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1.
Blood ; 142(10): 903-917, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37319434

RESUMO

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.


Assuntos
Proteína 7 Semelhante a Angiopoietina , Proteína 1 Inibidora de Diferenciação , Leucemia Mieloide Aguda , Animais , Camundongos , Proteína 7 Semelhante a Angiopoietina/genética , Proteína 7 Semelhante a Angiopoietina/metabolismo , Medula Óssea/metabolismo , Modelos Animais de Doenças , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Microambiente Tumoral , Humanos , Proteína 1 Inibidora de Diferenciação/metabolismo
2.
Plant Cell Rep ; 43(9): 219, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155298

RESUMO

KEY MESSAGE: Exogenous application of 24-epibrassinolide can alleviate oxidative damage, improve photosynthetic capacity, and regulate carbon and nitrogen assimilation, thus improving the tolerance of grapevine (Vitis vinifera L.) to drought stress. Brassinosteroids (BRs) are a group of plant steroid hormones in plants and are involved in regulating plant tolerance to drought stress. This study aimed to investigate the regulation effects of BRs on the carbon and nitrogen metabolism in grapevine under drought stress. The results indicated that drought stress led to the accumulation of superoxide radicals and hydrogen peroxide and an increase in lipid peroxidation. A reduction in oxidative damage was observed in EBR-pretreated plants, which was probably due to the improved antioxidant concentration. Moreover, exogenous EBR improved the photosynthetic capacity and sucrose phosphate synthase activity, and decreased the sucrose synthase, acid invertase, and neutral invertase, resulting in improved sucrose (190%) and starch (17%) concentrations. Furthermore, EBR pretreatment strengthened nitrate reduction and ammonium assimilation. A 57% increase in nitrate reductase activity and a 13% increase in glutamine synthetase activity were observed in EBR pretreated grapevines. Meanwhile, EBR pretreated plants accumulated a greater amount of proline, which contributed to osmotic adjustment and ROS scavenging. In summary, exogenous EBR enhanced drought tolerance in grapevines by alleviating oxidative damage and regulating carbon and nitrogen metabolism.


Assuntos
Brassinosteroides , Resistência à Seca , Fotossíntese , Esteroides Heterocíclicos , Vitis , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Carbono/metabolismo , Glucosiltransferases/metabolismo , Glutamato-Amônia Ligase/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Nitrato Redutase/metabolismo , Nitrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Esteroides Heterocíclicos/metabolismo , Esteroides Heterocíclicos/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Vitis/efeitos dos fármacos , Vitis/metabolismo , Vitis/fisiologia
3.
Plant Cell Rep ; 43(2): 30, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38195770

RESUMO

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.


Assuntos
Arachis , Açúcares , Arachis/genética , beta-Frutofuranosidase/genética , Estresse Salino , Sacarose
4.
Mycoses ; 67(1): e13680, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38214420

RESUMO

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.


Assuntos
Quimiocinas C , Foliculite , Malassezia , Humanos , Camundongos , Animais , Interferon gama , Interferons , Antígenos de Histocompatibilidade Classe II/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Inflamassomos , Regiões Promotoras Genéticas , Transativadores/genética , Transativadores/metabolismo , Quimiocinas/genética , Queratinócitos
5.
Blood Press ; 33(1): 2387025, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39216506

RESUMO

OBJECTIVE: Hypertension refers to the elevated blood pressure (BP) in arteries, with a BP reading of 140/90 mm Hg or higher in adults. Over 40% of >25-year-old population have suffered from hypertension. Thus, this study aimed to find novel diagnostic biomarkers for hypertension. METHODS: All hypertension-related mRNA and methylation datasets were downloaded from the GEO database. Liner model method was used to identify differentially expressed genes (DEGs) between hypertension and control groups. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis was employed to obtain functional information. CpG sites and the corresponding genes associated with hypertension were screened using epigenome-wide association study (EWAS) analysis. RESULTS: There were 37 DEGs between the hypertension group and control group, which were significantly enriched in 84 Biological Process terms, 31 Cellular Component terms, 18 Molecular Function terms and 9 signalling pathways. EWAS results indicated that 1072 CpG sites were associated with hypertension occurrence, corresponding to 1029 genes. After cross-analysis, complement factor D (CFD) and OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) with methylation modification were identified as diagnostic markers for hypertension. CONCLUSION: In conclusion, CFD and OTUB2 were potential biomarkers of hypertension occurrence. Our results will provide more information for hypertension diagnosis and would be more reliable combined with multiple biomarkers.


