Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 171
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nanotechnology ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000158

RESUMO

Cadmium telluride (CdTe) nanocrystals with thoil stabilizers as a group of nanomaterials have been applied widely in the fields of energy storage and transformation. The aim of this work is to develop anhydrous proton exchange membranes (PEMs) through introducing CdTe nanocrystals bearing the stabilizers of thioglycollic acid (tga) or mercaptopropionic acid (mpa) into the systems of sulfonated poly(ether ether ketone) (SPEEK) and polyurethane (PU). In the prepared SPEEK/PU/CdTe membranes, CdTe nanocrystals could provide the desirable properties such as improving mechanical strength and enhancing proton conductivity by combining phosphoric acid (PA) molecules. Successful preparation of SPEEK/PU/CdTe/PA membranes could be demonstrated by the identification of high and stable proton conductivity, satisfactory thermal/chemical stability and mechanical property. The fine appearance of membranes revealed the uniform dispersion of components without the fear of incompatibility. After the measurements on properties, the SPEEK(74%)/PU/CdTe-mpa(20/60/20)/100%PA membrane as the candidate of anhydrous PEMs, could show a great promise in high temperature proton exchange membrane fuel cells (PEMFCs). Specifically, the recommended membrane showed the proton conductivity of 1.18×10-1 S/cm at 160 °C associating with 3.96×10-2 S/cm at 100 °C lasting 600 h and 14.6 MPa at room temperature (RT). Mixing the inorganic CdTe nanocrystals with polymers to form the inorganic/organic composite membranes that is substantially more effective at exploiting anhydrous PEMs with more cheap polymers without functional groups to conduct protons.

2.
Artif Cells Nanomed Biotechnol ; 48(1): 435-442, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31916466

RESUMO

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

3.
J Phys Chem Lett ; 11(3): 1141-1147, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31951412

RESUMO

Double-electron electron resonance (DEER) can be used to track the structural dynamics of proteins in their native environment, the cell. This method provides the distance distribution between two spin labels attached at specific, well-defined positions in a protein. For the method to be viable under in-cell conditions, the spin label and its attachment to the protein should exhibit high chemical stability in the cell. Here we present low-temperature, trityl-trityl DEER distance measurements on two model proteins, PpiB (prolyl cis-trans isomerase from E. coli) and GB1 (immunoglobulin G-binding protein), doubly labeled with the trityl spin label, CT02MA. Both proteins gave in-cell distance distributions similar to those observed in vitro, with maxima at 4.5-5 nm, and the data were further compared with in-cell Gd(III)-Gd(III) DEER obtained for PpiB labeled with BrPSPy-DO3A-Gd(III) at the same positions. These results highlight the challenges of designing trityl tags suitable for in-cell distance determination at ambient temperatures on live cells.


Assuntos
Proteínas de Bactérias/química , Proteínas de Transporte/química , Ciclofilinas/química , Espectroscopia de Ressonância de Spin Eletrônica , Compostos de Tritil/química , Gadolínio/química , Marcadores de Spin
4.
Biochem Pharmacol ; 171: 113712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726048

RESUMO

Thymic epithelial cells (TECs) are crucial for the production of T-cells. Cancer therapies including cytotoxic drugs and ionizing radiations damage TECs resulting in abnormal T-cell production and function. Fortunately, TECs can regenerate after injury. The Janus kinase (Jak) pathway is important in supporting survival of TECs. Jak inhibitors are used to treat cancer and immune disorders. The impact of Jak inhibitors on recovery of TECs is unknown. We induced acute thymus injury in mice by using ionizing radiation and evaluated the impact of ruxolitinib on thymus regeneration. We also tested if ruxolitinib affected proliferation of TECs in vitro. An increase was observed in the recovery of thymus cells after acute injury in association with up-regulation of TEC-related growth factors including keratinocyte growth factor (Kgf), epidermal growth factor (Egf), insulin-like growth factor 1 (Igf1) and receptor activator of NF-κB ligand (Rankl). Giving ruxolitinib decreased levels of receptors of these growth factors on TECs and blocked growth factor-induced recovery of thymus cells in damaged thymii. Ruxolitinib also blocked growth factors-induced proliferation of TECs in vitro. Thymus regeneration was inhibited when ruxolitinib was given immediately after thymus injury but not when it was given 1 week later. These data may have implications for how ruxolitinib is used in clinical practices.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31786240

