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1.
Thromb Res ; 183: 69-75, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31670229

RESUMO

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction, leading to lower platelet count. Thalidomide is considered as a novel immunomodulatory drug for treating several autoimmune diseases. Whether thalidomide can ameliorate ITP remains unclear. This study aims to evaluate the effect of thalidomide on ITP mouse model. ITP mouse model was established through intraperitoneal injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin. Thalidomide (10, 20 or 50 mg/kg body weight) was intraperitoneally injected into mice followed by antibody injection. Then, peripheral blood and plasma was isolated for analysis of platelet count and the level of IFN-γ and IL-17 in plasma. Meanwhile, spleen was extracted to measure the expression of CD68, a macrophage marker. In addition, macrophage cell line RAW264.7 was cultured and treated with thalidomide followed by analysis of cell viability, apoptosis as well as cell cycle. Thalidomide prevented antiplatelet antibody-mediated platelet destruction in ITP mouse model. Compared with vehicle (phosphate-buffered saline), thalidomide significantly inhibited the secretion of IFN-γ and IL-17 in ITP mouse and reduced the expression of CD68 in spleen. After thalidomide treatment, the cell viability of RAW264.7 cell was significantly reduced and the cell number in S phase was also significantly decreased. In addition, the expression of cyclin E2 was significantly reduced. In conclusion, thalidomide prevents antiplatelet antibody-mediated platelet destruction in ITP mouse possibly through reducing the number of macrophages, suggesting that it might be a novel approach for treating ITP.

3.
BMC Pediatr ; 19(1): 139, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046723

RESUMO

BACKGROUND: It is still unclear if and at which trimester gestational weight gain is related to childhood adiposity. Thus we aimed to evaluate the association between trimester-specific gestational weight gain and body-fat compositions in Chinese children. METHODS: Maternal gestational weight were measured by trained nurses every 2 to 4 weeks from the first prenatal care, and body-fat compositions of 407 children from the Shanghai Obesity Cohort at 5 years of age were measured by nutritionist through bioelectrical impedance analysis. Overweight/obesity of children was defined according to the criteria of International Obesity Task Force. Logistic and linear regression models adjusted for potential confounders were conducted to evaluate the associations of gestational weight gains with childhood obesity and body-fat compositions. Two-sided P-value < 0.05 was considered statistically significant. RESULTS: Greater gestational weight gain in the 1st-trimester was significantly associated with a higher risk of childhood overweight/obesity [OR: 1.40 (95% CI: 1.06, 1.86)], fat mass index [ß: 0.25 (95% CI: 0.12, 0.38)], body fat percentage [ß: 1.04 (95% CI: 0.43, 1.65)], and waist-to-height ratio [ß: 0.005 (95% CI: 0.002, 0.008)]. A positive but nonsignificant association was found between greater 3rd-trimester gestational weight gain and a higher risk of offspring overweight/obesity, and we speculated that the association between 2nd-trimester gestational weight gain and offspring overweight/obesity is the "U" type. CONCLUSIONS: Weight gain in the first trimester gestation is positively correlated with the risk of childhood overweight/obesity and with body adiposity distributions of children at 5 years of age. Weight gain should be well controlled and monitored from early pregnancy.

4.
BMC Pediatr ; 19(1): 129, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31018838

RESUMO

BACKGROUND: Transient elastography (TE) using FibroScan with M probe has been widely used in adults for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). In this study, we aimed to assess the feasibility of this approach and reference values of CAP and LSM in healthy preschool children aged 5 years. METHODS: FibroScan-502 with M probe (Echosens, Paris, France) and bioelectrical impedance analysis (InBody 720, Biospace, South Korea) were prospectively conducted in healthy children aged 5 years from the Shanghai Prenatal Cohort Study. Linear regression models and piece-wise linear regression models were used to explore the factors associated with CAP and LSM. RESULTS: The success rate of a valid TE measurement was 96.5% in 452 healthy preschool children aged 5 years, and 436 children with 236 boys were included for further study. The median, inter quartile range (IQR) and the 5th-95th percentiles of CAP values were 171.50, 162.07-188.13 and 154.21-214.53 dB/m, respectively. The median, mean ± standard deviation and the 5th-95th percentiles of LSM were 3.20, 3.28 ± 0.86 and 2.00-4.78 kPa, respectively. In multivariate linear regression analyses, the CAP but not the LSM value was significantly positively correlated with such anthropometric index as body weight, body mass index, waist circumference, body fat content and body fat percentage. CONCLUSIONS: FibroScan-502 with M-probe can be used to measure CAP and LSM in preschool children aged 5 years. The 95th percentiles of CAP values and LSM were 214.53 dB/m and 4.78 kPa, respectively. Further study should be performed to explore the cut-off values of CAP and LSM for diagnosis of hepatic steatosis and fibrosis in children.