In the GSE24752 dataset, there were 37 differentially expressed genes between the hypertension group and the normal group.In the GSE42774 dataset, there were 1072 CpG sites, corresponding to 1029 genes, associated with hypertension occurrence.CFD and OTUB2 were potential biomarkers that were associated with hypertension occurrence.


Assuntos
Biomarcadores , Metilação de DNA , Hipertensão , Humanos , Hipertensão/genética , Hipertensão/diagnóstico , Estudo de Associação Genômica Ampla , Ilhas de CpG , Feminino
6.
J Environ Manage ; 370: 122684, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342839

RESUMO

Net-zero entrepreneurship is a novel concept introduced in the context of carbon neutrality, and exploring whether it can catalyze decarbonized economic growth is a worthy pursuit. This study constructs a comprehensive, low-carbon endogenous economic growth model to scrutinize the intricate nexus between net-zero entrepreneurship and decarbonized economic growth. Empirical validation employs a series of multiple regression models to rigorously test the hypotheses derived from the theoretical framework using an extensive dataset spanning Chinese provinces. The results reveal a nuanced landscape. (i) Net-zero entrepreneurship plays a remarkable role in promoting decarbonization growth, with considerable regional heterogeneity. (ii) Green technology progress exhibits a notable mediating effect. (iii) Environmental regulation and industrial structure optimization have positive moderating effects. (iv) The results passed alternative dependent variable and one-phase lag regression robustness tests. In a distinct contribution to entrepreneurship literature, this study augments the discourse on strategies to steer low-carbon transitions. The research findings indicate that net-zero entrepreneurship can accelerate the global decarbonization process, and green technology progress is a significant driving mechanism in this process. Additionally, it is essential to strengthen environmental agencies' regulatory oversight and optimize industrial structures to pave the way for transformative sustainable growth. In the future, more entrepreneurs should be encouraged to engage in green technology and business model innovation to contribute to global decarbonization efforts.

7.
Angew Chem Int Ed Engl ; 63(43): e202411298, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39011619

RESUMO

The engineering of tunable photoluminescence (PL) in single materials with a full-spectrum emission represents a highly coveted objective but poses a formidable challenge. In this context, the realization of near-full-spectrum PL emission, spanning the visible light range from 424 to 620 nm, in a single-component two-dimensional (2D) hybrid lead halide perovskite, (ETA)2PbBr4 (ETA+=(HO)(CH2)2NH3 +), is reported, achieved through high-pressure treatment. A pressure-induced phase transition occurs upon compression, transforming the crystal structure from an orthorhombic phase under ambient conditions to a monoclinic structure at high pressure. This phase transition driven by the adaptive and dynamic configuration changes of organic amine cations enables an effective and continuous narrowing of the band gap in this halide crystal. The hydrogen bonding interactions between inorganic layers and organic amine cations (N-H⋅⋅⋅Br and O-H⋅⋅⋅Br hydrogen bonds) efficiently modulate the organic amine cations penetration and the octahedral distortion. Consequently, this phenomenon induces a phase transition and results in red-shifted PL emissions, leading to the near-full-spectrum emission. This work opens a possibility for achieving wide PL emissions with coverage across the visible light spectrum by employing high pressure in single halide perovskites.