RESUMO

Chimeric antigen receptor (CAR)-T cell therapy, a new immunotherapy for relapsed and refractory (R/R) hematologic malignancies, can be accompanied by adverse events, including coagulation disorders. Here, we performed a comprehensive analysis of coagulation parameters in 100 patients with R/R hematologic malignancies after receiving CAR-T cell therapy to illuminate the profiles of coagulation disorders and to facilitate the management of coagulation disorders. A high incidence of coagulation disorders was observed, including elevated D-dimer (50/100, 50%), increased fibrinogen degradation product (45/100, 45%), decreased fibrinogen (23/100, 23%), prolonged activated partial thromboplastin time (16/100, 16%), and prolonged prothrombin time (10/100, 10%). Coagulation disorders occurred mainly during day 6 to day 20 after CAR-T cell infusion. The changes in coagulation parameters were associated with high tumor burden in acute lymphoblastic leukemia, more lines of prior therapies, lower baseline platelet count, and especially cytokine release syndrome (CRS). Disseminated intravascular coagulation (DIC) was found in 7 patients with grade ≥3 CRS and indicated a poor prognosis. Our study suggests that coagulation disorders are manageable in most patients after CAR-T cell therapy. Coexistence of DIC and severe CRS is closely related to nonrelapsed deaths during the acute toxicity phase, and effective and timely treatment is the key to reduce nonrelapse mortality for patients with DIC and severe CRS.

6.
Biomicrofluidics ; 13(6): 064121, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31832119

RESUMO

Assays for chemical biomarkers are a vital component in the ecosystem of noninvasive disease state assessment, many of which rely on quantification by colorimetric reactions or spectrophotometry. While modern advances in microfluidic technology have enabled such classes of devices to be employed in medical applications, the challenge has persisted in adapting the necessary tooling and equipment to integrate spectrophotometry into a microfluidic workflow. Spectrophotometric measurements are common in biomarker assays because of straightforward acquisition, ease of developing the assay's mechanism of action, and ease of tuning sensitivity. In this work, 3D-printed, discrete microfluidic elements are leveraged to develop a model system for assaying hyaluronidase, a urinary biomarker of bladder cancer, via absorbance spectrometry of gold nanoparticle aggregation. Compared to laboratory microtiter plate-based techniques, the system demonstrates equivalent performance while remaining competitive in terms of resource and operation requirements and cost.

7.
J Colloid Interface Sci ; 555: 722-730, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31416027

RESUMO

Spin coating technique is a simple and effective method to fabricate layered membranes and it has been widely used in the field of energy storage and transformation, biomaterials and electronics. The aim of this work is to develop anhydrous proton exchange membranes (PEMs) based on cheap polymers bearing the simple structure with spin coating technique. Successful fabrication of anhydrous PEMs based on polyvinylidene fluoride (PVDF) polymer, cadmium telluride (CdTe) nanocrystals and phosphoric acid (PA) molecules has been demonstrated by identification of high and stable proton conductivity. Specifically, (PVDF-CdTe-PA)5/85%PA membranes present the maximum proton conductivity of 7.70 × 10-2 S/cm at 160 °C and 1.42 × 10-2 S/cm at 140 °C lasting 620 h. The decreased proton conduction resistance is revealed from the drastic reduction of activation energy (Ea) owing to the layered structure and the adsorption of PA molecules. The introduction of CdTe nanocrystals to form the organic/inorganic composite membranes that is substantially more effective at improving proton conductivity and stiffness, showing great promise in solving the dilemma of proton conductivity and mechanical property. This study provides the support to exploit anhydrous PEMs with more cheap polymers using spin coating technique.

