RESUMEN
Cancer-associated fibroblast (CAF), an activated type of fibroblast, is a major stromal cell that contributes to tumor initiation and development in the tumor microenvironment (TME). We previously reported that fractionated radiation rather than acute radiation causes progressive damage to mitochondria and increases the generation of reactive oxygen species, playing an important role in the fibroblast activation in normal tissue injury. Activated fibroblasts then become CAF by interacting with tumor cells, promoting tumor growth in vivo. We here examined the chronic radiation effect on fibroblast activation. Acute radiation (<2.5 Gy) did not increase alpha-Smooth muscle actin, a CAF marker expression in healthy human cells, whereas chronic radiation (2.5 Gy) did. It can be concluded that the induction of fibroblast activation changes across acute radiation, fractionated radiation, and chronic radiation depending on the irradiation technique. This study highlights that radiation activates fibroblasts, playing a role in radiation-related tumor development via TME formation.
Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Fibroblastos/metabolismo , Humanos , Neoplasias/patología , Especies Reactivas de Oxígeno/metabolismo , Microambiente TumoralRESUMEN
OBJECTIVES: Compared to type 1 diabetes, the role of the immune and autoimmune pathogenetic mechanisms is much less studied in the type 2 diabetes. Toll-like receptors 4 (TLR4) have a leading role in inflammation, insulin resistance, and vascular damage. This study aimed to analyze the relationship between the polymorphisms in TLR4 gene and different stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications. MATERIALS AND METHODS: The study included 113 patients with the type 2 diabetes, 29 participants with prediabetes, and 28 controls. Polymerase chain reaction (PCR) was used for genotyping Asp299Gly and Thr399Ile polymorphism, followed by restriction analysis. RESULTS: The difference in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not significant. Patients with heterozygous genotype of Asp299Gly polymorphism had a higher prevalence of diabetic retinopathy (42.9%) than participants with homozygous genotype (9.0%) (OR [95%CI]=7.61 [1.41-41.08]; p=0.018). No association was established for diabetic polyneuropathy and nephropathy. Prevalence of chronic diabetes complications was not related to Thr399Ile polymorphism. CONCLUSION: Our study demonstrates that Asp299Gly and Thr399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Predisposición Genética a la Enfermedad , Receptor Toll-Like 4/genética , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Glucosa , Humanos , Polimorfismo de Nucleótido Simple , Estado PrediabéticoRESUMEN
The study aimed to differentiate the factors triggering porphyria cutanea tarda, paying special attention to the presumed role of hepatitis C virus infection. In a representative Bulgarian contingent, HCV-antibodies were identified using ELISA II and immunoblot. Seropositivity was significantly higher (p < 0.01) in the sporadic form (36 out of 57 patients; 63.2%) compared with the familiar form (4 out of 20 subjects; 20%). Alcohol abuse was the most common factor preceding the expression of open porphyria both in the sporadic and the familiar forms. In 10 sporadic cases, no precipitating factors were observed, except for the fact that they were anti-HCV positive. In another 2 anti-HCV positive patients, porphyria cutanea tarda was preceded by blood transfusions. Renewed consumption of alcohol after successful treatment was a common reason for relapse, but relapses were most frequent in anti-HCV positive patients (35 relapses in 12 patients), in whom other promoting factors were absent. Analysis of triggering factors shows that most probably hepatitis C virus infection could contribute to the expression of porphyria cutanea tarda and the association of both diseases is not coincidental.
Asunto(s)
Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/análisis , Hepatitis C/complicaciones , Porfiria Cutánea Tardía/virología , Adulto , Anciano , Bulgaria , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Hepatitis C/virología , Humanos , Immunoblotting , Hierro/uso terapéutico , Masculino , Persona de Mediana Edad , Porfiria Cutánea Tardía/diagnóstico , Porfiria Cutánea Tardía/terapia , Prevalencia , Recurrencia , Factores de RiesgoRESUMEN
Surface-activated silicas with methacrylate double bonds were introduced into a reaction medium where copolymerization of 1-vinyl-2-pyrrolidone (VP) and maleic anhydride (MA) took place. The copolymerization led to the formation of non-alternating copolymers of VP and MA. Each macromolecule of this copolymer consisted of alternately arranged regulated long sequences of VP units and single units of MA. The possibility for covalent bonding of beta-galactosidase to the MA units at different lengths of the VP sequences was studied. The content of coupled enzyme, as well as its activity, pH dependence and stability were determined.