8.
J Am Chem Soc ; 145(41): 22475-22482, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37797315

RESUMO

Hybrid organic-inorganic perovskites (HOIPs) have exhibited striking application potential in piezoelectric energy harvesting and sensing due to their high piezoelectricity, light weight, and solution processability. However, to date, the application of piezoelectric HOIPs in ultrasound detection has not yet been explored. Here, we report the synthesis of a pair of chiral two-dimensional piezoelectric HOIPs, R-(4-bromo-2-butylammonium)2PbBr4 and S-(4-bromo-2-butylammonium)2PbBr4 [R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4], which show low mechanical strength and significant piezoelectric strain coefficients that are advantageous for mechanoelectrical energy conversion. Benefiting from these virtues, the R-(BrBA)2PbBr4@PBAT and S-(BrBA)2PbBr4@PBAT [PBAT = poly(butyleneadipate-co-terephthalate)] composite films show prominent underwater ultrasound detection performance with a transmission effectivity of 12.0% using a 10.0 MHz probe, comparable with that of a polyvinylidene fluoride (PVDF) device fabricated in the same conditions. Density functional theory calculations reveal that R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4 have a beneficial acoustic impedance (5.07-6.76 MRayl) compatible with that of water (1.5 MRayl), which is responsible for the facile ultrasound-induced electricity generation. These encouraging results open up new possibilities for applying piezoelectric HOIPs in underwater ultrasound detection and imaging technologies.

9.
Crit Rev Food Sci Nutr ; 63(26): 8249-8260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35333679

RESUMO

With the awakening of consumers' awareness of sustainable development issues and demand for terroir wines, natural wines provide opportunities for the future development of the wine industry. Microbiomes are integral to viticulture and winemaking, where various microorganisms can exert positive and negative effects on grape health and wine quality. Communities of microorganisms associated with the vineyard play an important role in soil productivity as well as disease resistance developed by the vine. Wine is a fermented natural product, and the vineyard serves as a key point of entry for quality-modulating microbiota, particularly in wine fermentations that are conducted without the addition of exogenous yeasts. Thus, the sources and persistence of wine-relevant microbiota in vineyards critically impact its quality. In this review, we first examined that mimicking natural ecological cultivation to improve microbial diversity can enhance vineyard ecological services and reduce external inputs; then we examined that grape berries naturally possess all the elements of winemaking, including the nutrients for microbial growth, driving forces for the microbiota succession, and the enzymatic system for biochemical reactions; finally, we examined food safety, stability, specific interventions, and sustainability of natural wine industry-scale practices.


Assuntos
Microbiota , Vitis , Vinho , Vinho/análise , Vitis/química , Leveduras , Fazendas , Fermentação
10.
Eur Radiol ; 33(8): 5222-5235, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36892648

RESUMO

OBJECTIVES: To explore whether intravoxel incoherent motion (IVIM) parameters could evaluate liver regeneration preoperatively. METHODS: A total of 175 HCC patients were initially recruited. The apparent diffusion coefficient, true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f), diffusion distribution coefficient, and diffusion heterogeneity index (Alpha) were measured by two independent radiologists. Spearman's correlation test was used to assess correlations between IVIM parameters and the regeneration index (RI), calculated as 100% × (the volume of the postoperative remnant liver - the volume of the preoperative remnant liver) / the volume of the preoperative remnant liver. Multivariate linear regression analyses were used to identify the factors for RI. RESULTS: Finally, 54 HCC patients (45 men and 9 women, mean age 51.26 ± 10.41 years) were retrospectively analyzed. The intraclass correlation coefficient ranged from 0.842 to 0.918. In all patients, fibrosis stage was reclassified as F0-1 (n = 10), F2-3 (n = 26), and F4 (n = 18) using the METAVIR system. Spearman correlation test showed D* (r = 0.303, p = 0.026) was associated with RI; however, multivariate analysis showed that only D value was a significant predictor (p < 0.05) of RI. D and D*showed moderate correlations with fibrosis stage (r = -0.361, p = 0.007; r = -0.457, p = 0.001). Fibrosis stage showed a negative correlation with RI (r = -0.263, p = 0.015). In the 29 patients who underwent minor hepatectomy, only the D value showed a positive association (p < 0.05) with RI, and a negative correlation with fibrosis stage (r = -0.360, p = 0.018). However, in the 25 patients who underwent major hepatectomy, no IVIM parameters were associated with RI (p > 0.05). CONCLUSIONS: The D and D* values, especially the D value, may be reliable preoperative predictors of liver regeneration. KEY POINTS: • The D and D* values, especially the D value, derived from IVIM diffusion-weighted imaging may be useful markers for the preoperative prediction of liver regeneration in patients with HCC. • The D and D* values derived from IVIM diffusion-weighted imaging show significant negative correlations with fibrosis, an important predictor of liver regeneration. • No IVIM parameters were associated with liver regeneration in patients who underwent major hepatectomy, but the D value was a significant predictor of liver regeneration in patients who underwent minor hepatectomy.