6.
Br J Haematol ; 185(5): 836-851, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30916375

RESUMO

Refinement of risk stratification in Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukaemia (ALL) might aid the identification of patients who are likely to relapse. Abnormal S100 calcium binding protein A16 (S100A16) has been implicated in various cancers, but its function remains unclear. We found S100A16 transcript levels were higher in 130 adults with newly-diagnosed Ph-negative B-cell ALL compared with 33 healthy controls. In 115 of 130 patients who achieved first complete remission, those with high S100A16 transcript levels displayed a lower 3-year cumulative incidence of relapse (CIR; 34% [21, 47%] vs. 40% [48, 72%]; P = 0·012) and higher 3-year relapse-free survival (RFS; 65% [53, 78%] vs. 35% [23, 46%]; P = 0·012), especially when receiving chemotherapy only. In multivariate analysis a low S100A16 transcript level was independently-associated with a higher CIR (Hazard ratio [HR] = 3·74 [1·01-13·82]; P = 0·048) and inferior RFS (HR = 5·78 [1·91, 17·84]; P < 0·001). Function analysis indicated that knockdown of S100A16 promoted proliferation and anti-apoptosis and reduced chemosensitivity. S100A16 over-expression revealed an opposite trend, especially in a xeno-transplant mouse model. Western blotting analysis showed upregulation of PI3K/AKT and ERK1/2 in S100A16-knockdown and S100A16-overexpression B-cell ALL cell lines respectively. Inhibition assays suggested these two signalling pathways participated in the S100A16-mediated proliferation and survival effects in B-cell ALL cell lines. Trial Registration: Registered in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940]; http://www.chictr.org.cn.

7.
Chemosphere ; 226: 17-23, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30908964

RESUMO

BACKGROUND: Several per- and polyfluoroalkyl substances (PFAS) have been phased out due to their adverse effects, and replaced by the short-chain perfluorobutanesulfonic acid (PFBS). However, the long-term impacts of PFBS on human health are unknown. OBJECTIVE: We aimed to investigate the association between prenatal exposure to PFAS, especially PFBS and childhood adiposity at 5 years of age. METHODS: We conducted a prospective birth cohort study involving 1,140 pregnant women from 2012 to 2017 in Shanghai. Fetal umbilical cord blood was collected at birth. A total of 404 children (196 girls) completed the adiposity measurements using a bioelectrical impedance analysis method and cord plasma PFAS measurements using LC-MS/MS. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between PFAS and childhood adiposity. RESULTS: The median concentration of PFAS in the cord plasma ranged from 0.05 (PFBS) to 6.74 ng/mL (PFOA). Results of multivariable linear regression found that in girls, PFBS had a significant positive association with waist circumference and waist to height ratio (P-values < 0.05). Girls in the highest tertile of PFBS concentrations had more fat mass, as well as higher body fat percentage, waist circumference, and waist to height ratio compared to those in the lowest tertile. However, girls in the second tertile of PFDoA had lower body fat percentage, waist circumference and fat mass. CONCLUSIONS: Adiposity at 5 years of age shows a positive association with prenatal exposure to PFBS in girls. These findings need to be further verified in larger prospective studies.


Assuntos
Adiposidade/efeitos dos fármacos , Fluorcarbonetos/efeitos adversos , Obesidade/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Ácidos Sulfônicos/efeitos adversos , Adulto , Pré-Escolar , China , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Estudos Prospectivos
8.
Stem Cells Dev ; 28(10): 674-682, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30808254

RESUMO

Tunneling nanotubes (TNTs) are newly discovered tubular structures between two distant cells that facilitate the intercellular exchange of signals and components. Recent reports show that mesenchymal stem cells (MSCs) can rescue injured target cells and promote recovery from a variety of stresses via TNT-mediated mitochondrial transfer. In this study, we explored how TNTs form between bone marrow MSCs and endothelial cells (ECs) by using a human umbilical cord vein endothelial cell (HUVEC) model. TNT formation between MSCs and HUVECs could be induced by treating HUVECs with cytarabine (Ara-C), and human bone marrow mesenchymal stem cells (hBMMSCs) could transfer mitochondria to injured HUVECs through TNTs. Mitochondrial transfer from hBMMSCs to HUVECs via TNTs rescued the injured HUVECs by reducing apoptosis, promoting proliferation and restoring the transmembrane migration ability as well as the capillary angiogenic capacity of HUVECs. This study provides novel insights into the cell-cell communication between MSCs and ECs and supports the results of prior studies indicating that ECs promote hematopoietic regeneration. An improved understanding of MSC-EC cross-talk will promote the development of MSC-directed strategies for improving EC function and hematopoietic system regeneration following myelosuppressive and myeloablative injuries.

