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1.
J Agric Food Chem ; 72(7): 3302-3313, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38330904

RESUMO

Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, NMN biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, and efficiency, positioning it as a primary avenue for future NMN synthesis. Enzymatic NMN synthesis encompasses the nicotinamide-initial route and nicotinamide ribose-initial routes. Key among these is nicotinamide riboside kinase (NRK), pivotal in the latter route. The NRK-mediated biosynthesis is emerging as a prominent trend due to its streamlined route, simplicity, and precise specificity. The essential aspect is to obtain an engineered NRK that exhibits elevated activity and robust stability. This review comprehensively assesses diverse NMN synthesis methods, offering valuable insights into efficient, sustainable, and economical production routes. It spotlights the emerging NRK-mediated biosynthesis pathway and its significance. The establishment of an adenosine triphosphate (ATP) regeneration system plays a pivotal role in enhancing NMN synthesis efficiency through NRK-catalyzed routes. The review aims to be a reference for researchers developing green and sustainable NMN synthesis, as well as those optimizing NMN production.


Assuntos
Trifosfato de Adenosina , Mononucleotídeo de Nicotinamida , Mononucleotídeo de Nicotinamida/metabolismo , Trifosfato de Adenosina/metabolismo , Biocatálise , NAD/metabolismo
2.
Int J Ophthalmol ; 17(1): 82-91, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38239947

RESUMO

AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.

3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2105-2120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37782380

RESUMO

Bacoside A (gypenoside, Gyp) is a potent bioactive compound derived from Gynostemma pentaphyllum, known to exert inhibitory effects on various malignant tumors. However, the effects of Gyp on glioma as well as the underlying mechanisms remain unclear. In the present study, we first conducted a comprehensive investigation into the anti-glioma potential of gypenosides using network pharmacology to identify potential glioma-related targets. Protein-protein interaction networks were assembled, and GO and KEGG enrichment analyses were performed for shared targets. Experimental validation involved assessing the viability of U251 and U87 cell lines using the MTS method. Furthermore, trans-well and scratch migration assays evaluated the cell migration, while flow cytometry and Hoechst 33342 staining were utilized for apoptosis assessment. The study also monitored changes in autophagy flow through fluorescence microscopy. The expression levels of proteins pertinent to migration, apoptosis, and autophagy were tested using Western blotting. Findings revealed that Gyp upregulated apoptosis-related proteins (Bax and cleaved caspase-9), downregulated anti-apoptotic protein Bcl-2, and migration-associated matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, autophagy-related proteins (Beclin1 and LC3 II) were upregulated, and p62 protein expression was downregulated. Gyp displayed considerable potential in suppressing glioma progression by inhibiting cell proliferation, invasion, and migration and promoting apoptosis and autophagy. Gyp may offer potential clinical therapeutic choices in glioma management.


Assuntos
Apoptose , Glioma , Saponinas , Triterpenos , Humanos , Glioma/tratamento farmacológico , Glioma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células , Autofagia , Linhagem Celular Tumoral
4.
Front Pharmacol ; 11: 560543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362537

RESUMO

Gliomas are the most fatal malignant cerebral tumors. Temozolomide (TMZ), as the primary chemotherapy drug, has been widely used in clinics. However, resistance of TMZ still remains to poor defined. LncRNAs have been reported to play crucial roles in progression of various cancers and resistance of multiple drugs. However, the biological function and underlying mechanisms of most lncRNAs in glioma still remains unclear. Based on the TCGA database, a total of 94 differentially expressed lncRNAs, including 16 up-regulated genes and 78 downregulated genes were identified between gliomas and normal brain tissues. Subsequently, lncRNA DLEU1, HOTAIR, and LOC00132111 were tested to be significantly related to overall survival (OS) between high- and low-expression groups. Additionally, we verified that lncRNA DLEU1 was high expressed in 108 gliomas, compared with 19 normal brain tissues. And high expression of lncRNA DLEU1 predicted a poor prognosis (HR = 1.703, 95%CI: 1.133-2.917, p-value = 0.0159). Moreover, functional assays revealed that knockdown of lncRNA DLEU1 could suppress the proliferation by inducing cell cycle arrest at G1 phase and reducing the S phase by down-regulating the CyclinD1 and p-AKT, as the well as migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) markers, such as ZEB1, N-cadherin, ß-catenin and snail in glioma cells. Furthermore, silencing lncRNA DLEU1 suppressed TMZ-activated autophagy via regulating the expression of P62 and LC3, and promoted sensitivity of glioma cells to TMZ by triggering apoptosis. Conclusively, our study indicated that lncRNA DLEU1 might perform as a prognostic potential target and underlying therapeutic target for sensitivity of glioma to TMZ.

