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Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications. 相似文献
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The accumulation and preservation of peat soils in Everglades freshwater marshes and mangrove swamps is an essential process
in the ecological functioning of these ecosystems. Human intervention and climate change have modified nutrient dynamics and
hydroperiod in the Everglades and peat loss due to such anthropogenic activities is evident. However, not much is known on
the molecular level regarding the biogeochemical characteristics, which allow peat to be preserved in the Everglades. Lipid
biomarkers trapped within or bound to humic-type structures can provide important geochemical information regarding the origin
and microbial transformation of OM in peat. Four lipid fractions obtained from a Cladium peat, namely the freely extractable fraction and those associated with humin, humic acid, and fulvic acid fractions, showed
clear differences in their molecular distribution suggesting different OM sources and structural and diagenetic states of
the source material. Both, higher plant derived and microbial lipids were found in association with these humic-type substances.
Most biomarker distributions suggest an increment in the microbial/terrestrial lipid ratio from the free to humin to humic
to fulvic fractions. Microbial reworking of lipids, and the incorporation of microbial biomarkers into the humic-type fractions
was evident, as well as the preservation of diagenetic byproducts. The lipid distribution associated with the fulvic acids
suggests a high degree of microbial reworking for this fraction. Evidence for this 3D structure was obtained through the presence
of the relatively high abundance of α,ω-dicarboxylic acids and phenolic and benzenecarboxylic compounds. The increment in
structural complexity of the phenolic and benzencarboxylic compounds in combination with the reduction in the carbon chain
length of the dicarboxylic acids from the free to fulvic fraction suggests the latter to be structurally the most stable,
compacted and diagenetically altered substrate. This analytical approach can now be applied to peat samples from other areas
within the Everglades ecosystem, affected differently by human intervention with the aim to assess changes in organic matter
preservation. 相似文献
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Georges Hajje Youakim Saliba Tarek Itani Majed Moubarak Georges Aftimos Nassim Farès 《PloS one》2014,9(10)
The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease. 相似文献
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