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1.
Small ; 20(22): e2308630, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38100208

RESUMO

Sodium-ion hybrid capacitors (SIHCs) have attracted much attention due to integrating the high energy density of battery and high out power of supercapacitors. However, rapid Na+ diffusion kinetics in cathode is counterbalanced with sluggish anode, hindering the further advancement and commercialization of SIHCs. Here, aiming at conversion-type metal sulfide anode, taking typical VS2 as an example, a comprehensive regulation of nanostructure and electronic properties through NH4 + pre-intercalation and Mo-doping VS2 (Mo-NVS2) is reported. It is demonstrated that NH4 + pre-intercalation can enlarge the interplanar spacing and Mo-doping can induce interlayer defects and sulfur vacancies that are favorable to construct new ion transport channels, thus resulting in significantly enhanced Na+ diffusion kinetics and pseudocapacitance. Density functional theory calculations further reveal that the introduction of NH4 + and Mo-doping enhances the electronic conductivity, lowers the diffusion energy barrier of Na+, and produces stronger d-p hybridization to promote conversion kinetics of Na+ intercalation intermediates. Consequently, Mo-NVS2 delivers a record-high reversible capacity of 453 mAh g-1 at 3 A g-1 and an ultra-stable cycle life of over 20 000 cycles. The assembled SIHCs achieve impressive energy density/power density of 98 Wh kg-1/11.84 kW kg-1, ultralong cycling life of over 15000 cycles, and very low self-discharge rate (0.84 mV h-1).

2.
Exp Dermatol ; 33(1): e15011, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284208

RESUMO

Psoriasis is an immune-mediated inflammatory disease commonly accompanied by various metabolic disorders. It is widely known that biologics could affect the metabolic status and comorbidities in psoriasis patients, however, the effects of biologics on metabolism in psoriasis patients remain poorly understood. The aim of this study was to elucidate the characteristic changes of metabolic profiling in psoriasis vulgaris (PsV) patients before and after applying biologics. Plasma samples were collected from a retrospective cohort of 43 PsV patients. Non-targeted metabolomics analyses were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic profiles before and after applying adalimumab (ADA) or ixekizumab (IXE) for 4 weeks. Additionally, correlation analyses were conducted to investigate the associations between metabolite expression levels and clinical characteristics. The biologics significantly affected the metabolic profiles of PsV patients especially in glycerophospholipids (GPs). First, phosphatidylcholine (PC), unsaturated lysophosphatidylcholine (LPC), unsaturated lysophosphatidic acid (LPA) and unsaturated lysophosphatidylethanolamine (LPE) were significantly up-regulated, whereas phosphatidylethanolamine (PE), saturated LPC, saturated LPA and saturated LPE were predominantly down-regulated after biologic treatment. What is more, the changes in PE and LPA were mainly observed after applying IXE instead of ADA. Second, we also found GPs including PC, unsaturated LPC, unsaturated LPA and unsaturated LPE were primarily negatively correlated with disease severity, whereas, PE, saturated LPC, saturated LPA and saturated LPE displayed inverse correlations. Biologics could affect GP metabolism and facilitate the transition of metabolic status from a pro-inflammatory to an anti-inflammatory phenotype in PsV patients.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Estudos Retrospectivos , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Fosfatidilcolinas , Produtos Biológicos/uso terapêutico
3.
J Rheumatol ; 51(7): 678-681, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490673

