Folic acid-decorated PEGylated magnetite nanoparticles as efficient drug carriers to tumor cells overexpressing folic acid receptor.

The improved drug delivery systems (DDS) are needed for the targeted delivery of their therapeutic cargo (biologically active protein/peptide molecules, nucleic acids, vaccines, etc.) to diseased cells. Thus, we aimed to develop magnetite nanoparticles (FeO), stabilized with polyethylene glycol (PEG) and decorated (surface-functionalized) with folic acid (FA) (FeO@PEG@FA) to ensure targeted internalization in cells expressing the folic acid receptors (FR).

Apolipoprotein A-II, a Player in Multiple Processes and Diseases.

Apolipoprotein A-II (apoA-II) is the second most abundant apolipoprotein in high-density lipoprotein (HDL) particles, playing an important role in lipid metabolism. Human and murine apoA-II proteins have dissimilar properties, partially because human apoA-II is dimeric whereas the murine homolog is a monomer, suggesting that the role of apoA-II may be quite different in humans and mice. As a component of HDL, apoA-II influences lipid metabolism, being directly or indirectly involved in vascular diseases.

Deciphering the relationship between caveolae-mediated intracellular transport and signalling events.

The caveolae-mediated transport across polarized epithelial cell barriers has been largely deciphered in the last decades and is considered the second essential intracellular transfer mechanism, after the clathrin-dependent endocytosis. The basic cell biology knowledge was supplemented recently, with the molecular mechanisms beyond caveolae generation implying the key contribution of the lipid-binding proteins (the structural protein Caveolin and the adapter protein Cavin), along with the bulb coat stabilizing molecules PACSIN-2 and Eps15 homology domain protein-2. The current attention is focused also on caveolae architecture (such as the bulb coat, the neck, the membrane funnel inside the bulb, and the associated receptors), and their specific tasks during the intracellular transport of various cargoes.

Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand.

A wide variety of metal-based compounds have been obtained and studied for their antitumor activity since the intensely used cytostatic drugs (e.g., cisplatin) failed to accomplish their expected pharmacological properties.

VLA4-Enhanced Allogeneic Endothelial Progenitor Cell-Based Therapy Preserves the Aortic Valve Function in a Mouse Model of Dyslipidemia and Diabetes.

The number and function of endothelial progenitor cells (EPCs) are reduced in diabetes, contributing to deteriorated vascular repair and the occurrence of cardiovascular complications. Here, we present the results of treating early diabetic dyslipidemic mice or dyslipidemic with disease-matched EPCs modified to overexpress VLA4 (VLA4-EPCs) as compared with the treatment of EPCs transfected with GFP (GFP-EPCs) as well as EPCs from healthy animals. Organ imaging of injected PKH26-stained cells showed little pulmonary first-pass effects and distribution in highly vascularized organs, with splenic removal from circulation, mostly in non-diabetic animals.

Bio-Responsive Carriers for Controlled Delivery of Doxorubicin to Cancer Cells.

The cellular internalization of drug carriers occurs via different endocytic pathways that ultimately involve the endosomes and the lysosomes, organelles where the pH value drops to 6.0 and 5.0, respectively.

VCAM-1 Targeted Lipopolyplexes as Vehicles for Efficient Delivery of shRNA-Runx2 to Osteoblast-Differentiated Valvular Interstitial Cells; Implications in Calcific Valve Disease Treatment.

Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes.

Regulated cell death joins in atherosclerotic plaque silent progression.

Non-apoptotic regulated cell death (ferroptosis and necroptosis) leads to the release of damage-associated molecular patterns (DAMPs), which initiate and perpetuate a non-infectious inflammatory response. We hypothesize that DAMPs and non-apoptotic regulated cell death are critical players of atherosclerotic plaque progression with inadequate response to lipid-lowering treatment. We aimed to uncover the silent mechanisms that govern the existing residual risk of cardiovascular-related mortality in experimental atherosclerosis.

CRISPR/dCas9 Transcriptional Activation of Endogenous Apolipoprotein AI and Paraoxonase 1 in Enterocytes Alleviates Endothelial Cell Dysfunction.

Atherosclerosis is the main cause of cardiovascular diseases with high prevalence worldwide. A promising therapeutic strategy to reverse atherosclerotic process is to improve the athero-protective potential of high-density lipoproteins (HDL). Since the small intestine is a source of HDL, we aimed to activate transcription of the endogenous HDL major proteins, apolipoprotein AI (ApoAI) and paraoxonase 1 (PON1), in enterocytes, and to evaluate their potential to correct the pro-inflammatory status of endothelial cells (EC).

Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high-density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus.

Peripheral artery disease (PAD) is an atherosclerotic disorder affecting arteries of the lower limbs, the major risk factors including dyslipidemia and diabetes mellitus (DM). We aimed to identify alterations of the proteins in high-density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL and HDL were isolated from plasma of PAD patients with/without DM (PAD-DM/PAD) and healthy subjects (N).

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy.

Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell‒iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages.

Proteomic Analysis of Estrogen-Mediated Enhancement of Mesenchymal Stem Cell-Induced Angiogenesis In Vivo.

Therapeutic use of mesenchymal stem cells (MSCs) for tissue repair has great potential. MSCs from multiple sources, including those derived from human umbilical matrix, namely Wharton's jelly, may serve as a resource for obtaining MSCs. However, low in vivo engraftment efficacy of MSCs remains a challenging limitation.

Aortic valve disease in diabetes: Molecular mechanisms and novel therapies.

