene was a potential target of miR-141-3p. Expression of miR-141-3p was significantly increased in hypoxic H9c2 cells, and inhibition of miR-141-3p increased cell viability and reduced apoptosis. Also, miR-141-3p was shown to target 3'-UTR of RP105. Down-regulation of RP105 associated with hypoxia and its downstream PI3K/AKT pathway were significantly increased following miR-141-3p inhibition. The protective effect of miR-141-3p inhibition in hypoxic H9c2 cells was abolished by the absence of RP105 and inhibition of PI3K/AKT. CONCLUSIONS Inhibition of miR-141-3p reduced hypoxia-induced apoptosis in H9c2 cardiomyocytes in vitro by activating the RP105-dependent PI3K/AKT signaling pathway.

10.
Atherosclerosis ; 289: 94-100, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31487565

RESUMO

BACKGROUND AND AIMS: About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS: 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS: Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ±â€¯1.7 mm2vs. 1.9 ±â€¯1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS: Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.

11.
Transplant Proc ; 51(8): 2798-2807, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351770

RESUMO

PURPOSE: The objective of this research was to survey the therapeutic action of simvastatin (Sim) on intestinal ischemia/reperfusion injury (II/RI) by modulating Omi/HtrA2 signaling pathways. METHODS: Sprague Dawley rats were pretreated with 40 mg/kg Sim and then subjected to 1 hour of ischemia and 3 hours of reperfusion. The blood and intestinal tissues were collected, pathologic injury was observed, the contents of serum tumor necrosis factor-α and interleukin-6 (IL-6) were estimated, and superoxide dismutase, methane dicarboxylic aldehyde, and cysteinyl aspartate specific proteinase-3 (caspase-3) levels, as well as the expressions of Omi/HtrA2 and caspase-3, were measured in the intestinal tissues. RESULTS: Sim preconditioning mitigated the damnification of intestinal tissues by decreasing oxidative stress, inflammatory damage, and apoptosis and downregulating the expression of Omi/HtrA2 compared to the ischemia/reperfusion group, while Sim+Ucf-101 significantly augmented this effect. CONCLUSION: These results suggest that Sim may alleviate intestinal ischemia/reperfusion injury by modulating Omi/HtrA2 signaling pathways.


Assuntos
Anticolesterolemiantes/farmacologia , Serina Peptidase 2 de Requerimento de Alta Temperatura A/fisiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/análise , Caspase 3/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Pirimidinonas , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tionas
14.
BMC Med Genet ; 20(1): 104, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185929

RESUMO

BACKGROUND: A multidirectional relationship has been demonstrated between myocardial infarction (MI) and depression. However, the causal genetic factors and molecular mechanisms underlying this interaction remain unclear. The main purpose of this study was to identify potential candidate genes for the interaction between the two diseases. METHODS: Using a bioinformatics approach and existing gene expression data in the biomedical discovery support system (BITOLA), we defined the starting concept X as "Myocardial Infarction" and end concept Z as "Major Depressive Disorder" or "Depressive disorder". All intermediate concepts relevant to the "Gene or Gene Product" for MI and depression were searched. Gene expression data and tissue-specific expression of potential candidate genes were evaluated using the Human eFP (electronic Fluorescent Pictograph) Browser, and intermediate concepts were filtered by manual inspection. RESULTS: Our analysis identified 128 genes common to both the "MI" and "depression" text mining concepts. Twenty-three of the 128 genes were selected as intermediates for this study, 9 of which passed the manual filtering step. Among the 9 genes, LCAT, CD4, SERPINA1, IL6, and PPBP failed to pass the follow-up filter in the Human eFP Browser, due to their low levels in the heart tissue. Finally, four genes (GNB3, CNR1, MTHFR, and NCAM1) remained. CONCLUSIONS: GNB3, CNR1, MTHFR, and NCAM1 are putative new candidate genes that may influence the interactions between MI and depression, and may represent potential targets for therapeutic intervention.


