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Our initial approach to identify
2024-12-12
Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI 1670 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 incorp
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Toxicity is the main reason for the
2024-12-12
Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele
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Compounds were profiled for their inhibitory activity agains
2024-12-12
Compounds – were profiled for their inhibitory activity against dipeptidyl peptidase-IV Activity and/or Structure Homologues (DASH) [e.g. DPP2, DPP8 and DPP9] and non-DASH [eg. post-proline cleaving enzyme (PPCE), neutral endopeptidase (NEP), aminopeptidase P (APP), aminopeptidase N (APN)] enzymes.
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The use of one or more of psychotropic medications
2024-12-12
The use of one or more of psychotropic medications and hypnotics was associated with a higher risk of falls in the current study. Previous studies have also shown that these medications increase the risk of falls in the geriatric population.25, 26, 27, 28, 29, 30, 31 Clinicians should weigh the risk
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br Conclusions br Conflicts of interest br Acknowledgements
2024-12-12
Conclusions Conflicts of interest Acknowledgements This work was supported by Ege University Research Fund [BAP, 14-ECZ-030, 2016]. Introduction The interest in the effects of endocrine disrupting chemicals (EDCs) in the aquatic environment continues to increase over the past decade, sp
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486 2 br Disclaimer br Conflicts of
2024-12-12
Disclaimer Conflicts of interest Role of the Sponsor Acknowledgements Funding/support: This project was supported by a grant from the Department of Surgery (R5129), Western University and by the Institute for Clinical Evaluative Sciences (ICES) Western site. ICES is funded by an annual
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Inactivation of autophagy can also impact the surface intern
2024-12-12
Inactivation of autophagy can also impact the surface internalization of MHC I molecules, leading to increased antigen presentation. Inactivation of autophagy factors Atg5 and Atg7 in DCs causes elevation of MHC I surface levels by decreasing endocytosis due to a poor recruitment of adaptor-associat
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Neuropathic animals display increased sensitivity to the ant
2024-12-11
Neuropathic animals display increased sensitivity to the anti-nociceptive effect of baclofen and whilst the number and affinity of GABAB A 779 in the dorsal horn are not altered (Smith et al., 1994; Zemoura et al., 2016), GABAB receptors subunits (B1 and B2) are both down-regulated in sensory neuro
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There is limited information regarding hyperargininemia inci
2024-12-11
There is limited information regarding hyperargininemia incidence or prevalence. Reports of incidence vary by an order of magnitude: 0.5 to 5.0 per million [5], [6]. A relatively large U.S. study estimated 1.1 cases per million births [7], but it used an indirect methodology that introduces uncerta
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br The role of apelin
2024-12-11
The role of apelin in hepatic diseases The involvement of the apelin/APJ system in liver physiology and pathology has been proven in numerous studies (Table 6). For instance, in the experiment of Emam et al. [63] on rats suffering from hepatic injury, apelin decreased the levels of ALT, AST and L
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In glucose stimulated pancreatic cells B Raf activity is inc
2024-12-11
In glucose-stimulated pancreatic β-cells, B-Raf activity is increased, while Raf-1 activity is under the detection limit (Duan and Cobb, 2010). Thus, B-Raf is the primary protein kinase involved in the rapid activation of ERK1/2 in glucose-treated pancreatic β-cells. Expression of a dominant-negativ
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Plant defensins Vriens et al and
2024-12-11
Plant defensins (Vriens et al., 2014) and linear AMPs (Domingues et al., 2015, Liu et al., 2008) have been shown to present several modes of action. Among these different mechanisms, permeabilization of the fungal membrane has been described as a secondary effect of plant defensin action (Vriens et
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br Concluding Remarks Despite major advances
2024-12-11
Concluding Remarks Despite major advances in the development of antibody and small-molecule tumor angiogenesis inhibitors, therapy resistance, both innate and acquired, continues to limit further survival improvements for patients with cancer. Preclinical models of localized primary tumors and me
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Due to anatomical and physiologic characteristics of the eye
2024-12-11
Due to anatomical and physiologic characteristics of the eye, administration of ophthalmic medicines is difficult and many studies showed that only approximately 5% of the administrated dose are absorbed by intraocular tissues, making the treatment unfeasible for diseases located in posterior segmen
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66 4 receptor br The lipoxygenase pathway in diseases of the
2024-12-11
The 12/15-lipoxygenase pathway in diseases of the nervous system Conclusions and future perspectives Arachidonic 66 4 receptor and other polyunsaturated fatty acids, and their lipid metabolites, play very important roles in human health and disease. This review has outlined the functions of 1
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