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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: insertAPISummary
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Filename: controllers/Detail.php
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Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions. 89 adult male Sprague-Dawley rats received intraperitoneal fasudil injections (10 mg/kg/day) or saline vehicle for 18 days. Some of these animals were daily restraint-stressed from day 5-18 (2.5 h/day). 24 hr after treatments, rats were either evaluated for behavioral tests (active avoidance, anxiety-like behavior and object location) or euthanized for western blot analyses of hippocampal whole extract and synaptoneurosome-enriched fractions. We report that fasudil prevents stress-induced impairments in active avoidance, anxiety-like behavior and novel location preference, with no effect in unstressed rats. Chronic stress reduced phosphorylations of ERK-2 and CREB, and decreased levels of GluA1 and GluN2A in whole hippocampus, without any effect of fasudil. However, fasudil decreased synaptic GluA1 Ser831 phosphorylation in stressed animals. Additionally, fasudil prevented stress-decreased phosphorylation of GSK-3β at Ser9, in parallel with an activation of the mTORC1/4E-BP1 axis, both in hippocampal synaptoneurosomes, suggesting the activation of the AKT pathway. Our study provides evidence that chronic fasudil treatment prevents chronic stress-altered behaviors, which correlated with molecular modifications of antidepressant-relevant signaling pathways in hippocampal synaptoneurosomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739043 | PMC |
http://dx.doi.org/10.1016/j.ynstr.2020.100234 | DOI Listing |
The mis-folding and aggregation of intrinsically disordered proteins (IDPs) such as α-synuclein (αS) underlie the pathogenesis of various neurodegenerative disorders. However, targeting αS with small molecules faces challenges due to the lack of defined ligand-binding pockets in its disordered structure. Here, we implement a deep artificial neural network-based machine learning approach, which is able to statistically distinguish the fuzzy ensemble of conformational substates of αS in neat water from those in aqueous fasudil (small molecule of interest) solution.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Biopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland.
Treatment options for pulmonary arterial hypertension (PAH) have improved substantially in the last 30 years, but there is still a need for novel molecules that can regulate the excessive accumulation of pulmonary artery smooth muscle cells (PASMCs) and consequent vascular remodeling. One set of possible candidates are protein kinases. The study provides an overview of existing preclinical and clinical data regarding small-molecule protein kinase inhibitors in PAH.
View Article and Find Full Text PDFFront Neurosci
November 2024
Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China.
Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer's disease and Parkinson's disease).
View Article and Find Full Text PDFSci Rep
November 2024
The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, China.
Transmembrane domain-containing 7 (CMTM7) is a protein located at the plasma membrane. It plays a role in regulating the development and immune microenvironment of tumor cells. However, the impact of CMTM7 on hepatocellular carcinoma (HCC) is not well understood.
View Article and Find Full Text PDFVet Ophthalmol
November 2024
Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA.
Background: Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti-fibrotic effects of the FDA-approved drugs, angiotensin-converting enzyme inhibitor (ACE-I) lisinopril and rho-kinase inhibitor (ROCK-I) fasudil, alone and in combination, on the canine cornea using an established in vitro model.
Methods: To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (n = 20) were used.
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