Assuntos
Biologia Computacional/métodos , Mineração de Dados/métodos , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Infarto do Miocárdio/genética , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Reprodutibilidade dos Testes
15.
Stem Cell Res ; 38: 101466, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31141763

RESUMO

X-linked juvenile retinoschisis (XLRS) is one of the most severely affected genetic causes of irreversible retinal degeneration diseases in young males, especially school-age boys. Here, we generated induced pluripotent stem cells (iPSCs) from a Chinese 11-year-old male with clinically diagnosed XLRS. Urine sample was collected with appropriate cooperation, then isolated cells were expanded for subsequent reprogramming procedure using integration-free Sendai virus. The newly derived CSUASOi001-A iPS cell line harboring the c.304C > T mutation in the RS1 gene (p.R102W) provides a useful resource to investigate pathogenic mechanisms in XLRS.

16.
Acta Biomater ; 92: 115-131, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075513

RESUMO

In vitro generation of a functional retinal pigment epithelium (RPE) monolayer sheet is useful and promising for RPE cell therapy. Here, for the first time, we used induced pluripotent stem (iPS) supernatant as the conditioned medium (iPS-CM) and femtosecond laser intrastromal lenticule (FLI-lenticule) as a scaffold to construct an engineered RPE sheet. There are significant enhancements in RPE cell density, transepithelial electrical resistance (TER) and inhibitions of ultraviolet C (UVC)-irradiated apoptosis when RPE cells are cultured in iPS supernatant/Dulbecco's modified Eagle's medium (DMEM)-F12 of 1/2 (iPS-CM) compared with those in normal medium (NM, DMEM-F12). Using the assay of a panel of cytokines, combined with transcriptome and protein analyses, we discover that iPS-CM contains high levels of platelet-derived growth factor AA (PDGF-AA), insulin-like growth factor binding protein (IGFBP)-2, transforming growth factor (TGF)-α and IGFBP-6, which are responsible for the upregulation of gene and protein markers with RPE phenotypes and downregulation of gene and protein markers with epithelial-mesenchymal transition (EMT) phenotypes for RPE cells in iPS-CM when compared to those in NM. Moreover, compared to cultures on tissue culture plates (TCP), RPE cells on FLI-lenticule display more microvilli and cilium in accordance with the results in terms of RNA-Seq data, quantitative polymerase chain reaction (qPCR) expression, immunofluorescence staining, and western blot assays. Furthermore, acellular FLI-lenticule exhibits biocompatibility after rabbit subretinal implantation by 30 days through electroretinography and histological examination. Thus, we determined that engineered RPE sheets treated by iPS-CM in conjunction with FLI-lenticule scaffold aid in enhanced RPE characteristics and cilium assembly. Such a strategy to construct RPE sheets is a promising avenue for developing RPE cell therapy, disease models and drug screening tools. STATEMENT OF SIGNIFICANCE: In vitro generation of a functional RPE monolayer sheet is useful and promising for RPE cell therapy. Here, we constructed engineered RPE sheets treated by iPS-CM in conjunction with FLI-lenticule scaffolds to help in enhanced RPE characteristics and cilium assembly. Such a strategy to generate RPE sheets is a promising avenue for developing RPE cell therapy, disease models and drug screening tools.

17.
Br J Haematol ; 186(5): 717-723, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115044

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) is a severe, even fatal, inflammatory condition. Epstein-Barr virus (EBV) infection-associated HLH (EBV-HLH) is one of the most common types of secondary HLH. Etoposide is a key drug in HLH-94/04 regimen. We sought to identify the importance of etoposide in the initial treatment of EBV-HLH. Ninety-three patients with EBV-HLH of all ages admitted to our centre in 2017 were divided into two groups according to whether the initial treatment contained etoposide or not. The survival of the group whose initial therapy included etoposide (Group 1, 52 patients; 6-month survival rate 0·769) was significantly better than that of the group whose initial therapy did not include etoposide (Group 2, 41 patients; 6-month survival rate 0·269) (P < 0·001). In patients aged <18 years old, the survival of Group 1 patients was not significantly better than that of Group 2 patients (P = 0·447), in contrast to patients aged ≥18 years, where the survival of Group1 patients was significantly better than that of Group 2 patients (P < 0·001). We concluded that including etoposide in the initial treatment of EBV-HLH patients can improve their prognosis, especially adult patients. This may be because that adult patients are recognized as "higher risk" patients.

