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1.
CNS Neurosci Ther ; 30(9): e70025, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39228080

RESUMEN

AIMS: The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. METHODS: HD N171-82Q transgenic and WT mice received luteolin or vehicle for treatment at 6 weeks of age. The mice's body weight changes and survival rates were monitored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. RESULTS: Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle-treated HD group. Furthermore, the luteolin-treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin-treated HD mice compared to the vehicle-treated HD group. CONCLUSION: Luteolin holds promise as a therapeutic agent for improving survival outcomes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression.


Asunto(s)
Modelos Animales de Enfermedad , Proteína Huntingtina , Enfermedad de Huntington , Luteolina , Ratones Transgénicos , Animales , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/metabolismo , Luteolina/farmacología , Luteolina/uso terapéutico , Ratones , Proteína Huntingtina/genética , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Proteínas de Neurofilamentos/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Humanos
2.
PLoS One ; 19(9): e0302698, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39302983

RESUMEN

BACKGROUND: Snakebite statistics in Sudan are lacking despite the high estimated burden of the problem. One study in Sudan reported the presence of 17 medically significant snakes belonging to three major families: Burrowing asps, Elapidae, and Viperidae. These snakes usually become abundant during and after the rainy season, and most snakebite victims are farm workers. This study was set out based on the observed snakebite management, poor outcomes and lack of information on the healthcare provider's knowledge of this serious, deadly medical and health condition in snakebite-endemic regions of Sudan. MATERIALS AND METHODS: In August 2022, a descriptive cross-sectional survey was conducted involving 394 medical and healthcare providers in snakebite-endemic regions of Sudan (Gaddarif, Sinnar, Khartoum, and Kassala). A validated questionnaire was used. It consisted of seven sections addressing the study population demographic characteristics, knowledge of snakes, snakebites, and their management. Data analysis used various statistical tests using Microsoft Excel and the Statistical Package for Social Sciences (SPSS) version 20 (IBM SPSS Inc., Chicago, IL) was done. RESULTS: Among the 394 participants (44.7% males, 53.3% females), 58.1% demonstrated adequate knowledge of snakes, and 45.3% exhibited adequate knowledge of snakebites. A mere 25.9% received training in snakebite management, with 60.4% possessing adequate knowledge in this domain. Only 14% expressed high confidence in managing snakebites, and 40.9% reported having protocols for snakebite management at their health facilities. CONCLUSION: The study highlighted the inadequacy of healthcare providers' knowledge in snakebite-endemic areas in Sudan regarding snakes, snakebites and snakebites management. Urgent interventions, such as intensive continuing professional education and training, are essential to address this neglected medical and health problem.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Mordeduras de Serpientes , Serpientes , Mordeduras de Serpientes/epidemiología , Mordeduras de Serpientes/terapia , Humanos , Sudán/epidemiología , Femenino , Masculino , Personal de Salud/psicología , Adulto , Animales , Estudios Transversales , Encuestas y Cuestionarios , Persona de Mediana Edad
3.
Saudi Pharm J ; 31(12): 101871, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38125952

RESUMEN

Background: Huntington's disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 -HO-1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington's disease.

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