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Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses.

Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta s

Verteporfin-loaded microparticles for radiosensitization of preclinical lung and breast metastatic spine cancer.

OBJECTIVE: The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease. METHODS: The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP

Antifungal activity of free and alginate-encapsulated Punica granatum fruit peel extract against dermatophytes using a human nail model.

BACKGROUND: Dermatophytosis and onychomycosis are among the most prevalent superficial fungal infections worldwide and remain difficult to treat because of prolonged therapy, recurrence, and emerging antifungal resistance. Punica granatum fruit, pomegranate, has a peel rich in phenolic compounds with documented antimicrobial properties; however, the therapeutic application of plant-derived extracts may be limited by physicochemical instability and low bioavailability. AIMS: To evaluate the antifungal activity of a hydroalcoholic extract of pomegranate peel and its alginate-encapsulated formul

Increased serum levels of fractalkine and mobilisation of CD34+CD45- endothelial progenitor cells in systemic sclerosis.

BACKGROUND: The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. METHODS: We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34+ progenitor cell subsets. Colony-

Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2.

Platelet-leukocyte interactions amplify inflammatory reactions, but the underlying mechanism is still unclear. CLEC5A and CLEC2 are spleen tyrosine kinase (Syk)-coupled C-type lectin receptors, abundantly expressed by leukocytes and platelets, respectively. Whereas CLEC5A is a pattern recognition receptor (PRR) to flaviviruses and bacteria, CLEC2 is the receptor for platelet-activating snake venom aggretin. Here we show that dengue virus (DV) activates platelets via CLEC2 to release extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs). DV-induced EXOs (DV-EXOs) and M

Treprostinil treatment decreases circulating platelet microvesicles and their procoagulant activity in pediatric pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) results from pulmonary vascular disease and may eventually lead to right heart failure and death. Vasodilator therapy has greatly improved PAH prognosis. Circulating microvesicles are considered as surrogate markers of endothelial and hematopoietic cell activation. AIM: Thus, our purpose was to determine if MVs are upregulated in pediatric PAH such as reported in adult patients, and to analyze the impact of vasodilator therapies on MV count and function. PATIENTS: Population study consisted of 26 patients of median age 6.09 years, with Congen

A single dose and long lasting vaccine against pandemic influenza through the controlled release of a heterospecies tandem M2 sequence embedded within detoxified bacterial outer membrane vesicles.

The influenza A virus undergoes genetic drift and shift, leaving the general population susceptible to emerging pandemic strains, despite seasonal flu vaccination. Here we describe a single dose influenza vaccine derived from recombinant outer membrane vesicles (rOMVs) that display an antigen-mapped heterospecies tandem sequence of the M2 protein from the influenza A virus, released over 30days from poly(lactic-co-glycolide) (PLGA) microparticles. Four weeks post vaccination, BALB/c mice developed high anti-M2e IgG titers that were equivalent to those generated at 8weeks in a typical prime/boo

Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

OBJECTIVE: Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. MATERIAL AND METHODS: Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. RESULTS: Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus

Global REACH 2018: dysfunctional extracellular microvesicles in Andean highlander males with excessive erythrocytosis.

High altitude-related excessive erythrocytosis (EE) is associated with increased cardiovascular risk. The experimental aim of this study was to determine the effects of microvesicles isolated from Andean highlanders with EE on endothelial cell inflammation, oxidative stress, apoptosis, and nitric oxide (NO) production. Twenty-six male residents of Cerro de Pasco, Peru (4,340 m), were studied: 12 highlanders without EE (age: 40 ± 4 yr; BMI: 26.4 ± 1.7; Hb: 17.4 ± 0.5 g/dL, Spo2: 86.9 ± 1.0%) and 14 highlanders with EE (43 ± 4 yr; 26.2 ± 0.9; 24.4 ± 0.4 g/dL; 79.7 ± 1.6%). Microvesicles were iso

Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.

OBJECTIVE: Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc. METHODS: First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated da

Orchestrating bone healing: biomaterial-driven immunoengineering of the bone microenvironment for advanced regenerative therapies.

Bone regeneration is a multistage and tightly regulated process driven by coordinated interactions between the immune and skeletal systems. While inflammation is essential for initiating repair, its dysregulation contributes to delayed union, nonunion, and impaired healing commonly seen in trauma, chronic disease, and aging. Traditional interventions, including autografts and inert biomaterials, provide structural support but fail to engage or modulate the immune microenvironment that governs successful regeneration. Emerging research in osteoimmunology has revealed the centrality of immune ce

Potentiation of a Porous Silicon Therapeutic Vaccine in Colorectal Cancer via Oxaliplatin-Mediated Regulation of Myeloid-Driven Immunosuppression.

