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1.
Sci Rep ; 11(1): 431, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33432101

RESUMEN

The pool of ß-Amyloid (Aß) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for Aß peptides. We examined how a naturally occurring variant, e.g. Aß(1-38), interacts with the AD-related variant, Aß(1-42), and the predominant physiological variant, Aß(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that Aß(1-38) interacts differently with Aß(1-40) and Aß(1-42) and, in general, Aß(1-38) interferes with the conversion of Aß(1-42) to a ß-sheet-rich aggregate. Functionally, Aß(1-38) reverses the negative impact of Aß(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an Aß(1-42) phenotype in Caenorhabditis elegans. Aß(1-38) also reverses any loss of MTT conversion induced by Aß(1-40) and Aß(1-42) in HT-22 hippocampal neurons and APOE ε4-positive human fibroblasts, although the combination of Aß(1-38) and Aß(1-42) inhibits MTT conversion in APOE ε4-negative fibroblasts. A greater ratio of soluble Aß(1-42)/Aß(1-38) [and Aß(1-42)/Aß(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that Aß(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant Aß(1-42).


Asunto(s)
Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/efectos adversos , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/farmacología , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Animales Modificados Genéticamente , Encéfalo/metabolismo , Encéfalo/patología , Caenorhabditis elegans , Células Cultivadas , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo
2.
Appl Spectrosc ; 70(11): 1883-1890, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27324425

RESUMEN

Synchrotron micro X-ray fluorescence (XRF) spectroscopy with two-dimensional element mapping, micro X-ray diffraction (XRD), electron spin resonance spectroscopy (ESR) and atomic force microscopy (AFM) were used to investigate the chemical and structural nature of the enamel of a tooth from Troodon, a small theropod dinosaur. These methods show that the crystallites in the Troodon tooth are submicron-sized carbonated calcium hydroxyapatite, which are semi-randomly oriented with a preferred orientation of (002) towards the surface of the tooth. Transition metal ions are distributed in the voids between crystallite clusters. Comparison of the ESR spectra indicates that the Troodon tooth had less exposure to UV than a fossilized crocodile tooth.


Asunto(s)
Esmalte Dental/química , Dieta , Dinosaurios/anatomía & histología , Ambiente , Fósiles , Animales , Evolución Biológica , Esmalte Dental/fisiología , Dinosaurios/fisiología , Microscopía de Fuerza Atómica , Espectrometría por Rayos X , Difracción de Rayos X
3.
Toxicol Rep ; 2: 1014-1018, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-28962442

RESUMEN

Flaxseed as well as its oil component possess antitumor activities against different types of cancer and have been used by some patients as complementary and/or alternative medicine. Linoorbitides (LOBs) are one family of flaxseed compounds that has implications for anticancer and antioxidant activity. The cytotoxicity of [1-9-NαC]-linusorb-B3 (LOB3), [1-9-NαC]-linusorb-B2 (LOB2), [1-9-NαC],[1-Rs,Ss-MetO]-linusorb-B2 ([MetO]-LOB2) and [1-8-NαC],[1-Rs,Ss-MetO]-linusorb-B1 ([MetO]-LOB1) was measured against human breast cancer Sk-Br-3 and MCF7 cell lines and melanoma A375 cell line. Overall cytotoxicity is cell-type specific. It scales as the hydrophobicity and concentration of the LOBs with the most abundant LOB3 being the most cytotoxic. Oral administration of LOB3 as a potential therapeutic agent might not be applicable as a much too high and/or frequent dose would be required to achieve a serum concentration of 400-500 µg/mL due to bioavailability and pharmacokinetic factors. However, LOB3 may be suitable for topical treatment formulations or as a lead compound in developing anticancer LOB derivatives.

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