An update on the regulatory mechanisms of NLRP3 inflammasome activation

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(5), P. 1141 - 1160

Published: April 13, 2021

Abstract The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β triggering pyroptosis, which paramount importance variety physiological pathological conditions. Over past decade, considerable advances have been made elucidating molecular mechanisms underlying priming/licensing (Signal 1) assembly 2) NLRP3 activation. Recently, number studies indicated that step regulated by complicated at both transcriptional posttranslational levels. In this review, we discuss current understanding mechanistic details activation with particular emphasis on protein-protein interactions, modifications, spatiotemporal regulation machinery. We also present detailed summary multiple positive and/or negative regulatory pathways providing upstream signals culminate assembly. A better will provide opportunities for development methods prevention treatment inflammasome-related diseases.

Language: Английский

---

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(12), P. 911 - 946

Published: Nov. 1, 2020

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with closed loop structure. The majority circRNAs are formed by back-splicing process in pre-mRNA splicing. Their expression dynamically regulated and shows spatiotemporal patterns among cell types, tissues developmental stages. CircRNAs have important biological functions many physiological processes, their aberrant implicated human diseases. Due to high stability, becoming promising biomarkers diseases, such as cardiovascular autoimmune diseases cancers. In this review, we focus on the translational potential using blood liquid biopsy for We highlight abundant expression, essential significant correlations various components peripheral blood, including whole cells extracellular vesicles. addition, summarize current knowledge circRNA disease diagnosis or prognosis.

Language: Английский

---

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Aug. 17, 2023

Abstract Skin wounds are characterized by injury to the skin due trauma, tearing, cuts, or contusions. As such injuries common all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on role mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in wound repair. cell-free therapy, MSC-derived EVs shown significant application potential field repair as more stable and safer option than conventional therapy. Treatment based can significantly promote damaged substructures, including regeneration vessels, nerves, hair follicles. In addition, inhibit scar formation affecting angiogenesis-related antifibrotic pathways promoting macrophage polarization, angiogenesis, proliferation, migration, inhibiting excessive matrix production. Additionally, these structures serve scaffold for components used repair, be developed into bioengineered support trauma Through formulation standardized culture, isolation, purification, drug delivery strategies, exploration detailed mechanism will allow them clinical treatments conclusion, EVs-based therapies important prospects Here we provide comprehensive overview their current status, potential, associated drawbacks.

Language: Английский

---

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia

Bioengineering, Journal Year: 2025, Volume and Issue: 12(1), P. 92 - 92

Published: Jan. 20, 2025

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail adequately complexity CLI, identification alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on potential two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, nanovesicles artificially engineered nanosized vesicles. Both these represent promising avenues for intervention. They act as carriers bioactive cargo, including proteins, nucleic acids, lipids, that can modulate cellular responses associated with ischemic tissue repair angiogenesis. also assesses evolving landscape CLI through unique perspective The spans spectrum from early preclinical investigations latest translational advancements, providing comprehensive overview current state research this emerging field. These groundbreaking vesicle therapies hold immense revolutionizing treatment paradigms.

Language: Английский

---

Stem Cell-Derived Exosomes Prevent Aging-Induced Cardiac Dysfunction through a Novel Exosome/lncRNA MALAT1/NF-κB/TNF-α Signaling Pathway

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 14

Published: April 8, 2019

Aging is a risk factor for cardiovascular disease, and there no effective therapeutic approach to alleviate this condition. NF- κ B TNF- α have been implicated in the activation of aging process, but signaling molecules responsible inactivation remain unknown. Exosomes reported improve heart functions by releasing miRNA. Recent studies suggest that lncRNAs are more tissue-specific developmental stage-specific compared However, role lncRNA exosome-mediated cardiac repair has not explored. In present study, we focused on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which an associated with cell senescence. We discovered human umbilical cord mesenchymal stem cell- (UMSC-) derived exosomes prevent aging-induced dysfunction. Silencer RNA against MALAT1 blocked beneficial effects exosomes. summary, UMSC-derived dysfunction novel MALAT1, turn inhibits B/TNF- pathway. These findings will lead development therapies delay progression age-related diseases.

Language: Английский

---

Human Umbilical Cord Mesenchymal Stem Cell‐Derived Exosomes Attenuate Oxygen‐Glucose Deprivation/Reperfusion‐Induced Microglial Pyroptosis by Promoting FOXO3a‐Dependent Mitophagy

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Background . Mesenchymal stem cell‐derived exosomes (MSC‐exos) have been recognized as a promising therapeutic strategy for neonatal hypoxic‐ischemic brain damage (HIBD). Recently, microglial pyroptosis was shown to play vital role in the progression of HIBD. However, whether MSC‐exos improve HIBD by regulating remains unknown. Methods. Exosomes were isolated from human umbilical cord mesenchymal cells (huMSCs) and identified transmission electron microscopy (TEM), western blot, nanoparticle tracking analysis (NTA). BV‐2 subjected oxygen‐glucose deprivation/reoxygenation (OGD/R) induce ischemia/reperfusion (I/R) vitro CCK‐8, ELISA, Hoechst 33342/PI double staining performed detect cells. Conditioned medium (CM) exposed different treatments used investigate its effect on neuronal injury. Moreover, 3‐methyladenine (3‐MA) mitochondrial division inhibitor‐1 (mdi‐1) verify involvement mitophagy protection against OGD/R‐induced Finally, FOXO3a siRNA MSC‐exo‐induced inhibition. Results huMSCs successfully extracted. In OGD/R‐exposed cells, increased cell viability decreased expression NLRP3, cleaved caspase‐1, GSDMD‐N well release IL‐1 β IL‐18. Compared with CM treated PBS, significantly SH‐SY5Y LDH release. also TOM20 COX IV Additionally, 3‐MA mdi‐1 attenuated inhibition MSC‐exo treatment. Furthermore, partially abolished neuroprotective induced Conclusions Our findings demonstrated that enhance mitophagy, therefore protecting microglia I/R‐induced alleviating subsequent