RESUMO

OBJECTIVE: To determine the minimal important change (MIC) and meaningful change value (MCV) of the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the effect size (ES) of DAPSA. METHODS: This was a retrospective cohort study, recruiting 106 patients who agreed to participate in the research from the Department of Dermatology, Xiangya Hospital, between November 1, 2019, and April 1, 2023. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs of the DAPSA. The anchor question assessed whether the patient's well-being had changed since their previous visit, employing a 5-point Likert scale that ranged from "much improved" to "much deteriorated." RESULTS: The overall MIC value was 8.4 (95% CI 0.01-16.75). The MIC improvement was 9.5 (95% CI 0.89-18.14) and MIC deterioration was 1.1 (95% CI -9.81 to 12.05). The overall MCV was 10.5 (95% CI 4.34-16.72). MCV improvement was 11.4 (95% CI 5.95-16.95) and MCV deterioration was 1.1 (95% CI -9.81 to 12.05). The ES was 0.6. CONCLUSION: A change in DAPSA of 8.4 is indicative of an MIC, offering physicians an additional means to contextualize the patient's perception of disease activity during treatment, and a change in DAPSA of 10.5 is likely to be regarded as MCV. These values can enhance the utility of DAPSA in psoriatic arthritis clinical trials.


Assuntos
Artrite Psoriásica , Índice de Gravidade de Doença , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Psoriásica/diagnóstico , China , População do Leste Asiático , Estudos Longitudinais , Diferença Mínima Clinicamente Importante , Estudos Retrospectivos
4.
Hum Mol Genet ; 31(1): 57-68, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34346496

RESUMO

Ogt-mediated O-GlcNAcylation is enriched in the nervous system and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis have remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Ogt depletion in cultured hippocampal neurons impairs neuronal maturation, including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/ß-catenin signaling. Ectopic ß-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.


Assuntos
N-Acetilglucosaminiltransferases , beta Catenina , Animais , Humanos , Mamíferos , N-Acetilglucosaminiltransferases/genética , Neurogênese/genética , Neurônios , beta Catenina/genética
5.
Opt Express ; 31(4): 6327-6341, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36823892

RESUMO

To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

6.
Proc Natl Acad Sci U S A ; 117(14): 7755-7763, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32193337

RESUMO

Methionine metabolism is critical for the maintenance of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) pluripotency. However, little is known about the regulation of the methionine cycle to sustain ESC pluripotency. Here, we show that adenosylhomocysteinase (AHCY), an important enzyme in the methionine cycle, is critical for the maintenance and differentiation of mouse embryonic stem cells (mESCs). We show that mESCs exhibit high levels of methionine metabolism, whereas decreasing methionine metabolism via depletion of AHCY promotes mESCs to differentiate into the three germ layers. AHCY is posttranslationally modified with an O-linked ß-N-acetylglucosamine sugar (O-GlcNAcylation), which is rapidly removed upon differentiation. O-GlcNAcylation of threonine 136 on AHCY increases its activity and is important for the maintenance of trimethylation of histone H3 lysine 4 (H3K4me3) to sustain mESC pluripotency. Blocking glycosylation of AHCY decreases the ratio of S-adenosylmethionine versus S-adenosylhomocysteine (SAM/SAH), reduces the level of H3K4me3, and poises mESC for differentiation. In addition, blocking glycosylation of AHCY reduces somatic cell reprogramming. Thus, our findings reveal a critical role of AHCY and a mechanistic understanding of O-glycosylation in regulating ESC pluripotency and differentiation.


Assuntos
Metionina/metabolismo , Células-Tronco Pluripotentes/metabolismo , Adenosil-Homocisteinase/metabolismo , Animais , Autorrenovação Celular , Reprogramação Celular , Glicosilação , Células HEK293 , Humanos , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Células NIH 3T3
7.
Molecules ; 28(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37959812

RESUMO

The physical properties and nutritional quality of H. marmoreus by-products (HMB) dried by different methods were comprehensively evaluated by a rigorous statistical method of grey correlation analysis. The results indicated that different drying methods had significant impacts on the characteristics of HMB. Heat pump drying (HPD) was conducive to the preservation of protein and reducing sugar, and hot air drying (HAD) maintained a high content of total flavonoids. The highest fat, polysaccharide, and total phenolic contents were obtained by heated vacuum freeze-drying (H-VFD) treatment. The unheated vacuum freeze-drying (UH-VFD) treatment achieved bright colour, lacunose texture profile, and looser organization structure. The grey correlation analysis showed that UH-VFD and H-VFD had higher-weighted correlation degrees than HPD and HAD. HMB had many higher nutritional components than commodity specifications, especially protein, fat, polyphenols, and amino acids, and had potential applications in the food industry as functional foods and nutraceutical agents.


