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- La Spina, M, et al.
(author)
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Multiple Mechanisms Converging on Transcription Factor EB Activation by the Natural Phenol Pterostilbene
- 2021
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In: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2021, s. 7658501-
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Journal article (peer-reviewed)abstract
- Pterostilbene (Pt) is a potentially beneficial plant phenol. In contrast to many other natural compounds (including the more celebrated resveratrol), Pt concentrations producing significant effects in vitro can also be reached with relative ease in vivo. Here we focus on some of the mechanisms underlying its activity, those involved in the activation of transcription factor EB (TFEB). A set of processes leading to this outcome starts with the generation of ROS, attributed to the interaction of Pt with complex I of the mitochondrial respiratory chain, and spreads to involve Ca2+ mobilization from the ER/mitochondria pool, activation of CREB and AMPK, and inhibition of mTORC1. TFEB migration to the nucleus results in the upregulation of autophagy and lysosomal and mitochondrial biogenesis. Cells exposed to several μM levels of Pt experience a mitochondrial crisis, an indication for using low doses in therapeutic or nutraceutical applications. Pt afforded significant functional improvements in a zebrafish embryo model of ColVI-related myopathy, a pathology which also involves defective autophagy. Furthermore, long-term supplementation with Pt reduced body weight gain and increased transcription levels of Ppargc1a and Tfeb in a mouse model of diet-induced obesity. These in vivo findings strengthen the in vitro observations and highlight the therapeutic potential of this natural compound.
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| 5. |
- Wheatley, Lisa M., et al.
(author)
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Mind the gaps : Clinical trial concepts to address unanswered questions in aeroallergen immunotherapy-An NIAID/AHRQ Workshop
- 2019
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 143:5, s. 1711-1726
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Journal article (peer-reviewed)abstract
- The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT; (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized; (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.
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- Petronilli, V, et al.
(author)
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Flow-force relationships during energy transfer between mitochondrial proton pumps
- 1991
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In: Biochimica et Biophysica Acta - Bioenergetics. - 0005-2728 .- 1879-2650. ; 1058:2, s. 297-303
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Journal article (peer-reviewed)abstract
- The effect of inhibitors of proton pumps, of uncouplers and of permeant ions on the relationship between input force, , and output flows of the ATPase, redox and transhydrogenase H+-pumps in submitochondrial particles was investigated. It is concluded that: (1) The decrease of output flow of the transhydrogenase proton pump, defined as the rate of reduction of NADP+ by NADH, is linearily correlated with the decrease of input force, , in an extended range of , independently of whether the H+-generating pump is the ATPase or a redox pump, or whether is depressed by inhibitors of the H+-generating pump such as oligomycin or malonate, or by uncouplers. (2) The output flows of the ATPase and of the site I redox H+-pumps exhibit a steep dependence on . The flow-force relationships differ depending on whether the depression of is induced by inhibitors of the H+-generating pump, by uncouplers or by lipophilic anions. (3) With the ATPase as H+-consuming pump, at equivalent values, the output flow is more markedly inhibited by malonate than by uncouplers; the latter, however, are more inhibitory than lipophilic anions such as ClO4−. With redox site I as proton-consuming pump, at equivalent values, the output flow is more markedly inhibited by oligomycin than by uncouplers; again, uncouplers are more inhibitory than ClO4−. (4) The results provide further support for a delocalized interaction of transhydrogenase with other H+-pumps.
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