8.
Neurochem Res ; 44(11): 2681-2683, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31432305

RESUMO

In the original version of this article, unfortunately, the images in Fig. 4 and 7 are mixed. The correct version of the Fig.4 and 7 is given below.

9.
Part Fibre Toxicol ; 16(1): 27, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266526

RESUMO

BACKGROUND: Obesity is an uncontrolled global epidemic and one of the leading global public health challenges. Maternal exposure to ambient fine particulate matter (PM2.5) may adversely program offspring's adiposity, suggesting a specialized role of PM2.5 pollution in the global obesity epidemic. However, the vulnerable window for this adverse programming and how it is cross-generationally transmitted have not been determined. Therefore, in the present study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during different periods, and the development and adulthood adiposity of their four-generational offspring were assessed. RESULTS: Our data show that the pre-conceptional but not gestational exposure to CAP was sufficient to cause male but not female offspring's low birth weight, accelerated postnatal weight gain, and increased adulthood adiposity. These adverse developmental traits were transmitted into the F2 offspring born by the female but not male F1 offspring of CAP-exposed dams. In contrast, no adverse development was noted in the F3 offspring. CONCLUSIONS: The present study identified a pre-conceptional window for the adverse programming of adiposity by maternal exposure to PM2.5, and showed that it was maternally transmitted into the third generation. These data not only call special attention to the protection of women from exposure to PM2.5, but also may facilitate the development of intervention to prevent this adverse programming.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 223: 117225, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31255864

RESUMO

This article uses quantum chemical methods and various wave function analysis methods to firstly analyze the optical absorption spectrum and electron migration mechanism of rhodamine 6G molecular complexes on graphene substrates during electron or hole injection. Secondly, since the light absorption properties are very important during photocatalysis, the intermolecular interaction and electronic structure in both cases were calculated and analyzed. Not only the experimental results of the previous photocatalytic devices were explained, but also the physical mechanism was promoted, and the guiding recommendations for the future catalytic device design.

11.
Biomed Res Int ; 2019: 7201562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355278

RESUMO

Increasing evidence indicates that immunoglobulins are important for the regulation of various cancers including prostate cancer (PCa). However, the underlying mechanisms of IgG regulated PCa development remain to be further explored. Here, we demonstrated that IgG1 heavy chain (IGHG1) was increased in tissues from PCa patients. Inhibition of IGHG1 by antibody blocking or genetic knockdown suppressed cell growth and induced cell cycle arrest and ultimate apoptosis. Expression levels of c-Myc were positively correlated with the levels of IGHG1. Furthermore, MEK/ERK/c-Myc pathway lied downstream of IGHG1 in cultured prostate cancer cells. Inhibition of IGHG1 restrained the tumor growth in nude mice and inactivated MEK/ERK/c-Myc pathway both in vitro and in vivo. These findings suggest that IGHG1 play a crucial role during the development of prostate cancer and inhibition of IGHG1 may be a potential therapy in the treatment of PCa.


Assuntos
Proteínas de Transporte/genética , Proliferação de Células/genética , Neoplasias da Próstata/genética , Animais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-myc/genética
12.
Biol Blood Marrow Transplant ; 25(10): 1911-1919, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195136

RESUMO

High-dose chemotherapy and/or radiation given before an allogeneic hematopoietic cell transplantation severely damage thymic epithelial cells (TECs), resulting in poor post-transplant immune recovery. IL-22 mediates recovery of TECs via a proregenerative effect, but the precise mechanism by which this occurs is unknown. In this study, we found IL-22 improved thymus recovery after damage from irradiation in association with increased number of TECs. This effect was blocked by ruxolitinib, a JAK1/JAK2 inhibitor. IL-22 increased the number of TECs via a Stat3-dependent signaling in the mTEC1 murine thymic epithelial cell line. This, in turn, upregulated transcription of myeloid cell leukemia sequence 1 (Mcl1), resulting in increased number of TECs. Similar effects were seen in irradiated mice given IL-22. Defects in IL-22 resulted in delayed thymus recovery in irradiated mice and had an impact on levels of thymus function-related genes such as Foxn1, Aire, and Kgf. In mice, post-transplant use of IL-22 improved repair of TECs, increased the numbers of thymus T cells, increased the intrathymic levels of Aire, and increased the proportion of natural regulatory T cells, resulting in decreased severity of chronic graft-versus-host disease (GVHD). Our data highlight the critical role of the IL-22/Stat3/Mcl-1 pathway in the regeneration of TECs after damage from irradiation in mice and highlight circumstances where normalizing thymus T cell function with IL-22 decreases GVHD after allotransplants.