Assuntos
Agaricales , Animais , Dessecação/métodos , Liofilização/métodos , Proteínas
8.
Hum Mol Genet ; 29(5): 727-735, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-31751468

RESUMO

N 6-methyladenosine (m6A) modification of RNA is deposited by the methyltransferase complex consisting of Mettl3 and Mettl14 and erased by demethylase Fto and Alkbh5 and is involved in diverse biological processes. However, it remains largely unknown the specific function and mechanism of Fto in regulating adult neural stem cells (aNSCs). In the present study, utilizing a conditional knockout (cKO) mouse model, we show that the specific ablation of Fto in aNSCs transiently increases the proliferation of aNSCs and promotes neuronal differentiation both in vitro and in vivo, but in a long term, the specific ablation of Fto inhibits adult neurogenesis and neuronal development. Mechanistically, Fto deficiency results in a significant increase in m6A modification in Pdgfra and Socs5. The increased expression of Pdgfra and decreased expression of Socs5 synergistically promote the phosphorylation of Stat3. The modulation of Pdgfra and Socs5 can rescue the neurogenic deficits induced by Fto depletion. Our results together reveal an important function of Fto in regulating aNSCs through modulating Pdgfra/Socs5-Stat3 pathway.


Assuntos
Células-Tronco Adultas/citologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/fisiologia , Diferenciação Celular , Proliferação de Células , Células-Tronco Neurais/citologia , Neurogênese , Células-Tronco Adultas/metabolismo , Animais , Metiltransferases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neurais/metabolismo
9.
Hum Mol Genet ; 29(16): 2775-2787, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32766784

RESUMO

Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.


Assuntos
Adenosina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Lipídeos/genética , Neurogênese/genética , Neurônios/metabolismo , Adenosina/genética , Adipócitos/metabolismo , Células-Tronco Adultas/metabolismo , Animais , Encéfalo/metabolismo , Proliferação de Células/genética , Humanos , Aprendizagem/fisiologia , Memória/fisiologia , Camundongos , Camundongos Knockout , Células-Tronco Neurais/metabolismo
10.
Opt Express ; 30(17): 31322-31335, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36242217

RESUMO

Although the method of inserting colloidal quantum dots (QDs) into deep nano-holes fabricated on the top surface of a light-emitting diode (LED) has been widely used for producing effective Förster resonance energy transfer (FRET) from the LED quantum wells (QWs) into the QDs to enhance the color conversion efficiency, an important mechanism for enhancing energy transfer in such an LED structure was overlooked. This mechanism, namely, the nanoscale-cavity effect, represents a near-field Purcell effect and plays a crucially important role in enhancing the color conversion efficiency. Here, we demonstrate the results of LED performance, time-resolved photoluminescence (TRPL), and numerical simulation to elucidate the nanoscale-cavity effect on color conversion by inserting a photoresist solution of red-emitting QDs into the nano-holes fabricated on a blue-emitting QW LED. Based on the TRPL study of the inserted QDs in a nano-hole structure fabricated on an un-doped GaN template of no QW, it is found that the emission efficiency of the inserted QDs is significantly increased due to the nanoscale-cavity effect. From the simulation study, it is confirmed that this effect can also increase the FRET efficiency, particularly for those radiating dipoles in the QWs oriented perpendicular to the sidewalls of the nano-holes. In the nanoscale-cavity effect, the enhanced near field distribution inside a nano-hole excited by a light emitter modifies its own radiation behavior through the Purcell effect such that its far-field emission becomes stronger.

11.
Dermatology ; 238(2): 368-376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515096

RESUMO

BACKGROUND: Quick and accurate diagnosis of primary cutaneous amyloidosis (PCA) may be difficult because its symptoms are often subtle and nonspecific. OBJECTIVE: We sought to review the literature on the roles of various staining methods in the diagnosis of amyloidosis and demonstrate added benefits of using rapid 4,6-diamidino-2-phenylindole (DAPI) staining in the diagnosis of PCA. METHODS: Three groups of cases, namely, PCA, neurodermatitis, and prurigo nodularis, were retrieved from a computerized pathology database for study, and their paraffin-embedded tissue blocks were cut following standard procedures. The tissue sections were stained with three stains: hematoxylin-eosin (HE), Congo red, and DAPI stains, and examined under the microscope to compare the staining patterns of these three methods. We also performed amyloid keratin and apolipoprotein E (APOE) staining on the sections of PCA in order to further support our conclusion. The PCA sections were read by junior and senior dermatopathologists for comparison. RESULTS: The sensitivity of DAPI staining for PCA was significantly higher than that of Congo red staining and HE staining (p < 0.001). This statement holds true whether the experiment was grouped in one sample or was divided into groups of junior and senior dermatopathologists (p < 0.001). The DAPI-positive staining areas, except for the nuclei, were consistent with the amyloid deposition areas. In this study, DAPI staining had a sensitivity of 98.6% and a specificity of 100%. CONCLUSION: DAPI staining could serve as a useful technique to establish the diagnosis of PCA, and its high efficacy in diagnosing PCA makes it less dependent on the experience levels of the evaluators. Additionally, the binding of DAPI to the A-T-rich sequence of double-stranded DNA suggests that amyloid may contain DNA or a similarly structured nucleic acid.


Assuntos
Amiloidose , Indóis , Amiloidose/diagnóstico , Amiloidose/metabolismo , Amiloidose/patologia , Vermelho Congo , Humanos , Coloração e Rotulagem
12.
Molecules ; 27(6)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35335322

RESUMO

In this paper, we first elaborate on the effects of surface plasmon (SP) coupling on the modulation responses of the emission of a light-emitting diode (LED) and its down-converted lights through colloidal quantum dots (QDs). The results of our past efforts for this subject are briefly discussed. The discussions lay the foundation for the presentation of the new experimental data of such down-converted lights in this paper. In particular, the enhancement of the modulation bandwidth (MB) of a QD-based converted light through SP coupling is demonstrated. By linking green-emitting QDs (GQDs) and/or red-emitting QDs (RQDs) with synthesized Ag nano-plates via surface modifications and placing them on a blue-emitting LED, the MBs of the converted green and red emissions are significantly increased through the induced SP coupling of the Ag nano-plates. When both GQD and RQD exist and are closely spaced in a sample, the energy transfer processes of emission-reabsorption and Förster resonance energy transfer from GQD into RQD occur, leading to the increase (decrease) in the MB of green (red) light. With SP coupling, the MB of a mixed light is significantly enhanced.


Assuntos
Pontos Quânticos , Transferência Ressonante de Energia de Fluorescência , Luz
13.
PLoS Biol ; 16(8): e2005354, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30169503

RESUMO

Leptin is a well-known adipokine that plays a critical role in immune responses. To further explore the immunological roles of leptin, we developed a transgenic leptin pig controlled by the pig leptin (pleptin) promoter to overexpress leptin. Symptoms typically associated with systemic lupus erythematosus (SLE) were evident in this transgenic pig strain, including anemia, leukopenia, and thrombocytopenia as well as kidney and liver impairment. Histologically, there were increased immunoglobulin G (IgG) levels, elevated antiplatelet antibody (APA) levels, and deposition of immune complexes in the kidney and liver. In addition, anti-double-stranded DNA antibodies (dsDNAs), antinuclear antibodies (ANAs), and antinucleosome antibodies (ANuAs) were all significantly increased in serum immunological examinations. These findings were also accompanied by repression of the regulatory T cell (Treg) ratio. Significantly, glucocorticoid experimental therapies partially relieved the autoimmune responses and bleeding symptoms observed in these transgenic leptin pigs. Together, these results indicate that leptin plays a critical role in the development of autoimmune disorders and demonstrate that our transgenic leptin pigs can act as a valuable model of SLE.


