Extracellular vesicles are key players in mesenchymal stem cells’ dual potential to regenerate and modulate the immune system

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115203 - 115203

Опубликована: Фев. 9, 2024

MSCs are used for treatment of inflammatory conditions or regenerative purposes. complete cells and allogenic transplantation is in principle possible, but mostly autologous use preferred. In recent years, it was discovered that secrete extracellular vesicles. These active budded off vesicles carry a cargo. The cargo can be miRNA, protein, lipids etc. transported through the body fuse with target cells. Thereby, they influence phenotype modulate disease. have, like MSCs, immunomodulatory capacities. This review will focus on those features discuss their dual role. Besides immunomodulation, regeneration concentrate bone, cartilage, tendon, vessels nerves. Current clinical trials immunomodulation started last five years highlighted as well. summary, have great potential disease modulating entity treatment. Their characteristics need to taken into account often both important having best effect.

Язык: Английский

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Advances in nanomaterial-targeted treatment of acute lung injury after burns

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 18, 2024

Abstract Acute lung injury ( ALI ) is a common complication in patients with severe burns and has complex pathogenesis high morbidity mortality rates. A variety of drugs have been identified the clinic for treatment ALI, but they toxic side effects caused by easy degradation body distribution throughout body. In recent years, as understanding mechanism underlying improved, scholars developed new nanomaterials that can be safely effectively targeted ALI. Most these methods involve such lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles other nanomaterials, which are to reach tissues perform their functions through active targeting passive targeting, process involves cells organelles. this review, first, mechanisms pathophysiological features occurrence after burn reviewed, potential therapeutic targets summarized, existing classified, possible problems challenges discussed provide reference development

Язык: Английский

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Phosphorylation of FOXN3 by NEK6 promotes pulmonary fibrosis through Smad signaling

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 21, 2025

The transcriptional repressor FOXN3 plays a key role in regulating pulmonary inflammatory responses, which are crucial the development of fibrosis. However, its specific regulatory function lung fibrosis remains unclear. Here, we show that suppresses by inhibiting Smad activity. targets substantial number response gene promoters, facilitating Smad4 ubiquitination, disrupts association Smad2/3/4 complex with chromatin and abolishes response. In to pro-fibrotic stimuli, NEK6 phosphorylates at S412 S416, leading degradation. loss inhibits β-TrCP-mediated ubiquitination Smad4, stabilizing complex's responsive elements promoting activation, thus contributing Notably, found significant inverse expression pattern between clinical cases, underscoring importance NEK6-FOXN3-Smad axis pathological process This study identifies as suppressor signaling. facilitates disrupting target abolishing

Язык: Английский

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Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2023, Номер 38(1)

Опубликована: Ноя. 13, 2023

Adaptor associated kinase 1 (AAK1), a member of the Ark1/Prk1 family Ser/Thr kinases, is specific key regulating Thr156 phosphorylation at μ2 subunit adapter complex-2 (AP-2) protein. Due to their important biological functions, AAK1 systems have been validated in clinics for neuropathic pain therapy, and are being explored as potential therapeutic targets diseases caused by various viruses such Hepatitis C (HCV), Dengue, Ebola, COVID-19 amyotrophic lateral sclerosis (ALS). Centreing on advances drug discovery programs this field up 2023, inhibitors discussed from aspects structure-based rational molecular design, pharmacology, toxicology synthetic routes compounds interest review. The aim provide medicinal chemistry community with up-to-date information accelerate small molecule inhibitors.

Язык: Английский

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Mesenchymal stem cell-derived exosomes as delivery vehicles for non-coding RNAs in lung diseases

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 116008 - 116008

Опубликована: Дек. 9, 2023

The burden of lung diseases is gradually increasing with an increase in the average human life expectancy. Therefore, it necessary to identify effective methods treat and reduce their social burden. Currently, number studies focus on role mesenchymal stem cell-derived exosomes (MSC-Exos) as a cell-free therapy diseases. They show great potential for application more stable safer option than traditional cell therapies. MSC-Exos are rich various substances, including proteins, nucleic acids, DNA. Delivery Non-coding RNAs (ncRNAs) enables communicate target cells. significantly inhibit inflammatory factors, oxidative stress, promote normal proliferation, apoptosis by delivering ncRNAs. Moreover, carrying specific ncRNAs affect invasion, migration cancer cells, thereby playing managing cancer. detailed mechanisms clinical treatment disease were explored developing standardized culture, isolation, purification, administration strategies. In summary, MSC-Exo-based delivery have important prospects treating

Язык: Английский

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Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support

Microorganisms, Год журнала: 2024, Номер 12(3), С. 440 - 440

Опубликована: Фев. 21, 2024

To discover potential micro(mi)RNA biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep-sequencing analysis small RNA expression was performed on plasma samples from 40 patients hospitalized for (median 13.50 [IQR 9-24] days since symptoms initiation) 21 healthy noninfected individuals. A total 1218 different miRNAs were identified. When compared with donors, SARS-CoV-2-infected showed significantly (fold change [FC] > 1.2 adjusted p [padj] < 0.05) altered 190 miRNAs. The top-10 differentially expressed (DE) miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, miR-191-5p, which displayed FC padj values ranging 153 to 5 2.51 × 10-32 2.21 10-21, respectively, unequivocally diagnosed infection. No differences in blood cell counts biochemical parameters, including interleukin 6, ferritin, D-dimer, observed between COVID-19 high-flow oxygen therapy, low-flow or not requiring therapy. Notably, 31 deregulated found, when high- therapy compared. generates a specific miRNA signature patients. Specific profiles are associated prognosis flow.