13.
Gene Ther ; 26(7-8): 308-323, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31118475

RESUMO

Transmission of pain signals from primary sensory neurons to secondary neurons of the central nervous system is critically dependent on presynaptic voltage-gated calcium channels. Calcium channel-binding domain 3 (CBD3), derived from the collapsin response mediator protein 2 (CRMP2), is a peptide aptamer that is effective in blocking N-type voltage-gated calcium channel (CaV2.2) activity. We previously reported that recombinant adeno-associated virus (AAV)-mediated restricted expression of CBD3 affixed to enhanced green fluorescent protein (EGFP) in primary sensory neurons prevents the development of cutaneous mechanical hypersensitivity in a rat neuropathic pain model. In this study, we tested whether this strategy is effective in treating established pain. We constructed AAV6-EGFP-CBD3A6K (AAV6-CBD3A6K) expressing a fluorescent CBD3A6K (replacing A to K at position 6 of CBD3 peptide), which is an optimized variant of the parental CBD3 peptide that is a more potent blocker of CaV2.2. Delivery of AAV6-CBD3A6K into lumbar (L) 4 and 5 dorsal root ganglia (DRG) of rats 2 weeks following tibial nerve injury (TNI) induced transgene expression in neurons of these DRG and their axonal projections, accompanied by attenuation of pain behavior. We additionally observed that the increased CaV2.2α1b immunoreactivity in the ipsilateral spinal cord dorsal horn and DRG following TNI was significantly normalized by AAV6-CBD3A6K treatment. Finally, the increased neuronal activity in the ipsilateral dorsal horn that developed after TNI was reduced by AAV6-CBD3A6K treatment. Collectively, these results indicate that DRG-restricted AAV6 delivery of CBD3A6K is an effective analgesic molecular strategy for the treatment of established neuropathic pain.


Assuntos
Aptâmeros de Peptídeos/genética , Canais de Cálcio Tipo N/metabolismo , Dependovirus/genética , Terapia Genética/métodos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas do Tecido Nervoso/genética , Neuralgia/terapia , Animais , Aptâmeros de Peptídeos/química , Aptâmeros de Peptídeos/metabolismo , Bloqueadores dos Canais de Cálcio/química , Dependovirus/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Domínios Proteicos , Ratos , Ratos Sprague-Dawley
14.
Sci Rep ; 9(1): 7428, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092843

RESUMO

The X-chromosome linked inhibitor of apoptosis, XIAP, is mainly known as the inhibitor of caspases by direct interaction with caspases with its baculoviral IAP repeat (BIR) domains. XIAP has three BIR domains and each BIR domain contains a zinc binding site, normally known as zinc finger motif. Recent studies showed that XIAP is involved in copper homeostasis in cells and the BIR domains bind copper ion. However, structural details of the second and third BIR domain, BIR2 and BIR3, in XIAP, with copper as well as the binding modes are not known. In the present work we characterize the structural properties of BIR3 in solution by high resolution NMR and other biophysical techniques. The interaction of BIR3 with copper both in vitro and in cell lysates was analyzed. Our results show that BIR3 is able to form stable complexes both with Cu(II) and Cu(I), whereas zinc binding site is not affected and zinc retains tightly bound in the zinc finger during these interactions. Surprisingly, BIR3 has multiple binding sites for Cu(II) and Cu(I) but with varied binding affinities. In addition, the solvent exposed Cys351 is readily oxidized by Cu(II) resulting an intermolecular disulfide bond either between two BIR3 molecules or a mixed disulfide bond with glutathione in cell lysates.

