Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery

Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1148 - 1148

Published: Oct. 8, 2024

The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances Therapeutic LNPs: LNPs, composed ionizable lipids, phospholipids, cholesterol, polyethylene glycol (PEG) facilitate efficient cellular uptake cytosolic release while mitigating degradation by nucleases. However, synthetic entities, LNPs face challenges that alter their therapeutic efficacy safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides comprehensive overview latest advancements LNP research, focusing on preclinical assessments encompassing toxicity, reactogenicity, immunogenicity. Summary Outlook: Additionally, it outlines potential strategies addressing these offers insights into future research directions enhancing application therapeutics.

Language: Английский

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Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 11, 2024

Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as kidney largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples datasets available from 11 spaceflight-exposed mouse 5 human, 1 simulated rat 4 GCR-exposed missions. found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk nephrolithiasis is in part a primary phenomenon rather than solely secondary consequence bone loss; 2) remodelling nephron results expansion distal convoluted tubule size but loss overall density; 3) damage dysfunction when exposed Mars roundtrip dose-equivalent GCR.

Language: Английский

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Some morpholine tethered novel aurones: Design, synthesis, biological, kinetic and molecular docking studies

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 140, P. 106805 - 106805

Published: Aug. 23, 2023

Language: Английский

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Cathepsin B induces kidney diseases through different types of programmed cell death

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Cathepsin B (CTSB), a key cysteine protease, plays essential roles in physiological and pathological processes. As research progresses, interest how CTSB triggers different types of programmed cell death (PCD) to induce the onset development diseases is increasing. Several recent studies suggest that PCD mediated by play kidney diseases. In this review, we outline fundamental mechanisms which several discuss function various segments kidney. Moreover, explore possibilities prospects using as therapeutic target for

Language: Английский

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Tumor protease-activated theranostic nanoparticles for MRI-guided glioblastoma therapy

Theranostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1745 - 1758

Published: Jan. 1, 2023

Rationale: As a cancer, Glioblastoma (GBM) is highly lethal and difficult-to-treat. With the aim of improving therapies to GBM, we developed novel target-specific theranostic nanoparticles (TNPs) that can be selectively cleaved by cathepsin B (Cat B) release potent toxin monomethyl auristatin E (MMAE). Methods: We synthesized TNPs composed ferumoxytol-based nanoparticle carrier peptide prodrug with Cat-B-responsive linker tubulin inhibitor MMAE. hypothesized intratumoral Cat cleave our MMAE kill GBM cells. The ferumoxytol core enables in vivo drug tracking magnetic resonance imaging (MRI). incubated U87-MG cells or evaluated TNP content transmission electron microscopy Prussian blue staining. In addition, stereotaxically implanted 6- 8-week-old nude mice express fusion protein Green Fluorescence Protein firefly Luciferase (U87-MG/GFP-fLuc). then treated animals an intravenous dose (25 mg/kg ferumoxytol, 0.3 MMAE) control. also combination treatment radiation therapy. performed MRI before after injection. compared results for tumor normal brain tissue between control groups. monitored growth period 21 days. Results: successfully hydrodynamic size 41 ± 5 nm zeta potential 6 3 mV. TNP-treated demonstrated significantly higher iron than ferumoxytol-treated (98 1% vs. were iron-positive, respectively). found fewer live attached group (3.8 2.0 px2) (80.0 14.5 px2, p < 0001). studies decline signal (T2= 28 ms) but not 32 injections. When injection was combined therapy, signals dropped further (T2 = 24 ms). therapy extended median survival from days 45 group. Conclusion: new cleavable reported this work accumulate cause cell death, have synergistic effects

Language: Английский

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Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Current Topics in Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 22(21), P. 1776 - 1792

Published: July 27, 2022

The outbreak of the SARS-CoV-2 virus in late 2019 and spread COVID-19 pandemic have caused severe health socioeconomic damage worldwide. Despite significant research effort to develop vaccines, antiviral treatments, repurposed therapeutics effectively contain catastrophe, there are no available effective vaccines or drugs that can limit threat disease, so infections continue expand. To date, search for treatment remains a global challenge. Therefore, it is imperative therapeutic strategies SARS-CoV-2. Like other coronaviruses, invades infects human host cells via attachment its spike envelope glycoprotein cell receptor hACE2. Subsequently, several proteases facilitate viral entry proteolytic cleavage activation S protein. These include type II transmembrane serine (TTSPs), cysteine cathepsins B L, furin, trypsin, Factor Xa, among others. Given critical role coronavirus pathogenesis, their inhibition by small molecules has successfully targeted vitro, suggesting attractive targets infection. In this review, we focus on biochemical properties SARS-CoV-2, highlight molecule candidates been proposed through silico research.

Language: Английский

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Plant cathepsin B, a versatile protease

Frontiers in Plant Science, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 23, 2024

Plant proteases are essential enzymes that play key roles during crucial phases of plant life. Some mainly involved in general protein turnover and recycle amino acids for synthesis. Other cell signalling, cleave specific substrates players important genetically controlled molecular processes. Cathepsin B is a cysteine protease can do both because its exopeptidase endopeptidase activities. Animal cathepsin has been investigated many years, much known about mode action substrate preferences, but remains to be discovered this potent plants. development, germination, senescence, microspore embryogenesis, pathogen defence responses abiotic stress, including programmed death. This review discusses the structural features, activity enzyme differences between animal forms. We discuss maturation subcellular localisation provide detailed overview involvement life A greater understanding signalling processes involving needed applied discoveries biotechnology.

Language: Английский

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AEBS inhibition in macrophages: Augmenting reality for SERMs repurposing against infections

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 116544 - 116544

Published: Sept. 1, 2024

Language: Английский

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Synthetic Approaches of Epoxysuccinate Chemical Probes

ChemBioChem, Journal Year: 2023, Volume and Issue: 24(16)

Published: April 25, 2023

Synthetic chemical probes are powerful tools for investigating biological processes. They particularly useful proteomic studies such as activity-based protein profiling (ABPP). These methods initially used mimics of natural substrates. As the techniques gained prominence, more and elaborate with increased specificity towards given enzyme/protein families amenability to various reaction conditions were used. Among probes, peptidyl-epoxysuccinates represent one first types compounds investigate activity cysteine protease papain-like family enzymes. Structurally derived from substrate, a wide body inhibitors activity- or affinity-based bearing electrophilic oxirane unit covalent labeling active enzymes now exists. Herein, we review literature regarding synthetic approaches epoxysuccinate-based together their reported applications, chemistry inhibition supramolecular formation arrays.

Language: Английский

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Role of Cathepsin B Expression in Oral Squamous Cell Carcinoma: A Comprehensive Review

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

This comprehensive review delves into the intricate landscape of oral squamous cell carcinoma (OSCC) by examining role cathepsin B expression in its pathogenesis. OSCC, a prevalent and clinically significant malignancy, poses considerable global health burden, necessitating thorough exploration underlying molecular mechanisms. Cathepsin B, lysosomal cysteine protease, emerges as critical player influencing tumour initiation, invasion, metastasis. The begins with brief overview emphasizing epidemiological clinical features, followed exploring significance studying this context. In manuscript, structure function are elucidated, providing foundation for understanding aberrant OSCC. Clinical studies revealing correlations grade stage, along prognostic significance, scrutinized, offering insights potential diagnostic utility B. biological functions including impact on invasion modulation apoptosis, comprehensively discussed.

Language: Английский

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