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Recent studies have supported the
2024-07-09
Recent studies have supported the existence of an inward RAS regulatory mechanism in which AT1 receptors downregulate angiotensin-converting enzyme 2 (ACE2) and subsequently impair angiotensin-(1-7) generation and MAS functionality (Jessup et al., 2006, Gallagher et al., 2008, Xia et al., 2009, Pern
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Bay 11-7085 Intracellular Signaling Cascades From ligand sen
2024-07-09
Intracellular Signaling Cascades. From ligand sensitization to translation of genes, all cellular processes are dependent on the intracellular levels and activity of partners involved in the signaling pathway. These signaling events lead to critical post-translational modifications including phospho
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br Possible complementarity of trimming pathways Determining
2024-07-09
Possible complementarity of trimming pathways Determining the exact pathway for the generation or destruction of MHCI peptide ligands by ERAP1 is important for our understanding of the shaping of the immunopeptidome and for designing inhibitors that can manipulate it. It is also possible however
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sigma 1 receptor Acetaminophen N acetyl p aminophenol AAP Fi
2024-07-09
Acetaminophen (N-acetyl-p-aminophenol, AAP) (Fig. 1) is a medically important, low cost, readily available and commonly used over the counter analgesic and antipyretic drug [18,19]. Acetaminophen monotherapy is efficient and is safer than Aspirin and Ibuprofen [20]. The efficacy and tolerability in
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pyruvate dehydrogenase kinase Pregnane X receptor PXR is a n
2024-07-09
Pregnane X receptor (PXR) is a nuclear receptor that plays an important role in regulation of metabolism and disposition of structurally diverse xenobiotics as well as endogenous steroids and bile acids (Bertilsson et al., 1998, Kliewer et al., 1998, Lehmann et al., 1998). PXR regulates the metaboli
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A high throughput small molecule ACK biochemical inhibition
2024-07-09
A high-throughput small molecule ACK1 biochemical inhibition screen was performed in-house and led to the identification of 1μM inhibitor furanopyrimidine (). Further binding studies found GNE-317 to be both ATP-competitive and reversible. Early structure-activity relationship (SAR) work was perf
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Our initial approach to identify
2024-07-09
Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI CHIR-124 library as well as a virtual screening (VS) campaign, utilizing a publically available crystal structure of ACK1 (PDB code: ). A tolerance for protein flexibility was inc
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Previous reports indicate that the expression of AChRs and
2024-07-09
Previous reports indicate that the expression of AChRs and their clustering on myotubes are critical factors required to induce contacts on muscle fibers in a natural biological system [14], [15], [16], [17], [18], [19]. For instance, in NMJ development in the mouse, AChRs are pre-patterned at sites
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As also found by Stolarski et al inclusion of N
2024-07-09
As also found by Stolarski et al. [14], inclusion of N2O in the model is successful in reducing the effect of dynamics [13] in the lower stratosphere in the Northern Hemisphere (30–60°N in our case). The inclusion of N2O also decreased the error bars on the trend values, but the trend values still c
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bwx ACE inhibition is often thought to play a central role
2024-07-09
ACE inhibition is often thought to play a central role in the mechanisms of blood pressure reduction in vivo, and most ACE inhibitory (ACEi) peptides were characterized based on in vitro ACE inhibition. A relationship between in vitro ACE inhibition and antihypertensive activity, however, is not app
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br Acknowledgments This work was supported by a grant of
2024-07-09
Acknowledgments This work was supported by a grant of the Romanian National Authority for Scientific Research, CNCS – UEFISCDI, project no. PN-II-ID-PCE-2011-3-0571, awarded to F.A.M. D.V.N. was co-financed from the European Social Fund through Sectorial Operational Program Human Resources Develo
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At present drugs that specifically inhibit YAP
2024-07-09
At present, drugs that specifically inhibit YAP activity are not available. In fact, verteporfin, which was originally described as a specific inhibitor of YAP-TEAD interaction, has been recently shown to exert its activity through selective induction of proteotoxicity rather than through YAP inhibi
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Why do glutamate and glycine bind to
2024-07-08
Why do glutamate and glycine bind to the hsp90 inhibitor in such different ways? Given the overall structural similarity between the GluN2A and GluN1 LBDs, one might conclude that the LBDs also bind ligands via similar processes. NMDA receptors with engineered disulfide linkages that lock the GluN1
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The therapeutic potential of ML induced MET against cells
2024-07-08
The therapeutic potential of ML327-induced MET against ccr2 antagonist of mesenchymal origin has not been explored. In the present study, we hypothesized that induction of MET using ML327 would block the growth of ES cells and sensitize to TRAIL-mediated apoptosis. Herein, we report that ML327 induc
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Introduction Preeclampsia a serious hypertensive disorder th
2024-07-08
Introduction Preeclampsia, a serious hypertensive disorder that can occur during pregnancy, is a pregnancy-related disease characterized by the onset of euk 134 and proteinuria after the 20 t h week of gestation, and it occurs in about 5% of all pregnancies [1]. If left untreated, preeclampsia can
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