Small Molecule Inhibitor of Protein Kinase C DeltaI (PKCδI) Decreases Inflammatory Pathways and Gene Expression and Improves Metabolic Function in Diet-Induced Obese Mouse Model DOI Creative Commons
Brenna Osborne, Rekha Patel, Meredith Krause‐Hauch

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 943 - 943

Published: Nov. 18, 2024

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, survival. Caspase-3 cleavage of releases the C-terminal catalytic fragment (PKCδI_C), inflammation apoptosis. We previously demonstrated an increase in PKCδI_C human obese adipose tissue (AT) adipocytes. Subsequently, we designed small molecule drug called NP627 that specifically inhibited release vitro. Here, evaluate vivo safety efficacy diet-induced (DIO) mouse model. The results demonstrate treatment DIO mice increased glucose uptake AT well kidney, spleen, liver. Next, RNAseq analysis was performed on from NP627-treated mice. show increases ADIPOQ CIDEC, upregulation AMPK, PI3K-AKT, insulin signaling pathways, while inflammatory pathways were decreased post-NP627 administration. Further, levels lncRNAs associated with affected by treatment. In conclusion, study demonstrates NP627, small-molecule inhibitor activity, not toxic it improves function vivo.

Language: Английский

GAS5 lncRNA: A biomarker and therapeutic target in breast cancer DOI
Lakshmi Thangavelu, Ehssan Moglad, Gaurav Gupta

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155424 - 155424

Published: June 20, 2024

Language: Английский

Citations

11
Human Breast Milk Exosomes: Affecting Factors, Their Possible Health Outcomes, and Future Directions in Dietetics DOI Open Access
Elif Çelik, Özge Cemali, Teslime Özge Şahin

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(20), P. 3519 - 3519

Published: Oct. 17, 2024

Background: Human breast milk is a complex biological fluid containing multifaceted compounds that boost immune and metabolic system development support the short- long-term health of newborns. Recent literature suggests human substantial source nutrients, bioactive molecules, exosomes. Objectives: This review examines factors influencing exosomes noted in impacts on infant health. Furthermore, it discusses potential future prospects for exosome research dietetics. Methods: Through narrative existing literature, we focused milk, components their impact Results: Exosomes are single-membrane extracellular vesicles endosomal origin, with an approximate radius 20–200 nm. They natural messengers cells secrete to transport wide range diverse cargoes, including deoxyribonucleic acid, ribonucleic proteins, lipids between various cells. Some studies have reported could be transferred cause epigenetic changes. Thus, can affect gene expression cellular event regulation several tissues. Conclusions: In this manner, associated pathways, system, oxidative stress, cell cycle, they infants. However, there still much learn about functions, effectiveness, certain

Language: Английский

Citations

6
Exploring ncRNA-mediated pathways in sepsis-induced pyroptosis DOI
Asif Ahmad Bhat, Yassine Riadi, Muhammad Afzal

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 256, P. 155224 - 155224

Published: Feb. 23, 2024

Language: Английский

Citations

6
Long Non-Coding RNAs in Diabetic Cardiomyopathy: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training DOI
Jie Hu, Xudong Miao,

Li-Hua Yu

et al.

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

0
NPC86 Increases LncRNA Gas5 In Vivo to Improve Insulin Sensitivity and Metabolic Function in Diet-Induced Obese Diabetic Mouse Model DOI Open Access

Anna Kharitonova,

Rekha Patel, Brenna Osborne

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3695 - 3695

Published: April 14, 2025

In the United States, an estimated 38 million individuals (10% of population) have type 2 diabetes mellitus (T2D), while approximately 97.6 adults (38%) prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators gene expression and metabolism. We were first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in serum T2D patients established GAS5 as a biomarker for diagnosis onset prediction, now validated by other groups. further demonstrated depletion impaired glucose uptake, insulin receptor levels, inhibited signaling human adipocytes, highlighting its potential therapeutic target T2D. To address this, we developed NPC86, small-molecule compound stabilizes disrupting interaction with UPF-1, RNA helicase involved nonsense-mediated decay (NMD) regulates stability. NPC86 increased (IR) enhanced signaling, improved uptake vitro. this study, tested efficacy vivo diet-induced obese diabetic (DIOD) mouse model, treatment elevated gas5 tolerance, sensitivity, no observed toxicity or weight changes. A transcriptomics analysis adipose tissue revealed upregulation metabolic pathways, including oxidative phosphorylation glycolysis, inflammatory pathways downregulated. These findings highlight NPC86’s

Language: Английский

Citations

0
Noncoding RNAs as therapeutic targets in autophagy-related diabetic cardiomyopathy DOI
Mohammed Khaled Bin Break, Rahamat Unissa Syed, Weiam Hussein

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 256, P. 155225 - 155225

Published: Feb. 28, 2024

Language: Английский

Citations

1
Regulatory mechanism of LncRNA GAS5 in cognitive dysfunction induced by sevoflurane anesthesia in neonatal rats DOI
Xi Chen, Liang Yu, Nan Hu

et al.

Brain and Development, Journal Year: 2024, Volume and Issue: 47(1), P. 104295 - 104295

Published: Nov. 16, 2024

Language: Английский

Citations

0
Small Molecule Inhibitor of Protein Kinase C DeltaI (PKCδI) Decreases Inflammatory Pathways and Gene Expression and Improves Metabolic Function in Diet-Induced Obese Mouse Model DOI Creative Commons
Brenna Osborne, Rekha Patel, Meredith Krause‐Hauch

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 943 - 943

Published: Nov. 18, 2024

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, survival. Caspase-3 cleavage of releases the C-terminal catalytic fragment (PKCδI_C), inflammation apoptosis. We previously demonstrated an increase in PKCδI_C human obese adipose tissue (AT) adipocytes. Subsequently, we designed small molecule drug called NP627 that specifically inhibited release vitro. Here, evaluate vivo safety efficacy diet-induced (DIO) mouse model. The results demonstrate treatment DIO mice increased glucose uptake AT well kidney, spleen, liver. Next, RNAseq analysis was performed on from NP627-treated mice. show increases ADIPOQ CIDEC, upregulation AMPK, PI3K-AKT, insulin signaling pathways, while inflammatory pathways were decreased post-NP627 administration. Further, levels lncRNAs associated with affected by treatment. In conclusion, study demonstrates NP627, small-molecule inhibitor activity, not toxic it improves function vivo.

Language: Английский

Citations

0