S‐Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte‐Like Cells by Inhibiting Notch Signalling Pathway DOI Creative Commons

Xuesong Wang,

Yan Xu, Yue Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like (HLCs) is considered one the most promising strategies for alternative hepatocyte transplantation to treat end-stage liver disease. To advance this method, it crucial gain a deeper understanding mechanisms governing hepatogenic differentiation. study demonstrated that suppression intracellular domain release Notch pathway receptor via γ-secretase inhibitor N-[(3, 5-difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1, 1-dimethylethyl ester (DAPT) significantly promotes expression hepatocyte-related genes and proteins in HLCs. Increased inducible NO synthase (iNOS) during led elevated endogenous production. Biotin switch assays revealed gradual increase S-nitrosylation (SNO)-NOTCH1 decrease overall NOTCH1 addition exogenous donor S-nitrosoglutathione (GSNO) SNO dithiothreitol (DTT) further SNO-NOTCH1 MSCs mature hepatocytes. Briefly, our results fully modification extracellular by NO, leading formation SNO-NOTCH1, inhibiting signalling pathway. Our highlights critical role regulating offers new insights driving process.

Language: Английский

Cutting-edge biotherapeutics and advanced delivery strategies for the treatment of metabolic dysfunction-associated steatotic liver disease spectrum DOI
Juhyeong Hong, Yong‐Hee Kim

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 433 - 456

Published: Feb. 11, 2025

Language: Английский

Citations

1
Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases DOI Creative Commons
Marilena Durazzo, Arianna Ferro, Victor Navarro‐Tableros

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 121 - 121

Published: Jan. 14, 2025

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack clinically validated early-stage biomarkers limited availability effective anti-fibrotic therapies. Current research focused on uncovering pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic diseases, such as inflammation, hepatic stellate cell activation proliferation, extracellular matrix production, are being developed. Etiology-specific treatments, those for hepatitis B C viruses, already clinical use, efforts develop new, targeted therapies other diseases ongoing. In this review, we highlight major changes occurring patients affected metabolic dysfunction-associated steatotic disease, viral (Delta virus), autoimmune (autoimmune hepatitis, primary biliary cholangitis, sclerosing cholangitis). Further, describe how knowledge linked current well ongoing preclinical novel strategies, including nucleic acid-, mesenchymal stromal/stem cell-, vesicle-based options. Much development obviously still missing, but plethora promising potential treatment strategies holds promise future reversal increase group patients.

Language: Английский

Citations

0
Lipid Nanoparticles-Mediated mRNA Delivery to the Eye Affected by Ionizable Cationic Lipid DOI

Siyu Dong,

Zhaoqi Pan, Ming Chang

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Ionizable lipid serves as the key functional component in nanoparticles (LNPs) for efficient mRNA delivery. This study aims to systematically evaluate clinically approved ionizable DLin-MC3-DMA and SM102-based LNPs ocular delivery, with a comprehensive assessment of their physicochemical characteristics, delivery efficiency, biodistribution patterns within microenvironment. Enhanced green fluorescence protein or Luc encoding mRNA-loaded were formulated using microfluidic mixing technology characterized by dynamic light scattering, ζ-potential measurements, cryogenic transmission electron microscopy imaging. The two LNP systems different cationic lipids demonstrated distinct capabilities vitro transfection intraocular following intravitreal administration. Notably, SM102-LNPs exhibited superior performance compared MC3-LNPs, significantly higher efficiency retinal cells vitro, more expression minimal systemic distribution vivo. Safety that administration maintained excellent long-term biocompatibility throughout five-month period. establishes promising platform therapeutics.

Language: Английский

Citations

0
The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems DOI Creative Commons
Nargish Parvin, Tapas Kumar Mandal, Sang‐Woo Joo

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1366 - 1366

Published: Oct. 25, 2024

The COVID-19 pandemic has significantly accelerated progress in RNA-based therapeutics, particularly through the successful development and global rollout of mRNA vaccines. This review delves into transformative impact on RNA with a strong focus lipid nanoparticles (LNPs) as pivotal delivery platform. LNPs have proven to be critical enhancing stability, bioavailability, targeted mRNA, facilitating unprecedented success vaccines like those developed by Pfizer-BioNTech Moderna. Beyond vaccines, LNP technology is being explored for broader therapeutic applications, including treatments cancer, rare genetic disorders, infectious diseases. also discusses emerging systems, such polymeric viral vectors, which offer alternative strategies overcome existing challenges related immune responses, tissue-specific targeting. Additionally, we examine pandemic's influence regulatory processes, fast-tracked approvals therapies, surge research funding that spurred further innovation field. Public acceptance grown, laying groundwork future developments personalized medicine. By providing an in-depth analysis these advancements, this highlights long-term evolution therapeutics precision drug technologies.

Language: Английский

Citations

1
Recent advances in the bench-to-bedside translation of cancer nanomedicines DOI Creative Commons
Yang Liu, Yinchao Zhang, Huikai Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(1), P. 97 - 122

Published: Dec. 14, 2024

Cancer remains a complex and challenging medical problem, driving extensive research efforts. Despite significant progress in understanding its genetic molecular aspects, the quest for effective treatments continues. Nanomedicines have shown great potential revolutionizing cancer treatment by offering targeted controlled drug delivery, reducing side effects, improving patient outcomes. Accordingly, nanomedicines been focus of development clinical translation. As September 2024, search on ClinicalTrials.gov website using term "nanoparticles" revealed numerous ongoing planned trials. Motivated recent advances field, this review explores current frontier nanomedicine. supported chemotherapy, phototherapy sonodynamic therapy, nucleic acid immunotherapy. However, translating into practice has challenged interactions between nanoparticles biological systems, variable permeability retention tumors, safety concerns, difficulty achieving issues with scaling up manufacturing. Perspectives addressing these challenges are offered. Future opportunities nanomedicines, including modifying tumor microenvironment, integrating artificial intelligence big data, targeting new areas, also discussed. This underscores to revolutionize from standpoint.

Language: Английский

Citations

1
Lipid Nanoparticle-Mediated Liver-Specific Gene Therapy for Hemophilia B DOI Creative Commons
Brijesh Lohchania,

Porkizhi Arjunan,

Gokulnath Mahalingam

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1427 - 1427

Published: Nov. 9, 2024

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Citations

0
S‐Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte‐Like Cells by Inhibiting Notch Signalling Pathway DOI Creative Commons

Xuesong Wang,

Yan Xu, Yue Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like (HLCs) is considered one the most promising strategies for alternative hepatocyte transplantation to treat end-stage liver disease. To advance this method, it crucial gain a deeper understanding mechanisms governing hepatogenic differentiation. study demonstrated that suppression intracellular domain release Notch pathway receptor via γ-secretase inhibitor N-[(3, 5-difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1, 1-dimethylethyl ester (DAPT) significantly promotes expression hepatocyte-related genes and proteins in HLCs. Increased inducible NO synthase (iNOS) during led elevated endogenous production. Biotin switch assays revealed gradual increase S-nitrosylation (SNO)-NOTCH1 decrease overall NOTCH1 addition exogenous donor S-nitrosoglutathione (GSNO) SNO dithiothreitol (DTT) further SNO-NOTCH1 MSCs mature hepatocytes. Briefly, our results fully modification extracellular by NO, leading formation SNO-NOTCH1, inhibiting signalling pathway. Our highlights critical role regulating offers new insights driving process.

Language: Английский

Citations

0