Cell–cell communication: new insights and clinical implications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 7, 2024

Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell-cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, physiological regulation. Cells communicate direct contact or at a distance using ligand-receptor interactions. So cellular encompasses two processes: signal conduction generation intercellular transmission signals, transduction reception procession signals. Deciphering networks critical understanding metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by detailed description mechanisms molecule importance main signaling pathways they mediate maintaining biological functions. Then systematically introduce series human diseases caused abnormalities progress clinical applications. Finally, summarize various methods monitoring interactions, including imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, single-cell technologies. These aim to illustrate how functions depend on these interactions complexity regulatory regulate crucial processes, homeostasis, immune responses diseases. In addition, this enhances our processes occur after cell-cell binding, highlighting its application discovering new therapeutic targets biomarkers related precision medicine. This collective provides foundation developing targeted drugs personalized treatments.

Язык: Английский

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Isolation and usage of exosomes in central nervous system diseases

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(3)

Опубликована: Март 1, 2024

Abstract Background Exosomes are vesicles secreted by all types of mammalian cells. They characterized a double‐layered lipid membrane structure. serve as carriers for plethora signal molecules, including DNA, RNA, proteins, and lipids. Their unique capability effortlessly crossing the blood–brain barrier underscores their critical role in progression various neurological disorders. This includes, but is not limited to, diseases such Alzheimer's, Parkinson's, ischemic stroke. Establishing stable mature methods isolating exosomes prerequisite study biomedical significance. The extraction technologies include differential centrifugation, density gradient size exclusion chromatography, ultrafiltration, polymer coprecipitation, immunoaffinity capture, microfluidic, so forth. Each technology has its own advantages disadvantages, standards have been unified internationally. Aims review aimed to showcase recent advancements exosome isolation techniques thoroughly compare disadvantages different methods. Furthermore, significant research progress made using diagnosing treating central nervous system (CNS) emphasized. Conclusion varying result differences concentration, purity, exosomes. efficient separation facilitates widespread application, particularly diagnosis treatment CNS diseases.

Язык: Английский

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C‐Terminal Agrin Fragment as a Biomarker for Sarcopenia: A Systematic Review and Meta‐Analysis

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 30, 2025

Язык: Английский

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Extracellular Vesicles for the Diagnosis of Parkinson's Disease: Systematic Review and Meta‐Analysis

Movement Disorders, Год журнала: 2023, Номер 38(9), С. 1585 - 1597

Опубликована: Июль 14, 2023

Abstract Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, monitoring therapeutic response). Imaging, genetic, biochemical have been widely studied. In recent years, extracellular vesicles (EVs) become a promising material for biomarker development. Proteins molecular from any organ, including the central nervous system, can be packed into EVs transported to periphery easily obtainable biological specimens like blood, urine, saliva. We performed systematic review meta‐analysis of articles (published before November 15, 2022) reporting assessment in PD patients healthy controls (HCs). Biomarkers were analyzed using random effects calculated standardized mean difference (Std.MD). Several proteins ribonucleic acids identified patients, but only α‐synuclein (aSyn) leucine‐rich repeat kinase 2 (LRRK2) reported sufficient studies (n = 24 6, respectively) perform meta‐analysis. EV aSyn was significantly increased neuronal L1 cell adhesion molecule (L1CAM)–positive blood compared HCs (Std.MD 1.84, 95% confidence interval 0.76–2.93, P 0.0009). Further analysis sample isolation method indicated that L1CAM‐IP (immunoprecipitation) directly plasma best assessing patients. Upcoming neuroprotective clinical trials immediately need peripheral individuals at risk developing PD. Overall, improved sensitivity assays means they identify reflect changes brain. CNS‐derived will likely play major role development coming years. © 2023 The Authors. Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

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Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Язык: Английский

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Exosomal NEDD4L derived from HG+oxLDL-induced vascular endothelial cells accelerates macrophage M1 polarization and oxLDL uptake by ubiquitinating IκBα and PPARγ

Cell Biology and Toxicology, Год журнала: 2025, Номер 41(1)

Опубликована: Янв. 7, 2025

Vascular endothelial cell-derived exosomes are thought to mediate disease progression by regulating macrophage polarization. However, its mechanism in diabetes mellitus (DM)-related atherosclerosis (AS) progress is unclear. High-glucose (HG) and oxLDL were used induce human cardiac microvascular cells (HCMECs) mimic DM-related AS model. The conditioned medium (CM) from HG+oxLDL-induced HCMECs was incubated with THP1-M0 monocytes treated LPS or oxLDL. mRNA levels of M1/M2 polarization markers, NEDD4L, IκBα PPARγ determined qRT-PCR. Flow cytometry analyze marker. Dil-labeled oil red O staining performed assess uptake cells. inflammatory factors examined using ELISA. Transmission electron microscope for observing foam cell formation exosome morphology. protein p-Smad1/Smad1, p-Smad2/Smad2, p-IκBα/IκBα, p-P65/P65, anti-lipid metabolism-related NEDD4L tested western blot. interaction between assessed Co-IP assay. CM could promote M1 polarization, formation, inhibiter GW4869 eliminated these effects. overexpressed HCMECs, which be taken up Exosomal knockdown inhibited reducing the p-IκBα/IκBα p-P65/P65. reduce expression through ubiquitination. HCMECs-derived exosomal enhance ubiquitination facilitate uptake, thus accelerating AS.

Язык: Английский

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Evaluation of α‐synuclein in CNS‐originating extracellular vesicles for Parkinsonian disorders: A systematic review and meta‐analysis

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(12), С. 3741 - 3755

Опубликована: Июль 7, 2023

Abstract Background & Aims Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), share early motor symptoms but have distinct pathophysiology. As a result, accurate premortem diagnosis is challenging for neurologists, hindering efforts disease‐modifying therapeutic discovery. Extracellular vesicles (EVs) contain cell‐state‐specific biomolecules can cross the blood‐brain barrier to peripheral circulation, providing unique central nervous (CNS) insight. This meta‐analysis evaluated blood‐isolated neuronal oligodendroglial EVs (nEVs oEVs) α‐synuclein levels in disorders. Methods Following PRISMA guidelines, included 13 studies. An inverse‐variance random‐effects model quantified effect size (SMD), QUADAS‐2 assessed risk of bias publication was evaluated. Demographic clinical variables were collected meta‐regression. Results The 1,565 patients PD, 206 MSA, 21 DLB, 172 PSP, 152 CBS 967 healthy controls (HCs). Findings suggest that combined concentrations nEVs oEVs α‐syn higher PD compared HCs (SMD = 0.21, p 0.021), while lower PSP ‐1.04, 0.0017) or ‐0.41, < 0.001). Additionally, and/or did not significantly differ vs. contradicting literature. Meta‐regressions show demographic factors significant predictors concentrations. Conclusion results highlight need standardized procedures independent validations biomarker studies development improved biomarkers distinguishing

Язык: Английский

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Dual Role of Exosome in Neurodegenerative Diseases: A Review Study

Current Stem Cell Research & Therapy, Год журнала: 2023, Номер 19(6), С. 852 - 864

Опубликована: Июль 27, 2023

Extracellular vesicles (EVs) are one of the crucial means intercellular communication, which takes many different forms. They heterogeneous, secreted by a range cell types, and can be generally classified into microvesicles exosomes depending on their location function. Exosomes small EVs with diameters about 30-150 nm diverse sources.

Язык: Английский

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Advances in Purification, Modification, and Application of Extracellular Vesicles for Novel Clinical Treatments

Membranes, Год журнала: 2022, Номер 12(12), С. 1244 - 1244

Опубликована: Дек. 8, 2022

Extracellular vesicles (EV) are membrane surrounded by a lipid bilayer and include microvesicles, apoptotic bodies, exosomes, exomeres. Exosome-encapsulated microRNAs (miRNAs) released from cancer cells involved in the proliferation metastasis of tumor via angiogenesis. On other hand, mesenchymal stem cell (MSC) therapy, which is being employed regenerative medicine owing to ability MSCs differentiate into various cells, due humoral factors, including messenger RNA (mRNA), miRNAs, proteins, lipids, encapsulated exosomes derived transplanted cells. New treatments that advocate cell-free therapy using MSC-derived will significantly improve clinical practice. Therefore, highly purified perform their original functions desirable. In this review, we summarized advances purification, modification, application EVs as novel strategies treat some diseases.

Язык: Английский

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Role of Exosomes in the Pathogenesis and Theranostic of Alzheimer’s Disease and Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 11054 - 11054

Опубликована: Июль 4, 2023

Alzheimer’s disease (AD) and Parkinson’s (PD) are the most common neurodegenerative diseases (NDDs) threatening lives of millions people worldwide, including especially elderly people. Currently, due to lack a timely diagnosis proper intervention strategy, AD PD largely remain incurable. Innovative therapy highly desired. Exosomes small vesicles that present in various bodily fluids, which contain proteins, nucleic acids, active biomolecules, play crucial role intercellular communication. In recent years, exosomes pathogenesis, early diagnosis, treatment has attracted ascending attention. However, exact pathogenesis theragnostic not been fully illustrated. review, we first introduce biogenesis, components, uptake, function exosomes. Then elaborate on involvement PD. Moreover, application therapeutics is also summarized discussed. Additionally, serving as drug carriers deliver medications central nervous system specifically addressed. The potential explored, discussing their applications treatment, well current limitations. Given limitation exosomes, propose future perspectives for better utilizing NDDs. Hopefully, it would pave ways expanding biological fundamental research theranostics

Язык: Английский

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