Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0) DOI Open Access
Stephanie Venn‐Watson, Eric D. Jensen

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3746 - 3746

Published: April 16, 2025

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar AD in humans, they also develop shared age-associated co-morbidities identified as risk factors for including type 2 diabetes, ferroptosis, iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized (1) would amyloid beta (Aβ) plaques neuroinflammation paralleled of humans relation age-related progression, quantitative concentration, brain region; (2) dose-dependent activities relevant protecting health. Quantitative immunohistochemistry staining was used assess 68 tissues from archived brains 19 Navy evaluate associations among region, sex, age group. Further, activities, using a third-party panel intended screen potential therapeutics, were evaluated. Similar had the highest Aβ plaque density variation hippocampus (90th percentile 4.95 plaques/mm2), where increased with (p = 0.05). All measured markers detected, concentrations activated microglia (CD68+) (0.46 ± 0.38 cells/mm2). inhibitor two targets, fatty acid amide hydrolase (FAAH) (IC50 2.5 µM, 89% maximum inhibition at 50 µM relative URB597) monoamine oxidase B (MAO-B) 19.4 70% R(-)-Deprenyl). These demonstrated efficacy against formation neuroinflammation, protection function hippocampus. findings suggest that, addition co-morbidities, may play distinct role supporting health, especially higher concentrations.

Language: Английский

Conditional lethality and suppressor analysis of plasmid-based temperature-sensitive fabZ expression in Pseudomonas aeruginosa DOI Creative Commons
Zhenhua Chen,

Junpeng Lu,

Qing-Hai Tang

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108553 - 108553

Published: April 1, 2025

FabZ, a β-hydroxyacyl-ACP dehydratase in the Type II fatty acid synthesis pathway, is essential for viability of Pseudomonas aeruginosa by ensuring proper elongation and membrane stability. However, precise genetic interactions between fabZ lipid A biosynthesis genes, such as lpxA lpxC, well potential existence other suppressor genes P. aeruginosa, remain unclear. To explore these identify we constructed conditional mutant, ΔfabZ(p_ts-fabZ), deleting chromosomal gene complementing it with temperature-sensitive plasmid-borne copy. The ΔfabZ(p_ts-fabZ) mutant exhibited lethality cell morphology defects at restrictive temperature, confirming its essentiality. Genetic interaction analyses revealed that deletion or lpxC failed to rescue temperature. Through screening, isolated strain capable rescuing ΔfabZ identified lpxH using genome resequencing. Further analysis double (ΔfabZΔlpxH) produced odd-chain acids, pentadecanoic (C15:0) heptadecanoic (C17:0) through methyl ester (FAME) coupled gas chromatography-mass spectrometry (GC-MS), supplementation acids restored growth ΔlpxH(p_ts-lpxH) mutants suggesting their critical role These results indicate serves lethality, highlighting previously unrecognized compensatory mechanism involving stability aeruginosa.

Language: Английский

Citations

0
Pentadecanoic acid attenuates thioacetamide-induced liver fibrosis by modulating oxidative stress, inflammation, and ferroptosis pathways in rat DOI

Mohammad Aabis,

Priyanka Tiwari, Vinod Kumar

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Pentadecanoic acid (C15:0, PA) induces maternal mild insulin resistance and promotes the growth of the offspring partly though up regulating liver PPARα and MAPK signaling pathway DOI
Jun Wang, Shiqi Zheng, Ziying Li

et al.

Food & Function, Journal Year: 2024, Volume and Issue: 15(23), P. 11400 - 11414

Published: Jan. 1, 2024

1% PA can induce a mild decrease in the maternal glucose tolerance and lipolysis mainly by activated MAPK PPARα signaling.

Language: Английский

Citations

3
Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0) DOI Open Access
Stephanie Venn‐Watson, Eric D. Jensen

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3746 - 3746

Published: April 16, 2025

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar AD in humans, they also develop shared age-associated co-morbidities identified as risk factors for including type 2 diabetes, ferroptosis, iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized (1) would amyloid beta (Aβ) plaques neuroinflammation paralleled of humans relation age-related progression, quantitative concentration, brain region; (2) dose-dependent activities relevant protecting health. Quantitative immunohistochemistry staining was used assess 68 tissues from archived brains 19 Navy evaluate associations among region, sex, age group. Further, activities, using a third-party panel intended screen potential therapeutics, were evaluated. Similar had the highest Aβ plaque density variation hippocampus (90th percentile 4.95 plaques/mm2), where increased with (p = 0.05). All measured markers detected, concentrations activated microglia (CD68+) (0.46 ± 0.38 cells/mm2). inhibitor two targets, fatty acid amide hydrolase (FAAH) (IC50 2.5 µM, 89% maximum inhibition at 50 µM relative URB597) monoamine oxidase B (MAO-B) 19.4 70% R(-)-Deprenyl). These demonstrated efficacy against formation neuroinflammation, protection function hippocampus. findings suggest that, addition co-morbidities, may play distinct role supporting health, especially higher concentrations.

Language: Английский

Citations

0