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The current lack of effective treatments for
2022-02-18
The current lack of effective treatments for primary or metastatic UM leaves a large therapeutic gap for patients and clinicians underscoring an urgent need for the identification of additional pharmacological targets for therapeutic intervention. As YAP-targeting strategies have remained elusive th
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In T cells whereas SETDB is implicated
2022-02-18
In T cells, whereas SETDB1 is implicated in OX40-dependent repression of the Il17a locus in Th17 cells (Xiao et al., 2016), SUV39H1 controls Th2 cell stability by depositing H3K9me3 at the Ifng promoter (Allan et al., 2012). However, the deregulation of the Ifng locus observed in Suv39h1−/− cells ca
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Here we report the kinetics of inhibition of the
2022-02-18
Here, we report the kinetics of inhibition of the MYST HAT family member KAT8 by MG149, and a calculation of the inhibitory constant Ki of MG149 for KAT8. The inhibition of HATs by MG149 could be correlated to inhibition of histone acetylation in murine PCLS upon MG149 treatment, as determined by a
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br Conclusion Our data allow pharmacological
2022-02-18
Conclusion Our data allow pharmacological discrimination of diverse of H3 p-Cresyl sulfate antagonists that can be linked to their differential efficacy in preclinical and clinical disease settings (Fig. 6). Moreover, we identify the sigma-1 receptor as a common “off target” for H3 antagonists, a
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These agents can be divided into
2022-02-17
These agents can be divided into three categories based upon the therapeutic agent conjugated to the antibody; the most frequently explored are ADCs using a cytotoxic agent to be delivered directly to the tumor site. The second class has not been broadly used and consists of radionucleotides (Wong e
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Carbon monoxide another key product from the breakdown of he
2022-02-17
Carbon monoxide, another key product from the breakdown of heme by HO-1, also plays an important role in the vasculature. Like NO, CO is endogenously derived from the endothelium [68] and can weakly activate sGC by binding to its heme moiety [69]. CO was found to have vasodepressor activity in rats
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In the present study we observed a
2022-02-17
In the present study, we observed a decrease in body weight gain in Tg rats. It is uncertain whether this effect is due to Denr, Gpr81, or Gpr109a. In this regard, Gpr81 mice have been reported to have reduced body weight gain [28]. Moreover, a small clinical study has reported that obese patients t
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Niacin nicotinic acid is widely used to regulate abnormaliti
2022-02-17
Niacin (nicotinic acid) is widely used to regulate abnormalities in plasma lipid and lipoprotein metabolism, as evidenced by its potential for reducing atherosclerotic cardiovascular disease risks (Guyton, 1998), due to its ability to reduce circulating triglycerides and apolipoprotein-B containing
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Our inhibitor studies revealed the presence of a
2022-02-17
Our inhibitor studies revealed the presence of a signaling network triggered by dicarbonyl stress. Nevertheless, p38-MAPK activation was clearly necessary for NADPH-oxidase mediated production of ROS. This is consistent with data from other groups using different cell culture systems [37], [38], [39
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br Results br Discussion br Materials and Methods br Introdu
2022-02-17
Results Discussion Materials and Methods Introduction Deoxyribonucleic CAY10603 (DNA) is among the most important biopolymers in living organisms alongside carbohydrates and proteins. DNA is a linear polymer consisting of four types of nucleobases, deoxyribose, and phosphate. The backbon
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Ubiquitination of GlyRs subunit on plasma
2022-02-17
Ubiquitination of GlyRs-α1 subunit on plasma membrane has been shown to initiate the receptor phosphodiesterase inhibitor and subsequent degradation in lysosomes (Buttner et al., 2001). However, the specific E3 ligase responsible for GlyRs-α1 ubiquitination is largely unknown as yet. Also, the func
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While CART increased circulating levels of GIP and
2022-02-17
While CART increased circulating levels of GIP and GLP-1 in vivo, we were unable to detect any effect of exogenous CART on GIP and GLP-1 mRNA expression or GLP-1 secretion in vitro. There is no ready explanation for this discrepancy. The CART doses used (both in vivo and in vitro) have been shown to
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Further we examined the degradation of Cx Autophagy and
2022-02-17
Further, we examined the degradation of Cx43. Autophagy and the proteasome system have previously been implicated in Cx43 degradation (Falk et al., 2014). DEX inhibited communication between Rapalink-1 by promoting the degradation of Cx43 through autophagy in osteocytes (Gao et al., 2016). In our e
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br Acknowledgments The research leading
2022-02-17
Acknowledgments The research leading to these results was funded by European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 222719 – LIFECYCLE and by the Foundation for Science and Technology of Portugal (FCT), through projects PTDC/MAR-BIO/3890/2012 and PEst-C/
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Cys loop GABA receptors are well studied targets for
2022-02-17
Cys-loop GABA receptors are well-studied targets for insecticides and also play an important role in nematode biology. These receptors are also targets for the anthelmintic piperizine (Accardi et al., 2012). The nematode GABA receptor most studied is the UNC-49 receptor which plays a role in muscle
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