RESUMEN
Objective: Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) 2D 3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) 2D 3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. Methods: In vitro, HaCaT cells were treated with 1,25(OH) 2D 3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm 2, then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. Results: Compared with the HaCaT cells treated with 1,25(OH) 2D 3 or TAK-242, the cells treated with both 1,25(OH) 2D 3 and TAK-242 showed, 1) significantly lower production of ROS ( P < 0.05); 2) significantly less apoptosis of HaCaT cells ( P < 0.05); 3) significantly lower expression of NF- κB, Caspase-8, Cyto-C, Caspase-3 ( P < 0.05). Conclusion: The combination of 1,25(OH) 2D 3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) 2D 3 or TAK-242 alone.
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Células HaCaT , Receptor Toll-Like 4 , Humanos , FN-kappa B , Especies Reactivas de Oxígeno , Rayos Ultravioleta/efectos adversos , Colecalciferol/análogos & derivadosRESUMEN
Many industries produce large amounts of glycerol-based wastewater, which always contains hazardous organic chlorides. Compared with complicated biological treatments or physical adsorption, membrane separation decreases the cost and saves energy. Strong swelling of traditional thin-film composite (TFC) membranes influence the performance in the separation of organic molecules. Here we prepared TFC membranes with an acrylamide-grafted PAN support layer to copolymerize with m-phenylenediamine (MPD) and trimesoyl chloride (TMC). The link of separative layer and support layer was created like a zipper stitching to enhance the stability and resistance for the removal of organic molecules. An aquatic grass-like layer of acrylamide enlarges the surface area and hydrophilicity with superior separation performances (15.8 LMH bar-1 flux, 72.0% rejection of dichloropropanol (DCP) and 64.6% rejection of glycerol (Gl)). The trade-off upper bound was improved to a high level. We also established the simulations of evaporation using Aspen Plus and mathematical models of reverse osmosis to calculate the energy consumption corresponding to the recycle of glycerol-based wastewater. The experimental and theoretical results illustrate the advantages of acrylamide-grafted TFC membranes in the ap-plications to concentrate organic solutes and treat wastewater.
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Antineoplásicos Alquilantes/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/farmacología , Ginkgo biloba/química , Neoplasias Mamarias Animales/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Línea Celular , Línea Celular Tumoral , RatonesRESUMEN
OBJECTIVE: To explore the protective effects of dexmedetomidine (Dex) against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms. METHODS: HK-2 cells were exposed to either glucose or glucose+Dex for 6 h. The production of ROS, morphology of HK-2 cells, and cell cycle were detected. Moreover, the expression of AKT, p-AKT, ERK, p-ERK, PI3K, E-Cadherin, Claudin-1, and α-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126. RESULTS: Compared with HK-2 cells exposed to high level of glucose, the HK-2 cells exposed to both high level of glucose and Dex showed: (1) lower level of ROS production; (2) cell morphology was complete; (3) more cells in G1 phase; (4) lower expression of p-AKT, p-ERK and α-SMA, higher expression of E-Cadherin and Claudin-1. PI3K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT, p-ERK and α-SMA, and increased the expression of E-Cadherin and Claudin-1. CONCLUSION: Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glucosa/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Línea Celular , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To identify the important risk factors for type 2 Diabetes Mellitus (T2DM) and develop effective strategies to address the problem of T2DM. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2DM. METHODS: Based on the criteria of inclusion and exclusion, we extracted, pooled, analyzed and assessed the case-control studies of ApoE polymorphism and T2DM published in PubMed, Web of Science, Medline, WanFang, VIP, and CNKI databases by R soft-ware (version 3.4.3). We used Random-effect models when heterogeneity was present in between-study, and fixed-effect models otherwise. RESULTS: We had 59 studies covering 6,872 cases with T2DM and 8,250 controls, and compared the alleles and genotypes of ApoE between cases and controls. When we conducted a comparison between ApoE ε4 and ε3 alleles, we produced a pooled OR of 1.18 (95% CI: 1.09-1.28; P < 0.001). ApoE ε2/ε2 genotype displayed a possible association with T2DM (OR = 1.46; 95% CI: 1.11-1.93; P = 0.007), ε3/ε4 genotype showed a 1.11-fold risk (OR = 1.11; 95% CI: 1.01-1.22; P = 0.039) and ε4/ε4 genotype had a 1.71-fold risk of developing T2DM (OR = 1.71; 95% CI: 1.33-2.19; P < 0.001) when they were compared with ε3/ε3 genotype. CONCLUSION: There is an association between ApoE polymorphism and T2DM: allele ε4 and genotypes (ε2/ε2, ε3/ε4, and ε4/ε4) are associated with the increased risk for the development of T2DM, and they may be risk factors for T2DM.