Language: Английский

---

Serum Extracellular Vesicle-Derived circHIPK3 and circSMARCA5 Are Two Novel Diagnostic Biomarkers for Glioblastoma Multiforme

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(7), P. 618 - 618

Published: June 27, 2021

Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving prognosis of this currently incurable disease. We suggest use serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic for diagnosis. EVs were isolated by size exclusion chromatography from sera 23 5 grade 3 glioma (GIII) patients, 10 unaffected controls (UC). The expression two candidate circRNAs (circSMARCA5 circHIPK3) was assayed droplet digital PCR. CircSMARCA5 circHIPK3 significantly less abundant in sEVs patients with respect to UC (fold-change (FC) −2.15 −1.92, respectively) GIII (FC −1.75 −1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on sEV-derived circSMARCA5 circHIPK3, allowed us distinguish (area under (AUC) 0.823 (0.667–0.979) 0.855 (0.704 1.000), a 95% confidence interval (CI), Multivariable ROC performed combining preoperative neutrophil lymphocyte (NLR), platelet (PLR) monocyte (LMR) ratios, three known prognostic markers, an improvement accuracy (AUC 0.901 (0.7912 CI). Our data good GBM, especially when associated NLR, PLR LMR.

Language: Английский

---

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 26, 2021

Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic are to restore blood flow, which reduce disability but time limited. The interruption flow in contributes intricate pathophysiological processes. Oxidative stress and inflammatory activity two early events the cascade cerebral injury. These factors reciprocal causation directly trigger development autophagy. Appropriate autophagy brain recovery by reducing oxidative activity, while dysfunction aggravates Abundant evidence demonstrates beneficial impact mesenchymal stem cells (MSCs) secretome on MSCs through suppressing reactive oxygen species (ROS) nitrogen (RNS) generation transferring healthy mitochondria damaged cells. Meanwhile, exert anti-inflammation properties production cytokines extracellular vesicles, inhibiting proinflammatory activation, pyroptosis, alleviating blood–brain barrier leakage. Additionally, regulation imbalances gives rise neuroprotection against Altogether, have been promising candidate due their pleiotropic effect.

Language: Английский

---

Engineering Bioactive M2 Macrophage‐Polarized, Anti‐inflammatory, miRNA‐Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials

Small, Journal Year: 2022, Volume and Issue: 18(34)

Published: July 8, 2022

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during process of healing, but detailed mechanism miRNA-mediated intercellular communication between myoblasts macrophages remains unclear. Here, it is reported that secrete miRNAs-enriched exosomes in inflammatory environment, through which miR-224 transferred into inhibit M2 polarization. Further data demonstrate WNT-9a may be a direct target for macrophage In turn, secretome M1 impairs promotes proliferation. Single-cell integration analysis suggests elevation exosome-derived caused by activation key factor E2F1 demonstrates RB/E2F1/miR-224/WNT-9a axis. vivo results show treatment with antagomir-224 or liposomes containing inhibitors suppresses fibrosis improves recovery. These findings indicate importance crosstalk via miRNA-containing regulation polarization differentiation/proliferation healing. This study provides strategy treating injury designing polarization-enabling anti-inflammatory miRNA-based bioactive material.

Language: Английский

---

Potential Therapeutic Strategies for Skeletal Muscle Atrophy

Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 44 - 44

Published: Dec. 26, 2022

The maintenance of muscle homeostasis is vital for life and health. Skeletal atrophy not only seriously reduces people’s quality increases morbidity mortality, but also causes a huge socioeconomic burden. To date, no effective treatment has been developed skeletal owing to an incomplete understanding its molecular mechanisms. Exercise therapy the most atrophy. Unfortunately, it suitable all patients, such as fractured patients bedridden with nerve damage. Therefore, mechanism crucial developing new therapies In this review, PubMed was systematically screened articles that appeared in past 5 years about potential therapeutic strategies Herein, we summarize roles inflammation, oxidative stress, ubiquitin-proteasome system, autophagic-lysosomal pathway, caspases, calpains expound drug targets progress against This review focuses on current treatments atrophy, including (active substances traditional Chinese medicine, chemical drugs, antioxidants, enzyme inhibitors, hormone etc.), gene therapy, stem cell exosome (muscle-derived cells, non-myogenic exosomes), cytokine physical (electroacupuncture, electrical stimulation, optogenetic technology, heat low-level laser therapy), nutrition support (protein, essential amino acids, creatine, β-hydroxy-β-methylbutyrate, vitamin D), other (biomaterial adjuvant intestinal microbial regulation, oxygen supplementation). Considering many have propose combination proper individual needs, which may yield better outcomes.

Language: Английский

---