RESUMEN
A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study in vitro showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.
Asunto(s)
Ciclohexilaminas/farmacología , Etanol/toxicidad , Ferroptosis/efectos de los fármacos , Hierro/metabolismo , Hepatopatías Alcohólicas/genética , Hígado/efectos de los fármacos , Fenilendiaminas/farmacología , Adenina/análogos & derivados , Adenina/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Animales , Autofagia/efectos de los fármacos , Autofagia/genética , Línea Celular , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Femenino , Ferroptosis/genética , Regulación de la Expresión Génica , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Imidazoles/farmacología , Indoles/farmacología , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hepatopatías Alcohólicas/etiología , Hepatopatías Alcohólicas/patología , Hepatopatías Alcohólicas/prevención & control , Ratones , Ratones Endogámicos C57BL , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Transducción de Señal , Vitamina E/farmacologíaRESUMEN
BACKGROUND: Our study aims to explore the knowledge, attitude, and practice (KAP) and its influencing factors of medication among residents in Haikou, the capital city of Hainan Province, and inform the development of interventions to reduce residents' medication errors. METHODS: A cross-sectional questionnaire survey was conducted to investigate the KAP of medication among Haikou residents and its influencing factors from March to September 2019. RESULTS: A total of 471 valid questionnaires were collected (245 online and 226 offline), with an effective recovery rate of 94.2%. The average score of KAP of medication were 52.2±13.08, 27.34±8.14, and 51.54±9.22, respectively. The knowledge score reached "good" in the evaluation criteria of the questionnaire, and the attitude and practice scores were "fair". Multiple linear regression analysis revealed the medication knowledge increased with age; a lower education degree was associated with less knowledge and more medication errors, and a higher education level was associated with more access to medication knowledge. CONCLUSIONS: Education on rational drug use should be performed via multiple ways to promote rational drug use and reduce risky medication behaviors, particularly among residents with low education degrees, e.g., drug counseling and guidance, regularly push medication science popularization, public welfare lecture on rational drug use, organize and compile popular science books.
Asunto(s)
Consejo , Conocimientos, Actitudes y Práctica en Salud , Estudios Transversales , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess the feasibility of MTT colorimetric assay for testing the in vitro chemosensitivity of breast cancer cells to 5 fluorouracil (5-Fu). METHODS: The chemosensitivity of human breast carcinoma cell lines MCF-7 and MDA-MB-435S to 5-Fu at different concentrations was evaluated with MTT assay. RESULTS: 5-FU treatment resulted in dose-dependent growth inhibition of the breast cancer cells with both low and high metastatic capacities. CONCLUSIONS: MTT assay may help select appropriate chemotherapeutic agents and provides evidence for individualized chemotherapy for breast cancer.