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Extracellular Vesicles (EVs) Derived from Senescent Endothelial Cells Promote Platelet Activation.

Thrombotic cardiovascular diseases are frequent side effects of cancer therapy with cytotoxic drugs such as Doxorubicin. Endothelial cell senescence is emerging as a critical mechanism underlying endothelial dysfunction in this context. Senescent cells, although unable to proliferate, secrete bioactive molecules that alter the tissue microenvironment, a feature known as the senescence-associated secretory phenotype (SASP). Besides soluble molecules, senescent cells also release extracellular vesicles (EVs). Previous studies indicate that senescent endothelial cells produce a secretome that pro…

Macrophage metabolic reprogramming via HIF-1α-glycolysis drives osteoblast ferroptosis and bone loss through an IL-6-STAT3-dependent redox axis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is characterized by exacerbated bone resorption and inadequate bone formation, with macrophag … radation. This suppressed glycolytic flux and M1 polarization, reducing IL-6 secretion. The altered secretome protected osteoblasts from ferroptosis by inhibiting the IL-6/p-STAT3/HIF-1α/TFRC axis and rebalancing GPX4/ACSL4. Osteogenic differentiation was restored. In OVX rats, VPA improved bone mass and microstructure, effects abolished by DMOG. CONCLUSIO …

A pancreatic cancer organoid-macrophage co-culture using starPEG-heparin hydrogel deciphers tumor-immune cell interactions.

Macrophages are among the most abundant immune cells in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) and play a … phenotypes observed by multiplex immunohistochemistry in the matched primary PDAC tissues. Cytokine secretome profiling revealed PDO-specific differences, indicating distinct underlying macrophage polarization subtypes. Collectively, our starPEG-heparin hydrogel-based 3D co-culture enables hypothesis-driven and physiologically relevant studies of tumor-macr …

The Role of Tumor-Intrinsic HuR in Modeling the Pancreatic Tumor Microenvironment: Molecular Mechanisms and Therapeutic Opportunities.

Pancreatic ductal adenocarcinoma (PDAC) remains largely refractory to therapy, due in part to the complex interplay between tumor cells and … hymal transition, stabilizes key transcripts involved in metabolic adaptation, and alters the tumor secretome to influence extracellular matrix deposition and fibroblast behavior. We further explore the role of HuR in regulating immune cell function and the immune landscape of PDAC. Notably, HuR-driven TME remodeling reinforces environmental stressors that …

Characterisation of human in vitro tumour-associated macrophage models to define translational relevance.

Tumour-associated macrophages (TAMs) are key components of the tumour microenvironment with a demonstrated ability to modulate anti-tumour T … ion on human monocyte-derived macrophages, as well as active T-cell immunosuppression. We performed secretome characterization of these tumour-conditioned media (TCM) to shed light on cancer cell-derived soluble factors that may contribute to TAM polarisation. Furthermore, we characterized the proteomic and transcriptomic signatures of macrophages exposed t …

Extracellular vesicles from mesenchymal stromal cells: an emerging therapy for intractable neonatal disorders.

Neonatal disorders affecting different organs are highly multifactorial and involve a complex interplay among prematurity, inflammation, oxi … bility to modulate inflammation, promote repair, and support organ maturation. By delivering a rich secretome of proteins, lipids, and regulatory RNAs, MSC-EVs retain the regenerative benefits of mesenchymal stromal cells while offering improved safety and storage. This review provides a comprehensive overview of MSC-EV therapy for neonatal disorders, focus …

Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia.

BACKGROUND: Mesenchymal stem cells (MSCs) and their secretome have significant potential in promoting hair follicle development. However, the effects of MSC therapy have been reported to vary due to their heterogeneous characteristics. Different sources of MSCs or culture systems may cause heterogeneity of exosomes. AIM: To define the potential of human adipose-derived MSC exosomes (hADSC-Exos) and human umbilical cord-derived MSC exosomes (hUCMSC-Exos) for improving dermal papillary cell proliferation in androgenetic alopecia. METHODS: We conducted liquid chromatography-mass spectrometry pr…

Человеческие печени MSCs сохраняют свои основные клеточные свойства в хроническо воспламенённой печени.

Каждая 25-ая смерть во всем мире связана с патологией печени. Необходимо срочно разработать новые подходы к лечению заболеваний печени и протоколы для сохранения жизненно важных функций пациентов, включенных в список ожидания трансплантации печени. Мезенхимальные стволовые клетки (МСЦ) играют важную роль в поддержании целостности печени и улучшении состояния печени после вливания. Вместе с тем остается неясным, являются ли МСЦ, изолированные от хронически воспаленных печени, аналогичными по своим основным свойствам клеточным свойствам МСЦ, получаемым из здоровой печени. Мы провели большое коли

Совпадение в аннотации оригинала
Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols f … adhesion molecules, and the hallmarks of senescence, as well as cell proliferation, migration, and secretome. Only the expression of some immune checkpoints and toll-like receptors was different. Evidently, MSCs with unchanged cellular properties are present in human liver even at late stages of inflammatory diseases. These cells can be isolated and used a …

Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies.

Aging, tau pathology, and chronic inflammation in the brain play crucial roles in synaptic loss, neurodegeneration, and cognitive decline in tauopathies, including Alzheimer's disease. Senescent cells accumulate in the aging brain, accelerate the aging process, and promote tauopathy progression through their abnormal inflammatory secretome known as the senescence-associated secretory phenotype (SASP). Tau oligomers (TauO)-the most neurotoxic tau species-are known to induce senescence and the SASP, which subsequently promote neuropathology, inflammation, oxidative stress, synaptic dysfunction, …

Schwann cells acquire a repair phenotype after assembling into spheroids and show enhanced in vivo therapeutic potential for promoting peripheral nerve repair.

The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has … n. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively …

Advances in the applications of mesenchymal stem cell-conditioned medium in ocular diseases.

Mesenchymal stem cell-conditioned medium (MSC-CM), also known as secretome, is secreted by MSC and contains a variety of bioactive factors with anti-inflammatory, anti-apoptotic, neuroprotection, and proliferation effects. Increasing evidence proved that MSC-CM plays an important role in various diseases, including skin, bone, muscle, and dental diseases. However, the role of MSC-CM in ocular diseases is not quite clear, Therefore, this article reviewed the composition, biological functions, preparation, and characterization of MSC-CM and summarized current research advances in different sourc…

Autocrine/paracrine growth hormone in cancer progression.

It is now apparent that growth hormone (GH), an anterior pituitary hormone predominantly regulating postnatal somatic growth and metabolism, … ignaling pathways and specific transcriptome signatures and enhances the expression of an oncogenic secretome to promote these functions. Hence, extrapituitary expression of GH in cancer promotes cancer progression independent of endocrine hGH, and may be considered as a validated target in oncology.

Borrelia PeptideAtlas: A proteome resource of common Borrelia burgdorferi isolates for Lyme research.

Lyme disease, caused by an infection with the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America. B. … ptideAtlas http://www.peptideatlas.org/builds/borrelia/. Included is information on total proteome, secretome, and membrane proteome of these B. burgdorferi strains. Proteomic data collected from 35 different experiment datasets, with a total of 855 mass spectrometry runs, identified 76,936 distinct peptides at a 0.1% peptide false-discovery-rate, which map …

Mycobacterium abscessus: insights from a bioinformatic perspective.

Mycobacterium abscessus is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic … from the analysis of genomes, microbiomes, genomic variations, phylogeny, proteome, transcriptome, secretome, antibiotic resistance, and vaccine design to further our understanding. The utility of genome-based studies in comprehending disease progression, surveillance, tracing transmission routes, and epidemiological outbreaks on a global scale has been hi …

Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis.

Prenylcysteine Oxidase 1 (PCYOX1) is an enzyme involved in the degradation of prenylated proteins. It is expressed in different tissues including vascular and blood cells. We recently showed that the secretome from Pcyox1-silenced cells reduced platelet adhesion both to fibrinogen and endothelial cells, suggesting a potential contribution of PCYOX1 into thrombus formation. Here, we show that in vivo thrombus formation after FeCl3 injury of the carotid artery was delayed in Pcyox1-/- mice, which were also protected from collagen/epinephrine induced thromboembolism. The Pcyox1-/- mice displayed …

Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells.

ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of …

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

Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic stroke are to restore blood flo … l injury. Abundant evidence demonstrates the beneficial impact of mesenchymal stem cells (MSCs) and secretome on cerebral ischemic injury. MSCs reduce oxidative stress through suppressing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and transferring healthy mitochondria to damaged cells. Meanwhile, MSCs exert anti-inflammatio …

Proteomics of Cryptococcus neoformans: From the Lab to the Clinic.

Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsena … hlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein-protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, …

MSC Based Therapies-New Perspectives for the Injured Lung.

Chronic lung diseases pose a tremendous global burden. At least one in four people suffer from severe pulmonary sequelae over the course of … possibilities to boost the therapeutic efficacy of MSC application and to take advantage of the MSC secretome. The presented review summarizes the most recent advances and highlights joint mechanisms of MSC action across disease entities which provide the basis to timely tackle this global disease burden.

Lymphoangiocrine signals promote cardiac growth and repair.

Recent studies have suggested that lymphatics help to restore heart function after cardiac injury1-6. Here we report that lymphatics promote … roduce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal …