Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Theranostics ; 8(19): 5452-5468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555557

RESUMO

Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.


Assuntos
Adipócitos/patologia , Ácidos Graxos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Neoplasias Peritoneais/fisiopatologia , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Animais , Anoikis , Antígenos CD36/biossíntese , Carnitina O-Palmitoiltransferase/biossíntese , Linhagem Celular Tumoral , Sobrevivência Celular , Técnicas de Cocultura , Modelos Animais de Doenças , Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Proteínas de Membrana Transportadoras/análise , Proteínas de Membrana Transportadoras/genética , Camundongos Nus , Modelos Teóricos , Regulação para Cima
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(9): 782-786, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30463648

RESUMO

Objective To investigate the effect of platelet and macrophage on the proliferation of methicillin-resistant Staphylococcus aureus (MRSA) in vitro, to explore the mechanisms of the inhibition effect, and to further reveal platelet function. Methods LB culture system with 4×108 CFU/mL MRSA inoculation concentration was established in vitro. Leukocyte-free platelets with a number of 200×109/L (platelet group) and macrophages with a number of 1×109/L (macrophage group) were added, respectively. The system without platelets and macrophages was used as negative control (control group). The absorbance of bacterial solution of the two groups was measured for reflect the proliferation of MRSA at different time points. After 2 hours culture, the bacterial liquid was collected for plating after double dilution, and the concentration of bacterial liquid was obtained through calculation after colony counting. Flow cytometry was also performed to verify the phagocytosis of macrophages and the capture ability of platelets. Results Both macrophages and platelets showed suppressive effect on the proliferation of MRSA compared to control group, while the effect of platelets was more significant. Conclusion Platelets have stronger inhibitory ability on MRSA proliferation in vitro than macrophages.

3.
Methods Mol Biol ; 1842: 43-54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196400

RESUMO

Mesenchymal stromal cells are an important component of the adult hematopoietic stem cell niche. They are a diverse population of cells that include a hierarchy of primitive, intermediate, and mature osteoprogenitors that support HSCs and supply the bone with matrix producing osteoblast. To understand the different roles played by individual types of progenitors, it is necessary to separate individual populations and analyze them in a controlled environment. Here we describe two transplantation models, an ectopic bone forming assay and an intravenous injection assay, in which niche components can be isolated and manipulated to dissect their individual properties.

4.
Am J Cancer Res ; 8(5): 763-777, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29888101

RESUMO

The tumor microenvironment (TME) is a key factor regulating tumor cell invasion and metastasis. The effects of biochemical factors such as stromal cells, immune cells, and cytokines have been previously investigated. Owing to restrictions by the natural barrier between physical and biochemical disciplines, the role of physical factors in tumorigenesis is unclear. However, with the emergence of interdisciplinary mechanobiology and continuous advancements therein in the past 30 years, studies on the effect of physical properties such as hardness or shear stress on tumorigenesis and tumor progression are constantly renewing our understanding of mechanotransduction mechanisms. Shear stress, induced by liquid flow, is known to actively participate in proliferation, apoptosis, invasion, and metastasis of tumor cells. The present review discusses the progress and achievements in studies on tumor fluid microenvironment in recent years, especially fluid shear stress, on tumor metastasis, and presents directions for future study.

5.
EBioMedicine ; 32: 31-42, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29807832

RESUMO

Mesenchymal stromal cells (MSCs) based therapy is a promising approach to treat inflammatory disorders. However, therapeutic effect is not always achieved. Thus the mechanism involved in inflammation requires further elucidation. To explore the mechanisms by which MSCs respond to inflammatory stimuli, we investigated whether MSCs employed inflammasomes to participate in inflammation. Using in vitro and in vivo models, we found that canonical NLRP3 and non-canonical caspase-11 inflammasomes were activated in bone-associated MSCs (BA-MSCs) to promote the inflammatory response. The NLRP3 inflammasome was activated to mainly elicit IL-1ß/18 release, whereas the caspase-11 inflammasome managed pyroptosis. Furthermore, we sought a small molecule component (66PR) to inhibit the activation of inflammasomes in BA-MSCs, which consequently improved their survival and therapeutic potential in inflammation bowel diseases. These current findings indicated that MSCs themselves could directly promote the inflammatory response by an inflammasome-dependent pathway. Our observations suggested that inhibition of the proinflammatory property may improve MSCs utilization in inflammatory disorders.


Assuntos
Caspases/genética , Inflamação/terapia , Transplante de Células-Tronco Mesenquimais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Caspases/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
6.
Mol Med Rep ; 17(6): 8010, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29767253

RESUMO

An interested reader drew to the attention of the Editorial Board of Molecular Medicine Reports that certain data featured in the above paper had been published in 2014 in the same journal, in an article featuring several of the same authors [Zhang X, Hu X, Mu S, Zhan Y, An Q, Liu Z and Huang X: "Apogossypolone inhibits the proliferation of LNCaP cells in vitro and in vivo", Mol Med Rep 10: 1184­1194, 2014]. Specifically, data in Fig. 2A of the above paper (the Apogossypol, 15 µmol/l data panel) had appeared in Fig. 3B, c in the 2014 paper. The authors responded to our original enquiry asking for an explanation concerning the data that had been shared between these papers, and confirmed that the inclusion of the same data in the two papers had occurred in error. Subsequently, they were able to identify the proper data for the affected figure of the above paper, and a corrected version of Fig. 2 is printed here. We apologize to the readership of the Journal for any inconvenience caused. [the original article was published in the Molecular Medicine Reports 11: 4142­4148, 2015; DOI: 10.3892/mmr.2015.3326].

7.
FASEB J ; 32(7): 3707-3716, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29430991

RESUMO

Platelets (PLTs) are classically used in the clinical setting to maintain hemostasis. Recent evidence supports important roles for PLTs in host inflammatory and immune responses, and PLT-rich plasma has been demonstrated to inhibit the growth of bacteria in vitro and in vivo; however, few studies have examined whether PLTs can inhibit bacterial growth directly, and related mechanisms have not been elucidated further. Accordingly, in this study, we evaluated the effects of PLTs on bacterial growth. We washed and purified PLTs from peripheral blood, then confirmed that PLTs significantly inhibited the growth of Staphylococcus aureus when cocultured in vitro. Moreover, PLTs damaged DNA and blocked cell division in S. aureus. During coculture, PLT-derived TGF-ß1 was dramatically down-regulated compared with that in PLT culture alone, and the addition of TGF-ß1 to the coculture system promoted the inhibition of PLTs on S. aureus. Analysis of a murine S. aureus infection model demonstrated that the depletion of PLTs exacerbated the severity of infection, whereas the transfusion of PLTs alleviated this infection. Our observations demonstrate that PLTs could directly inhibit the growth of S. aureus by damaging DNA and blockage cell division, and that PLT-derived TGF-ß1 may play an important role in this machinery.-Xu, J., Yi, J., Zhang, H., Feng, F., Gu, S., Weng, L., Zhang, J., Chen, Y., An, N., Liu, Z., An, Q., Yin, W., Hu, X. Platelets directly regulate DNA damage and division of Staphylococcus aureus.

8.
Mol Med Rep ; 17(5): 6927, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29436677

RESUMO

An interested reader drew to the attention of the Editorial Board of Molecular Medicine Reports that certain data in the above paper had already been published in a previous study featuring several of the same authors [Zhang XQ, Huang XF, Hu XB, Zhan YH, An QX, Yang SM, Xia AJ, Yi J, Chen R, Mu SJ and Wu DC: "Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro". Asian J Androl 12: 697-708, 2010]. Specifically, Figs. 2A and 5C were originally featured, either in their entirety or in part, as Figs 6C and 2G, respectively, in the Asian J Androl paper. Following an internal investigation, the Editorial Board was able to confirm that these data were published previously in the Asian J Androl paper, and therefore it has been decided that the above-mentioned paper should be retracted on account of the incidences of data sharing. The authors have agreed to this decision, and we apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Molecular Medicine Reports 10: 1184-1194, 2014; DOI: 10.3892/mmr.2014.2379].

9.
Biosci Rep ; 37(5)2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-28864783

RESUMO

During storage in blood banks, red blood cells (RBCs) undergo the mechanical and metabolic damage, which may lead to the diminished capacity to deliver oxygen. At high altitude regions, the above-mentioned damage may get worse. Thus, more attention should be paid to preserve RBCs when these components need transfer from plain to plateau regions. Recently, we found that mesenchymal stromal cells (MSCs) could rescue from anemia, and MSCs have been demonstrated in hematopoietic stem cells (HSCs) transplantation to reconstitute hematopoiesis in vivo by us. Considering the functions and advantages of MSCs mentioned above, we are trying to find out whether they are helpful to RBCs in storage duration at high altitudes. In the present study, we first found that mice MSCs could be preserved in citrate phosphate dextrose adenine-1 (CPDA-1) at 4 ± 2°C for 14 days, and still maintained great viability, even at plateau region. Thus, we attempted to use MSCs as an available supplement to decrease RBCs lesion during storage. We found that MSCs were helpful to support RBCs to maintain biochemical parameters and kept RBCs function well on relieving anemia in an acute hemolytic murine model. Therefore, our investigation developed a method to get a better storage of RBCs through adding MSCs, which may be applied in RBCs storage as a kind of cellular additive into preservation solution.


Assuntos
Preservação de Sangue/métodos , Eritrócitos/citologia , Células-Tronco Mesenquimais/citologia , Anemia/terapia , Animais , Sobrevivência Celular , Células Cultivadas , Transfusão de Eritrócitos , Camundongos , Camundongos Endogâmicos C57BL
10.
Mol Cancer ; 16(1): 79, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-28407774

RESUMO

Cancer cells are frequently confronted with metabolic stress in tumor microenvironments due to their rapid growth and limited nutrient supply. Metabolic stress induces cell death through ROS-induced apoptosis. However, cancer cells can adapt to it by altering the metabolic pathways. AMPK and AKT are two primary effectors in response to metabolic stress: AMPK acts as an energy-sensing factor which rewires metabolism and maintains redox balance. AKT broadly promotes energy production in the nutrient abundance milieu, but the role of AKT under metabolic stress is in dispute. Recent studies show that AMPK and AKT display antagonistic roles under metabolic stress. Metabolic stress-induced ROS signaling lies in the hub between metabolic reprogramming and redox homeostasis. Here, we highlight the cross-talk between AMPK and AKT and their regulation on ROS production and elimination, which summarizes the mechanism of cancer cell adaptability under ROS stress and suggests potential options for cancer therapeutics.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Animais , Progressão da Doença , Metabolismo Energético , Homeostase , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Fosforilação , Ligação Proteica , Transdução de Sinais
11.
Stem Cells Dev ; 26(7): 495-502, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28052733

RESUMO

The intrinsic basis of cancer-related anemia (CRA) is erythropoiesis disorder, which is a common complication of cancer and exerts a negative influence on the life quality of cancer patients. Cell therapy using mesenchymal stromal cells (MSCs) is considered as a promising method in cancer treatment. Furthermore, MSCs have been used to cure few type of anemia and be considered as a potential strategy to recover anemia radically. However, none reports its application in CRA treatment. In CRA model mice, we found that the number of lin-c-kit+Sca-1+ and Sca-1+ MSCs was decreased. And CRA resulted in an increased number of proerythroblasts and basophilic erythroblasts and decreased number of orthochromatic erythroblasts. Furthermore, in CRA model mice transplanted with Sca-1+ MSCs and MSCs, the levels of red blood cell count and Hb in peripheral blood were obviously increased. And the accumulation of proerythroblasts and basophilic erythroblasts was inhibited. In addition, the expression patterns of GATA-1 and GATA-2, which is pivotal to anemia, were remarkably recovered. Our results demonstrated that either MSCs or its subpopulation could effectively recover CRA erythropoiesis through GATA-1/GATA-2 signaling, which outstrips the traditional symptomatic therapy.


Assuntos
Anemia/etiologia , Eritroblastos/citologia , Eritropoese/fisiologia , Melanoma/complicações , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Animais , Modelos Animais de Doenças , Melanoma/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos Endogâmicos C57BL
12.
Sci Rep ; 6: 38632, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27929130

RESUMO

In this study, we identified a CD105+CD90.1-CD133-CD55- (CD133-CD55-) population in the fetal skeletal element that can generate bone and bone marrow. Besides osteoblasts and chondrocytes, the CD133-CD55- common progenitors can give rise to marrow reticular stromal cells and perivascular mesenchymal progenitors suggesting they function as the fetal common skeletal progenitor. Suppression of CXCL12 and Kitl expression in CD133-CD55- common progenitors severely disrupted the BM niche formation but not bone generation. Thus, CD133-CD55- common progenitors are the main source of CXCL12 and Kitl producing cells in the developing marrow.


Assuntos
Antígeno AC133/metabolismo , Antígenos CD55/metabolismo , Osteoblastos/metabolismo , Animais , Ataxina-1/metabolismo , Biomarcadores , Medula Óssea/metabolismo , Diferenciação Celular , Quimiocina CXCL12/metabolismo , Condrócitos/metabolismo , Ensaio de Unidades Formadoras de Colônias , Imunofenotipagem , Camundongos , Camundongos Knockout , Osteoblastos/citologia , Osteogênese , Fenótipo , Nicho de Células-Tronco
13.
Nat Commun ; 7: 13095, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27721421

RESUMO

Microenvironment cues received by haematopoietic stem cells (HSC) are important in regulating the choice between self-renewal and differentiation. On the basis of the differential expression of cell-surface markers, here we identify a mesenchymal stromal progenitor hierarchy, where CD45-Ter119-CD31-CD166-CD146-Sca1+(Sca1+) progenitors give rise to CD45-Ter119-CD31-CD166-CD146+(CD146+) intermediate and CD45-Ter119-CD31-CD166+CD146-(CD166+) mature osteo-progenitors. All three progenitors preserve HSC long-term multi-lineage reconstitution capability in vitro; however, their in vivo fates are different. Post-transplantation, CD146+ and CD166+ progenitors form bone only. While Sca1+ progenitors produce CD146+, CD166+ progenitors, osteocytes and CXCL12-producing stromal cells. Only Sca1+ progenitors are capable of homing back to the marrow post-intravenous infusion. Ablation of Sca1+ progenitors results in a decrease of all three progenitor populations as well as haematopoietic stem/progenitor cells. Moreover, suppressing production of KIT-ligand in Sca1+ progenitors inhibits their ability to support HSCs. Our results indicate that Sca1+ progenitors, through the generation of both osteogenic and stromal cells, provide a supportive environment for hematopoiesis.


Assuntos
Hematopoese , Células-Tronco Mesenquimais/citologia , Nicho de Células-Tronco , Animais , Antígenos CD/metabolismo , Células da Medula Óssea/citologia , Osso e Ossos/citologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Injeções Intravenosas , Camundongos Endogâmicos C57BL , Fenótipo , Fator de Células-Tronco/metabolismo , Células Estromais/citologia
14.
Cell Biol Int ; 40(5): 549-59, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26861667

RESUMO

Mesenchymal stromal cells (MSCs) have been characterized as an important component of hematopoietic niche, which are capable of modulating the immune system through interaction with a wide range of immune cells. Marginal zone B cells, one main type of mature B lymphocytes, play a central role in eliciting antibody response against pathogens. However, how MSCs and its subpopulations regulate marginal zone B cells commitment is unknown yet. In this study, we assessed the contribution of Sca-1(+) MSCs on marginal zone B cells commitment. Our results showed that Sca-1(+) MSCs inhibit the commitment of marginal zone B lymphocytes. The inhibition was exerted through lowered Caspase-3 expression. Furthermore, we found marginal zone B lymphocytes in spleen of Caspase-3 knockout mice decreased and Caspase-3 knockout Sca-1(+) MSCs accounted for the MZB lymphocytes decrease. In conclusion, our investigation provided clues about Sca-1(+) MSCs regulation on the commitment of marginal zone B cells through Caspase-3 gene.


Assuntos
Antígenos Ly/metabolismo , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/fisiologia , Animais , Antígenos Ly/genética , Linfócitos B/citologia , Linfócitos B/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Diferenciação Celular/fisiologia , Proteínas de Membrana/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Baço/citologia , Baço/metabolismo
15.
Stem Cells Dev ; 25(1): 18-26, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26422691

RESUMO

α4ß7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed ß7 integrin. These ß7(+) HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over ß7(-) HSCs. On the other hand, HSCs that lacked ß7 integrin (ß7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that ß7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, ß7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the α4ß7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that ß7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.


Assuntos
Moléculas de Adesão Celular/metabolismo , Movimento Celular/genética , Sobrevivência de Enxerto/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/fisiologia , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/metabolismo , Animais , Células da Medula Óssea/citologia , Células Cultivadas , Feminino , Células-Tronco Hematopoéticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica , Nicho de Células-Tronco/genética
16.
PLoS One ; 10(5): e0125747, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25993514

RESUMO

Natural autoreactive B cells are important mediators of autoimmune diseases. Receptor editing is known to play an important role in both central and peripheral B cell tolerance. However, the role of allelic inclusion in the development of natural autoreactive B cells is not clear. Previously, we generated µ chain (TgV(H)3B4I) and µ/κ chains (TgV(H/L)3B4) transgenic mice using transgene derived from the 3B4 hybridoma, which produce poly-reactive natural autoantibodies. In this study, we demonstrate that a considerable population of B cells edited their B cells receptors (BCRs) via light chain or heavy chain allelic inclusion during their development in TgV(H)3B4I mice. Additionally, allelic inclusion occurred more frequently in the periphery and promoted the differentiation of B cells into marginal zone or B-1a cells in TgV(H)3B4I mice. B cells from TgV(H/L)3B4 mice expressing the intact transgenic 3B4 BCR without receptor editing secreted poly-reactive 3B4 antibody. Interestingly, however, B cell that underwent allelic inclusion in TgV(H)3B4I mice also produced poly-reactive autoantibodies in vivo and in vitro. Our findings suggest that receptor editing plays a minor role in the positive selection of B cells expressing natural poly-reactive BCRs, which can be positively selected through heavy chain allelic inclusion to retain their poly-reactivity in the periphery.


Assuntos
Alelos , Linfócitos B/imunologia , Seleção Genética , Animais , Camundongos , Camundongos Endogâmicos C57BL
17.
Int Immunopharmacol ; 26(1): 50-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25773667

RESUMO

Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+) MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.


Assuntos
Ataxina-1/imunologia , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/prevenção & controle , Células-Tronco Mesenquimais/imunologia , Animais , Transplante de Células , Feminino , Citometria de Fluxo , Doença Enxerto-Hospedeiro/imunologia , Infusões Intravenosas , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Baço/citologia , Baço/imunologia , Análise de Sobrevida
18.
Mol Med Rep ; 11(6): 4142-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25672487

RESUMO

Apogossypol, a gossypol derivative, is a novel small­molecule inhibitor of the Bcl­2 family proteins and has been demonstrated to have anti­tumor activities. Prostate cancer is the most common malignancy in males, for which chemotherapy is the usual treatment option in clinical practice. The aim of the present study was to investigate the growth inhibitory effects of apogossypol on prostate cancers in vitro and in vivo. An MTT assay and a colony formation assay were used to assess the anti­survival and anti­proliferation effects of apogossypol in LNCaP cells. Immunofluorescence was performed in order to detect the expression levels of apoptosis­associated proteins in xenograft tumors following apogossypol treatment. Apogossypol exerted strong anti­tumor effects on LNCaP cells in a dose­dependent manner. Furthermore, immunofluorescence revealed that apogossypol inhibited the growth and proliferation of prostate cancer cells by downregulating Bcl­2 protein expression and activating caspase­3 and ­8. In addition, the in vivo study indicated that apogossypol significantly inhibited tumor growth in a dose­dependent manner with reduced toxicity compared with gossypol. In conclusion, the present study indicated that apogossypol effectively inhibited the growth and proliferation of prostate cancer cells and may be a potential agent for prostate cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Gossipol/análogos & derivados , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/análise , Caspase 3/metabolismo , Caspase 8/análise , Caspase 8/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Gossipol/uso terapêutico , Humanos , Masculino , Camundongos Nus , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
19.
Mol Med Rep ; 10(3): 1184-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25060748

RESUMO

The aim of the present study was to investigate the anti­tumor effect of apogossypolone (ApoG2) on human LNCaP cells in vitro and in vivo. Cell viability was evaluated using an MTT assay. Cell autophagy and apoptosis were detected by flow cytometry and using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively. Morphological autophagy alterations were observed by transmission electron microscopy. The formation of acidic vesicular organelles was assessed by acridine orange staining and fluorescence microscopy. Quantitative polymerase chain reaction (qPCR) was conducted to detect the expression levels of apoptosis­associated protein B­cell lymphoma 2 (Bcl­2) and Bak. The models of transplantation tumors in nude mice were established via subcutaneous injection of LNCaP cells. Growth of LNCaP cells was inhibited by ApoG2 treatment. Flow cytometry demonstrated that ApoG2 induced apoptosis in LNCaP cells. The Bcl­2 expression was decreased while Bak expression was increased. In addition, activation of cysteine aspartate protease (caspase)­3 and ­8 was observed and 3­methyladenine (3­MA) enhanced apoptosis of LNCaP cells. Furthermore, nude mice treated with ApoG2 demonstrated a significant decrease in tumor volume and a significant increase in cell viability. Immunohistochemical analysis of tumor tissues demonstrated that ApoG2 enhanced caspase­3, ­8, LC­3B and beclin­1 expression and reduced the expression of Bcl­2. ApoG2 was able to effectively suppress the growth of LNCaP cells through the induction of autophagy and apoptosis.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Gossipol/análogos & derivados , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1 , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Gossipol/farmacologia , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo
20.
Biomed Rep ; 2(1): 39-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24649066

RESUMO

The aim of this study was to investigate the application of plasma exchange in small intestinal transplantation between ABO blood type-incompatible patients. A small intestinal transplantation case between ABO-incompatible individuals is hereby presented and analyzed. The main treatment included plasma exchange, splenectomy and immunosuppression. The patient undergoing small intestinal transplantation exhibited stable vital signs. A mild acute rejection reaction developed ~2 weeks after the surgery, which the patient successfully overcame. The subsequent colonoscopy and pathological examination revealed no signs of acute rejection. In conclusion, plasma exchange in combination with anti-immune rejection therapy proved to be an effective scheme for the management of small intestinal transplantation between ABO-incompatible patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA