RESUMEN
BACKGROUND: Psoriasis is a chronic immune-mediated skin disorder. Systemic inflammation plays an important role in the pathogenesis of psoriasis. METHODS: A total of 477 patients with psoriasis vulgaris (PsV, n = 347), generalized pustular psoriasis (GPP, n = 37), erythrodermic psoriasis (PsE, n = 45), arthritic psoriasis (PsA, n = 25) and mixed psoriasis (n = 23), and 954 healthy control subjects were included in the study. Demographic, clinical, and laboratory information were collected and compared between subgroups. RESULTS: Compared with the healthy control group, patients with psoriasis had higher total white blood cell (WBC), neutrophil, platelet counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), but lower hemoglobin (Hb) levels, lymphocyte and red blood cell (RBC) counts. NLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups, with GPP group being the highest. PLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups. There was no significant correlation between the psoriasis area severity index (PASI) score and either the NLR or PLR in the PsV group. CONCLUSIONS: Elevated NLR and PLR were associated with psoriasis and differed between subtypes, suggesting that they could be used as markers of systemic inflammation in psoriasis patients.
Asunto(s)
Inflamación/inmunología , Linfocitos/inmunología , Neutrófilos/inmunología , Psoriasis/inmunología , Piel/patología , Adulto , Biomarcadores , Femenino , Hemoglobinas/metabolismo , Humanos , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Psoriasis/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND/AIMS: To develop a suitable hepatocyte-like cell model that could be a substitute for primary hepatocytes with essential transporter expression and functions. Induced hepatocyte-like (iHep) cells directly reprogrammed from mice fibroblast cells were fully characterized. METHODS: Naïve iHep cells were transfected with nuclear hepatocyte factor 4 alpha (Hnf4α) and treated with selected small molecules. Sandwich cultured configuration was applied. The mRNA and protein expression of transporters were determined by Real Time PCR and confocal. The functional transporters were estimated by drug biliary excretion measurement. The inhibition of bile acid efflux transporters by cholestatic drugs were assessed. RESULTS: The expression and function of p-glycoprotein (P-gp), bile salt efflux pump (Bsep), multidrug resistance-associated protein 2 (Mrp2), Na+-dependent taurocholate cotransporting polypeptide (Ntcp), and organic anion transporter polypedtides (Oatps) in iHep cells were significantly improved after transfection of hepatocyte nuclear factor 4 alpha (Hnf4α) and treatment with selected inducers. In vitro intrinsic biliary clearances (CLb,int) of optimized iHep cells for rosuvastatin, methotrexate, d8-TCA (deuterium-labeled sodium taurocholate acid) and DPDPE ([D-Pen2,5] enkephalin hydrate) correlated well with that of sandwich-cultured primary mouse hepatocytes (SCMHs) (r2 = 0.984). Cholestatic drugs were evaluated and the results were compared well with primary mice hepatocytes. CONCLUSION: The optimized iHep cells expressed functional drug transporters and were comparable to primary mice hepatocytes. This study suggested direct reprogramming could provide a potential alternative to primary hepatocytes for drug candidate hepatobiliary disposition and hepatotoxicity screening.
Asunto(s)
Anticolesterolemiantes/metabolismo , Reprogramación Celular , Factor Nuclear 4 del Hepatocito/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Anticolesterolemiantes/análisis , Anticolesterolemiantes/toxicidad , Ácidos y Sales Biliares/metabolismo , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Encefalina D-Penicilamina (2,5)/análisis , Encefalina D-Penicilamina (2,5)/metabolismo , Encefalina D-Penicilamina (2,5)/toxicidad , Fibroblastos/citología , Fibroblastos/metabolismo , Expresión Génica/efectos de los fármacos , Factor Nuclear 4 del Hepatocito/genética , Hepatocitos/citología , Hepatocitos/metabolismo , Proteínas de Transporte de Membrana/genética , Metotrexato/análisis , Metotrexato/metabolismo , Metotrexato/toxicidad , Ratones , Ratones Endogámicos ICR , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Rosuvastatina Cálcica/análisis , Rosuvastatina Cálcica/metabolismo , Rosuvastatina Cálcica/toxicidad , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Simportadores/genética , Simportadores/metabolismoRESUMEN
OBJECTIVE: Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac. We aimed to study the role of Elmo1 in the malignant migration of ovarian cancer. METHODS: Engulfment and cell motility 1 expression was evaluated in specimens from 93 patients with serous ovarian cancer (SOC) by immunohistochemical staining. Next, Elmo1-RNAi cells were established by validated small interference RNAs. Cell proliferation and cell motility were observed and compared with Dock180-RNAi cells. To confirm their synergetic contribution to forming focal adhesion and activating Rac1, Rac1-GTP level was measured by GST pull-down assay and immunofluorescence was used to observe focal adhesion formation both in Elmo1-RNAi and Dock180-RNAi cells. RESULTS: Engulfment and cell motility 1 was mainly overexpressed in high-grade SOC tissues. Western blot analysis demonstrated that both Elmo1 and Dock180 expressions were hampered in Elmo1-RNAi cells. Compared with the negative control, decreased colony formation and cell invasion were observed in Elmo1-RNAi cells and Dock180-RNAi cells. Consistently, both exhibited reduced Rac1-GTP level and inhibited focal adhesion formation. CONCLUSIONS: Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Proteínas de Unión al GTP rac/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Adhesión Celular , Ciclo Celular , Proliferación Celular , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Guanosina Trifosfato/metabolismo , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , ARN Interferente Pequeño/genética , Células Tumorales Cultivadas , Proteínas de Unión al GTP rac/antagonistas & inhibidores , Proteínas de Unión al GTP rac/genéticaRESUMEN
Gestational diabetes mellitus (GDM) is a major public health issue, and the aim of the present study was to identify the factors associated with GDM. Databases were searched for observational studies until August 20, 2020. Pooled odds ratios (ORs) were calculated using fixed- or random-effects models. 103 studies involving 1,826,454 pregnant women were identified. Results indicated that maternal age ≥ 25 years (OR: 2.466, 95% CI: (2.121, 2.866)), prepregnancy overweight or obese (OR: 2.637, 95% CI: (1.561, 4.453)), family history of diabetes (FHD) (OR: 2.326, 95% CI: (1.904, 2.843)), history of GDM (OR: 21.137, 95% CI: (8.785, 50.858)), macrosomia (OR: 2.539, 95% CI: (1.612, 4.000)), stillbirth (OR: 2.341, 95% CI: (1.435, 3.819)), premature delivery (OR: 3.013, 95% CI: (1.569, 5.787)), and pregestational smoking (OR: 2.322, 95% CI: (1.359, 3.967)) increased the risk of GDM with all P < 0.05, whereas history of congenital anomaly and abortion, and HIV status showed no correlation with GDM (P > 0.05). Being primigravida (OR: 0.752, 95% CI: (0.698, 0.810), P < 0.001) reduced the risk of GDM. The factors influencing GDM included maternal age ≥ 25, prepregnancy overweight or obese, FHD, history of GDM, macrosomia, stillbirth, premature delivery, pregestational smoking, and primigravida.
Asunto(s)
Diabetes Gestacional/epidemiología , Adulto , Diabetes Gestacional/diagnóstico , Femenino , Humanos , Estilo de Vida , Edad Materna , Salud Materna , Estudios Observacionales como Asunto , Paridad , Embarazo , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Adulto JovenAsunto(s)
Neoplasias Endometriales , Esplenosis , Humanos , Esplenosis/diagnóstico , Esplenosis/diagnóstico por imagen , Esplenosis/patología , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/diagnóstico , Diagnóstico Diferencial , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Pelvis , EsplenectomíaRESUMEN
In this study, the beneficial effect of paeonol on acute alcohol-induced liver injury and the basic mechanisms were investigated. in vitro, HepG2 cells were treated with paeonol for 24â¯h before it were exposed to alcohol for 24â¯h. in vivo, male C57BL/6 mice were used to establish alcohol-induced liver injury models by oral gavage of alcohol (5â¯g/kg BW). Paeonol pretreatment showed statistically significant reduction in alcohol-induced ROS, MDA, IL-1ß, IL-6, TNF-α, and nitric oxide, while GSH content was retained (Pâ¯<â¯0.05). Furthermore, paeonol treatment resulted in the increase of Nrf2 nuclear translocation, the increase of NQO-1 and HO-1 expression, and the suppression of NF-κB p65 nuclear translocation. However, pretreatment with NAM (inhibitor of SIRT1) not only inhibited the effect of paeonol on reducing nuclear translocation of NF-κBp65, but also inhibited the effect of paeonol on promoting the expression of nuclear Nrf2, NQO1 and HO-1. Besides, paeonol pretreatment at test doses significantly ameliorated alcohol-induced edema, hepatocyte necrosis and hepatic cord irregular. These results demonstrated that paeonol has the high potential for relieving acute alcohol-induced liver injury.
Asunto(s)
Acetofenonas/administración & dosificación , Alcoholismo/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Sirtuina 1/metabolismo , Acetofenonas/farmacología , Alcoholismo/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacosRESUMEN
2'-O-galloylhyperin (2'-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2'-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2'-O-GH significantly inhibited hydrogen peroxide (H2O2)-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H2O2-stimulated HepG2 cells were remarkably inhibited by 2'-O-GH. Furthermore, 2'-O-GH stimulation resulted in a fast and dramatic activation of Akt and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with the increased expression of heme oxygenase-1 (HO-1) and levels of glutathione (GSH). Meanwhile, histopathological evaluation of the liver also revealed that 2'-O-GH effectively ameliorated CCl4-induced the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Therefore, these results suggested the hepatoprotective effect of 2'-O-GH might be correlated with its antioxidant and free radical scavenger effect.
Asunto(s)
Antioxidantes/metabolismo , Ácido Gálico/análogos & derivados , Hígado/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Quercetina/análogos & derivados , Animales , Elementos de Respuesta Antioxidante/efectos de los fármacos , Apoptosis/efectos de los fármacos , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Ácido Gálico/farmacología , Células Hep G2/efectos de los fármacos , Células Hep G2/patología , Humanos , Peróxido de Hidrógeno/farmacología , Hígado/metabolismo , Hígado/patología , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Ratones Endogámicos ICR , Sustancias Protectoras/farmacología , Quercetina/farmacologíaRESUMEN
Complete resection is pivotal to improve survival to epithelial ovarian cancer (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is involved in multiple signaling pathways and it has opposite roles in different cancers. The present study aimed to identify C3G expression in ovarian tissue samples from patients with EOC and to explore its association with tumor grade. Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues with serous histology were stained for C3G by immunohistochemistry. To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery of SOC. Knockdown of C3G suppressed cell invasion, intravasation and extravasation, and reduced Rap1 activity and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9. These results suggest that C3G is involved in the metastatic spread of EOC.