Assuntos
Leptina/imunologia , Leptina/fisiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Animais , Animais Geneticamente Modificados/fisiologia , Anticorpos Antinucleares/sangue , Complexo Antígeno-Anticorpo , Autoimunidade , Modelos Animais de Doenças , Imunoglobulina G/genética , Leptina/metabolismo , Nucleossomos , Regiões Promotoras Genéticas/genética , Suínos , Linfócitos T Reguladores/imunologia
14.
Arch Gynecol Obstet ; 303(3): 767-775, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011886

RESUMO

OBJECTIVE: The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. METHODS: Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan-Meier method and log-rank test. RESULTS: 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050-2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7 months in patients with preoperative HCT ≥ 35% and 61.7 months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65 years, BMI ≥ 25.0 kg/m2, ascites volume ≤ 500 mL, ASA score < 3, albumin ≥ 35 g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110 g/mL), low albumin (< 35 g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. CONCLUSIONS: Preoperative low HCT was a valuable predictor for EOC patients' poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.


Assuntos
Biomarcadores/sangue , Carcinoma Epitelial do Ovário/sangue , Hematócrito/estatística & dados numéricos , Neoplasias Ovarianas/sangue , Adulto , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Hematócrito/métodos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida
15.
J Surg Oncol ; 122(6): 1207-1217, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32705686

RESUMO

OBJECTIVE: We aimed to evaluate the ability of the fluorescent monoclonal antibody probe COC183B2-Cy7 (Cy7-conjugated COC183B2 antibody) to detect tiny metastatic lesions of ovarian cancer and thus guide precise tumor resection. METHODS: The expression of the tumor-associated antigen OC183B2 in lymph nodes and SKOV3-Luc cells was detected using immunohistochemistry and immunofluorescence. A subcutaneous mouse tumor model and an intraperitoneal ovarian cancer metastasis model were constructed using SKOV3-Luc cells. Near-infrared fluorescence (NIRF) imaging was performed to determine the imaging parameters and evaluate the ability of COC183B2-Cy7 to detect tiny metastatic lesions. RESULTS: OC183B2 was expressed in metastatic lymph nodes and SKOV3-Luc cells. NIRF imaging of the subcutaneous mouse tumor model showed that the tumor background ratio was significantly higher in the COC183B2-Cy7 group than in the control group at different time points postinjection. Biodistribution study showed that COC183B2-Cy7 did not accumulate in other organs. COC183B2-Cy7 can detect tiny metastatic lesions of ovarian cancer. The smallest intraperitoneal metastatic tumor detected by COC183B2-Cy7 was approximately 1 mm. CONCLUSIONS: COC183B2-Cy7 probe has relatively high specificity and sensitivity. Our study suggests that COC183B2-Cy7 probe is a promising diagnostic tool for the complete and accurate resection of malignant lesions in fluorescence-guided surgery.


Assuntos
Anticorpos Monoclonais/imunologia , Fluorescência , Corantes Fluorescentes/farmacocinética , Imagem Óptica/métodos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Cirurgia Assistida por Computador/métodos , Animais , Antígenos de Neoplasias/imunologia , Apoptose , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/cirurgia , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
World J Surg Oncol ; 18(1): 66, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252772

RESUMO

BACKGROUND: To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS: The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS: In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS: COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.


Assuntos
Anticorpos Antineoplásicos/imunologia , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Corantes Fluorescentes , Neoplasias Ovarianas/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Animais , Antígenos de Neoplasias/análise , Carcinoma Epitelial do Ovário/imunologia , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia
17.
J Allergy Clin Immunol ; 144(4): 1025-1035.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31251950