15.
Chembiochem ; 20(15): 1953-1958, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30958607

RESUMO

Accumulation of filamentous aggregates of α-synuclein (AS) in Lewy bodies and neurites is characteristic of neurodegenerative diseases such as Parkinson's disease. Inhibition of AS fibrillation is helpful for understanding of AS aggregate structure and for developing chemical therapies. Herein, we report that the PtII -containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. PtII thus contrasts strongly with reported transition-metal ions such as MnII , FeIII , and CuII , which accelerate AS aggregation. Interaction between PtII and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtII to AS did not change the protein's overall random coil structure, as indicated by solution-state two-dimensional NMR and circular dichroism spectroscopy; and a solution of the AS⋅PtII complex remained free of filamentous aggregates. Our results constitute interesting new information about the biological chemistry of metal ions in Parkinson's disease and might open new lines of research into the suppression of filamentous aggregation.

16.
PLoS One ; 14(2): e0210774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30721238

RESUMO

With wetlands categorized as one of the three major ecosystems, the study of wetland health has global environmental implications. Multiple regression models were employed to establish relationships between Landsat-8 images, vegetation indices and field measured biomass in the Yellow River Delta Nature Reserve. These models were then used to estimate the spatial distribution of wetland vegetative biomass. The relationships between wetland vegetative biomass and soil factors (organic matter, nitrogen, phosphorus, potassium, water soluble salt, pH and moisture) were modeled. We were able to achieve higher correlations and improved model fits using vegetative indices and spectral bands 1-5 as independent variables. Several important soil factors were isolated, including soil moisture and salt concentrations, which affect wetland biomass spatial distributions. Overall, wetland biomass decreased from land to the ocean and from the river courses outward.


Assuntos
Biomassa , Modelos Biológicos , Áreas Alagadas , China
17.
J Abnorm Child Psychol ; 47(3): 381-392, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29754200

RESUMO

We examined the bidirectional relations between peer relations and attention problems from middle childhood through adolescence. Using data from the Longitudinal Study of Chinese Children and Adolescents (LSCCA, N = 2157, 51.9% male), three key aspects of peer relations (acceptance, rejection, and victimization) were assessed annually from 9 to 16 years of age. Attention problems were assessed at 9 and 15 years. Latent growth modeling indicated that greater attention problems at age 9 were linked with a lower intercept for peer acceptance, and higher intercepts for rejection and victimization. Also, prior lower acceptance and greater rejection and victimization, along with a higher increase over time in rejection and lower decrease over time in victimization, predicted attention problems at age 15. Cross-lagged analysis showed that attention problems were associated with less subsequent peer acceptance and greater subsequent rejection and victimization. Only peer rejection (but neither victimization nor acceptance) predicted more subsequent attention problems. Findings point to bidirectional associations between attention problems and peer relations in the developmental transition across adolescence. Evidence for differential bidirectionality of attention problems with the multiple peer experience (group versus dyadic; good versus bad) emerged, and future replications are needed.

18.
J Cell Physiol ; 234(6): 8918-8927, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30341912

RESUMO

Spinal cord injury (SCI) is a highly severe disease and it can lead to the destruction of the motor and sensory function resulting in temporary or permanent disability. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt that play a critical role in central nervous system (CNS) injury. However, the exact roles of lncRNAs and messenger RNAs (mRNAs) in the early acute phase of SCI remain to be elucidated. We examined the expression of mRNAs and lncRNAs in a rat model at 2 days after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. Subsequently, a comprehensive bioinformatics analysis was also performed to clarify the interaction between DE mRNAs. A total of 3,193 DE lncRNAs and 4,308 DE mRNAs were identified between the injured group and control group. Classification, length distribution, and chromosomal distribution of the dysregulated lncRNAs were also performed. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. A protein-protein interaction (PPI) network indicated that IL6, TOP2A, CDK1, POLE, CCNB1, TNF, CCNA2, CDC20, ITGAM, and MYC were the top 10 core genes. The subnetworks from the PPI network were identified to further elucidate the most significant functional modules of the DE mRNAs. These data may provide novel insights into the molecular mechanism of the early acute phase of SCI. The identification of lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for SCI.

