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The present results indicate that oxidative damage
2021-11-29
The present results indicate that oxidative damage in CFS muscles is not due to the decline in the efficiency of antioxidative enzymes. This suggests that there is an increase in the generation of reactive oxygen species consistent with a mitochondrial origin of the damage. Mitochondria represent th
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The CNP pGC B cGMP pathway has been reported
2021-11-29
The CNP/pGC-B/cGMP pathway has been reported to be potent inhibitor of fibrosis, from an intrinsic compensatory protective response as well as a therapeutic in cardiorenal injury and disease states [6,12,13,22,30]. Indeed, fibrosis is a progressive process leading to increased risk for morbidity and
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A repertoire of cytotoxic payloads is
2021-11-29
A repertoire of cytotoxic payloads is increasing; among those, MMAE has been utilized for the highly effective ADC brentuximab vedotin. However, the ADCs which utilized MMAE to target GCC in solid tumors have shown a poor efficacy suggesting that various tumor types respond differently to a given to
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In summary we discovered azaindole substituted hydroxypyrido
2021-11-29
In summary, we discovered 7-azaindole substituted -hydroxypyridone as a potent zinc-binding GLO1 inhibitor (IC=11nM) through lead generation from HTS and structure-based inhibitor design. The X-ray cocrystal structure and the comparison of binding energies with the indole counterpart revealed that
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Several reports have shown that the ICD of CLRs is
2021-11-29
Several reports have shown that the ICD of CLRs is involved in the desensitization process of this superfamily. The analysis of our chimeric constructs between GlyRα1 and GLIC revealed differences in desensitization properties. In contrast, other ion channel properties such as channel block and ion
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It is becoming increasingly apparent
2021-11-29
It is becoming increasingly apparent that membrane lipids play a critical role in modulating and regulating protein function. For example, embedding the homologous SLC1 transporter GltPh in a POPE bilayer allowed a third Na+ binding site to be identified from MD simulations [42], and the binding ene
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With rare exceptions the biological
2021-11-26
With rare exceptions, the biological role of γ-secretase cleavage of substrates other than Notch 1 has been ignored during proof of concept preclinical repurposing studies. For example, in the GSI AD trial, many individuals noted changes in hair color, apparently due to inhibition of tyrosinase, ano
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Several observations about structure activity relationships
2021-11-26
Several observations about structure–activity relationships can be made from this series, including that: (1) all lead compounds are NSAIDs of the 2-arylpropionic metabotropic glutamate receptor class, (2) analogues with -oriented aryl substituents showed the best inhibition of FAAH, and (3) replaci
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Management of HIV treatment with
2021-11-26
Management of HIV-1 treatment with HIV PIs can be complicated due to wide inter-patient variability in catalase inhibitor levels. In certain scenarios, therapeutic drug monitoring (TDM) has been recommended as a useful approach to individualize therapy for HIV-infected patients [[9], [10], [11], [1
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GSK has also been used as PET radiotracer in the
2021-11-26
GSK-189254 has also been used as PET radiotracer (in the form of [11C]-GSK-189254, also used as [11C]-AZ12807110 by Jucaite et al. (Jucaite et al., 2013)) to assess H3R occupancy (Ashworth et al., 2010), and is currently used in an image-based phase I clinical trial study for investigating GSK-23951
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mi2 receptor The electroconductive or electrocatalytic prope
2021-11-26
The electroconductive or electrocatalytic properties of conductive moieties including polymers in combination with carbon or metal-based nanomaterials have also been explored. For example, Dong et al. (2017) developed a portable electrochemical immunosensor by creating a film of Prussian blue chitos
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SKF 83566 hydrobromide Newly identified evidence has put imm
2021-11-26
Newly identified evidence has put immune checkpoint inhibitors into the spotlight. However, even though they have been reported to achieve optimistic outcomes [67], there is still a provocative question about their limitations [68]. The solid evidence above has provided us with translational values
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br Materials and Methods A human skin SCC
2021-11-26
Materials and Methods A431 (human skin SCC) and HT-297.T (human AK) cell lines were purchased from ATCC (Manassas, VA) and were maintained in DMEM supplemented with 10% fetal calf serum, 4 mM L-Gln, 1 mM sodium pyruvate, 100 U/mL penicillin, and 1 μg/mL streptomycin. Human HK1 and HK2 plasmids we
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br HO and cerebral malaria
2021-11-26
HO-1 and cerebral malaria In a post-mortem evaluation of human cerebral (falciparum) malaria, strong HO-1 immunostaining was consistently noted in microglia/macrophages within and surrounding the pathognomonic Durck’s granulomas (Schluesener et al., 2001). As witnessed in cerebral trauma specimen
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The data presented here support a dynamic
2021-11-26
The data presented here support a dynamic and complex interplay among labile heme, BACH1 and HO-1. It appears also that metabolites of heme degradation may participate in the mechanistic regulation of the various factors examined. Our results point to the possibility that the HO-1 pathway restricts
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