Assuntos
Carcinoma Hepatocelular , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Regeneração Hepática , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Movimento (Física) , Hiperplasia , Fibrose
11.
Oral Dis ; 29(1): 195-205, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34110666

RESUMO

OBJECTIVES: Pleiotrophin (PTN), a secreted extracellular matrix-associated protein, plays an important role in regulating the osteo/dentinogenic differentiation potential of dental pulp stem cells (DPSCs). Our previous study has demonstrated that PTN expression in young DPSCs was is 10-fold higher than that in aged DPSCs. However, the role of PTN on the in maintaining the stemness of senescent DPSCs remains unclear. The present study aimed to investigate the effect of PTN on senescent DPSCs in vitro. MATERIALS AND METHODS: Dental pulp stem cells were isolated from human third molars. PTN was knocked down using short hairpin RNAs to study the role of PTN on the senescence of DPSCs. DPSCs with aging performance were obtained by a replicative senescence cell model was obtained by the long-term culture of DPSCs to the 15th passage in vitro (P15). We then investigated the effect of PTN on senescent DPSCs (P15 DPSCs). Real-time RT-PCR, western blotting, alizarin red staining, quantitative calcium analysis, SA-ß-Gal staining, CFSE, and cell-counting kit-8 (CCK8) assays were used to study cellular senescence and function. RESULTS: The depletion of PTN increased the ratio of SA-ß-gal-positive cells, upregulated the expression of p16, and down-regulated the expression of TERT and p-p38. Furthermore, 50 pg/ml of PTN recombinant protein rescued these changes the altered ratio of SA-ß-gal-positive cells, decreased the expression of p16, enhanced TERT and p-p38 expression, as well as telomere activity, caused by PTN depletion and long-term culture. The15th passage cells displayed typical aging characteristic, including high ratio of SA-ß-gal-positive cells, increased aging-related gene expression, decreased proliferation rate, high level of Cyclin D expression, and impaired osteo/dentinogenic differentiation potential. However, 50 pg/ml of PTN recombinant protein could partially reverse these alteration rescue these changes. CONCLUSIONS: The present study demonstrated that PTN could protect DPSCs from senescence by improving the proliferation and osteo/dentinogenic differentiation ability, probably through the p38 MAPK pathway.


Assuntos
Proteínas de Transporte , Citocinas , Polpa Dentária , Células-Tronco , Humanos , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Proteínas da Matriz Extracelular/fisiologia , Osteogênese , Proteínas Recombinantes/farmacologia , Células-Tronco/fisiologia , Proteínas de Transporte/fisiologia , Citocinas/fisiologia
12.
Int J Mol Sci ; 24(9)2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37175416

RESUMO

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.


Assuntos
Filamentos Intermediários , Morfina , Ratos , Animais , Morfina/farmacologia , Fosforilação , Ratos Sprague-Dawley , Aprendizagem , Inibidores de Histona Desacetilases/farmacologia
13.
Angew Chem Int Ed Engl ; 62(12): e202218675, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36656542

RESUMO

The chemical diversity and structural flexibility of lead halide perovskites (LHPs) offer tremendous opportunities to tune their optical properties through internal molecular engineering and external stimuli. Herein, we report the wide-range and ultrapure photoluminescence emissions in a family of homologous 2D LHPs, [MeOPEA]2 PbBr4-4x I4x (MeOPEA=4-methoxyphenethylammonium; x=0, 0.2, 0.425, 0.575, 1) enabled through internal chemical pressure and external hydrostatic pressure. The chemical pressure, induced by the C-H⋅⋅⋅π interactions and halogen doping/substitution strengthens the structural rigidity to give sustained narrow emissions, and regulates the emission energy, respectively. Further manipulation of physical pressure leads to wide-range emission tuning from 412 to 647 nm in a continuous and reversible manner. This work could open up new pathways for developing 2D LHP emitters with ultra-wide color gamut and high color purity which are highly useful for pressure sensing.

