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Chemical chaperones mitigate chronic short sleep induced cognitive impairment (Exhibit (Pennsylvania Convention Center); In-Person) - Jun 19, 2024 - Abstract #AAIC2024AAIC_4488;
2-month-old male and female C57BL/6 mice underwent 4 weeks of CSS for 8hrs/day; 3 days/week by exposure to an enriched environment with or without 4-phenyl butyrate (PBA) treatment... Our data suggest that relieving proteostatic stress with chemical chaperones mitigates the effects of CSS on learning and memory.
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Preclinical, Journal: 4-PBA exerts brain-protective effects against sepsis-associated encephalopathy in a mouse model of sepsis. (Pubmed Central) - Apr 1, 2024
Our data suggest that relieving proteostatic stress with chemical chaperones mitigates the effects of CSS on learning and memory. Our results suggest that administration of 4-PBA treatment significantly attenuates ERS, alleviates cognitive decline, reduces inflammatory damage, and restores mitochondrial dynamics via the IRE1?/Xbp1s-Ca2+-associated pathway, which provides a new potential therapeutic approach to SAE.
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Design and synthesis of lanthanide phosphate coordination polymers (Hall F-H (Indiana Convention Center)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_9152;
(2) and (4) synthesized both PCL and poly gamma-functionalized CL with various linkages at the gamma position, including benzyl, 4-phenyl butyrate, acetate, and bromo with PDI=1.22-1.84. Based on kinetic studies and synthesized block copolymers like poly (?-myrcene)-b-poly (isoprene) and poly (?-myrcene)-b-PMMA, all our catalytic systems demonstrated the quasi-living behavior.R = TEP (triethyl phosphate), TIBP (triisobutylphosphate), and TEHP (tris(2-ethylhexyl) phosphate)Z = Benzyl, 4-Phenyl butyrate, Acetate, Bromo, gamma-2-[2-(2-methoxyethoxy)ethoxy]ethoxy
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Preclinical, Journal: Reducing ER stress with chaperone therapy reverses sleep fragmentation and cognitive decline in aged mice. (Pubmed Central) - Jun 22, 2022
We administered the chemical chaperone 4-phenyl butyrate (PBA) to aged and young mice, and monitored sleep and cognitive behavior...Together, these results indicate that restoring proteostasis improves sleep and cognition in a wild-type mouse model of aging. The implications of these results could have an impact on the development of therapies to improve health span across the aging population.
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Journal: Modifying gap junction communication in cancer therapy. (Pubmed Central) - Dec 23, 2021
The implications of these results could have an impact on the development of therapies to improve health span across the aging population. An enhancement of GJIC function by HDACi and ATRA increased cytotoxicity and could be effective in the presence of Dexamethasone, when combined with ATRA or VPA.
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Journal: Perfluorooctanoic acid activates the unfolded protein response in pancreatic acinar cells. (Pubmed Central) - Jun 24, 2021
PFOA treatment led to increased cytosolic Ca levels and induction of the UPR was blocked by an inhibitor of the inositol 1,4,5-trisphosphate receptor. These findings indicate that PFOA-induced ER stress may be the mechanistic trigger leading to oxidative stress in the pancreas.
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Journal: Interplay between Endoplasmic Reticulum (ER) Stress and Autophagy Induces Mutant p53H273 Degradation. (Pubmed Central) - Mar 19, 2021
ER stress inhibition with chemical chaperone 4-phenyl butyrate (PBA) impaired mutp53 downregulation, which is similar to IRE1α/XBPI specific inhibition, reducing cancer cell death...Recently discovered small molecules targeting components of the UPR show promise as a novel anticancer therapeutic intervention. However, our findings showing UPR activation during mutp53 degradation indicate that caution is necessary in the design of therapies that inhibit UPR components.
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Journal: A Small Molecule, 4-Phenylbutyric Acid, Suppresses HCV Replication via Epigenetically Induced Hepatic Hepcidin. (Pubmed Central) - Feb 23, 2021
A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation...Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.
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Clinical, Journal: Analysis of ALMS1 gene variants in seven patients with Alström syndrome (Pubmed Central) - Feb 18, 2021
ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
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[VIRTUAL] A role for cellular stress in age-related sleep impairments and cognitive decline (Poster Networking Lounge) - Aug 16, 2020 - Abstract #ESRS2020ESRS_616;
These results suggest that reducing cellular stress improves cognition in a wildtype mouse model of aging. While sleep and histological data analyses are still in progress, the implications of these results could have an impact on the development of therapies to improve healthspan in the growing aged population.
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