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1.
EMBO Rep ; 25(5): 2441-2478, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38649663

RESUMEN

Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.


Asunto(s)
Proteínas Argonautas , Caveolina 1 , MicroARNs , Metástasis de la Neoplasia , Animales , Humanos , Ratones , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Caveolina 1/metabolismo , Caveolina 1/genética , Línea Celular Tumoral , Vesículas Extracelulares/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , MicroARNs/genética , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patología , Unión Proteica , Sirtuina 2/metabolismo , Sirtuina 2/genética
2.
Int J Mol Sci ; 24(15)2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37569411

RESUMEN

Rheumatoid arthritis (RA) is a systemic disease characterized by non-infectious inflammation of the joints and surrounding tissues, which can cause severe health problems, affect the patient's daily life, and even cause death. RA can be clinically diagnosed by the occurrence of blood serological markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). However, about 20% of RA patients exhibit negative results for both markers, which makes RA diagnosis difficult and, therefore, may delay the effective treatment. Previous studies found some evidence that human leukocyte antigen (HLA)-related genes might be the susceptibility genes for RA and their polymorphisms might contribute to varieties of susceptibility and disease severity. This study aimed for the genetic polymorphisms of the RA patient genome and their effects on the RA patient's serological makers, RF and anti-CCP. A total of 4580 patients' electronic medical records from 1992 to 2020 were retrieved from the China Medical University Hospital database. The most representative single-nucleotide polymorphisms (SNPs) were identified through a genome-wide association study (GWAS) followed by enzyme-linked immunosorbent assay (ELISA) validation using the blood from 30 additional RA patients. The results showed significant changes at the position of chromosome 6 with rs9270481 being the most significant locus, which indicated the location of the HLA-DRB1 gene. Further, patients with the CC genotype at this locus were more likely to exhibit negative results for RF and anti-CCP than those with the TT genotype. The C allele was also more likely to be associated with negative results for RF and anti-CCP. The results demonstrated that a genetic polymorphism at rs9270481 affected the expression of RF and anti-CCP in RA patients, which might indicate the necessity to develop a personalized treatment plan for each individual patient based on the genetic profile.

3.
Telemed J E Health ; 28(7): 1035-1043, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34939839

RESUMEN

Introduction: Access to quality mental health medication management (MM) in the United States is limited, even among those with employment-based health insurance. This implementation, feasibility, and outcome study sought to design and evaluate an evidence-based telemental health MM service using a collaborative care model (CoCM). Materials and Methods: CoCM MM was available to adult employees/dependents through their employer benefits, in addition to therapy. Outcomes included Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) collected at baseline and throughout participation. This analysis was not deemed to be human subjects research by the Western Institutional Review Board. Results: Over 17 months, 212 people enrolled and completed >2 assessments; the enrollees were 58.96% female with average age of 32.00 years (standard deviation [SD] = 7.38). In people with moderate to severe depression or anxiety, PHQ-9 and GAD-7 scores reduced by an average of 7.27 (SD = 4.80) and 6.71 (SD = 5.18) points after at least 12 ± 4 weeks in the program. At 24 ± 4 weeks, the PHQ-9 and GAD-7 reductions were on average 7.17 (SD = 5.00) and 6.03 (SD = 5.37), respectively. Approximately 65.88% of participants with either baseline depression or anxiety had a response on either the PHQ-9 or GAD-7 at 12 ± 4 weeks and 44.71% of participants experienced remission; at 24 ± 4 weeks, 56.41% had response and 41.03% experienced remission. Conclusions: An evidence-based CoCM telemedicine service within an employee behavioral health benefit is feasible and effective in reducing anxiety and depression symptoms when using measurement-based care. Widespread implementation of a benefit like this could expand access to evidence-based mental health MM.


Asunto(s)
Trastorno Depresivo , Telemedicina , Adulto , Ansiedad/terapia , Trastornos de Ansiedad/terapia , Atención a la Salud , Depresión/terapia , Trastorno Depresivo/terapia , Femenino , Humanos , Masculino
4.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36362336

RESUMEN

Diabetes mellitus (DM) is a common chronic metabolic disease, and the C57BLKsJ-db/db mice are good animal models for type 2 diabetes mellitus (T2DM). In this study, Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression of adiponectin in the liver tissues of T2DM mice with different disease courses (4, 16, and 32 weeks). Adiponectin expression reduced in the liver tissues of T2DM mice in different disease courses. The genotypic and allelic frequencies of the adiponectin gene rs1063538 and rs2241766 single nucleotide polymorphisms (SNPs) in a Taiwanese population (570 T2DM patients and 1700 controls) were investigated. Based on the genetic distribution of the rs2241766 locus, the distribution frequency of the T allele in the T2DM group (72.8%) was higher than in the control group (68.8%). Individuals carrying the G allele had a 0.82-fold greater risk of developing T2DM than individuals carrying the T allele. Differences were evident in the genotypic and allelic distributions (p < 0.05). Enzyme-linked immunosorbent assay (ELISA) was used to measure changes in serum adiponectin protein concentrations in the healthy population and in patients with T2DM. Serum adiponectin concentration in patients with T2DM was lower than in the control group. In summary, adiponectin was determined to be a T2DM susceptibility gene and may be involved in T2DM progression.


Asunto(s)
Adiponectina , Diabetes Mellitus Tipo 2 , Ratones , Animales , Adiponectina/metabolismo , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Frecuencia de los Genes , Estudios de Casos y Controles
6.
Telemed J E Health ; 27(1): 47-54, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32311301

RESUMEN

Background: Many employees experience high levels of stress in the workplace, which negatively impact their productivity and well-being. Effective stress management interventions exist, but are inaccessible due to insufficient numbers of mental health providers, long waiting times to initiate care, high out-of-pocket cost of care, and stigma related to receiving psychotherapy. Introduction: The purpose of this study was to test the efficacy, in real-world circumstances, of a structured, cognitive behavioral coaching (CBC) program delivered through video or telephone. Materials and Methods: Retrospective data on 289 subjects who had sought support for emotional health through a behavioral health benefit offered through employers were examined. Changes in perceived stress and well-being over the course of the program were measured using the Perceived Stress Scale (PSS) and Warwick-Edinburgh Mental Well-being Scale (WEMWBS), respectively. Rates of reliable change and satisfaction with the coaching program were also assessed. Results: Scores on both the PSS and WEMWBS improved between baseline and follow-up. Approximately 61.9% (n = 289) of participants demonstrated reliable improvement on either measure. Discussion: CBC is a promising intervention that has the potential to significantly expand access to effective and more affordable interventions for emotional health care. Conclusions: Coaching, when delivered by accredited professionals trained in cognitive behavioral theory and interventions and working in real-world settings, can be efficacious in decreasing perceived stress and increasing well-being when delivered through video or telephone.


Asunto(s)
Tutoría , Cognición , Humanos , Salud Mental , Estudios Retrospectivos , Encuestas y Cuestionarios
7.
BMC Psychiatry ; 20(1): 497, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33032569

RESUMEN

BACKGROUND: Treatment recommendations suggest that suicidal ideation will decrease following successful psychotherapy for depression. However, findings from the empirical research are equivocal in this regard. It is possible suicidal ideation does not respond to empirically supported treatment (EST) for depression or that suicidal ideation limits the efficacy of ESTs for depression. METHODS: Data from 793 patients who sought EST for depression was analyzed using t-tests and multiple linear regression. RESULTS: Both patients with (n = 233) or without suicidal ideation (n = 560) were significantly less depressed following treatment. A significant reduction in suicidal ideation was also observed. At baseline, 233 (29.4%) patients reported suicidal ideation, whereas only 90 (11.3%) patients reported suicidal ideation at follow-up. The relationship between suicidal ideation at baseline and depression scores at follow-up was not significant. CONCLUSIONS: Patients with suicidal ideation who receive short-term EST can experience significant reductions in both depressive symptoms and suicidal ideation. Findings suggest that suicidal ideation at baseline does not impact treatment efficacy, but additional research that directly tests moderation is needed.


Asunto(s)
Depresión , Ideación Suicida , Depresión/terapia , Humanos , Psicoterapia , Resultado del Tratamiento
8.
Int J Med Sci ; 17(1): 13-20, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31929734

RESUMEN

Diabetes mellitus (DM) is a chronic disease found worldwide. Notably, BKS.Cg- Dock7m +/+ Leprdb/JNarl mice are useful animal models for studying type 2 diabetes mellitus (T2DM). In this study, we investigated casein kinase 2 alpha 1 (CSNK2A1) gene and protein expression in the liver tissues of mice at different ages (4, 16, and 32 weeks) using real-time quantitative polymerase chain reactions, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay. Our data paved the way for exploring BKS.Cg- Dock7m +/+ Leprdb/JNarl in the mouse model by demonstrating a significant increase in gene and protein expression in T2DM (+Leprdb/+Leprdb) mouse liver when compared to control (+Dock7m/+Dock7m) mouse liver. We also observed that CSNK2A1 protein level in the serum of T2DM patient group was higher than that of the control group, although the data was not statistically significant. Based on our findings, we can now understand the role of CSNK2A1 gene upregulation when encountering T2DM pathologies.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Obesidad/genética , Receptores de Leptina/genética , Anciano , Animales , Glucemia , Quinasa de la Caseína II/genética , Diabetes Mellitus Tipo 2/patología , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/genética , Humanos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Obesidad/patología
9.
Int J Mol Sci ; 21(3)2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-32024007

RESUMEN

Taiwania (Taiwania cryptomerioides) is an important tree species in Taiwan because of the excellent properties of its wood and fascinating color qualities of its heartwood (HW), as well as the bioactive compounds therein. However, limited information is available as to the HW formation of this species. The objective of this research is to analyze the differentially expressed genes (DEGs) during the HW formation process from specific Taiwania xylem tissues, and to obtain genes that might be closely associated with this process. The results indicated that our analyses have captured DEGs representative to the HW formation process of Taiwania. DEGs related to the terpenoid biosynthesis pathway were all up-regulated in the transition zone (TZ) to support the biosynthesis and accumulation of terpenoids. Many DEGs related to lignin biosynthesis, and two DEGs related to pinoresinol reductase (PrR)/pinoresinol lariciresinol reductase (PLR), were up-regulated in TZ. These DEGs together are likely involved in providing the precursors for the subsequent lignan biosynthesis. Several transcription factor-, nuclease-, and protease-encoding DEGs were also highly expressed in TZ, and these DEGs might be involved in the regulation of secondary metabolite biosynthesis and the autolysis of the cellular components of ray parenchyma cells in TZ. These results provide further insights into the process of HW formation in Taiwania.


Asunto(s)
Cupressaceae/genética , Perfilación de la Expresión Génica/métodos , Proteínas de Plantas/genética , Madera/metabolismo , Cupressaceae/metabolismo , Regulación de la Expresión Génica de las Plantas , Lignina/metabolismo , Metabolismo Secundario , Terpenos/metabolismo , Xilema/metabolismo
10.
Int J Mol Sci ; 21(18)2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32942691

RESUMEN

Aging kidneys are characterized by an increased vulnerability to glomerulosclerosis and a measurable decline in renal function. Evidence suggests that renal and systemic klotho and sirtuin 1 (SIRT1) deficiencies worsen kidney damage induced by exogenous stresses. The aim of this study was to explore whether resveratrol would attenuate concanavalin A (Con A)-induced renal oxidative stress and advanced glomerulosclerosis in aged mice. Aged male C57BL/6 mice were treated orally with resveratrol (30 mg/kg) seven times (12 h intervals) prior to the administration of a single tail-vein injection of Con A (20 mg/kg). The plasma and urinary levels of kidney damage markers were evaluated. The kidney histopathology, renal parameters, and oxidative stress levels were measured. Furthermore, klotho was downregulated in mouse kidney mesangial cells that were pretreated with 25 µM resveratrol followed by 20 µg/mL Con A. The urinary albumin/creatinine ratio, blood urea nitrogen, kidney mesangial matrix expansion, tubulointerstitial fibrosis, and renal levels of α-smooth muscle actin, transforming growth factor beta, fibronectin, procollagen III propeptide, and collagen type I significantly increased in Con A-treated aged mice. Aged mice kidneys also showed markedly increased levels of 8-hydroxydeoxyguanosine (8-OH-dG) and reactive oxygen species (ROS), with reduced superoxide dismutase activity and levels of glutathione, klotho, and SIRT1 after Con A challenge. Furthermore, in kidney mesangial cells, klotho silencing abolished the effects of resveratrol on the Con A-mediated elevation of the indices of oxidative stress and the expression of glomerulosclerosis-related factors. These findings suggest that resveratrol protects against Con A-induced advanced glomerulosclerosis in aged mice, ameliorating renal oxidative stress via the SIRT1-mediated klotho expression.


Asunto(s)
Envejecimiento/efectos de los fármacos , Concanavalina A/farmacología , Glucuronidasa/metabolismo , Enfermedades Renales/tratamiento farmacológico , Resveratrol/farmacología , Sirtuina 1/metabolismo , Regulación hacia Arriba/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Envejecimiento/metabolismo , Animales , Línea Celular , Fibronectinas/metabolismo , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/metabolismo , Proteínas Klotho , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo
11.
Environ Toxicol ; 34(5): 652-658, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30724446

RESUMEN

Prospective cohort studies have indicated that a highly nickel-polluted environment may severely affect human health, resulting in such conditions as respiratory tract cancers. Such exposure can trigger vascular endothelial growth factor (VEGF) expression. However, the signal transduction pathways leading to VEGF induction by nickel compounds are not well understood. This study revealed the occurrence of VEGF induction in human non-small-cell lung cancer H460 cells exposed to NiCl2 . Moreover, exposing H460 cells to NiCl2 activated extracellular signal-regulated protein kinase (ERK), nuclear factor kappa B (NFκB), and protein kinase B (Akt) as well as downregulated AMP activated protein kinase (AMPK) expression. The mitogen-activated protein kinase (MAPK) and ERK inhibitor significantly blocked NiCl2 -induced ERK activation and VEGF production. Pretreating H460 cells with a PI3K/Akt inhibitor substantially inhibited NiCl2 -induced VEGF expression and reduced Akt, ERK, and NFκB phosphorylation. Furthermore, 5-aminoimidazole-4-carboxamide ribonucleoside-induced AMPK activation improved VEGF expression in NiCl2 -treated H460 cells significantly. These results indicate that NiCl2 induces VEGF production through Akt, ERK, NFκB activation and AMPK suppression and mediates various types of pathophysiological angiogenesis.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Contaminantes Ambientales/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Níquel/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación
12.
Int J Cancer ; 143(6): 1440-1455, 2018 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-29658109

RESUMEN

Cells expressing mesenchymal/basal phenotypes in tumors have been associated with stem cell properties. Cancer stem cells (CSCs) are often resistant to conventional chemotherapy. We explored overcoming mesenchymal CSC resistance to chemotherapeutic agents. Our goal was to reduce CSC numbers in vivo, in conjunction with chemotherapy, to reduce tumor burden. Analysis of clinical samples demonstrated that COX-2/PGE2 /EP4 signaling is elevated in basal-like and chemoresistant breast carcinoma and is correlated with survival and relapse of breast cancer. EP4 antagonism elicts a striking shift of breast cancer cells from a mesenchymal/CSC state to a more epithelial non-CSC state. The transition was mediated by EP4 antagonist-induced extracellular vesicles [(EVs)/exosomes] which removed CSC markers, mesenchymal markers, integrins, and drug efflux transporters from the CSCs. In addition, EP4 antagonism-induced CSC EVs/exosomes can convert tumor epithelial/non-CSCs to mesenchymal/CSCs able to give rise to tumors and to promote tumor cell dissemination. Because of its ability to induce a CSC-to-non-CSC transition, EP4 antagonist treatment in vivo reduced the numbers of CSCs within tumors and increased tumor chemosensitivity. EP4 antagonist treatment enhances tumor response to chemotherapy by reducing the numbers of chemotherapy-resistant CSCs available to repopulate the tumor. EP4 antagonism can collaborate with conventional chemotherapy to reduce tumor burden.


Asunto(s)
Neoplasias de la Mama/patología , Ciclooxigenasa 2/química , Dinoprostona/antagonistas & inhibidores , Resistencia a Antineoplásicos , Vesículas Extracelulares/patología , Células Madre Neoplásicas/patología , Subtipo EP4 de Receptores de Prostaglandina E/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Movimiento Celular , Proliferación Celular , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Transición Epitelial-Mesenquimal , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Invasividad Neoplásica , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Transducción de Señal , Carga Tumoral , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Stem Cells ; 35(2): 425-444, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27506158

RESUMEN

Prostaglandin E2 (PGE2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE2 /prostaglandin E receptor 4 (EP4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFß signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP4 ) antagonism. EP4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFß and PI3K/Akt pathways. EP4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE2 /EP4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444.


Asunto(s)
Dinoprostona/metabolismo , Vesículas Extracelulares/metabolismo , Glándulas Mamarias Humanas/citología , Microdominios de Membrana/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Transducción de Señal , Células Madre/citología , Células Madre/metabolismo , Animales , Anticuerpos Neutralizantes/metabolismo , Biomarcadores/metabolismo , Caveolas/metabolismo , Adhesión Celular , Línea Celular , Movimiento Celular , Forma de la Célula , Ciclooxigenasa 2/metabolismo , Células Epiteliales/citología , Células Epiteliales/metabolismo , Vesículas Extracelulares/ultraestructura , Femenino , Humanos , Integrinas/metabolismo , Microdominios de Membrana/ultraestructura , Ratones Endogámicos C57BL , Prostaglandina-E Sintasas/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/antagonistas & inhibidores , Esferoides Celulares/citología , Proteínas de Unión al GTP rab/metabolismo
14.
Int J Mol Sci ; 19(11)2018 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-30453650

RESUMEN

Diabetic retinopathy (DR) is a severe and recurrent microvascular complication in diabetes. The multifunctional response gene to complement 32 (RGC-32) is involved in the regulation of cell cycle, proliferation, and apoptosis. To investigate the role of RGC-32 in the development of DR, we used human retinal microvascular endothelial cells under high-glucose conditions and type 2 diabetes (T2D) mice (+Leprdb/ + Leprdb, db/db). The results showed that RGC-32 expression increased moderately in human retinal endothelial cells under hyperglycemic conditions. Histopathology and RGC-32 expression showed no significant changes between T2D and control mice retina at 16 and 24 weeks of age. However, RGC-32 expression was significantly decreased in T2D mouse retina compared to the control group at 32 weeks of age, which develop features of the early clinical stages of DR, namely reduced retinal thickness and increased ganglion cell death. Moreover, immunohistochemistry showed that RGC-32 was predominantly expressed in the photoreceptor inner segments of control mice, while the expression was dramatically lowered in the T2D retinas. Furthermore, we found that the level of anti-apoptotic protein Bcl-2 was decreased (approximately 2-fold) with a concomitant increase in cleaved caspase-3 (approximately 3-fold) in T2D retina compared to control. In summary, RGC-32 may lose its expression in T2D retina with features of DR, suggesting that it plays a critical role in DR pathogenesis.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/metabolismo , Proteínas Nucleares/metabolismo , Retina/metabolismo , Animales , Apoptosis , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/patología , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Factores de Tiempo
15.
BMC Musculoskelet Disord ; 18(1): 69, 2017 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-28173856

RESUMEN

BACKGROUND: We have previously described the association between rheumatoid arthritis (RA) prevalence and the two mutY Homolog (E. coli) (MUTYH) SNPs (rs3219463 and rs3219476) among the Taiwanese population. This present study will aim to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA. METHODS: The cohort study included 368 Taiwan's Han Chinese RA patients and 364 healthy controls. Blood samples collected from the participants were analyzed to determine their serum MUTYH levels and to identify rs3219463 SNP of MUTYH from their genomic DNA. RESULTS: Our data resulted in a statistically significant difference in genotype frequency distributions at rs3219463 for RA patients and controls (p < 0.0002). Also, the patients with G carrier at rs3219463 were less likely to suffer from painful joints (p < 0.006) and DAS28 scores (p < 0.003). Furthermore, the increase in serum level of MUTYH was also observed in RA patients (p < 0.005). CONCLUSIONS: Our study showed that RA is associated with rs3219463 SNP in EGFR gene and an increased serum level of the MUTYH protein. These findings suggest MUTYH is worthy of further investigation as a therapeutic target for RA.


Asunto(s)
Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , ADN Glicosilasas/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Artritis Reumatoide/sangre , Estudios de Cohortes , ADN Glicosilasas/sangre , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Proyectos Piloto , Factores de Riesgo
16.
Eur Respir J ; 48(1): 179-86, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27126689

RESUMEN

We sought to present the epidemiology of idiopathic pulmonary fibrosis (IPF) in adults 18-64 years old in the USA.From adults aged 18-64 years in a large administrative claims data in 2004-2010, patients with IPF were identified using diagnosis codes. We estimated annual incidence and cumulative prevalence of IPF over time, and examined potential risk factors for the IPF diagnosis.The annual cumulative prevalence increased steadily in the first few years (from 13.4 cases per 100 000 persons in 2005 to 18.2 cases in 2010 per 100 000 persons), which is likely due to a methodological reason, while the annual incidence of IPF decreased over time (from 7.9 cases per 100 000 person-years in 2005 to 5.8 cases in 2010 per 100 000 person-years). The overall decrease was mainly driven by a decreasing trend in the younger patients (aged 18-44 years), while the incidence in older patients remained stable. Consistent trends were observed in subgroups defined by previously published more restrictive algorithms for diagnosis. Older age and male sex were associated with a higher incidence of disease (p<0.05).In US adults younger than 65 years, we observed a decreasing incidence of IPF over time which may partially explain the plateau of cumulative prevalence in the last few years of our data.


Asunto(s)
Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Adolescente , Adulto , Distribución por Edad , Algoritmos , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Regresión , Estudios Retrospectivos , Distribución por Sexo , Estados Unidos/epidemiología , Adulto Joven
17.
Lung ; 194(2): 227-34, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26861885

RESUMEN

PURPOSE: Idiopathic pulmonary fibrosis (IPF) produces symptoms and activity limitations that impair health-related quality of life (HRQOL). The Patient-Reported Outcomes Measurement Information System(®) (PROMIS(®)) includes measures of self-reported health and HRQOL for a range of conditions. This study evaluated the HRQOL of individuals with IPF using PROMIS measures and examined associations between HRQOL and key symptoms or supplemental oxygen need. METHODS: Individuals who reported being told by a doctor that they have IPF completed an online battery of measures at baseline and 7-10 days later (for test-retest reliability). Measures included a brief survey of demographic and health-related questions, the PROMIS-29 profile, the Modified Medical Research Council Dyspnea Scale (MMRC), PROMIS dyspnea severity short form, A Tool to Assess Quality of life in IPF (ATAQ-IPF) and one cough item from the Functional Assessment of Chronic Illness Therapy (FACIT). RESULTS: 220 individuals were included in the final sample. Except for sleep disturbance, all PROMIS domain scores significantly (p < .01) differed by MMRC level. Supplemental oxygen users were more impaired than non-users in fatigue, physical function, and social role participation (p < 0.01). The test-retest reliability was acceptable to excellent (>0.7) for all scales, but was lower for sleep disturbance (0.64). CONCLUSIONS: People with IPF report substantial deficits in HRQOL across a range of PROMIS domains, and deficits vary by dyspnea and cough severity. These deficits warrant monitoring in clinical practice and consideration when investigating new therapies. Further research is required to further evaluate the psychometric performance of the PROMIS-29 in IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Anciano , Anciano de 80 o más Años , Costo de Enfermedad , Tos/diagnóstico , Tos/fisiopatología , Tos/psicología , Disnea/diagnóstico , Disnea/fisiopatología , Disnea/psicología , Fatiga/diagnóstico , Fatiga/fisiopatología , Fatiga/psicología , Femenino , Estado de Salud , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/terapia , Masculino , Salud Mental , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Índice de Severidad de la Enfermedad , Participación Social , Factores de Tiempo
18.
Endocr Pract ; 20(3): 221-31, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24246342