14.
Proc Natl Acad Sci U S A ; 116(3): 890-899, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30593567

RESUMO

The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene, THPO, is identified as a potential predictor of relapse. In a mouse model of human t(8;21) leukemia, E2-2 suppression accelerates leukemogenesis. Taken together, these results reveal that, in contrast to HEB and E2A, which facilitate AML1-ETO-mediated leukemogenesis, E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. The three E proteins thus define a heterogeneity of AETFC, which improves our understanding of the precise mechanism of leukemogenesis and assists development of diagnostic/therapeutic strategies.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Leucemia Mieloide Aguda/etiologia , Proteínas de Fusão Oncogênica/metabolismo , Proteína 1 Parceira de Translocação de RUNX1/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Leucemia Mieloide Aguda/metabolismo , Recidiva
15.
J Cell Mol Med ; 25(19): 9460-9472, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34464509

RESUMO

Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii-induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii-induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1-dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Regulação da Expressão Gênica , Interações Hospedeiro-Parasita/genética , Fator Regulador 3 de Interferon/metabolismo , Toxoplasma/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Células Cultivadas , Imunofluorescência , Proteína Forkhead Box O1/metabolismo , Humanos , Fator Regulador 3 de Interferon/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Toxoplasmose/genética , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia
16.
Langmuir ; 37(14): 4370-4379, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33792321

RESUMO

Self-propulsion of droplets is of great significance in many fields. The spontaneous horizontal motion and self-jumping of droplets have been well realized in various ways. However, there is still a lack of an effective method to enable a droplet to rotate spontaneously and steadily. In this paper, by employing an acid droplet and a liquid metal, the spontaneous and steady rotation of droplets is achieved. For an acid droplet, it may spontaneously move when it is deposited on the surface of the liquid metal. By adjusting experimental parameters to the proper range, the self-rotation of droplet happens. This phenomenon originates from the fluctuation of the droplet boundary and the collective movement of bubbles that are generated by the chemical reactions between the acid droplet and liquid metal. This rotation has a simpler implementation method and more steady rotation state. Its angular velocity is much higher than that driven by other mechanisms. Moreover, the movements of acid droplets on the liquid metal are classified according to experimental conditions. The internal flow fields, the movements and distribution of bubbles, and the fluctuation of the droplet boundary are also explored and discussed. The theoretical model describing the rotational droplet is given. Our work may deepen the understanding of the physical system transition affected by chemical reactions and provide a new way for the design of potential applications, e.g., micro- and nanodevices.

17.
Connect Tissue Res ; 62(5): 495-507, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32580608

RESUMO

Purpose: Pleiotrophin (PTN) is a heparin-binding growth-associated molecule and expressed in ameloblasts and odontoblasts throughout tooth maturation. Our previous study has shown that PTN expressed more than 20-fold higher in dental tissue than dental stem cells. However, the role of PTN on proliferation and osteo/dentinogenesis of dental pulp stem cells (DPSCs) is unclear. The purpose of the present study was to investigate the role of PTN on the DPSCs' function.Methods: DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) was used to knock down the PTN expression in DPSCs. Real-time RT-PCR, alizarin red staining, quantitative calcium analysis, in vivo transplantation and cell counting kit-8 (CCK8) assay were used to study the function of DPSCs. Possible mechanism was studied by RNA sequencing.Results: After PTN depletion, ALP activity and mineralization ability of DPSCs decreased. Expression of DMP-1 and BSP weakened. Proliferation of DPSCs at 48 h and 72 h was inhibited. Furthermore, 50 pg/mL PTN recombinant protein rescued the impaired osteo/dentinogenic differentiation potential and proliferation ability caused by PTN depletion. In addition, RNA sequencing showed 221 genes were downregulated and 233 genes upregulated in PTN depleted DPSCs. Several genes including BMP2 and IGFBP5 might be associated with PTN function on the DPSCs. P53 and the AMPK signaling pathways were involved. LncRNA analysis displayed 47 significantly upregulated lncRNA and 31 downregulated lncRNA comparing PTN depleted DPSCs with the control.Conclusion: Our research demonstrated that PTN has a positive role in maintaining DPSCs proliferation and osteo/dentinogenic differentiation potential.