5.
Front Oncol ; 10: 536875, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134160

RESUMO

Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.

6.
Mol Pharm ; 13(9): 2881-90, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27089240

RESUMO

The wet form of age-related macular degeneration (AMD) is a leading cause of blindness among elderly Americans and is characterized by abnormal vessel growth, termed choroidal neovascularization (CNV). Integrin α5ß1 is a transmembrane receptor that binds matrix macromolecules and proteinases to stimulate angiogenesis. We recently demonstrated that integrin α5ß1 plays a critical role in the development of choroidal neovascularization. In this study, we determined the role and underlying mechanisms of integrin α5ß1 in angiogenesis in human choroidal endothelial cells and evaluated the antiangiogenic effects of delivering a combination therapy of ATN-161, an integrin α5ß1 inhibitor, and an anti-VEGF monoclonal antibody to rats with laser-induced CNV. Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates vasculogenesis and angiogenesis through a pathway that is distinct from the integrin α5ß1 signaling pathway. Our results indicate that fibronectin binds to integrin α5ß1 and synergizes VEGF-induced angiogenesis via two independent signaling pathways, FN/integrin α5ß1/FAK/ERK1/2 and FN/integrin α5ß1/FAK/AKT. Integrin α5 knockdown by shRNA inhibits endothelial cell migration, tube formation, and proliferation, while ATN-161 only partially decreases integrin α5 function. Treatment with ATN-161 combined with anti-VEGF antibody showed joint effects in attenuating angiogenesis. In summary, our results provide the first evidence for the mechanisms by which integrin α5ß1 is involved in ocular pathological neovascularization in vivo, suggesting that dual inhibition of integrin α5ß1 and VEGF may be a promising novel therapeutic strategy for CNV in wet AMD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Integrina alfa5beta1/metabolismo , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Anticorpos Monoclonais/imunologia , Western Blotting , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neovascularização de Coroide/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Fibronectinas/metabolismo , Imunofluorescência , Masculino , Ligação Proteica , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
BMC Pregnancy Childbirth ; 16: 87, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27113723

RESUMO

BACKGROUND: Infection with hepatitis B virus (HBV) in pregnant women may be a threat for both mothers and fetuses. This study was performed to explore the impact of maternal HBV carrier status on pregnancy outcomes. METHODS: We conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University between January 1, 2012 and September 30, 2015. A consecutive sample of 21,004 pregnant women, 513 asymptomatic HBV carriers and 20,491 non-HBV controls, was included in this study. The main outcomes of interest were selected pregnancy outcomes including miscarriage, stillbirth, preterm birth (PTB), gestational diabetes (GDM), intrahepatic cholestasis of pregnancy (ICP), preterm premature rupture of the membrane (PPROM), low birth weight (LBW), small for gestational age (SGA) and Apgar scores. The incidence of adverse pregnancy outcomes between asymptomatic HBV carriers and non-HBV controls were compared using the chi-square test and logistic regression. P values were two sided, and P <0.05 was considered to indicate statistical significance. RESULTS: The incidences of stillbirth, PTB, GDM, ICP, PPROM, LBW, and SGA were similar between the HBV carrier and non-HBV groups. The proportion of miscarriage was significantly higher among the HBV carriers than the controls (9.36% vs 5.70%; P <0.001). After using multivariate modelling to adjust for possible socio-demographical variables and obstetric complications, women with HBV carrier status were still more likely to have miscarriage (adjusted OR 1.71, 95% CI 1.23-2.38). In addition, the incidences of other maternal and neonatal outcomes were similar between the two groups. CONCLUSION: Maternal HBV carrier status may be an independent risk factor for miscarriage and careful surveillance is warranted.