19.
Int Immunopharmacol ; 67: 194-201, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557822

RESUMO

Defect of thymus results in poor posttransplant immune recovery and dysfunction of immune tolerance after allogeneic hematopoietic cell transplants (allo-HCT). Improving thymus regeneration represents a potential strategy to accelerate recovery of T-cell immunity. IL-22 was reported to mediate thymus regeneration after injury. In this study, we found donor T-cell is a major source of IL-22 in allotransplant recipient. Through applying IL-22 knock out (IL-22KO) mice in allo-HCT, we found donor T-cell derived IL-22 promotes thymus regeneration in association with increased level of intra-thymic IL-22. IL-22KO T-cell-transplanted recipients show deficient thymus recovery which is reversed by injection of exogenous IL-22. T-cell derived IL-22 promotes proliferation of thymic epithelial cells (TECs) in vitro. In addition, donor T-cell derived IL-22 increases expression level of Aire in the thymus and decreases skin chronic graft-versus-host disease (GVHD). Furthermore, short-term use of exogenous IL-22 posttransplant accelerates recovery of thymus without increasing severity of acute GVHD. Our data indicate that cross-talk between T-cell and TECs is an important mechanism to mediate reconstitution of T-cell immunity after allo-HCT.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/terapia , Interleucinas/farmacologia , Linfócitos T/metabolismo , Timo/fisiologia , Animais , Linhagem Celular , Sobrevivência Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Regulação da Expressão Gênica , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Timo/efeitos dos fármacos , Doadores de Tecidos , Transplante Homólogo
20.
Exp Hematol ; 68: 80-88.e2, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30195077

RESUMO

BCR-ABL1-independent mechanisms had been thought to mediate drug resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia (CML). The pro-oncogenic anterior gradient 2 (AGR2) mediates drug resistance of cancer cells. In this study, we observed an increased level of AGR2 in TKI-resistant CML cells. Silence of AGR2 in dasatinib-resistant K562 (K562DR) cells led to restored sensitivity to dasatinib both in vitro and in vivo. Exposure to dasatinib induced upregulation of AGR2 in K562 cells, which indicated a probable treatment-related drug resistance. We further investigated the potential interaction between microRNA (miRNA) and AGR2 in K562DR cells and found that downregulation of miR-217 was associated with overexpression of AGR2 in K562DR cells. Luciferase reporter assay identified that miR-217 negatively regulated expression of AGR2 through binding the 3'-untranslated region of AGR2. Hypermethylation of the CpG island on the promoter region of the MIR217 gene is a probable reason for the downregulation of miR-217 in dasatinib-treated K562 cells. Forced expression of miR-217 led to decreased expression of AGR2 as well as compromised TKI-resistant potential of K562DR cells. Similarly, overexpression of miR-217 resensitized K562DR cells to dasatinib treatment in a murine xenograft transplantation model. TKI treatment-induced drug resistance is correlated with a decrease of miR-217 and upregulation of AGR2. The miR-217/AGR2 interaction might be a potential therapeutic target in treating CML patients with TKI resistance.


Assuntos
Antineoplásicos/farmacologia , Regulação Leucêmica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MicroRNAs/fisiologia , Proteínas de Neoplasias/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas/genética , RNA Neoplásico/fisiologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Metilação de DNA , Dasatinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Camundongos , Camundongos Endogâmicos NOD , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas de Neoplasias/metabolismo , Regiões Promotoras Genéticas , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas/metabolismo , RNA/metabolismo , Interferência de RNA , RNA Neoplásico/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Organismos Livres de Patógenos Específicos , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA