Journal of Pharmacology and Experimental Therapeutics
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Brimonidine, a selective alpha2-adrenoceptor agonist, displays putative retinal cyto-neuroprotective activity in vitro and in vivo. An intravitreal sustained-release brimonidine implant, Brimonidine Posterior Segment Drug Delivery System (brimonidine DDS), allowing targeted drug delivery to the retina, has been developed for potential clinical application. This study evaluates the in vivo posterior segment pharmacokinetics of brimonidine DDS implant in the monkey eye, and applies translational p...
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#1Todd M. Hillhouse (UWGB: University of Wisconsin–Green Bay)H-Index: 8
#1Todd M. Hillhouse (UWGB: University of Wisconsin–Green Bay)H-Index: 1
Last. Emily M. Jutkiewicz (UM: University of Michigan)H-Index: 26
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There are no Food and Drug Administration-approved medications for cocaine use disorder, including relapse. The mu-opioid receptor (MOPr) partial agonist buprenorphine, alone or in combination with naltrexone, has been shown to reduce cocaine positive urine tests and cocaine seeking in rodents. However, there are concerns over the abuse liability of buprenorphine. Buprenorphine9s partial agonist and antagonist activity at the nociception-receptor (NOPr) and kappa-opioid receptor (KOPr), respecti...
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#1Alex Mabou Tagne (UCI: University of California, Irvine)H-Index: 2
#2Yannick Fotio (UCI: University of California, Irvine)H-Index: 4
Last. Daniele Piomelli (UCI: University of California, Irvine)H-Index: 115
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Evidence suggests that Δ9-tetrahydrocannabinol (Δ9-THC), the intoxicating component of cannabis, may cause enduring changes in the structure and function of adolescent brain circuits implicated in nociceptive responding. Yet, whether such changes might persistently disrupt nociceptive behaviors remains unknown. In the present study, we subjected C57BL6/J mice of both sexes to once-daily injections of Δ9-THC (5 mg-kg-1, intraperitoneal) or vehicle throughout adolescence (PND 30-43) and, when the ...
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#1Asvelt J. Nduwumwami (PSU: Pennsylvania State University)H-Index: 1
#2Jeremy A. Hengst (PSU: Pennsylvania State University)H-Index: 15
Last. Jong K. Yun (PSU: Pennsylvania State University)H-Index: 24
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Agents that induce immunogenic cell death (ICD) alter the cellular localization of calreticulin (CRT) causing it to become cell surface exposed within the plasma membrane lipid raft microdomain (ectoCRT) where it serves as a damage associated molecular pattern that elicits an antitumor immune response. We have identified the sphingolipid metabolic pathway as an integral component of the process of ectoCRT exposure. Inhibition of the sphingosine kinases (SphKs) enhances mitoxantrone-induced produ...
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The (pro)renin receptor (PRR) is a single-transmembrane protein that regulates the local renin-angiotensin system and participates in various intracellular signaling pathways, thus exhibiting a significant physio-pathological relevance in cellular homeostasis. A soluble form of PRR (sPRR) is generated through proteases-mediated cleavage of the full-length PRR and secreted into extracellular spaces. Accumulating evidence indicates pivotal biological functions of sPRR in various physiopathological...
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#1Yan-Jye Shyong (UCSD: University of California, San Diego)H-Index: 1
#2Yadira Sepulveda (UCSD: University of California, San Diego)
Last. Palmer Taylor (UCSD: University of California, San Diego)H-Index: 93
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Inhibition of acetylcholinesterase (AChE) by certain organophosphates (OP) can be life-threatening and requires reactivating antidote accessibility to the peripheral and central nervous systems to reverse symptoms and enhance survival parameters. In considering dosing requirements for oxime antidotes in OP exposures that inactivate AChE, clearance of proton ionizable, zwitterionic antidotes is rapid and proceeds with largely the parent antidotal compound being cleared by renal transporters. Such...
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In Alzheimer9s disease (AD), the double-strand RNA-dependent kinase PKR/EIF2AK2 is activated in brain with increased phosphorylation of its substrate eukaryotic initiation factor 2α (eIF2α). AD risk-promoting factors, such as ApoE4 allele or the accumulation of neurotoxic amyloid-beta oligomers (AβO), have been associated with activation of PKR-dependent signalling. Here, we report the discovery of a novel potent and selective PKR inhibitor (SAR439883) and demonstrate its neuroprotective pharmac...
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#1Huijiao Lin (Beihua University)H-Index: 1
#2Xinyun Zhang (Beihua University)H-Index: 1
Last. He Li (Beihua University)H-Index: 8
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Anwulignan is one of monomer compounds in the lignans from Schisandra sphenanthera. In this study, we observed the effect of anwulignan on the intestinal ischemia/reperfusion (II/R) injury in male SD rats and explored the underlying mechanisms. The results showed that the pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathological injury of jejunum; enhance the autonomic tension of jejunum smooth musc...
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#1Dengpiao Xie (VCU: Virginia Commonwealth University)
#2Juan Wang (Sichuan University)
Last. Ningjun Li (VCU: Virginia Commonwealth University)H-Index: 23
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Background: Inhibition of HIF-prolyl hydroxylase (PHD) has been shown to protect against various kidney diseases. However, there are controversial reports on the effect of PHD inhibition in renoprotection. The present study determined whether delivery of PHD2 siRNA using a siRNA carrier, folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA), would mainly target kidneys and protect against renal ischemia/reperfusion injury (I/R). Methods: The renal I/R was generated by clipping ...
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#1Keivan Golshiri (EUR: Erasmus University Rotterdam)H-Index: 2
#2Ehsan Ataei Ataabadi (EUR: Erasmus University Rotterdam)H-Index: 2
Last. Ingrid M. Garrelds (Erasmus University Medical Center)H-Index: 35
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Diminished nitric oxide - cGMP -mediated relaxation plays a crucial role in cardiovascular ageing, leading to decreased vasodilation, vascular hypertrophy and stiffening, and ultimately cardiovascular dysfunction. Ageing is the time-related worsening of physiological function due to complex cellular and molecular interactions, and is at least partly driven by DNA damage. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in Ercc1Δ/- mice provides us an efficient tool to accelerate vasc...
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