Язык: Английский

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Cow’s Milk Protein May Induce Allergy and Inflammation in Intestinal Epithelial Cells Through Regulating HOTAIR Expression and NF‐κB Signaling Pathway

Journal of Food Biochemistry, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Background: Cow’s milk protein allergy (CMPA) is associated with activation of proinflammatory signaling pathways and overexpression inflammatory mediators. Long noncoding RNA (LncRNA) HOX transcript antisense intergenic (HOTAIR) a LncRNA, which involved in the occurrence development many biological processes diseases. HOTAIR can prevent necrotizing enterocolitis. This study aims to explore effect on NCM‐460 cells its mechanism action HOTAIR. Methods: were induced by cow’s establish vitro cell models. CCK‐8 EdU staining used for evaluating effects viability proliferation. ELISA was comparing levels cytokines. TUNEL conducted apoptosis. Expression detected RT‐qPCR. The expression NF‐κB pathway–related molecules explored evaluate improving ALI. Results: decreased also Moreover, it induce antiproliferative proapoptotic cells, LncRNA partially reverse protein. In addition, reversed signaling. Conclusions: may inflammation intestinal epithelial through regulating pathways.

Язык: Английский

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Native and Engineered Extracellular Vesicles for the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Small Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Extracellular vesicles (EVs) are lipid bilayer nanoparticles naturally released from cells, playing a crucial role in intercellular communication. They modulate gene expression and regulate physiological pathological processes, including acute lung injury (ALI) respiratory distress syndrome (ARDS). Research has shown that EVs contain variety of active components, biocompatible small size, do not trigger immune rejection, making the infusion exogenous promising therapeutic tool. With further research, engineering strategies have been proposed to enhance clinical potential EVs. These involve modifying either donor cells secrete or themselves can be engineered circumvent limitations native In this review, an overview biological properties is provided current treating ALI/ARDS, along with latest research findings, summarized. The challenges opportunities for translation as novel tool also discussed, offering new insights into treatment ALI/ARDS using EV technology.

Язык: Английский

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Small molecule inhibitors of hnRNPA2B1–RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles

Nucleic Acids Research, Год журнала: 2025, Номер 53(5)

Опубликована: Фев. 27, 2025

Abstract Extracellular vesicles (EVs) are cell-secreted membranous particles contributing to intercellular communication. Coding and noncoding RNAs can be detected as EV cargo, RNA-binding proteins (RBPs), such hnRNPA2B1, have been circumstantially implicated in EV-RNA sorting mechanisms. However, the contribution of competitive RBP–RNA interactions responsible for RNA-sorting outcomes is still unclear, especially predicting content. We designed a reverse proteomic analysis exploiting identify intracellular protein binders vitro. Using cells expressing recombinant hnRNPA2B1 normalize interactions, we prioritized network heterogeneous nuclear ribonucleoproteins purine-rich RNA sequences subsequently validated secreted through short fluorescent oligos. Then, GGGAG-enriched probe that efficiently interacted with full-length human protein. exploited interaction conduct pharmacological screening inhibitors protein–RNA binding. Small molecules were orthogonally biochemical cell-based approaches. Selected drugs remarkably impacted EV-RNAs reduced an RNA-dependent, EV-mediated paracrine activation NF-kB recipient cells. These results demonstrate relevance post-transcriptional mechanisms possibility quality developing innovative strategies targeting discrete functions.

Язык: Английский

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Sevoflurane Mediates LINC00339/miR‐671‐5p/PSMB2 Axis to Improve Cardiomyocytes Against Hypoxia/Reoxygenation Injury

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(4)

Опубликована: Март 27, 2025

ABSTRACT Ischemia/reperfusion (I/R) causes a deterioration in heart function, leading to myocardial infarction. It is aimed at investigating the protective mechanism of sevoflurane (Sevo) on cardiomyocytes by constructing cellular model hypoxic/reoxygenation (H/R) this study.[Human hybrid] epithelioid cells (AC16) were induced H/R establish I/R injury and Sevo postconditioning. The expression long intergenic non‐protein coding RNA 339 (LINC00339), microRNA‐671‐5p (miR‐671‐5p) proteasome 20S subunit beta 2 (PSMB2) was detected quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Viability apoptosis AC16 cell counting kit‐8 (CCK‐8) assay flow cytometry, respectively. levels interleukin‐6 (IL‐6), IL‐10, tumor necrosis factor‐a (TNF‐a), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH‐Px) superoxide dismutase (SOD), detected. LINC00339 upregulated relative Control group, whereas decreased cardiomyocytes. viability increased, apoptosis, oxidative stress, inflammatory responses postconditioning group but effect partially reversed overexpression. negatively regulated miR‐671‐5p, miR‐671‐5p upregulation could alleviate damage PSMB2, downstream target gene inhibit exerts H/R‐induced cardiomyocyte injury, which may be achieved interfering with LINC00339/miR‐671‐5p/PSMB2 expression.

Язык: Английский

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