Assuntos
Vírus da Hepatite B , Hepatite B/complicações , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/virologia , Adulto , Índice de Apgar , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Colestase Intra-Hepática/epidemiologia , Colestase Intra-Hepática/virologia , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/virologia , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Ruptura Prematura de Membranas Fetais/virologia , Hepatite B/virologia , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/virologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , Estudos Prospectivos , Fatores de Risco , Natimorto/epidemiologia
8.
Curr Eye Res ; 41(3): 318-25, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25860821

RESUMO

PURPOSE: To compare the effectiveness of two isolation systems for stemness, proliferation and mesenchymal contamination of ex vivo cultured limbal epithelial cells (LECs). METHODS: Whole explant and dispase digestion methods were used to isolate LECs. For whole explant isolation, one limbal explant was cultivated up to four consecutive times (through LEC1 to LEC4). The performance of LECs isolated with both systems was evaluated according to the following parameters: immunofluorescent staining for adenosine 5'-triphosphate-binding cassette member 2 (ABCG2), p63, cytokeratin 3 (K3), Ki67, and vimentin, and flow cytometry analysis for ABCG2, Ki67 and vimentin. RESULTS: Twelve LEC cultures were established using whole explant isolation, and nine LEC cultures were established using dispase digestion isolation. In immunofluorescent staining analysis, the ABCG2, p63 and Ki67 expressions were higher in LECs isolated with dispase compared to any LECs isolated with explant. Only the differences in ABCG2 and Ki67 were statistically significant. Further, LEC4 isolated with explant had the highest percentage of cells positive for vimentin, and LEC1 had the highest percentage of cells positive for K3. However, no significant differences were detected. In flow cytometry analysis, the expressions of ABCG2 and Ki67 were statistically higher for LECs isolated with dispase compared to any LECs isolated with explant. CONCLUSION: Dispase digestion isolation technique was significantly superior to explant isolation techniques in terms of progenitor and proliferative cell contents.


Assuntos
Separação Celular/métodos , Epitélio Corneano/citologia , Limbo da Córnea/citologia , Técnicas de Cultura de Órgãos , Proteólise , Células-Tronco/citologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Endopeptidases/farmacologia , Epitélio Corneano/metabolismo , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Antígeno Ki-67/metabolismo , Limbo da Córnea/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Vimentina/metabolismo , Adulto Jovem
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(4): 1216-20, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26314477

RESUMO

Aplastic anemia is a disease characterized by low bone marrow hematopoietic function and derease of whole blood cells caused by a variety of reasons. Its pathogenesis includes abnormality of hematopoietic stem cells (seed theory), hematopoietic microenvironment (soil theory) and immune function (such as worms theory). These 3 causes of disease interact each other and facilitate the development of aplastic anemia, thereby increase the complexity of the etiological diagnosis and uncertainty of treatment. On this basis, this review summarizes the latest research progress on the blood supply of bone marrow microcirculation in the hematopoietic microenvironment, stromal cells, cytokins, the immune function of dendritic cells, natural killer cells, T cell subgroup, the secretion of cytokines, cell signal transduction, and hematopoietic stem cell gene abnormality to provides the theoretic basis for the diagnosis and treatment of aplastic anemia.


Assuntos
Anemia Aplástica , Medula Óssea , Citocinas , Células-Tronco Hematopoéticas , Humanos
10.
Chin Med J (Engl) ; 128(9): 1154-9, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25947396

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the older population. In China, treatment of age-related ocular diseases is becoming a priority in eye care services. This study was to investigate the clinical characteristics and quality of life of Chinese patients with wet AMD and current treatment types, to evaluate short-term gains in different treatments, and to investigate associations between visual function and vision-related quality of life (VRQoL). METHODS: A prospective, observational, noninterventional study was conducted. Basic data were collected from patients with clinical diagnoses of wet AMD before clinical assessments at baseline. VRQoL was measured with the Chinese version of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Correlations of the NEI VFQ-25 subscale scores with best-corrected visual acuity (BCVA) and between-group differences were analyzed. RESULTS: A total of 80 wet AMD patients were enrolled, with the mean age of 68.40 years. About one-quarter of wet AMD patients received intravitreal (IVT) ranibizumab treatment, and 67% of them were treated on a pro re nata basis. The visual acuity of patients treated with IVT ranibizumab at month 3 after treatment was significantly increased, whereas patients treated with traditional Chinese medicine achieved no significant improvement. Cronbach's α for the NEI VFQ-25 subscales ranged from 0.697 to 0.843. Eight subscale and overall composite scores were moderately correlated with the BCVA of the better-seeing eye. Significant differences in the overall NEI VFQ-25 scores and other subscales were observed between patients with BCVA in the better-seeing eye of less than 50 letters and the others. CONCLUSIONS: Patients treated with IVT ranibizumab experienced better vision improvement at short-term follow-up. The Chinese version of the NEI VFQ-25 is a valid and reliable tool for assessing the VRQoL of Chinese wet AMD patients.


Assuntos
Degeneração Macular/fisiopatologia , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/fisiopatologia
11.
Am J Ophthalmol ; 156(1): 106-115.e2, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23791371

RESUMO

PURPOSE: To compare safety and functional outcomes of vitrectomy with or without preoperative intravitreal bevacizumab (IVB) for proliferative diabetic retinopathy (PDR). DESIGN: A meta-analysis of randomized controlled trials. METHODS: PubMed, Medline, EMBASE, and Cochrane Controlled Trials Register were searched to identify potentially relevant randomized controlled trials. A total of 394 participants with 414 eyes in 8 trials were analyzed using RevMan 5.1 software. The primary measures included intraoperative bleeding, total surgical time, and early and late recurrent hemorrhage. RESULTS: Vitrectomy with IVB pretreatment achieved shorter overall surgical time (mean difference = -26.89 minutes, 95% confidence interval [CI] -31.38 to -22.39, P < .00001) and smaller number of endodiathermy applications (mean difference = -3.46, 95% CI -6.43 to -0.49, P = .02) compared to vitrectomy alone. The IVB group was also associated with less intraoperative bleeding (odds ratio [OR] = 0.10; 95% CI 0.02 to 0.46; P = .003) and recurrent vitreous hemorrhage within first month (OR = 0.35; 95% CI 0.21 to 0.58; P < .0001), but the proportion of recurrent vitreous hemorrhage after the first month was comparable between both groups. There were no significant differences in other complication rates between the 2 groups, with the exception of iatrogenic retinal break, which was more likely with the vitrectomy-alone group (OR = 0.27, 95% CI 0.12 to 0.63, P = .003). Results were robust to sensitivity analyses. CONCLUSIONS: Adjuvant intravitreal injection of bevacizumab prior to vitrectomy in PDR patients significantly eased the procedure, diminished intraoperative complications, and reduced early postoperative hemorrhage without increasing the risk of vision-threatening complications. Further trials should determine the optimal interval and dosage for IVB injection.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Retinopatia Diabética/terapia , Vitrectomia , Bevacizumab , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Humanos , Complicações Intraoperatórias , Injeções Intravítreas , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
12.
Zhonghua Yi Xue Za Zhi ; 93(7): 524-7, 2013 Feb 19.
Artigo em Chinês | MEDLINE | ID: mdl-23660322

RESUMO

OBJECTIVE: To investigate the changes and relation between macular morphology and macular visual function in different degrees of diabetic macular edema. METHODS: Seventy-eight eyes of 41 diabetic retinopathy patients were included and graded for diabetic macular edema as follows:31 were graded as no macular edema (NE), 26 as non-clinically significant macular edema (NCSME), and 21 as clinically significant macular edema (CSME). Best corrected visual acuity, macular sensitivity, and macular thickness of all included eyes were examed and quantified. Macular sensitivity and retinal fixation were investigated with MP-1 microperimetry. Optical coherence tomography (OCT) was used to quantify macular thickness. RESULTS: Macular thickness significantly increased and macular sensitivity markedly decreased from the NE to the CSME group (P < 0.01), Visual acuity obviously decreased in the CSME group (P < 0.01) compared to the NE and NCSME group, but there was no statistical difference between the NE group and NCSME group. Retinal fixation type was not significantly different among three groups. Visual acuity and macular sensitivity correlated significantly in these three groups (r = -0.751, P < 0.01; r = -0.583, P < 0.01; r = -0.679, P < 0.01). The correlations were noted between retinal sensitivity and macular thickness as well as between visual acuity and macular thickness in the CSME group (r = -0.465, P < 0.05; r = 0.599, P < 0.01), but not in the NE group or in the NCSME group. CONCLUSIONS: Patients will have retinal morphologic and functional changes in early stage of DME, both of which are significantly related as the disease develops. MP-1 microperimetry proved to be consistent with VA in the evaluation of visual function, and may be more sensitive to investigate the changes of macular visual function in the early stage of macular edema.


Assuntos
Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Edema Macular/patologia , Edema Macular/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/patologia , Retinopatia Diabética/complicações , Feminino , Humanos , Macula Lutea/patologia , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
13.
Eur J Immunol ; 43(4): 1034-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23322406

RESUMO

Ag receptor engagement triggers lymphocyte activation and proliferation by activating several transcription factors including NF-κB. Caspase recruitment domain (CARD) containing membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) is an essential adaptor protein that links Ag receptors to NF-κB activation. Here, we identify stress-induced-phosphoprotein 1 homology and U-box containing protein 1 (STUB1) as a CARMA1-associated protein. STUB1 constitutively interacted with CARMA1, and the interaction was intensified by TCR stimulation. Downregulation of STUB1 expression by RNAi markedly diminished TCR-induced canonical NF-κB activation and IL-2 production. Furthermore, overexpression of STUB1 enhanced the ubiquitination of CARMA1, whereas knockdown of STUB1 abolished the endogenous ubiquitination of CARMA1 induced by TCR stimulation. Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys-27 linked, which is important for CARMA1-mediated NF-κB activation. These data provide the first evidence that ubiquitination of CARMA1 by STUB1 promotes TCR-induced NF-κB signaling.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Guanilato Ciclase/metabolismo , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Catálise , Linhagem Celular , Ativação Enzimática , Humanos , Interleucina-2/biossíntese , NF-kappa B/metabolismo , Ligação Proteica , Receptores de Antígenos de Linfócitos T/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
14.
Graefes Arch Clin Exp Ophthalmol ; 251(3): 681-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22695935

RESUMO

BACKGROUND: Transconjunctival sutureless vitrectomy is appealing to vitreoretinal surgeons around the world. However, its use versus 20-gauge vitreoretinal surgery is still controversial. The aim of this meta-analysis was to compare the safety and functional outcomes of transconjunctival sutureless vitrectomy versus 20-gauge vitrectomy for vitreoretinal surgery. METHODS: Data sources, including PubMed, Medline, EMBASE, and Cochrane Controlled Trials Register, were searched to identify potentially relevant randomized controlled trials. A meta-analysis was performed using RevMan 5.0 software. The primary factors included patients' discomfort, operating time and early postoperative complications. Visual acuity and surgically induced astigmatism were chosen as secondary outcomes. RESULTS: A total of 471 participants with 479 eyes in eight trials between 2005 and 2011 were analyzed. Transconjunctival sutureless vitrectomy was associated with significantly fewer patients suffering from postoperative discomfort at 1 day (odds ratio [OR] 0.07; 95 % confidence interval [CI] 0.01 to 0.49; p = 0.007) and 7 days (OR 0.14; 95 % CI 0.03 to 0.73; p = 0.02) follow-up, and was more effective in reducing surgically induced astigmatism (mean difference -0.23D; 95 % CI -0.31 to -0.15; p < 0.00001) compared to 20-gauge vitrectomy. The sutureless group achieved shorter wound opening (mean difference -1.97 minutes; 95 % CI -2.69 to -1.25; p < 0.00001) as well as wound closure time (mean difference -4.55 minutes; 95 % CI -5.43 to -3.66; p < 0.00001), but the overall surgery time was comparable (mean difference -0.14 minutes; 95 % CI -3.52 to 3.24; p = 0.93). There were no significant differences in the complication rates between the two groups with the exception of postoperative hypotony, which was more likely with the sutureless group (OR 3.73; 95 % CI 1.43 to 9.76; p = 0.007). CONCLUSIONS: According to the present data, transconjunctival sutureless vitrectomy offered significantly less postoperative discomfort and decreased surgically induced astigmatism without increasing the risk of vision-threatening complications. Further trials with contemporary equipment and larger sample size are suggested to confirm this conclusion.


