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1.
Bioorg Chem ; 82: 332-339, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30428413

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and is the most common cause of dementia in the elderly. The main hallmark of AD is the deposition of insoluble amyloid (Aß) outside the neuron, leading to amyloid plaques and neurofibrillary tangles in the brain. Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6), a novel porphyrin-peptide, has both microperoxidase activity and cell permeability. In the present study, DhHP-6 efficiently inhibited the aggregation of Aß and reduced the ß-sheet percentage of Aß from 89.1% to 78.3%. DhHP-6 has a stronger affinity (KD = 100 ±â€¯12 µM) for binding with Aß at Phe4, Arg5, Val18, Glu11 and Glu22. In addition, DhHP-6 (100 µM) significantly prolonged lifespan, alleviated paralysis and reduced Aß plaque formation in the Aß1-42 transgenic Caenorhabditis elegans CL4176 model of AD. Our results demonstrate that DhHP-6 is a potential drug candidate that efficiently protects a transgenic C. elegans model of Alzheimer's disease by inhibiting Aß aggregation.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Caenorhabditis elegans/química , Depuradores de Radicales Libres/farmacología , Hemina/análogos & derivados , Oligopéptidos/farmacología , Fragmentos de Péptidos/metabolismo , Multimerización de Proteína/efectos de los fármacos , Péptidos beta-Amiloides/genética , Animales , Animales Modificados Genéticamente , Materiales Biomiméticos/farmacología , Caenorhabditis elegans/genética , Hemina/farmacología , Longevidad/efectos de los fármacos , Simulación del Acoplamiento Molecular , Parálisis/tratamiento farmacológico , Fragmentos de Péptidos/genética , Peroxidasas/química , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta
2.
Front Public Health ; 10: 1052610, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36711357

RESUMEN

During the COVID-19 pandemic, many buildings in northeast China have had clusters of infected cases in the vertical layout. There is speculation that vertical aerosol transmission occurs. The houses in northeast China are airtight, and range hoods may be used for a long period of time when cooking. The pathway and factors influencing vertical aerosol transmission are worth studying. To elucidate a viral aerosol transmission pathway, we selected a multistory apartment and a high-rise building in Changchun city, Jilin province, China, to conduct an in-depth investigation and on-site simulation experiments. According to epidemiological investigation information on infected cases, building structures, drainage, ventilation, etc., we used fluorescent microspheres to simulate the behaviors of infected people, such as breathing and flushing the toilet after defecation, to discharge simulated viruses and track and monitor them. The field simulation experiment confirmed the transmission of fluorescent microsphere aerosols to other rooms in two types of buildings using a vertical aerosol transmission pathway of toilet flush-sewage pipe-floor drain without a water seal. Our study showed that, in the absence of a U-shaped trap or floor drain water seal whether in a multistory apartment or high-rise residential building, there is a transmission pathway of "excretion of virus through feces-toilet flushing-sewage pipe-floor drain without water seal," which will cause the vertical transmission of viral aerosol across floors during the COVID-19 pandemic. Moreover, the negative pressure generated by turning on the range hood when closing doors and windows increase aerosol transmission. Based on this negative pressure, prevention and control measures for residential buildings in northeast China during the COVID-19 pandemic were proposed.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Aguas del Alcantarillado , Aerosoles y Gotitas Respiratorias , China/epidemiología
3.
Free Radic Res ; 51(5): 529-544, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28503972

RESUMEN

Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 µM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans.


Asunto(s)
Envejecimiento/efectos de los fármacos , Estrofantinas/farmacología , Animales , Antioxidantes/farmacología , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Evaluación Preclínica de Medicamentos , Factores de Transcripción Forkhead/metabolismo , Estrés Oxidativo , Paraquat/toxicidad , Transporte de Proteínas , Especies Reactivas de Oxígeno/metabolismo
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