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists into porous silicon microparticles. While effective in models with lower disease burden, its efficacy against advanced colorectal cancer (CRC) was less promising due to the accumulation of myeloid-derived suppressor cells (MDSCs) in TMEs. In this study, we investigated whether µGC

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer.

BackgroundSeveral biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor.Patients and methodsWe assessed potential biomarkers in 161 NSCLC patients and 42 control patients. Enzyme-linked immunosorbent assay methods were used to evaluate three biomar

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… The level of endothelial cell-derived microparticles (EDMP) has also been identified as a prognostic biomarker for NSCLC. 13 , 14 , 60 Fleitas et al 13 reported that circulating levels of EDMP and circulating endothelial cells correlate with prognosis, and could be useful prognostic markers for patients …

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19.

This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFlo™) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 polymerase chain reaction-positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate-to-severe acute respiratory distress syndrome. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety en

Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD mice.

Secreted microvesicles (MVs) are potent inflammatory triggers that stimulate autoreactive B and T cells, causing Type 1 Diabetes in non-obese diabetic (NOD) mice. Proteomic analysis of purified MVs released from islet cells detected the presence of endogenous retrovirus (ERV) antigens, including Env and Gag sequences similar to the well-characterized murine leukemia retroviruses. This raises the possibility that ERV antigens may be expressed in the pancreatic islets via MV secretion. Using virus-like particles produced by co-expressing ERV Env and Gag antigens, and a recombinant gp70 Env prote

The composition and daily variation of microparticles in whole blood in stable coronary artery disease.

INTRODUCTION: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers. MATERIALS AND METHODS: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5-1.0 μm, positive for annexin, and their expression of

Nanoparticle- and MSC-reinforced thermosensitive chitosan hydrogel for controlled antibiotic release and bone regeneration.

Critical-sized bone defects pose major challenges in orthopedic tissue engineering due to their limited self-repair capacity and high risk of infection. To address these issues, we developed an injectable, thermoresponsive, and biodegradable chitosan (CS)-based hydrogel reinforced with mesoporous zinc-silicate (mZS) nanoparticles and platelet-derived microparticles (PMPs). The mZS nanoparticles, characterized by a rod-like zinc core encapsulated in a mesoporous silica sheath, exhibited a hydrodynamic diameter of 1423.45 ± 222.43 d.nm and a zeta potential of -24.03 ± 0.90 mV. Incorporation of β

Platelet-derived S100A9 contributes to endotheliopathy in alcohol-associated hepatitis.

Alcohol-associated liver disease (ALD) is a growing global health concern, with alcohol-associated hepatitis (AH) leading to the highest morbidity and mortality. Available therapies are limited and often inadequate. Platelets contribute in a variety of ways to liver disease pathogenesis, but their role in AH remains largely unexplored. In this study, we addressed the hypothesis that platelets contribute to pathological inflammation in AH. Using patient samples and a multiomics approach, we found that platelets undergo proinflammatory transcriptomic and proteomic changes in AH, with 2 alarmins,

Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction.

AIMS: Previous studies have demonstrated improved cardiac function following myocardial infarction (MI) after administration of endothelial progenitor cells (EPCs) into ischaemic myocardium. A growing body of literature supports paracrine effectors, including extracellular vesicles (EVs), as the main mediators of the therapeutic benefits of EPCs. The direct use of paracrine factors is an attractive strategy that harnesses the effects of cell therapy without concerns of cell engraftment or viability. We aim to reproduce the beneficial effects of EPC treatment through delivery of EPC-derived EVs

Natural phenolic acid-based self-assembly promotes anti-tumor immune amplification by ATP-ADO axis regulation and its spiky structure.

The integration of bioactive micro-nano drug carrier components with rational design of morphological structures is poised to address the therapeutic challenge in anti-tumor immunotherapy focusing on immunogenic cell death (ICD). In this article, based on ATP-adenosine (ADO) axis regulation induced by ellagic acid (EA), the spiky self-assembly (EZ) was tailored with EA and Zn2+, and next engineered to construct ATP and pH dual-responsive EZ@MTPP for anti-tumor immune amplification. Following intratumoral injection, the spiky structure of EZ@MTPP enabled efficient local retention, then the ATP-