Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage DOI Creative Commons
Yingying Gong, Meilin Wei, Xiaopei Cao

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 23, 2024

Abstract Background Diabetes, a global epidemic, is the leading cause of mortality globally. The aim this study to get better understanding pathophysiology diabetes. Methods Palmitic acid (PA)-treated β-cells, db/db mice and high fat diet (HFD)-fed mouse model type 2 diabetes were established. H&E was used assess histological changes pancreas. IHC, FISH, western blot or qRT-PCR employed detect expression key molecules in primary islets lipotoxic β-cells. Cell behaviors detected by MTT, EdU incorporation assay, TUNEL assay glucose-induced insulin secretion (GSIS). associations among circMlxipl, Mbnl1 Rbbp6 validated RIP RNA pull-down assays, direct binding between Hdac3 promoter examined ChIP luciferase assays. Co-IP interaction ChREBP Rbbp6, as well ubiquitination ChREBP. Results upregulated, but circMlxipl downregulated from diabetic overexpression protected against PA-induced impairments β-cells through modulating back-splicing suppressing served transcriptional repressor Mbnl1, it implicated circMlxipl-mediated protection via regulating Lack inhibited Rbbp6-mediated ubiquitin-proteasomal degradation In vivo studies revealed that knockdown alleviated symptoms circMlxipl-regulated mice. Conclusion Mbnl1-mediated alternative splicing regulates Rbbp6-involved turnover inhibit lipotoxicity-induced β-cell damage.

Language: Английский

Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines DOI Creative Commons
Wen‐Jing Xiao, Wenjie Jiang, Zheng Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Language: Английский

Citations

1
Diagnosis of diabetes and hypertension: A performance comparison between transcriptome data and clinical data DOI
Pratheeba Jeyananthan,

T.A.P. Dharmasena,

W.D.A. Nuwansiri

et al.

Gene Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102176 - 102176

Published: Feb. 1, 2025

Language: Английский

Citations

0
Advancements in precision medicine: multi-omics approach for tailored metformin treatment in type 2 diabetes DOI Creative Commons
Najeha Anwardeen, Khaled Naja, Mohamed A. Elrayess

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 28, 2024

Metformin has become the frontline treatment in addressing significant global health challenge of type 2 diabetes due to its proven effectiveness lowering blood glucose levels. However, reality is that many patients struggle achieve their glycemic targets with medication and cause behind this variability not been investigated thoroughly. While genetic factors account for only about a third response variability, potential influence metabolomics gut microbiome on drug efficacy opens new avenues investigation. This review explores different molecular signatures uncover how complex interplay between genetics, metabolic profiles, microbiota can shape individual responses metformin. By highlighting insights from recent studies identifying knowledge gaps regarding metformin-microbiota interplay, we aim highlight path toward more personalized effective management strategies moving beyond one-size-fits-all approach.

Language: Английский

Citations

1
THE EFFECTIVENESS OF EXERCISE APPLICATION IN GENETICALLY PREDISPOSED OBESITY AND DIABETES DOI Creative Commons

Yu. Yu Mazur,

V. M. Ilyin,

В. А. Пастухова

et al.

Bulletin of Problems Biology and Medicine, Journal Year: 2024, Volume and Issue: 1(3), P. 36 - 36

Published: Jan. 1, 2024

Language: Английский

Citations

0
Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage DOI Creative Commons
Yingying Gong, Meilin Wei, Xiaopei Cao

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 23, 2024

Abstract Background Diabetes, a global epidemic, is the leading cause of mortality globally. The aim this study to get better understanding pathophysiology diabetes. Methods Palmitic acid (PA)-treated β-cells, db/db mice and high fat diet (HFD)-fed mouse model type 2 diabetes were established. H&E was used assess histological changes pancreas. IHC, FISH, western blot or qRT-PCR employed detect expression key molecules in primary islets lipotoxic β-cells. Cell behaviors detected by MTT, EdU incorporation assay, TUNEL assay glucose-induced insulin secretion (GSIS). associations among circMlxipl, Mbnl1 Rbbp6 validated RIP RNA pull-down assays, direct binding between Hdac3 promoter examined ChIP luciferase assays. Co-IP interaction ChREBP Rbbp6, as well ubiquitination ChREBP. Results upregulated, but circMlxipl downregulated from diabetic overexpression protected against PA-induced impairments β-cells through modulating back-splicing suppressing served transcriptional repressor Mbnl1, it implicated circMlxipl-mediated protection via regulating Lack inhibited Rbbp6-mediated ubiquitin-proteasomal degradation In vivo studies revealed that knockdown alleviated symptoms circMlxipl-regulated mice. Conclusion Mbnl1-mediated alternative splicing regulates Rbbp6-involved turnover inhibit lipotoxicity-induced β-cell damage.

Language: Английский

Citations

0