Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo, further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.
About one-third of patients with suspected IBS had fructose intolerance. When compliant, symptoms improved on fructose-restricted diet despite moderate impact on lifestyle; noncompliance was associated with persistent symptoms. Fructose intolerance is another jigsaw piece of the IBS puzzle that may respond to dietary modification.
Fructose intolerance may cause unexplained GI symptoms. The higher yield of positive tests in our initial study may be due to referral bias or testing conditions; lower test dose produced a lower yield. Nonetheless, recognition and treatment of fructose intolerance may help many patients.
Fructose intolerance may cause unexplained GI symptoms. The higher yield of positive tests in our initial study may be due to referral bias or testing conditions; lower test dose produced a lower yield. Nonetheless, recognition and treatment of fructose intolerance may help many patients.
Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP) conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP) self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP) NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP) NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.
This paper describes the manufacturing method and properties of a superalloy as a gas turbine blade material and a thermal barrier coating to protect it. The development process of superalloy and characteristics of each casting method were introduced. In particular, the single crystal superalloys were analyzed for creep and tensile properties with temperature according to chemical composition. In addition, the theories of creep life prediction models were summarized and comparative analysis was performed. Finally, the manufacturing processes of thermal barrier coatings were introduced, and the characteristics and effects of mechanical, thermal, and durability characteristics of each manufacturing process are described. We believe that this comprehensive review will help not only the gas turbine industry/community, but also material scientists, measurement physicists/engineers, and theorists interested in superalloys and high-temperature ceramics.
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