Assuntos
Microcirurgia/métodos , Técnicas de Sutura , Vitrectomia/métodos , Cirurgia Vitreorretiniana , Túnica Conjuntiva/cirurgia , Bases de Dados Factuais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acuidade Visual
15.
J Biol Chem ; 287(24): 20081-7, 2012 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-22528498

RESUMO

T-cell receptor (TCR)-induced T-cell activation is a critical event in adaptive immune responses. The engagement of TCR complex by antigen along with the activation of the costimulatory receptors trigger a cascade of intracellular signaling, in which caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) is a crucial scaffold protein. Upon stimulation, CARMA1 recruits downstream molecules including B-cell CLL/lymphoma 10 (Bcl10), mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1), and TRAF6 to assemble a specific TCR-induced signalosome that triggers NF-κB and JNK activation. In this report, we identified protein kinase Cδ (PKCδ) as a CARMA1-associated protein by a biochemical affinity purification approach. PKCδ interacted with CARMA1 in TCR stimulation-dependent manner in Jurkat T cells. Overexpression of PKCδ inhibited CARMA1-mediated NF-κB activation, whereas knockdown of PKCδ potentiated TCR-triggered NF-κB activation and IL-2 secretion in Jurkat T cells. Reconstitution experiments with PKCδ kinase-dead mutant indicated that the kinase activity of PKCδ was dispensable for its ability to inhibit TCR-triggered NF-κB activation. Furthermore, we found that PKCδ inhibited the interaction between MALT1 and TRAF6, but not the association of CARMA1 with PKCθ, Bcl10, or MALT1. These observations suggest that PKCδ is a negative regulator in T cell activation through inhibiting the assembly of CARMA1 signalosome.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Guanilato Ciclase/metabolismo , Ativação Linfocitária/fisiologia , NF-kappa B/metabolismo , Proteína Quinase C-delta/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/fisiologia , Linfócitos T/enzimologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína 10 de Linfoma CCL de Células B , Proteínas Adaptadoras de Sinalização CARD/genética , Caspases/genética , Caspases/metabolismo , Guanilato Ciclase/genética , Células HEK293 , Humanos , Interleucina-2/genética , Interleucina-2/metabolismo , Células Jurkat , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína Quinase C-delta/genética , Receptores de Antígenos de Linfócitos T/genética , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo
16.
Chin Med J (Engl) ; 124(16): 2474-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21933590

RESUMO

BACKGROUND: It was well known that tangential vitreoretinal traction and epiretinal membrane play important roles during the formation of macular hole (MH) associated with retinal detachment (RD) in highly myopic eyes. But it was not clear about the correlations between anteroposterior traction, posterior vitreous cortex (PVC) and MH-RD. The vitreous status in highly myopic eyes were analyzed to explore the effect of PVC in the role of MH-RD formation. METHODS: Sixteen consecutive highly myopic eyes with RD due to MH were retrospectively analyzed from January 2009 to April 2009. The preoperative examinations for detecting posterior vitreous detachment (PVD) and vitreoretinal traction included B-mode ultrasonography and optical coherence tomography (OCT). The residual PVC and PVD were confirmed intraoperatively during triamcinolone acetonide (TA) assisted vitrectomy. RESULTS: Under ultrasonography, the preoperative PVD patterns were stratified as: complete PVD in three (19%) eyes, partial PVD in eight (50%) eyes, and no PVD in five (31%) eyes. OCT confirmed vitreoretinal traction and no complete PVD in 10 (63%) eyes, including anteroposterior traction in four eyes and tangential traction in six eyes. During TA-assisted vitrectomy, it was confirmed that no complete PVD existed in 16 eyes, including six eyes (38%) finally diagnosed of partial PVD, and five (31%) eyes with vitreoschisis. Anteroposterior vitreoretinal traction around MH is always in conjunction with partial PVD (67%), and high proportion (80%) of vitreoschisis is associated with tangential vitreoretinal traction. Comparing with the precision of TA staining of PVD diagnosis, the coincidence rate of ultrasonography was 69% (P = 0.02), and that of OCT was 63% (P < 0.01). CONCLUSIONS: The residual PVC due to partial PVD or vitreoschisis may cause the anteroposterior or tangential traction of macular area, which contributes to the formation of MH and subsequent RD in highly myopic eyes. And it is necessary to realize the vitreoretinal relationship and assess the status of PVC synthetically for surgery by combined ultrasonography and OCT preoperatively and TA staining intraoperatively.