RESUMO

BACKGROUND: Fc receptor γ subunit (FcRγ)-related receptors expressed on antigen-presenting cells (APCs) enhance allergen sensitization and allergic inflammation. DNA demethylation of the high-affinity IgE receptor γ subunit gene (FCER1G) leads to FcRγ and FcεRI overexpression on monocytes from patients with atopic dermatitis. OBJECTIVE: We investigated epigenetic mechanisms underlying FCER1G demethylation and upregulation of FcRγ-related receptors on APCs and the consequent effect on allergic responses. METHODS: Effects of thymic stromal lymphopoietin (TSLP) on expression of FcRγ and its related receptors and methylation or hydroxymethylation of FCER1G in human monocytes were assessed. Recruitment of ten-eleven translocation protein (TET) 2 to FCER1G by TSLP-activated phosphorylated signal transducer and activator of transcription 5 (pSTAT5) was evaluated. Effects of TSLP on expression of FcRγ-related receptors and costimulatory receptors on monocyte-derived dendritic cells (DCs) and the ability of DCs to take up ovalbumin were analyzed. TSLP-induced TH polarization and related cytokine production were also analyzed. RESULTS: pSTAT5 activation by TSLP resulted in TET2 recruitment to FCER1G, leading to FCER1G demethylation and subsequent upregulation of FcRγ-related receptors on monocytes. TSLP not only stimulated monocyte-derived DC maturation but also maintained their allergen uptake ability, likely through maintenance and upregulation of FcRγ-related receptors. Allergen sensitization and upregulation of TH2/TH17-related cytokines contributed to TSLP-DC-induced TH2/TH17 polarization. The latter was attenuated on neutralization with a dectin-2 antibody. CONCLUSIONS: TSLP mediated upregulation of FcRγ-related receptors on APCs through activation of pSTAT5, which recruited TET2 to induce FCER1G demethylation. TSLP-induced allergic TH2/TH17 polarization likely depends on dectin-2-mediated allergen sensitization and upregulation of TH2/TH17-related cytokines.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Citocinas/imunologia , Dermatite Atópica/imunologia , Lectinas Tipo C/imunologia , Receptores Fc/biossíntese , Citocinas/metabolismo , Metilação de DNA , Dermatite Atópica/metabolismo , Epigênese Genética , Humanos , Receptores Fc/imunologia , Transdução de Sinais/imunologia , Células Th17/imunologia , Células Th2/imunologia , Ativação Transcricional/imunologia , Regulação para Cima
18.
Hum Mol Genet ; 26(13): 2398-2411, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28398475

RESUMO

Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of adult neural stem cells in vivo, which leads to impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we went on to perform genome-wide m6A profiling and observed dynamic m6A modification during postnatal neurodevelopment. The loss of FTO led to the altered expression of several key components of the brain derived neurotrophic factor pathway that were marked by m6A. These results together suggest FTO plays important roles in neurogenesis, as well as in learning and memory.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Neurogênese/genética , Animais , Peso Corporal/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular/genética , Regulação da Expressão Gênica , Memória , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Obesidade/genética
19.
Exp Dermatol ; 28(2): 198-201, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30480843

RESUMO

Psoriasis is a common chronic disease with accelerated epidermal cell growth. Solute carrier family 2 member 1 (SLC2A1), also named GLUT1, transports glucose and its analogues into cells. With elevated membrane-bound GLUT1, psoriatic keratinocytes uptake more glucose with increased glucose metabolism. Competition between glucose and its analogues can serve as a strategy to inhibit glycolysis as well as proliferation. In this study, we investigated the expression patterns of GLUT1 in keratinocytes in the human psoriasis vulgaris and imiquimod-induced psoriasis model, and determined that the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG) can relieve the psoriatic lesions. We found membrane-enriched GLUT1 in psoriasis keratinocytes, which suggested some potential for glucose metabolic target therapy based on the glycolytic microenvironment. Furthermore, 2-DG was able to relieve the psoriatic lesions in an in vivo animal model which provides a new possible therapeutic strategy.


Assuntos
Desoxiglucose/farmacologia , Transportador de Glucose Tipo 1/metabolismo , Queratinócitos/metabolismo , Psoríase/metabolismo , Animais , Transporte Biológico , Membrana Celular/metabolismo , Proliferação de Células , Células Epidérmicas/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glicólise , Humanos , Queratinócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Resultado do Tratamento
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