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Apolipoproteínas E/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , Alelos , Apolipoproteínas E/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Predisposición Genética a la Enfermedad , Genotipo , HumanosAsunto(s)
Dimetoato/análogos & derivados , Resistencia a la Insulina , Insulina/sangre , Hígado/efectos de los fármacos , Plaguicidas/toxicidad , Animales , Glucemia/efectos de los fármacos , Colesterol/sangre , Dimetoato/toxicidad , Hígado/metabolismo , Masculino , Ratones Endogámicos ICR , Transducción de Señal/efectos de los fármacos , Triglicéridos/sangreRESUMEN
A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.
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Agresión , Conducta Impulsiva , Exposición Profesional , Intoxicación por Organofosfatos/complicaciones , Plaguicidas/efectos adversos , Intento de Suicidio/estadística & datos numéricos , Adulto , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Organofosfatos/efectos adversos , Factores de RiesgoRESUMEN
Paraquat (PQ) is a widely used herbicide, and lung is the primary target of PQ poisoning. Metallothionein (MT) is a potent antioxidant and free radical scavenger, and has been shown to play a protective role in lung injury induced by different stressors. This study was undertaken to evaluate the protective potential of MT against PQ-induced acute lung injury using MT-I/II null (MT(-/-)) mice. Wild-type (MT(+/+)) mice and MT(-/-) mice were given one intragastric administration of 50mg/kg PQ for 24h, and it was revealed that MT(-/-) mice were more susceptible to PQ-induced acute lung injury than MT(+/+) mice evidenced by the following findings. As compared with MT(+/+) mice, MT(-/-) mice presented more severe histopathological lesions in the lung, higher pulmonary malondialdehyde content, and more reduced pulmonary antioxidative enzymes activities. PQ also induced more apoptosis in pneumocytes from MT(-/-) mice, and the expressions of apoptosis-related proteins Bax, Bcl-2, cleaved-caspase-3, and the ratio of Bax/Bcl-2 were all more significantly increased in PQ-treated MT(-/-) mice. Our results clearly demonstrate that endogenous MT can attenuate PQ-induced acute lung injury, possibly through the mechanisms of anti-oxidation and anti-apoptosis.
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Lesión Pulmonar Aguda/prevención & control , Antioxidantes , Apoptosis/fisiología , Herbicidas/toxicidad , Metalotioneína/fisiología , Paraquat/toxicidad , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/enzimología , Animales , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Ratones , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To investigate variations of plasma endothelin (ET) and its clinical significance in portal hypertensive patients with esophageal variceal hemorrhage. METHODS: Sixty-six patients with portal hypertension were randomly divided into 2 groups. Group I (32 patients) received general therapy and Group II (34 patients) received general therapy and UTI after hemorrhage. The plasma ET concentration and liver function were determined at 1, 2, 4, 7, 10, and 14 d after the hemorrhage. Another 20 patients without the hemorrhage were elected as the control group. RESULTS: At 7 and 14 d after the hemorrhage, the levels of TBIL, ALT and AST were elevated at first and then decreased in Groups I and II. The decrease of TBIL, ALT and AST levels was significantly faster in Group II than in Group I (P < 0.05, P < 0.01, P < 0.05, respectively) on 14 d after the hemorrhage. At 1 d after the hemorrhage the ET concentration was markedly increased in Group I and II as compared with the control group (P < 0.01). Then it was gradually decreased on 10 d after the hemorrhage. The ET concentration in Group II was decreased more rapidly than that in Group I on 2, 4 and 7 d after the hemorrhage (P < 0.05; P < 0.01; P < 0.05, respectively). The ET concentration was positively correlated to TBIL levels in groups I and II (r = 0.734, P < 0.01). And the decreased index of ET concentration was negatively correlated to the increased index of TBIL (r = -0.486, P < 0.05). CONCLUSION: The increased plasma ET in portal hypertensive patients with hemorrhage may contribute to liver injury. UTI can protect the liver function by inhibiting ALT, AST, TBIL and ET level.
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Endotelina-1/sangre , Várices Esofágicas y Gástricas/etiología , Glicoproteínas/uso terapéutico , Hipertensión Portal/complicaciones , Adulto , Anciano , Várices Esofágicas y Gástricas/sangre , Femenino , Humanos , Hipertensión Portal/sangre , Fallo Hepático/prevención & control , Masculino , Persona de Mediana Edad , Inhibidores de Tripsina/uso terapéuticoRESUMEN
AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats. METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M(7), M(14), and M(21)) in which the rats were kiued on the seventh day, the 14(th) d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C(7), C(14) and C(21)) corresponding to the models. The expression of TNF-alpha and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique. RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82+/-1.83 vs 11.61+/-0.86 cmH(2)O, 20.90+/-3.27 vs 11.43+/-1.55 cmH(2)O and 20.68+/-2.27 vs 11.87+/-0.79 cmH(2)O respectively, P<0.01), as well as the number (9.3+/-1.6 vs 5.1+/-0.8, 11.1+/-0.8 vs 5.4+/-1.3 and 11.7+/-1.5 vs 5.2+/-1.1 respectively, P<0.01) and the total vascular area (78 972.6+/-3 527.8 vs 12 993.5+/-4 994.8 mum(2), 107 207.5+/-4 6461.4 vs 11 862.6+/-5 423.2 mum(2) and 110 241.4+/-49 262.2 vs 11 973.7+/-3 968.5 mum(2) respectively, P<0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNF-alpha and VEGF in M(21) was significantly higher (2.23+/-0.30 vs 1.13+/-0.28 and 1.65+/-0.38 vs 0.56+/-0.30 for TNF-alpha and VEGF respectively, P<0.01), whereas there was no difference in M(7) (1.14+/-0.38 vs 1.06+/-0.27 and 0.67+/-0.35 vs 0.50+/-0.24 for TNF-alpha and VEGF respectively, P>0.05) and M(14) (1.20+/-0.25 vs 1.04+/-0.26 and 0.65+/-0.18 vs 0.53+/-0.25 for TNF-alpha and VEGF respectively, P>0.05). And the expression of TNF-alpha and VEGF in M(21) was significantly higher than that in M(7) (2.23+/-0.30 vs 1.14+/-0.38 and 1.65+/-0.38 vs 0.67+/-0.35 for TNF-alpha and VEGF respectively, P<0.01) and M(14) (2.23+/-0.30 vs 1.20+/-0.25 and 1.65+/-0.38 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P<0.01), but there was no difference between M(7) and M(14) (1.14+/-0.38 vs 1.20+/-0.25 and 0.67+/-0.35 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P>0.05). CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-alpha and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.
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Várices Esofágicas y Gástricas/metabolismo , Esófago/metabolismo , Hipertensión Portal/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Presión Sanguínea , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/patología , Esófago/irrigación sanguínea , Esófago/patología , Hipertensión Portal/complicaciones , Hipertensión Portal/patología , Masculino , Membrana Mucosa/irrigación sanguínea , Membrana Mucosa/metabolismo , Ratas , Ratas Sprague-Dawley , Rotura , Venas/patologíaRESUMEN
OBJECTIVE: To investigate the prevention of esophageal varices recurrence by laser inducing esophageal mucosal fibrosis. METHODS: Our study included 42 patients after esophageal varices eradicated by endoscopic varices ligation, and they were divided into 2 groups randomly, each group included 21 patients. One group was assigned to received laser treatment, and indocyanine green solution (1 mg/ml) was injected submucosally, a diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. Another group was controlling without any treatments. All patient were followed up by endoscopy every 3 months until 12 months. RESULTS: Laser irradiation was performed safely without any major complications. And lower esophageal mucosa produced fibrosis widely after laser irradiated 1 month. After 12 months follow up, the cumulative recurrence rate was significantly lower than the control group, 14% (3/21) vs 43% (9/21) (chi(2) = 4.20, P < 0.05). CONCLUSIONS: Our study indicates that laser inducing mucous fibrosis is safely and can prevent recurrence of esophageal varices.