Assuntos
Perfurações Retinianas/etiologia , Descolamento do Vítreo/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/fisiopatologia , Descolamento Retiniano/fisiopatologia , Estudos Retrospectivos
17.
Chin Med J (Engl) ; 124(11): 1647-52, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21740770

RESUMO

BACKGROUND: Idiopathic choroidal neovascularization (ICNV) is an uncommon disorder affecting primarily individuals younger than the age of 50 years. In CNV patients, no apparent cause can be determined. This study aimed to evaluate the functional and morphological change of the retina with ICNV in young adults. METHODS: In this retrospective study, 32 eyes of 32 patients with subfoveal or juxta/extra foveal ICNV had been admitted into the Shanghai First People's Hospital from January 2009 to July 2010. The functional changes were evaluated using the best corrected visual acuity (BCVA) and the microperimetry in the macular area. The morphology changes were evaluated using optical coherence tomography (OCT), the color fundus photography and the fluorescein angiography. RESULTS: Seventeen patients with juxta/extra foveal and 15 subfoveal CNV were investigated. The mean logarithm of the minimum angle of resolution (LogMAR) BCVA was 0.39, the mean central retinal thickness (CRT) was 334 µm, and the mean sensitivity (MS) was 11.8 decibels (dB). In the subfoveal group, there was a strong correlation between CRT and BCVA (r = -0.675, F = 2.167, P < 0.01); as well as that between CRT and MS (r = -0.681, F = 22.91, P < 0.01). While in the juxta/extra foveal CNV group, the correlation of CRT and BCVA was not significant (r = -0.071, F = 1.018, P > 0.05); neither was the correlation of CRT and MS (r = -0.142, F = 36.54, P > 0.05). The microperimetry (MP-1) test revealed 17 (53%) patients with stable fixation, 9 (28%) with relatively unstable and 6 (19%) with unstable fixation. Fixation stability correlated positively with sensitivity in the central 2° diameter area (r = 0.380, F = 3.213, P < 0.05) and the duration of symptoms (r = 0.401, F = 7.933, P < 0.05). CONCLUSIONS: ICNV was associated with reduced total MS, unstable fixation and eccentric fixation. These findings emphasized functional change in ICNV is beyond the BCVA and regular morphology change, which provided additional information of functional evaluation in clinical practice.


Assuntos
Neovascularização de Coroide/fisiopatologia , Acuidade Visual/fisiologia , Adulto , Estudos Transversais , Feminino , Angiofluoresceinografia , Humanos , Masculino , Tomografia de Coerência Óptica , Adulto Jovem
18.
Asian Pac J Cancer Prev ; 12(9): 2179-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22296352

RESUMO

AIM: The purpose of this study was to investigate relationships between green tea consumption and gastric cancer development. METHODS: A population-based case-control study including 200 cases and 200 controls was conducted in the southwest area of China from May 2010 to February 2011. A self-designed questionnaire was used to collect data on factors influencing gastric cancer development, including tea drinking, conditional logistic regression being used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Cases with higher economic status had a reduced risk of gastric cancer, while those with cancer family history, drinking and smoking showed increased risk. Hot and very hot tea temperature was significantly related to high risk of gastric cancer with ORs (95%Cl) of 1.82 (1.03-3.52) and 3.07 (1.78-7.36), respectively. Further analysis indicated elevated risk of gastric cancer in former drinkers, former smokers and current drinkers when the measured tea temperature was hot. CONCLUSION: Drinking tea at high temperature increases the gastric cancer risk, especially in drinkers and smokers.


Assuntos
Neoplasias Gástricas/epidemiologia , Chá , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Intervalos de Confiança , Feminino , Hábitos , Temperatura Alta , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias Gástricas/etiologia , Inquéritos e Questionários
19.
Zhonghua Yan Ke Za Zhi ; 46(7): 580-4, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21054963

RESUMO

OBJECTIVE: To investigate whether hyperglycemia affect the expression of glycosyltransferases and Enzyme-catalyzed glycosylation in the retina of diabetic rat. METHOD: It was an experimental study. RT-PCR was used to analyze the mRNA level of six glycosyltransferases in the retina of streptozocin diabetic rats; Lectin blot assay with RCA-I was performed to investigate the level of Galß 1→4GlcNAc or N-glycans on total retinal glycoproteins. RESULTS: mRNA level of six glycosyltransferases in the retina of streptomycin diabetic rats and of normal rat is: O-linked N-acetylglucosamine transferase (0.1650 ± 0.1160 versus 0.1160 ± 0.036); UDP-Gal: betaGlcNAc beta1,3-galactosyltransferase (0.0186 ± 0.0122 versus 0.0152 ± 0.0047); alpha 1,4-galactosyltransferase (0.0040 ± 0.0040 versus 0.0054 ± 0.0022); mannoside acetylglucosaminyltransferase 1 (0.0228 ± 0.0166 versus 0.0187 ± 0.0050); UDP-glucose ceramide glucosyltransferase (0.0129 ± 0.0096 versus 0.0116 ± 0.0040); UDP-Gal: betaGlcNAc beta 1,4-galactosyltransferase 1 (0.0157 ± 0.0010 versus 0.0081 ± 0.0016). The mRNA level of UDP-Gal: betaGlcNAc beta 1,4-galactosyltransferase 1 was up-regulated in the retina of streptomycin diabetic rats (t = 6.847, P = 0.002). Consistent with this, the level of Galß 1→4GlcNAc of glycoproteins in streptomycin diabetic rat's retina was strengthened compared with that in control rats. CONCLUSIONS: The results from this study showed that Hyperglycemia could up-regulate the expression of UDP-Gal: betaGlcNAc beta 1,4-galactosyltransferase 1 and strengthen the level of Galß 1→4GlcNAc of glycoproteins in the retina of streptomycin diabetic rats. Our initial results will contribute to the research for the relation between the Enzyme-catalyzed Glycosylation and the etiopathogenesis of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Glicosiltransferases/metabolismo , Retina/metabolismo , Animais , Produtos Finais de Glicação Avançada , Glicosilação , Masculino , Ratos , Ratos Sprague-Dawley
20.
Environ Toxicol Pharmacol ; 28(2): 259-64, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21784013

RESUMO

Cigarette smoke has been widely investigated in terms of epidemiology and pathological endpoints in relation to human lung diseases and animal study. In this study we exposed Wistar rats to cigarette smoke at concentrations of 20% and 60% to explore potential molecular mechanisms at the protein level. Exposures were conducted twice a day, 5 days a week for 43 weeks. As a major metabolite of nicotine in cigarette, cotinine level in rat urine was determined by HPLC-MS. A dose-dependent analysis indicated that cotinine may be used as an exposure marker of cigarette smoke. Expression of receptor for advanced glycation endproducts (RAGE), an immunoglobulin super family that triggers the intracellular signal cascade reaction leading to inflammation and its ligand S100A6 (calgranulin) in bronchial epithelial cells and lung tissues of rats, were found to be positive correlated with cotinine levels, indicating that RAGE and S100A6 may be attributable to inflammation and oxidative damage caused by cigarette smoke.

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