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br Conclusion br Conflicts of interest
2024-09-18
Conclusion Conflicts of interest Introduction RNA interference is a specific post-transcriptional gene silencing mechanism within a cell via the transfection of microRNAs (miRNA), exogenous small interfering RNAs (siRNA) or small hairpin RNAs (shRNA) [1–3]. Transfection of shRNA can be done
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br Conflict of interest br Acknowledgements We thank
2024-09-18
Conflict of interest Acknowledgements We thank Ann Jackman, Mike Ormerod and members of Julian Downward's and Alan Ashworth's groups for helpful discussions. This work was supported by grant number PEM/GME/D391/40 from the Kidani Trust (S. Kaye) and by Keele University. Introduction Autota
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br Dual role of autophagy
2024-09-18
Dual role of autophagy in human diseases Emerging evidence suggests that autophagy serves as a double-edged sword in several human diseases, such as CNS diseases (Rubinsztein et al., 2015), arteriosclerosis (Schrijvers et al., 2011) and cancer (Ozpolat and Benbrook, 2015). Likewise, currently the
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br Autophagy in the central nervous system The autophagic
2024-09-18
Autophagy in the central nervous system The autophagic process appears to be very important for the cells of the central nervous system, as it allows to maintain the functional integrity of the nervous tissue. Indeed macroautophagy is involved in the regulation of homeostasis of the CNS, playing
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It is increasingly evident that many metabolic genes are ass
2024-09-18
It is increasingly evident that many metabolic genes are associated with cancer progression of various tumor cells, including NSCLC. In particular, GLUT1 overexpression has been reported in NSCLC, and correlations between GLUT1 expression and a number of clinical parameters such as gender, smoking s
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In the present study we showed
2024-09-18
In the present study, we showed that 15-LOX metabolites, which are the precursors of anti-inflammatory and pro-resolving lipid mediators, were decreased in the unaffected skin area of the OS model rats by comprehensive lipidomics analyses. Furthermore, subsequent microarray analyses demonstrated tha
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Cerebral ischemia occurs following the occlusion of
2024-09-18
Cerebral ischemia occurs following the occlusion of a cerebral artery by a thrombus and causes cell swelling due to cytotoxic edema and BBB disruption with vasogenic edema (Loreto and Reggio, 2010, Nakaji et al., 2006, Shibata et al., 2004). Vasogenic edema is directly linked to alteration of the BB
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In addition unconventional mechanisms of internalization can
2024-09-14
In addition, unconventional mechanisms of internalization cannot be ignored. It is generally believed that the conventional homologous internalization of a GPCR depends on the activation of G proteins, since GRK activation requires the pre-activation of G proteins (Fig. 2). Feng et al. demonstrated
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p450 inhibitors Earlier studies with SERMs identified that d
2024-09-14
Earlier studies with SERMs identified that distinct chemical scaffolds have the ability to induce unique conformational changes in the ER, resulting in interaction with different cofactor subsets. The same has been demonstrated with SARMs, which induce distinct conformational changes compared to tes
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The first and the best characterized mechanism
2024-09-14
The first and the best-characterized mechanism of receptor-dependent internalization of Aβ is mediated via the α7-nicotinic 279 3 receptor receptor [82]. Lipoprotein receptor protein represents the second best-studied route that facilitates the uptake of Aβ by neurons, involving additional molecule
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WKY and SHR strains have important differences mainly
2024-09-14
WKY and SHR strains have important differences mainly in their sympathetic status but also in the activity of the RAS. The development of hypertension in SHR is clearly related to an increase in sympathetic activity [51], [11]. In addition, increased renal sympathetic nerve activity led to an increa
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br Introduction The structural similarities between puromyci
2024-09-14
Introduction The structural similarities between puromycin (1, Fig. 1) and the aminoacyl adenyl terminal of aminoacyl–tRNA allow it to terminate the protein synthesis process by causing premature release of a polypeptide from the ribosome [1], [2]. Tremendous progress in the study of puromycin an
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Our initial approach to identify hits
2024-09-14
Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI IT-901 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 inco
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At the last follow up nine patients had discontinued pyridos
2024-09-14
At the last follow-up, nine patients had discontinued pyridostigmine within the first year postoperatively. Only one patient required pyridostigmine at a higher dose, but this was accompanied by successful weaning of prednisolone. None of the 5 patients who were on pyridostigmine treatment alone pri
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br Introduction Lung cancer is the leading
2024-09-13
Introduction Lung cancer is the leading cause of cancer death worldwide and is one of the most refractory of solid tumors along with pancreatic cancer. Since 1975 there have been notable improvements in the 5-year survival rate of patients with lung cancer [1]. This improvement in survival is tho
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