Valve disease and particularly calcific aortic valve disease (CAVD) and diabetes (DM) are progressive diseases constituting a global health burden for all aging societies (Progress in Cardiovascular Diseases. 2014;56(6):565: Circulation Research. 2021;128(9):1344).

P-selectin targeted RAGE-shRNA lipoplexes alleviate atherosclerosis-associated inflammation.

The receptor for advanced glycation end products (RAGE) plays a central role in the chronic inflammatory process associated with atherosclerosis development. We aimed to develop lipoplexes carrying RAGE-short hairpin (sh) RNA, targeted to the adhesion molecule P-selectin, selectively expressed on the surface of activated endothelium (Psel-lipo/shRAGE) to down-regulate RAGE expression as a therapeutic strategy for atherosclerosis. In vitro, Psel-lipo/shRAGE lipoplexes were efficiently taken up by activated endothelial cells (EC), decreased the expression of RAGE protein, and proved to be functional by reducing the monocyte adhesion to activated EC.

MiR-223-3p levels in the plasma and atherosclerotic plaques are increased in aged patients with carotid artery stenosis; association with HDL-related proteins.

Background: Cardiovascular diseases are still the main cause of death worldwide. Our aim was to analyse the link between miR-223-3p levels, dysfunctional HDL and the age of patients with carotid artery stenosis (CAS).

Methods And Results: Thirty-two CAS patients enrolled for endarterectomy were divided in 2 groups: aged over 65 years (n = 19) and under 65 years (n = 13).

A novel platform for drug testing: Biomimetic three-dimensional hyaluronic acid-based scaffold seeded with human hepatocarcinoma cells.

Hepatic cancer is one of the most widespread maladies worldwide that requires urgent therapies and thus reliable means for testing anti-cancer drugs. The switch from two-dimensional (2D) to three-dimensional (3D) cell cultures produced an improvement in the in vitro outcomes for testing anti-cancer drugs. We aimed to develop a novel hyaluronic acid (HA)-based 3D cell model of human hepatocellular carcinoma (HepG2 cells) for drug testing and to assess comparatively in 3D vs.

The Multifaceted Role of Extracellular Vesicles in Glioblastoma: microRNA Nanocarriers for Disease Progression and Gene Therapy.

Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles (EVs), a heterogeneous group of cell-derived vesicles, transport miRNAs, mRNAs and intracellular proteins, and have been shown to promote horizontal malignancy into adjacent tissue, as well as resistance to conventional therapies.

Extracellular Vesicles: Versatile Nanomediators, Potential Biomarkers and Therapeutic Agents in Atherosclerosis and COVID-19-Related Thrombosis.

Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.

Synthesis, Characterization, and In Vitro Insulin-Mimetic Activity Evaluation of Valine Schiff Base Coordination Compounds of Oxidovanadium(V).

Type 2 diabetes became an alarming global health issue since the existing drugs do not prevent its progression. Herein, we aimed to synthesize and characterize a family of oxidovanadium(V) complexes with Schiff base ligands derived from L-/D-valine (val) and salicylaldehyde (sal) or -vanillin (van) as insulin-mimetic agents and to assess their potential anti-diabetic properties. Two new oxidovanadium(V) complexes, [{VO(R-salval)(HO)}(μ-O){VO(R-salval)}] and [{VO(R-vanval)(CHOH)}(μ-O)], and their S-enantiomers were synthesized and characterized.

Detection of Vascular Reactive Oxygen Species in Experimental Atherosclerosis by High-Resolution Near-Infrared Fluorescence Imaging Using VCAM-1-Targeted Liposomes Entrapping a Fluorogenic Redox-Sensitive Probe.

Excessive production of reactive oxygen species (ROS) and the ensuing oxidative stress are instrumental in all phases of atherosclerosis. Despite the major achievements in understanding the regulatory pathways and molecular sources of ROS in the vasculature, the specific detection and quantification of ROS in experimental models of disease remain a challenge. We aimed to develop a reliable and straightforward imaging procedure to interrogate the ROS overproduction in the vasculature and in various organs/tissues in atherosclerosis.

Alginate/poloxamer hydrogel obtained by thiol-acrylate photopolymerization for the alleviation of the inflammatory response of human keratinocytes.

Hydrogel-based wound dressings have been intensively studied as promising materials for wound healing and care. The mixed-mode thiol-acrylate photopolymerization is used in this paper for alginate/poloxamer hydrogels formation. First, the alginate was modified with thiol groups using the esterification reaction with cysteamine, and second, the terminal hydroxyl groups of poloxamer were esterified with acryloyl chloride to introduce polymerizable acrylate groups.

One step forward: extracellular mitochondria transplantation.

Mitochondria play a key role in cellular energy production and contribute to cell metabolism, homeostasis, intracellular signalling and organelle's quality control, among other roles. Viable, respiratory-competent mitochondria exist also outside the cells. Such extracellular/exogenous mitochondria occur in the bloodstream, being released by platelets, activated monocytes and endothelial progenitor cells.

Aggregated LDL turn human macrophages into foam cells and induce mitochondrial dysfunction without triggering oxidative or endoplasmic reticulum stress.

Uptake of modified lipoproteins by macrophages turns them into foam cells, the hallmark of the atherosclerotic plaque. The initiation and progression of atherosclerosis have been associated with mitochondrial dysfunction. It is known that aggregated low-density lipoproteins (agLDL) induce massive cholesterol accumulation in macrophages in contrast with native LDL (nLDL) and oxidized LDL (oxLDL).

Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies.

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients.

Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events.

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs ( = 35) and with CVEs ( = 12), during 1 year follow-up.