A HGF Mutation in the Familial Case of Primary Lymphedema: A Report.

Lymphedema is a disorder that leads to excessive swelling due to lymphatic insufficiency, resulting in the accumulation of protein-rich interstitial fluid. Primary lymphedema predominantly impacts the lower extremities and is frequently linked to hereditary factors. This condition is known to be associated with variants in several genes, such as FOXC2, FLT4, and SOX18. However, many cases remain unexplained, suggesting undiscovered gene associations. This study describes a novel mutation in the hepatocyte growth factor (HGF) gene, a previously hypothesized candidate for lymphedema pathogenesis. This mutation was identified in affected members of a multigenerational family presenting with primary leg lymphedema, consistent with an autosomal dominant inheritance pattern.

PRP of T2DM Patient Immobilized on PCL Nanofibers Stimulate Endothelial Cells Proliferation.

Diabetic foot ulcers (DFU) are a common complication of Type 2 Diabetes Mellitus (T2DM). Development of bioactive wound healing covers is an important task in medicine. The use of autologous platelet-rich plasma (PRP) consisting of growth factors, cytokines and components of extracellular matrix is a perspective approach for DFU treatment, but we previously found that some T2DM PRP samples have a toxic effect on mesenchymal stem cells (MSCs) in vitro. Here, we covalently immobilized T2DM PRP proteins on polycaprolactone (PCL) nanofibers, and the growth of endothelial cells on the PCL-COOH-PRP was investigated. Additionally, the level of NO reflecting the cytotoxic effects of PRP, angiogenin, and VEGF levels were measured in T2DM PRP samples. The results showed that the application of PCL-COOH-PRP nanofibers allows to remove the cytotoxicity of T2DM PRP and to improve endothelial cell adhesion and proliferative activity. We showed that the origin of T2DM PRP (the level of PRP toxicity or presence/absence of DFU) does not influence the efficiency of cell growth on PCL-COOH-PRP, and on the level of angiogenin, vascular epidermal growth factor (VEGF) in PRP itself.

Markers of Restenosis after Percutaneous Transluminal Balloon Angioplasty in Patients with Critical Limb Ischemia.

Among cardiovascular diseases, chronic obliterating lesions of the arteries of lower extremities, which are one of the important problems of modern healthcare, are distinguished. In most cases, the cause of damage to the arteries of lower extremities is atherosclerosis. The most severe form is chronic ischemia, characterized by pain at rest and ischemic ulcers, ultimately increasing the risk of limb loss and cardiovascular mortality. Therefore, patients with critical limb ischemia need limb revascularization. Percutaneous transluminal balloon angioplasty is one of the least invasive and safe approaches, with advantages for patients with comorbidities. However, after this procedure, restenosis is still possible. Early detection of changes in the composition of some molecules as markers of restenosis will help screen patients at the risk of restenosis, as well as find ways to apply efforts for further directions of inhibition of this process. The purpose of this review is to provide the most important and up-to-date information on the mechanisms of restenosis development, as well as possible predictors of their occurrence. The information collected in this publication may be useful in predicting outcomes after surgical treatment and will also find new ways for the target implication to the mechanisms of development of restenosis and atherosclerosis.

Apolipoprotein A-I Supports MSCs Survival under Stress Conditions.

Clinical trials have shown the safety of mesenchymal stem/stromal cells (MSCs) transplantation, but the effectiveness of these treatments is limited. Since, transplanted MSCs will undergo metabolic disturbances in the bloodstream, we investigated the influence of blood plasmas of type 2 diabetes (T2D) patients on MSCs viability and examined whether apolipoprotein A-I (apoA-I) could protect cells from stressful conditions of serum deprivation (SD), hypoxia, and elevated concentrations of reactive oxygen species (ROS). ApoA-I exhibits anti-inflammatory, immune activities, improves glycemic control, and is suitable for T2D patients but its influence on MSCs remains unknown. For the first time we have shown that apoA-I decreases intracellular ROS and supports proliferative rate of MSCs, thereby increasing cell count in oxidation conditions. ApoA-I did not influence cell cycle when MSCs were predominantly in the G0/G1 phases under conditions of SD/hypoxia, activated proliferation rapidly, and reduced apoptosis during MSCs transition to the oxygenation or oxidation conditions. Finally, it was found that the blood plasma of T2D individuals had a cytotoxic effect on MSСs in 39% of cases and had a wide variability of antioxidant properties. ApoA-I protects cells under all adverse conditions and can increase the efficiency of MSCs transplantation in T2D patients.

Electrospun Fibers and Sorbents as a Possible Basis for Effective Composite Wound Dressings.

Skin burns and ulcers are considered hard-to-heal wounds due to their high infection risk. For this reason, designing new options for wound dressings is a growing need. The objective of this work is to investigate the properties of poly (ε-caprolactone)/poly (vinyl-pyrrolidone) (PCL/PVP) microfibers produced via electrospinning along with sorbents loaded with Argovit™ silver nanoparticles (Ag-Si/Al2O3) as constituent components for composite wound dressings. The physicochemical properties of the fibers and sorbents were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The mechanical properties of the fibers were also evaluated. The results of this work showed that the tested fibrous scaffolds have melting temperatures suitable for wound dressings design (58-60 °C). In addition, they demonstrated to be stable even after seven days in physiological solution, showing no macroscopic damage due to PVP release at the microscopic scale. Pelletized sorbents with the higher particle size demonstrated to have the best water uptake capabilities. Both, fibers and sorbents showed antimicrobial activity against Gram-negative bacteria Pseudomona aeruginosa and Escherichia coli, Gram-positive Staphylococcus aureus and the fungus Candida albicans. The best physicochemical properties were obtained with a scaffold produced with a PCL/PVP ratio of 85:15, this polymeric scaffold demonstrated the most antimicrobial activity without affecting the cell viability of human fibroblast. Pelletized Ag/Si-Al2O3-3 sorbent possessed the best water uptake capability and the higher antimicrobial activity, over time between all the sorbents tested. The combination of PCL/PVP 85:15 microfibers with the chosen Ag/Si-Al2O3-3 sorbent will be used in the following work for creation of wound dressings possessing exudate retention, biocompatibility and antimicrobial activity.

Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem.

BACKGROUND: Currently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. METHODS: In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. RESULTS: An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema. CONCLUSIONS: Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.