Assuntos
Polpa Dentária , Proteínas de Transporte , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Citocinas , Humanos , Osteogênese , RNA Longo não Codificante , Células-Tronco
18.
Korean J Parasitol ; 58(3): 237-247, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32615737

RESUMO

Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.


Assuntos
Células Dendríticas/metabolismo , Interações Hospedeiro-Parasita , NADPH Oxidase 4/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Toxoplasma/fisiologia , Animais , Linhagem Celular , Regulação para Baixo , Humanos , Camundongos
19.
Opt Lett ; 44(23): 5727-5730, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774764

RESUMO

Thermally activated delayed fluorescence (TADF) white organic light-emitting diodes (WOLEDs) with simplified structures have great potential for daily lighting applications. However, the complicated energy and charge transfer processes between TADF emitters impede the development of single-layer white TADF systems. Here we demonstrate high-efficiency WOLEDs with single-emissive layers composed of blue and yellow TADF emitters with appropriate steric hindrances and energy gaps, which optimize the energy transfer from blue to yellow dopants for rational exciton allocation. As a consequence, the single-emissive-layer WOLEDs achieve the maximum external quantum efficiency beyond 20% and small roll-offs, which are among the best results of full-TADF WOLEDs.

20.
J Magn Reson Imaging ; 49(1): 253-261, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29734492

RESUMO

BACKGROUND: The pathological grade of esophageal carcinoma is highly determinant of patient prognosis, but it still cannot be adequately evaluated preoperatively. Compared with conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM) diffusion-weighted MRI can separate true molecular diffusion and perfusion in tissues and has been shown to be useful in characterizing malignant tumors. There is no report that compared IVIM and conventional DWI in grading esophageal carcinoma. PURPOSE: To prospectively determine the diagnostic performance of conventional DWI and IVIM models in differentiating the pathological differentiated grade of esophageal carcinoma. STUDY TYPE: Prospective. POPULATION: A cohort comprising 81 patients with newly diagnosed esophageal squamous cell carcinoma (ESCC) between December 2015 and August 2017 were evaluated. FIELD STRENGTH/SEQUENCE: 3.0T, axial echo-planer imaging, fast spin echo (FSE) sequence, IVIM sequence (b = 0, 20, 50, 80, 100, 150, 200, 400, 600, 800, 1000, 1200). ASSESSMENT: Apparent diffusion coefficient (ADC), true ADC (ADCslow ), pseudo ADC (ADCfast ), and perfusion fraction (f) of each tumor were calculated by two independent radiologists. Histopathologic grade was used as the reference standard. STATISTICAL TESTS: Games-Howell test; diagnostic accuracy; Spearman correlation; intraclass correlation coefficient; and Bland-Altman analysis. Receiver operating characteristics (ROC) curves. RESULTS: ADCslow demonstrated the highest area under curve (AUC) with a value of 0.830 (95% confidence interval [CI]: 0.730-0.904) and 0.816 (95% CI: 0.714-0.893) by two radiologists, followed by ADC with a value of 0.754 (95% CI: 0.646-0.843) and 0.761 (95% CI: 0.653-0.848). Good correlation was obtained between the histologic grade and ADCslow (r(R1) = 0.748, r(R2) = 0.720) and ADC (r(R1) = 0.576, r(R2) = 0.571). DATA CONCLUSION: ADCslow and ADC had a significantly higher performance than the ADCfast and f, and ADCslow had a significantly higher performance than the ADC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:253-261.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Área Sob a Curva , Biópsia , Imagem de Difusão por Ressonância Magnética , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Prognóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes
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