RESUMO
Prediabetes is defined as a state of moderate hyperglycemia. Here, we used freeze-dried seeds of Stenocereus stellatus (white tunillo) as a possible therapeutic strategy for the treatment of prediabetes. In the aqueous extract of freeze-dried seeds of white tunillo, polyphenols were identified using the Folin-Ciocalteu technique, separated by UPLC and analyzed by infrared spectrophotometry. Five well-defined peaks with good resolution were observed in the chromatogram of the aqueous extract obtained by UPLC. Two of these peaks corresponded to polyphenols with similarity to quercetin and rutin. The subchronic oral administration of freeze-dried seeds of white tunillo for 14 days in a prediabetes model in female Wistar rats reversed hyperglycemia and glucose intolerance. Treatment with the freeze-dried seeds reversed the decrease in the hepatic expression of Akt, eNOS, and p-eNOSSer1177 but did not reverse the decrease in MnSOD, catalase, and GPx1. No changes in the expression of GPx4 and p-AktSer473 were observed in the pathological state or with the treatment but there was an increase in the expression and activity of eNOS. The bioactive compounds present in the freeze-dried seeds of Stenocereus stellatus could provide guidelines for studying the mechanisms of action through which they reverse signs of prediabetes.
Assuntos
Liofilização , Extratos Vegetais , Estado Pré-Diabético , Ratos Wistar , Sementes , Animais , Feminino , Sementes/química , Ratos , Estado Pré-Diabético/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Polifenóis/farmacologia , Polifenóis/química , Modelos Animais de Doenças , Glicemia/metabolismoRESUMO
Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.
RESUMO
The use of oral anticoagulants (OA) is problematic due to its association with hemorrhagic complications. OA metabolism relies on the CYP2C9 complex. Genetic variations compromising metabolic competence of this complex may explain the risk of excessive and hazardous anticoagulation. A pharmacogenetics-based approach to this issue could be beneficial for choosing adequate dose and duration of treatment, in addition to having a better understanding of pharmacological interactions to which OA are susceptible. However, evidence from several basic and clinical studies indicates that both a complicated system of regulation of expression of multiple genes and the influence of a wide variety of epigenetic factors could be responsible for adverse drug reactions associated with the use of OA. Emphasis on understanding the gene-environment interactions could attain new paths to facilitate the use of these important drugs in the quotidian clinical practice.
Assuntos
Anticoagulantes/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Epigênese Genética , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Biotransformação/genética , Citocromo P-450 CYP2C9 , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , FarmacogenéticaRESUMO
La presente revisión menciona las características del factor de necrosis tumoral-a y el papel que esta citocina juega en el desarrollo de la lesión ateromatosa. Se describe, al detalle los efectos que tiene esta citocina sobre células endoteliales vasculares en condiciones normales así como de alto riesgo. Se propone que el TNF-a posee un papel central en el desarrollo inicial y en el progreso de la placa ateromatosa debido a que al afectarse los mecanismos de autorregulación de la célula endotelial la concentración de TNF-a se eleva de manera importante a nivel local generando, junto con la presencia local de diversos factores conocidos de riesgo, un microambiente autoperpetuable que favorece el desarrollo de la lesion ateromatosa.