18.
Blood ; 133(23): 2465-2477, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-30992265

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Adulto , Feminino , Humanos , Masculino
19.
ACS Appl Mater Interfaces ; 11(19): 17333-17340, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31013429

RESUMO

Rechargeable metallic lithium batteries are considered as promising candidates for next-generation energy storage due to their high energy densities. However, safety concerns associated with electrolyte flammability and dendrite growth hinder their practical applications. Nonflammable liquid electrolytes have attracted significant attention recently, but they are mainly based on expensive ionic liquids, fluorinated solvents, or with highly concentrated salt. Here we design a novel trisalt electrolyte composed of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)-lithium bis(oxalato)borate (LiBOB)-LiPF6 in EC/PC solvent, which is not flammable even in contact with fire. Moreover, it creates unique protection of solid electrolyte interphase (SEI) film on lithium metal anode that allows 400 cycles of Li/Li(NiMnCo)1/3O2 cells with a capacity retention of 97.0% at 0.83 mA cm-2. This work illustrates that low-cost fluorine-free carbonate solvents can also realize nonflammable electrolyte with high performance, which opens new opportunities to promote safety and energy density of rechargeable lithium batteries simultaneously.

20.
Biomed Pharmacother ; 112: 108736, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970526

RESUMO

INTRODUCTION: The purpose of the experiment was to survey the therapeutic function of resveratrol (RES)-loaded poly(ethylene glycol)-poly(phenylalanine) (PEG-PPhe) on intestinal ischemia/reperfusion injury (II/RI) via the interaction between CSE/H2S and iNOS/NO compared to free RES in diabetic rats. METHODS: Diabetic rats were pretreated with 20 mg/kg of RES or the RES/PEG-PPhe complex and then subjected to 1 h of ischemia and 3 h of reperfusion. Blood and intestines were collected, intestinal pathological injury was estimated, and the contents of body weight, weights of different tissues, blood glucose, serum insulin, HOMA index, serum nitric oxide (NO) and serum sulfureted hydrogen (H2S) were observed. The dry/wet intestine ratios, the activity of superoxide dismutase (SOD); the contents of methane dicarboxylic aldehyde (MDA), glutathione (GSH), H2S, and NO; and the concentrations of inducible nitric oxide synthase (iNOS) and cystathionine-γ-lyase (CSE) were observed in the intestinal tissues. RESULTS: A significant reduction of weights of different tissues, blood glucose, pathological damage, dry/wet ratios, MDA, NO, iNOS expression and a significant increasement of body weight, serum insulin, HOMA index, SOD, GSH, H2S, CSE expression were observed in both treatment groups. However, a greater reduction of weights of different tissues, blood glucose (7.49-13.49 mmol/L for 72 h vs. the control) and pathological damage, iNOS expression, dry/wet ratios (6.14 ± 0.29 vs. 8.51 ± 0.42), MDA (5.01 ± 0.71 nmol vs. 9.98 ± 0.67 nmol), NO (0.52 ± 0.09 µmol vs. 0.99 ± 0.08 µmol in intestinal tissue; 19.29 ± 0.89 µmol vs. 45.23 ± 1.17 µmol in serum) was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all); a greater increasement of body weight, serum insulin, HOMA index, SOD (39.79±1.78 U vs. 11.84 ± 1.02 U), GSH (31.25 ± 1.19 mg vs. 10.13 ± 0.64 mg), H2S (39.52 ± 1.32 nmol vs. 13.02 ± 1.03 nmol in intestinal tissue; 9.78 ± 0.79 µmol vs. 3.11 ± 0.85 µmol in serum), CSE expression was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all). In addition, aminoguanidine (AMI, iNOS inhibitor) reduced I/R injury, and dl-propargylglycine (PAG, CSE inhibitor) increased I/R injury. CONCLUSIONS: The interaction between CSE/H2S and the iNOS/NO-mediated resveratrol/poly(ethylene glycol)-poly(phenylalanine) complex alleviates intestinal ischemia/reperfusion injuries in diabetic rats.


Assuntos
Diabetes Mellitus Experimental/complicações , Portadores de Fármacos/química , Intestinos/efeitos dos fármacos , Fenilalanina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/uso terapêutico , Animais , Cistationina gama-Liase/metabolismo , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Sulfeto de Hidrogênio/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenilalanina/administração & dosagem , Polietilenoglicóis/administração & dosagem , Substâncias Protetoras/administração & dosagem , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Resveratrol/administração & dosagem
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