Extracellular Vesicle Mitochondrial DNA Reflects Podocyte Mitochondrial Stress and Is Associated with Relapse in Nephrotic Syndrome.

Idiopathic childhood nephrotic syndrome is a common glomerulopathy comprising proteinuria, hypoalbuminemia, and edema. Podocyte dysfunction is central to this disease process. Extracellular vesicles are released from stressed cells and can represent a molecular snapshot of the parent cell of origin.

Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis.

Urinary extracellular vesicles (uEVs) and immune mediators have emerged as potential minimally invasive renal biomarkers. Even though active lupus nephritis (LN) is associated with immune complex deposition, tissue inflammation, and podocyte damage, it remains unclear how these parameters are simultaneously altered in systemic lupus erythematosus (SLE). Thus, we aimed to evaluate uEVs as biomarkers in LN, in association with urinary immune mediators.

Roadblocks of Urinary EV Biomarkers: Moving Toward the Clinic.

Despite remarkable interest in the biomarker potential of urinary extracellular vesicles (uEVs) and the identification of numerous promising candidates, their clinical translation still presents multiple challenges. The opportunities for successful translation are obvious, yet the main roadblocks on the way have hardly been systematically considered and more coordinated approaches are needed to overcome them. In the present review article, we have identified the most relevant roadblocks of clinical translation of urinary EV-based biomarkers and discuss possible solutions to overcome them.

The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan.

The gradual decline in physiological functions that comes with aging contributes to a range of chronic diseases, such as Alzheimer's, type 2 diabetes, heart failure, and osteoarthritis. Significant advancements in human longevity due to socioeconomic development have resulted in a foreseeable and substantial strain on the global healthcare system. In fact, there is now a shift in research focus towards enhancing healthspan.

Functional significance of extracellular vesicles as mediators of cardiometabolic and cardiorenal diseases upon aging.

Aging increases the risk of cardiometabolic and cardiorenal disease and this is associated with cellular dysregulation including oxidative stress, chronic inflammation, insulin resistance and senescence. Extracellular vesicles (EV) facilitate inter-organ communication and are now well established as important pathophysiological mediators in many aging-associated diseases. Our knowledge of EV biosynthesis, cargo composition, cellular targeting and functional effects has expanded significantly over the past decade.

miR-486-5p Inhibits eNOS and Angiogenesis in Cultured Endothelial Cells by Targeting MAML3.

Kidney ischemia-reperfusion (I/R) is associated with endothelial injury. Administration of miRNA (miR)-486-5p protects against rat kidney I/R injury, with localisation to capillary endothelial cells, although it inhibits I/R-induced endothelial nitric oxide synthase (eNOS) protein expression. Here, we studied the effect of miR-486-5p on eNOS and endothelial cell function and determined its mRNA targets.

Deciphering Platelets: Are They Cells or an Evolved Form of Extracellular Vesicles?

Platelets are abundant in blood, where they maintain the integrity of the vasculature. Megakaryocytes, the cells responsible for platelet genesis, produce membrane protrusions from which as many as 5000 anucleate platelets can be released into the bloodstream. Platelets lack genomic DNA but contain different molecules, such as RNA, as well as organelles transmitted from the parent megakaryocyte.

Unlocking the potential of extracellular vesicles in nephrology: what does MISEV2023 add?

Extracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, scientific attention shifted toward their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers have begun exploring whether extracellular vesicles mediate intercellular signaling inside the nephron and between the kidney and other organs throughout the body.

Systematic review of microRNAs in human acute kidney injury.

Introduction: Early diagnosis of acute kidney injury (AKI) is limited with current tools. MicroRNAs (miRNAs) are implicated in AKI pathogenesis in preclinical models, but less is known about their role in humans. We conducted a systematic review to identify dysregulated miRNAs in humans with AKI.

Damage-Associated Molecular Patterns and Pattern Recognition Receptors in the Podocyte.

Podocytes possess immune system components allowing for a variety of innate responses to endogenous and exogenous stimuli. Recently, several groups have linked inappropriate innate immune signaling to podocyte injury, particularly chronic, sustained injury; however, the immune capabilities of podocytes have not been fully elucidated. Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from damaged cells, including podocytes, and can elicit an inflammatory response and recruit immune cells to areas of injury.

Sex-specific Associations of Aldosterone and Renin With Body Composition: A Population-based Cohort Study.

Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood.

Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population.

Design: Population-based cohort study.

Evaluation of resazurin phenoxazine dye as a highly sensitive cell viability potency assay for natural killer cell-derived extracellular vesicle-based cancer biotherapeutics.

Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro.

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis.

Background:  Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction.

miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.

Aim: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia-reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function.

Unraveling the molecular landscape of kAE1: a narrative review.

Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. Its main function is to exchange bicarbonate and chloride ions between the blood and urine to maintain blood pH at physiological threshold.

Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta-analysis.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia.

A clinically relevant large-scale biomanufacturing workflow to produce natural killer cells and natural killer cell-derived extracellular vesicles for cancer immunotherapy.

Natural killer cell-derived extracellular vesicles (NK-EVs) have shown promising potential as biotherapeutics for cancer due to their unique attributes as cytotoxic nanovesicles against cancer cells and immune-modulatory activity towards immune cells. However, a biomanufacturing workflow is needed to produce clinical-grade NK-EVs for pre-clinical and clinical applications. This study established a novel biomanufacturing workflow using a closed-loop hollow-fibre bioreactor to continuously produce NK-EVs from the clinically relevant NK92-MI cell line under serum-free, Xeno-free and feeder-free conditions following GMP-compliant conditions.

Biodistribution of mesenchymal stromal cell-derived extracellular vesicles administered during acute lung injury.

Background: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising cell-free therapy for acute lung injury (ALI). To date, no studies have investigated their biodistribution in ALI or discerned the timing of administration for maximal lung targeting, which are crucial considerations for clinical translation. Our study aimed to characterize a mouse model of ALI and establish the distribution kinetics and optimal timing of MSC-EV delivery during lung injury.

Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology.

Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis of hypertension were analyzed-chronic angiotensin (Ang) II-infused and renin-overexpressing (TTRhRen) mice, spontaneously hypertensive (SHR), and Goldblatt two-kidney one-clip (2K1C) rats.

Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

Background: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.

Objectives: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy.

Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a 'one-stop-shop' for renal assessment in cases of suspected AKI and CKD.

Annexin A5 Inhibits Endothelial Inflammation Induced by Lipopolysaccharide-Activated Platelets and Microvesicles via Phosphatidylserine Binding.

Sepsis is caused by a dysregulated immune response to infection and is a leading cause of mortality globally. To date, no specific therapeutics are available to treat the underlying septic response. We and others have shown that recombinant human annexin A5 (Anx5) treatment inhibits pro-inflammatory cytokine production and improves survival in rodent sepsis models.

Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review.

Background Aims: Interest in cell-based therapy using extracellular vesicles (EVs) is intensifying, building upon promising preclinical research and a handful of published clinical studies. Registered clinical trials remain small, heterogeneous in design and underpowered to determine safety and efficacy on their own. A scoping review of registered studies can identify opportunities to pool data and perform meta-analysis.

The Application of an Extracellular Vesicle-Based Biosensor in Early Diagnosis and Prediction of Chemoresponsiveness in Ovarian Cancer.

Background: Ovarian cancer (OVCA) is the most fatal gynecological cancer with late diagnosis and plasma gelsolin (pGSN)-mediated chemoresistance representing the main obstacles to treatment success. Since there is no reliable approach to diagnosing patients at an early stage as well as predicting chemoresponsiveness, there is an urgent need to develop a diagnostic platform for such purposes. Small extracellular vesicles (sEVs) are attractive biomarkers given their potential accuracy for targeting tumor sites.