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1.
BMC Plant Biol ; 21(1): 340, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273968

RESUMO

BACKGROUND: TLPs (Tubby-like proteins) are widespread in eukaryotes and highly conserved in plants and animals. TLP is involved in many biological processes, such as growth, development, biotic and abiotic stress responses, while the underlying molecular mechanism remains largely unknown. In this paper we characterized the biological function of cucumber (Cucumis sativus L.) Tubby-like protein 8 (CsTLP8) in Arabidopsis. RESULTS: In cucumber, the expression of the tubby-like protein CsTLP8 was induced by NaCl treatment, but reduced by PEG (Polyethylene Glycol) and ABA (Abscisic Acid) treatment. Subcellular localization and transcriptional activation activity analysis revealed that CsTLP8 possessed two characteristics of classical transcription factors: nuclear localization and trans-activation activity. Yeast two-hybrid assay revealed interactions of CsTLP8 with CsSKP1a and CsSKP1c, suggesting that CsTLP8 might function as a subunit of E3 ubiquitin ligase. The growth activity of yeast with ectopically expressed CsTLP8 was lower than the control under NaCl and mannitol treatments. Under osmotic and salt stresses, overexpression of CsTLP8 inhibited seed germination and the growth of Arabidopsis seedlings, increased the content of MDA (Malondialdehyde), and decreased the activities of SOD (Superoxide Dismutase), POD (Peroxidase) and CAT (Catalase) in Arabidopsis seedlings. Overexpression of CsTLP8 also increased the sensitivity to ABA during seed germination and ABA-mediated stomatal closure. CONCLUSION: Under osmotic stress, CsTLP8 might inhibit seed germination and seedling growth by affecting antioxidant enzymes activities. CsTLP8 acts as a negative regulator in osmotic stress and its effects may be related to ABA.


Assuntos
Ácido Abscísico/metabolismo , Cucumis sativus/metabolismo , Germinação , Pressão Osmótica , Proteínas de Plantas/metabolismo , Sementes , Transdução de Sinais , Antioxidantes/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/crescimento & desenvolvimento , Plântula/metabolismo , Sementes/embriologia , Cloreto de Sódio , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
2.
Mol Med Rep ; 20(4): 3388-3394, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432140

RESUMO

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. MicroRNAs (miRNAs) are a group of endogenous small non­coding RNAs that regulate target genes, and play a critical role in many biological processes. However, the underlying mechanism of specific miRNA, miR­130a­3p, in AS remains largely unknown. Therefore, the present study aimed to explore the underlying mechanism of miR­130a­3p in the development of AS. In the present study, it was revealed that miR­130a­3p was downregulated in T cells from HLA­B27­positive AS patients compared with the HLA­B27­negative healthy controls. Next, bioinformatics software TargetScan 7.2 was used to predict the target genes of miR­130a­3p, and a luciferase reporter assay indicated that HOXB1 was the direct target gene of miR­130a­3p. Furthermore, it was determined that HOXB1 expression was upregulated in T cells from HLA­B27­positive AS patients. In addition, the results of the present study indicated that miR­130a­3p inhibitor significantly inhibited cell proliferation ability and induced cell apoptosis of Jurkat T cells, while the miR­130a­3p mimic promoted proliferation ability and inhibited cell apoptosis of Jurkat T cells. Notably, all the effects of the miR­130a­3p mimic on Jurkat T cells were reversed by HOXB1­plasmid. Collectively, our data indicated that miR­130a­3p was decreased in T cells from AS patients and it could regulate T­cell survival by targeting HOXB1.


Assuntos
Apoptose/imunologia , Regulação para Baixo/imunologia , MicroRNAs/imunologia , Espondilite Anquilosante/imunologia , Linfócitos T/imunologia , Adulto , Sobrevivência Celular/imunologia , Feminino , Antígeno HLA-B27/imunologia , Proteínas de Homeodomínio/imunologia , Humanos , Células Jurkat , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/patologia , Linfócitos T/patologia
3.
Diabetes Ther ; 10(2): 535-547, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30725399

RESUMO

INTRODUCTION: Studies of the effects of stem cell therapy on type 2 diabetes mellitus (T2DM) have not reached consistent results. Our meta-analysis aimed to systematically evaluate the efficacy of autologous bone marrow-derived stem cells (ABM-MNCs) on T2DM. METHODS: We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published between 1980 and May 2018. Two researchers screened the literature independently following the inclusion and exclusion criteria. Meta-analysis of the pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated based on either a fixed- or random-effects model. RESULTS: We identified six studies with 206 participants investigating the effects of autologous bone marrow stem cell therapy on T2DM after screening 102 studies found after the initial search. According to the pooled estimates, compared with the control group, after 12-month follow-up the ABM-MNC therapy group had a lower level of HbA1c (MD, - 1.18; 95% CI, - 1.40 to 0.95) and lower required insulin dose (MD, - 2.05; 95% CI, - 3.55 to - 0.55). HbA1c decreased after ABM-MNC therapy compared with before (12 months: MD, - 1.22; 95% CI, - 1.43 to - 1.0). We also observed a significant decrease in insulin requirement after 3-, 6-, 9-, and 12-month follow-up in the ABM-MNC group, respectively. CONCLUSION: Autologous stem cell therapy showed a beneficial effect on T2DM.

4.
Gastroenterology ; 155(5): 1578-1592.e16, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30063921

RESUMO

BACKGROUND & AIMS: Bile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis. METHODS: We measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport. RESULTS: Hepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet-induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids. CONCLUSIONS: We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase/metabolismo , Transportadores de Ânions Orgânicos/fisiologia , Animais , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Fatores de Crescimento de Fibroblastos/análise , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transportadores de Ânions Orgânicos/análise , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Transcrição Sp1/fisiologia , Fator de Transcrição RelA/fisiologia
5.
Platelets ; 29(7): 702-708, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29119850

RESUMO

Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis.


Assuntos
Plaquetas/metabolismo , Dopamina/metabolismo , Megacariócitos/metabolismo , Estresse Oxidativo , Transdução de Sinais , Trombopoese , Animais , Apoptose , Caspase 3/metabolismo , Dopamina/farmacologia , Citometria de Fluxo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Megacariócitos/citologia , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Trombopoese/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Blood ; 129(19): 2667-2679, 2017 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-28264799

RESUMO

Thrombosis is a common complication of chronic kidney disease (CKD), but the causes and mechanisms of CKD-associated thrombosis are not well clarified. Here, we show that platelet activity is remarkably enhanced in CKD mice, with increase of serum indoxyl sulfate (IS), a typical uremic toxin, which cannot be effectively cleared by routine dialysis. Ex vivo and in vitro experiments reveal that IS displays a distinct ability to enhance platelet activities, including elevated response to collagen and thrombin, increases in platelet-derived microparticles, and platelet-monocyte aggregates. The flow chamber assay and carotid artery thrombosis model demonstrate that IS-induced platelet hyperactivity contributes to thrombus formation. Further investigations disclose that reactive oxygen species (ROS)-mediated p38MAPK signaling plays a key role in IS-induced platelet hyperactivity. Moreover, we show that Klotho, which is expressed dominantly in the kidneys, has the capacity to counteract IS-induced platelet hyperactivity by inhibiting ROS/p38MAPK signaling, whereas Klotho reduction may aggravate the effect of IS on platelet activation in CKD and klotho+/- mice. Finally, we demonstrate that Klotho protein treatment can protect against IS-induced thrombosis and atherosclerosis in apoE-/- mice. Our findings uncover the mechanism of platelet hyperactivity induced by IS and provide new insights into the pathogenesis and treatment of CKD-associated thrombosis.


Assuntos
Plaquetas/efeitos dos fármacos , Indicã/efeitos adversos , Ativação Plaquetária/efeitos dos fármacos , Insuficiência Renal Crônica/induzido quimicamente , Trombose/induzido quimicamente , Animais , Plaquetas/patologia , Glucuronidase/administração & dosagem , Glucuronidase/metabolismo , Glucuronidase/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/metabolismo , Trombose/tratamento farmacológico , Trombose/metabolismo
7.
Blood ; 127(8): 1024-35, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26644453

RESUMO

The effect of sympathetic stimulation on thrombopoiesis is not well understood. Here, we demonstrate that both continual noise and exhaustive exercise elevate peripheral platelet levels in normal and splenectomized mice, but not in dopamine ß-hydroxylase-deficient (Dbh(-/-)) mice that lack norepinephrine (NE) and epinephrine (EPI). Further investigation demonstrates that sympathetic stimulation via NE or EPI injection markedly promotes platelet recovery in mice with thrombocytopenia induced by 6.0 Gy of total-body irradiation and in mice that received bone marrow transplants after 10.0 Gy of lethal irradiation. Unfavorably, sympathetic stress-stimulated thrombopoiesis may also contribute to the pathogenesis of atherosclerosis by increasing both the amount and activity of platelets in apolipoprotein E-deficient (ApoE(-/-)) mice. In vitro studies reveal that both NE and EPI promote megakaryocyte adhesion, migration, and proplatelet formation (PPF) in addition to the expansion of CD34(+) cells, thereby facilitating platelet production. It is found that α2-adrenoceptor-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation is involved in NE- and EPI-induced megakaryocyte adhesion and migration, and PPF is regulated by ERK1/2 activation-mediated RhoA GTPase signaling. Our data deeply characterize the role of sympathetic stimulation in the regulation of thrombopoiesis and reevaluate its physiopathological implications.


Assuntos
Plaquetas/citologia , Movimento Celular , Megacariócitos/citologia , Trombopoese , Animais , Western Blotting , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Modelos Animais de Doenças , Epinefrina/metabolismo , Epinefrina/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Megacariócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Estresse Fisiológico/fisiologia , Sistema Nervoso Simpático/fisiologia
8.
Huan Jing Ke Xue ; 29(9): 2654-8, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19068660

RESUMO

PM10 was collected at the urban and suburban sites of Zhengzhou city during autumn. High solution field emission scanning electron microscopy (FESEM) and image analysis (IA) were used to analyse the morphology and size distribution of individual particles in PM10. Plasmid DNA assay was employed to investigate the bioreactivity of PM10. The results showed that the coal fly ash particles were dominated in the PM10 at the urban site while mineral particles were dominated at the suburban site. The number-size distribution showed that the PM10 at the urban site was mainly concentrated in the range of 0.1 microm to 0.4 microm, but the PM10 at the suburban site was scattered in a relatively wider size range. The volume-size distribution demonstrated that the PM10 from both urban and suburban sites occurred mainly in the size range > 1 microm. These facts showed that by number the fine particles were prevailing in the PM10, while by volume (mass) the coarse particles had a major contribution to the total PM10. The results from plasmid assay showed that the bioreactivity of the urban PM10 was obviously higher than that of the suburban PM10.


Assuntos
Poluentes Atmosféricos/análise , Carbono/análise , Monitoramento Ambiental , Material Particulado/análise , Poluentes Atmosféricos/química , China , Carvão Mineral , Cinza de Carvão , Tamanho da Partícula , Material Particulado/química , Saúde da População Urbana
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