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In the spinal cord EAAT constitutes of all high affinity
2022-08-24
In the spinal cord, EAAT1 constitutes 40% of all high-affinity EAATs, and it is abundantly present in lumbar dorsal horn (Queen et al., 2007). In physiological conditions, EAATs remove glutamate from the synaptic cleft by co-transporting glutamate and sodium into adjacent glial cells. The inefficien
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In conclusion starting from the weakly potent GSM
2022-08-23
In conclusion, starting from the weakly potent GSM , exploration of various spacer groups between the triazole ring and the aromatic JNJ-7706621 led to the discovery of a new series of potent gamma secretase modulators, with an improved drug-like profile—compared with the originally reported series
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Clinical trials of all GSIs
2022-08-23
Clinical trials of all GSIs have ended prematurely, raising the question on our understanding of their target, the γ-secretase/presenilin. Development of compounds to target γ-secretase and reduce Aβ production is complicated by the fact that γ-secretase/presenilin has critical biological function,
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We show here that FXR is a point of
2022-08-23
We show here that FXR is a point of convergence of heredity (H) and environmental (E) risk factors for CRC (re the Tomasetti and Vogelstein model). Our studies demonstrate that the APC mutation and high-fat diet independently and cooperatively increase the BA pool that results in the repression of F
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phalloidin Fpr which belongs the family of the formyl peptid
2022-08-23
Fpr1, which belongs the family of the formyl peptide receptors with FPRL1 and FPRL2, is the principal receptor for formylated peptides which prototype is the tri-peptide fMLF. Fpr1 is highly expressed on neutrophils and macrophages [6,30], promotes their migration into the mucosa and lumen in respon
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In the light of the above
2022-08-23
In the light of the above-mentioned considerations, it is interesting to note that the FPR-related research with regards to bias agonism did not prosper during considerably during the last decade (possible exceptions are [[8], [9], [10], [11]]. However, with new insights in receptor chemistry and fu
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br Results br Discussion Impaired BBB
2022-08-22
Results Discussion Impaired BBB functions evoke vasogenic edema, which elevates intracranial pressure and leads to a life-threatening condition (Sperk, 1994, Unterberg et al., 2004, Simard et al., 2007). In addition, vasogenic edema formation results in the worsen consequence contributing to p
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Tumor specific CD cytolytic T lymphocytes CTLs recognizing t
2022-08-22
Tumor-specific CD8+ cytolytic T lymphocytes (CTLs) recognizing tumor antigenic peptide/major histocompatibility complexes-I (pMHC-I) presented on tumor cells play an important role in antitumor immunity [12]. However, immune tolerance including central (natural) or peripheral (acquired) tolerance be
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In addition to lifestyle factors genetic
2022-08-22
In addition to lifestyle factors, genetic factors may also influence the efficacy of antineoplastic drugs in breast cancer patients.16, 17 The HER2 gene contains several single nucleotide polymorphisms (SNPs). Two of the most investigated HER2 SNPs are Ile655Val (rs1136201) and Ala1170Pro (rs1058808
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FoxM a downstream target of
2022-08-22
FoxM1, a downstream target of Gli, has been mainly related to calcium sensing receptor regulation and cellular proliferation in tumor (Alvarez-Fernandez and Medema, 2013, Halasi and Gartel, 2013, Teh et al., 2002). Especially, FoxM1 is a regulator of G1/S and G2/M transitions and M-phase progressio
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br Mechanism of HH pathway activation in NSCLC Despite the
2022-08-22
Mechanism of HH pathway activation in NSCLC Despite the role of the HH pathway in basal cell carcinoma and medulloblastoma, it has been postulated that epithelial tumors do not demonstrate cell autonomous HH ligand activity. The main evidence comes from the study by Yauch et al showing no correla
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br Hydroxamic acids br Inhibitors with
2022-08-22
Hydroxamic acids Inhibitors with reporting modalities Dual or more HDAC inhibitors Conclusion Finally, non-human HDAC such as Schistosoma mansoni HDAC8 are targeted for parasitic diseases and recent work highlight the interest of HDACs in viral infections. Despite their discovery in the
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br Acknowledgments br Introduction Histone
2022-08-22
Acknowledgments Introduction Histone deacetylases (HDACs) related to tumor suppressor genes have become promising targets for the treatment of cancer [1,2]. Under the normal physiological conditions, Histone acetyltransferases (HATs) and histone deacetylases (HDACs) together regulate the acety
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Organisms can adapt to increasing ROS production
2022-08-22
Organisms can adapt to increasing ROS production by up-regulating antioxidant defences, such as the activities of antioxidant enzymes (Livingstone, 2003). Failure of antioxidant defences to detoxify excess ROS production can lead to significant oxidative damage including enzyme inactivation, protein
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br Conflict of interest br Acknowledgement
2022-08-22
Conflict of interest Acknowledgement Exposure to tobacco smoke in early life has been found to increase the risk of developing asthma and lung function deficits in adolescence and adulthood., , , , However, not all children exposed to tobacco smoke in early life develop asthma, which sugges
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