RESUMEN

OBJECTIVE: To assess the association between oral antidiabetic drug (OAD) treatment concordance with National Kidney Foundation (NKF) guidelines and related economic and clinical outcomes in patients with type 2 diabetes mellitus (T2DM) and stage 3 to 5 chronic kidney disease (CKD). METHODS: Analysis of nationwide health administrative claims and laboratory findings for the years 2005 to 2010 for a commercially insured U.S. population. T2DM patients age 18 to 64 years were selected if they had stage 3 to 5 CKD as identified using medical claims (International Classification of Diseases-9-CM codes 585.3-585.6), evidence of dialysis procedures, or laboratory findings showing an estimated glomerular filtration rate <60 mL/min/1.73 m2 (date of first CKD as the index date). OADs prescribed during the 6 months following the index date were evaluated to determine guideline concordance. Outcomes examined included glycemic control, healthcare costs and resource utilization, and severe hypoglycemic events. Regression models were used to assess the association between guideline nonconcordance and outcomes. RESULTS: Of the final study sample (N = 3,300), 58.3% were nonconcordant with guidelines. After adjusting for patient characteristics, the nonconcordant patients were more likely to have severe hypoglycemic events (hazard ratio, 1.24; 95% confidence interval [CI], 1.03-1.49) and less likely to have glycemic control (odds ratio [OR], 0.70; 95% CI, 0.57-0.85) than guideline-concordant patients. Likelihood of hospital admission (OR, 0.95; 95% CI, 0.79-1.15) and annual total healthcare costs (adjusted difference, -$2,227; P = .051) were similar between cohorts. CONCLUSION: In T2DM patients with moderate to severe CKD, OAD treatment not concordant with guidelines is associated with a higher risk of severe hypoglycemic events and uncontrolled glycemic levels.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Adhesión a Directriz , Hipoglucemiantes/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Administración Oral , Adolescente , Adulto , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad
19.
J Clin Lab Anal ; 28(6): 435-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24652666

RESUMEN

BACKGROUND: Kawasaki disease (KD) patients who experience a cardiovascular complication known as a coronary artery aneurysm (CAA) are at high risk of developing ischemic heart disease, which may lead to sudden death. The etiology of CAA in KD patients is unclear, and this study aims to clarify the relationship between steroid receptor coactivator-1 (SRC-1) gene polymorphisms and CAA pathogenesis. METHODS: We investigated four SRC-1 gene polymorphisms (rs11894248, rs17791703, rs7572475, and rs9309308) and their correlation with KD with CAA susceptibility in 327 Taiwanese people (279 KD patients without CAA and 48 KD patients with CAA). RESULTS: The results indicated a statistically significant difference in genotype and allele frequency distributions at the SRC-1 four single nucleotide polymorphisms (SNPs) between KD patients with and without CAA (P < 0.01). Additionally, Smad3 gene polymorphism (rs12901071) is well known to be associated with KD patients. In our results, Smad3 SNP did not provide a statistically significant difference between KD patients with and without CAA. CONCLUSION: Our data show that SRC-1 polymorphisms may be the underlying cause of CAA; therefore, the polymorphisms examined in this study warrant further investigation.


Asunto(s)
Aneurisma Coronario/genética , Predisposición Genética a la Enfermedad , Síndrome Mucocutáneo Linfonodular/complicaciones , Coactivador 1 de Receptor Nuclear/genética , Polimorfismo Genético , Pueblo Asiatico , Preescolar , Aneurisma Coronario/complicaciones , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Síndrome Mucocutáneo Linfonodular/genética , Taiwán
20.
J Clin Lab Anal ; 28(2): 118-23, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24395651

RESUMEN

BACKGROUND: X-ray repair cross-complementing group 3 (XRCC3) plays a crucial role in mammalian DNA repair processes. The polymorphism of XRCC3, rs861539 (Thr > Met at codon 241), is common in populations worldwide. This study analyzed the relationship between this functional single nucleotide polymorphism and systemic lupus erythematosus (SLE) in the Han Chinese population in Taiwan (HC-TW). METHODS: Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism on 163 SLE patients and 191 healthy participants in the control group. RESULTS: The data showed that the genotype frequency at codon 241 did not differ significantly between the SLE patients and the healthy participants in the control group; however, the allele frequency analysis indicated a significant difference between these groups. In addition, we used the genotype and allele frequencies of 191 healthy HC-TW participants for comparison with HapMap populations. The results indicated a significant difference of XRCC3 Thr241Met allele and genotype frequencies between the HC-TW population and HapMap populations, except for the other Han Chinese populations. A prior study showed that Thr241 > Met substitution in XRCC3 protein was positive as damaging and functional consequences as well. CONCLUSION: This is the first study to demonstrate the difference of XRCC3 Thr241 > Met variant between the HC-TW population and HapMap population.


Asunto(s)
Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Alelos , Sustitución de Aminoácidos/genética , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Haplotipos/genética , Humanos , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Taiwán
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