9.
Nanoscale ; 11(6): 2959-2965, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30693936

RESUMO

Ratiometric fluorescent sensors, which can provide a built-in correction for environmental effects, have attracted significant attention for analytical sensing and optical imaging with the potential to provide a precise and quantitative analysis. Herein, we report a strategy based on dye-sensitized upconversion for the design of dual-excitation upconverion ratiometric probes possessing same emission peaks under a large separation in the excitation spectra (980 nm and 808 nm). Specifically, effective enhancement of upconversion luminescence could be attributed to Cy787 dyes present on the surface of nanoparticles, and it subsequently decreased upon the addition of ClO- under an 808 nm irradiation, whereas the signal under 980 nm excitation remained essentially constant, thus allowing for quantitative ratiometric monitoring of ClO-. The rationally designed dye-sensitized upconverion nanosystem exhibits excellent sensitivity for ClO- with a quantification limit of 3.6 nM in aqueous solutions. We have also demonstrated that the designed nanoprobe is a promising material for semi-quantitative detection of ClO- in an arthritis mouse model.


Assuntos
Corantes Fluorescentes/metabolismo , Ácido Hipocloroso/análise , Nanocompostos/química , Nanotecnologia/métodos , Imagem Óptica/métodos , Animais , Artrite Experimental/diagnóstico por imagem , Camundongos
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(4): 1129-1136, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111419

RESUMO

OBJECTIVE: To establish a MDS mouse model with iron overload and to study the effect of iron overload on MDS. METHODS: The exogenous mutant gene RUNX1-S291fs was inserted into the mice bone marrow mononuclear cell's genome in mice by retrovirus and transplanted into C57BL/6 mice irradiated by 60 Co γ-ray. After 8 weeks,intraperitoneal injection of iron was performed to establish an MDS mouse model with iron overload. After 24 weeks of transplantation, the peripheral blood, bone marrow, femur, liver and spleen of mice were taken, then the morphological characteristics of peripheral blood and bone marrow cells were observed by Wright's staining; the liver, spleen and bone marrow were stained with Prussian blue to observe the iron deposition. The surface antigens of bone marrow cells were detected by flow cytometry. Bone marrow mononuclear cells and spleen tissue proteins were detected by Western blot to confirm the transfection of RUNX1-S291fs gene and expression of protein. The blood routine and transplanted cell chimeric rate of mice were monitored periodically. RESULTS: Compared with the empty plasmid control mice, levels of leukocyte and hemoglobin as well as platelet were decreased in RUNX1-S291fs mutant mice; the peripheral blood cells and bone marrow cells showed pathological hematopoiesis; the liver and spleen enlarged significantly; the tissue structure of femur, liver and spleen was abnormal; the expression of bone marrow cell surface antigens was abnormal. Bone marrow cells and spleen tissue expressed the RUNX1-S291fs protein. Compared with the controlled mice injected with normal saline, iron deposition occurred in the bone marrow, liver and spleen stained with Prussian blue in the mice injected with iron agent. CONCLUSION: Mice engineered to carry exogenous mutant gene RUNX1-S291fs and injected with iron showed pathologic features of MDS and iron overload, resulting in establishing MDS iron overloaded mouse model successfully, which lays a foundation for studying the effect of iron overload on MDS.


Assuntos
Sobrecarga de Ferro , Animais , Medula Óssea , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Baço
11.
Haematologica ; 103(10): 1627-1634, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29903757

RESUMO

There is increasing clinical evidence to suggest a suppressive effect on hematopoiesis in myelodysplastic syndrome patients with iron overload. However, how iron overload influences hematopoiesis in myelodysplastic syndrome (MDS) remains unknown. Here, the RUNX1S291fs-transduced bone marrow mononuclear cells were yielded and transplanted into lethally irradiated recipient mice together with radioprotective bone marrow cells to generate MDS mice. Eight weeks post transplantation, the recipient mice received an intraperitoneal injection of 0.2 mL iron dextran at a concentration of 25 mg/mL once every other day for a total of 8 times to establish an iron overload model. In the present study, we show that iron overload impairs the frequency and colony-forming capacity of normal hematopoietic stem and progenitor cells, especially in erythroid, in MDS mice, which is due, at least in part, to growth differentiation factor 11-induced reactive oxygen species, shortening survival of MDS mice. Given that we are the first to construct an iron overload model in MDS mice, we hope this model will be helpful for further exploring the influence and mechanism of iron overload on MDS.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1733-1737, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262907

RESUMO

OBJECTIVE: To investigate the effects of Cyclin A1 on the proliferation of SKM-1 cells and its underlying role in myelodysplastic syndrome (MDS). METHODS: Cyclin A1 was knocked down with its small interfering RNA (siRNA). The efficiency of siRNA transfection was measured by Western blot and RT-PCR. Then the proliferation of SKM-1 cells and the expression of CDK2,RUNX1 and SRSF2 with and without knockdown of Cyclin A1 recorded and analysed respectively. RESULTS: Cyclin A1 was knocked down by siRNA after transfected for 48 h. The kncokdown of Cyclin A1 inhibited the proliferation of SKM-1 cells and down-regulated the expression of CDK2, RUNX1 and SRSF2, and these effects were at least partially mediated through RUNX1 and SRSF2 signaling pathway. CONCLUSION: Cyclin A1 plays an important role in the proliferation of SKM-1 cells. These findings provide new insights into the pathogenesis of MDS, and it may be a potential target in the treatment of MDS.


Assuntos
Proliferação de Células , Ciclina A1/metabolismo , Síndromes Mielodisplásicas/metabolismo , RNA Interferente Pequeno , Apoptose , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Síndromes Mielodisplásicas/patologia
13.
Mol Med Rep ; 16(5): 7163-7169, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901521

RESUMO

The aim of the present study was to investigate the effects of AdipoRon, an adiponectin receptor agonist, on adipogenesis in C3H10T1/2 cells and to explore the underlying mechanisms. C3H10T1/2 cells were treated with increasing doses of AdipoRon for 8 days, and Oil Red O staining was used to assess lipid accumulation. The protein and mRNA expression levels of adipogenic transcription factors and adipocyte­specific genes were examined by western blotting and reverse transcription quantitative polymerase chain reaction, respectively. AdipoRon treatment inhibited lipid accumulation in C3H10T1/2 cells in a dose­dependent manner and significantly suppressed the expression of adipogenic transcription factors, including peroxisome proliferator­activated receptor Î³, CAAT/enhancer binding protein (C/EBP)­ß and C/EBPα. In addition, cells treated with AdipoRon exhibited a significant decrease in the expression of adipocyte­specific genes, including fatty acid binding protein 4, fatty acid synthase, leptin, adiponectin, and stearoyl­CoA desaturase­1. Notably, AdipoRon significantly increased the phosphorylation of adenosine monophosphate­activated protein kinase (AMPK) and acetyl­CoA carboxylase (ACC). The results indicated that AdipoRon exerted an inhibitory effect on adipogenesis in C3H10T1/2 cells by downregulating the expression of adipogenic transcription factors and adipocyte­specific genes and by promoting the phosphorylation of AMPK and ACC, which suggested that AdipoRon may be a potential drug to prevent and treat diseases caused by abnormal adipogenesis, such as obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Piperidinas/farmacologia , Receptores de Adiponectina/agonistas , Acetil-CoA Carboxilase/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Leptina/genética , Leptina/metabolismo , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo
14.
J Cataract Refract Surg ; 43(2): 207-214, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28366368

RESUMO

PURPOSE: To evaluate the risk factors and potential diagnostic criteria for pseudophakic cystoid macular edema (CME) in diabetic patients after phacoemulsification. SETTING: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Prospective nonrandomized study. METHODS: Diabetic patients were followed for up to 6 months after cataract surgery and examined to evaluate their foveal thickness, macular sensitivity, and corrected distance visual acuity. Multiple statistical analyses were performed to determine risk factors and diagnostic criteria for pseudophakic CME. RESULTS: The duration, type of diabetes, stage of diabetic retinopathy, nuclear opalescence grading, glycosylated hemoglobin A1c (HbA1c), and ultrasound time were correlated with the change in foveal thickness and macular sensitivity after cataract surgery. Unsupervised data analysis showed 3 groups of patients as follows: nonpseudophakic CME, level 1 pseudophakic CME, and level 2 pseudophakic CME. Subclinical level 1 patients had a 30% to 40% increase in foveal thickness 1 month postoperatively, while level 2 patients had at least a 40% increase in foveal thickness and a 20% decrease in macular sensitivity. The incidence of clinical pseudophakic CME was 3.2% in diabetic patients as per the diagnostic criteria. The change in macular sensitivity was more consistent and correlated with foveal thickness. CONCLUSIONS: The duration, severity, type of diabetes, hardness of the lens, and HbA1c were risks for pseudophakic CME in diabetic patients after cataract surgery. A 40% or more increase in foveal thickness and 20% or more decrease in macular sensitivity offer an objective and reliable diagnostic standard to report pseudophakic CME in diabetics.

15.
Ann Hematol ; 96(7): 1085-1095, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28421266

RESUMO

The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes. In order to explore the mechanism, male C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250 mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and the blood of each mouse was collected for the analysis of the T lymphocyte subsets and T cell apoptosis. The results showed that iron overload could reduce the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also found that iron overload induced the apoptosis of T lymphocytes and increased its ROS level. Furthermore, these effects could be partially recovered after treating with antioxidant N-acetyl-L-cysteine (NAC) or iron chelator deferasirox (DFX). Taken together, these observations indicated that iron overload could selectively affect peripheral T lymphocytes and induce an impaired cellular immunity by increasing ROS level.


Assuntos
Sobrecarga de Ferro/metabolismo , Síndromes Mielodisplásicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Subpopulações de Linfócitos T/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Complexo CD3/sangue , Relação CD4-CD8 , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Sobrecarga de Ferro/sangue , Contagem de Linfócitos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo
17.
PLoS One ; 11(2): e0149543, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26895498

RESUMO

OBJECTIVE: The therapeutic use of thiazolidinediones (TZDs) causes unwanted hematological side effects, although the underlying mechanisms of these effects are poorly understood. This study tests the hypothesis that rosiglitazone impairs the maintenance and differentiation of hematopoietic stem/progenitor cells, which ultimately leads to hematological abnormalities. METHODS: Mice were fed a rosiglitazone-supplemented diet or a normal diet for 6 weeks. To induce hematopoietic stress, all mice were injected once with 250 mg/kg 5-fluorouracil (5-Fu) intraperitoneally. Next, hematopoietic recovery, hematopoietic stem/progenitor cells (HSPCs) subsets, and myeloid differentiation after 5-Fu treatment were evaluated. The adipogenesis induced by rosiglitazone was assessed by histopathology and oil red O staining. The effect of adipocytes on HSPCs was studied with an in vitro co-culture system. RESULTS: Rosiglitazone significantly enhanced bone marrow adipogenesis and delayed hematopoietic recovery after 5-Fu treatment. Moreover, rosiglitazone inhibited proliferation of a granulocyte/monocyte progenitor (GMP) cell population and granulocyte/macrophage colony-stimulating factor (GM-CSF) colonies, although the proliferation and mobilization of Lin-c-kit+Sca-1+ cells (LSK) was maintained following hematopoietic stress. These effects could be partially reversed by the selective PPARγ antagonist BADGE. Finally, we demonstrated in a co-culture system that differentiated adipocytes actively suppressed the myeloid differentiation of HSPCs. CONCLUSION: Taken together, our results demonstrate that rosiglitazone inhibits myeloid differentiation of HSPCs after stress partially by inducing bone marrow adipogenesis. Targeting the bone marrow microenvironment might be one mechanism by which rosiglitazone impairs stress-induced hematopoiesis.


Assuntos
Adipogenia/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Tiazolidinedionas/efeitos adversos , Adipócitos/efeitos dos fármacos , Animais , Linhagem Celular , Feminino , Fluoruracila , Células-Tronco Hematopoéticas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Células Progenitoras Mieloides/efeitos dos fármacos , Mielopoese/efeitos dos fármacos , PPAR gama/metabolismo , Rosiglitazona , Estresse Fisiológico
18.
Br J Ophthalmol ; 100(8): 1087-92, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26608028

RESUMO

AIMS: To evaluate the efficacy of lens removal plus intraocular lens (IOL) implantation for spherophakia with secondary glaucoma. METHODS: A series of 19 patients (n=24 eyes) were split into two groups according to the degree of zonular abnormality as follows: group 1 (within the range of one quadrant, n=7 eyes) and group 2 (beyond the range of one quadrant, n=17 eyes). The patients in group 1 underwent phacoemulsification+capsular tension ring (CTR)+IOL, whereas patients in group 2 underwent pars plana lensectomy with scleral-fixated posterior chamber (PC) IOL implantation. The best corrected visual acuity (BCVA) (logMAR unit) and intraocular pressure (IOP) were documented at presentation and at 1 day, 7 days, 3 months, 1 year and 3 years postoperatively. RESULTS: The IOP in both groups significantly decreased after surgery (group 1:28.84±5.36 mm Hg at presentation, 15.86±0.79 mm Hg at the 3-year visit, t=6.34, p=0.000; group 2:26.18±12.16 mm Hg at presentation, 14.54±3.40 mm Hg at the 3-year visit, t=3.80, p=0.01). The BCVA increased from 0.79±0.36 at baseline to 0.44±0.38 at the 3-year follow-up but did not reach a significantly different level in group 1 (t=1.72, p=0.11), whereas the BCVA significantly increased from 1.15±0.75 at baseline to 0.43±0.38 at the 3-year visit in group 2 (t=3.45, p=0.02). CONCLUSIONS: Both phacoemulsification+CTR+IOL and lensectomy with scleral-fixated PC IOL implantation are effective in lowering the IOP and enhancing the visual acuity in patients with spherophakia and secondary glaucoma.


Assuntos
Catarata/complicações , Glaucoma/etiologia , Implante de Lente Intraocular/métodos , Cristalino/cirurgia , Facoemulsificação/métodos , Acuidade Visual , Adulto , Feminino , Seguimentos , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Masculino , Estudos Prospectivos , Fatores de Tempo , Trabeculectomia , Resultado do Tratamento
19.
Sci Rep ; 5: 10181, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-25970748

RESUMO

Iron overload, caused by hereditary hemochromatosis or repeated blood transfusions in some diseases, such as beta thalassemia, bone marrow failure and myelodysplastic syndrome, can significantly induce injured bone marrow (BM) function as well as parenchyma organ dysfunctions. However, the effect of iron overload and its mechanism remain elusive. In this study, we investigated the effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs) from a mouse model. Our results showed that iron overload markedly decreased the ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen species (ROS). This finding is supported by the results of NAC or DFX treatment, which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term and multi-lineage engrafment of iron overload HSCs after transplantation. Therefore, all of these data demonstrate that iron overload injures the hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be helpful for the treatment of iron overload in patients with hematopoietic dysfunction.


Assuntos
Medula Óssea/metabolismo , Medula Óssea/patologia , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Transplante de Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Modelos Animais de Doenças , Sobrevivência de Enxerto , Hematopoese Extramedular , Células-Tronco Hematopoéticas/patologia , Masculino , Camundongos , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
PLoS One ; 10(3): e0120629, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25768922

RESUMO

OBJECTIVE: The increase in adipocytes induced by chemotherapeutic drugs may play a negative role in hematopoietic recovery. However, the mechanism underlying adipocyte differentiation of mesenchymal stem cells (MSCs) in hematopoietic stress is still unknown. Hence, the involvement of reactive oxygen species (ROS) in adipocyte differentiation under hematopoietic stress was investigated in vitro and in vivo. METHODS: The roles of cellular ROS in adipogenesis were investigated in vivo through an adipocyte hyperplasia marrow model under hematopoietic stress induced by arabinosylcytosine (Ara-C) and in vitro via adipocyte differentiation of human MSCs. ROS levels were detected using the CM-H2DCFDA probe and Mito-SOX dye. Adipogenesis was evaluated by histopathology and oil red O staining, whereas detection of mRNA levels of antioxidant enzymes and adipogenesis markers was performed using quantitative real-time polymerase chain reaction analysis. RESULTS: ROS were found to play an important role in regulating adipocyte differentiation of MSCs by activating peroxisome proliferator-activated receptor gamma (PPARγ,) while the antioxidant N-acetyl-L-cysteine acts through ROS to inhibit adipocyte differentiation. The elevated ROS levels induced by Ara-C were caused by both over-generation of mitochondrial ROS and reduction of antioxidant enzymes (Cu/Zn Superoxide dismutase and catalase). Our findings suggest that a mitochondrial-targeted antioxidant could diminish adipocyte differentiation.


Assuntos
Adipócitos/citologia , Adipogenia , Citarabina/farmacologia , Hematopoese/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Piperidinas/farmacologia
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