Abdominal aortic aneurysm (AAA) is one of the most dangerous cardiovascular diseases, occurring mainly in men over the age of 55 years. As it is asymptomatic, patients are diagnosed very late, usually when they suffer pain in the abdominal cavity. The late detection of AAA contributes to the high mortality rate. Many environmental, genetic, and molecular factors contribute to the development and subsequent rupture of AAA. Inflammation, apoptosis of smooth muscle cells, and degradation of the extracellular matrix in the AAA wall are believed to be the major molecular processes underlying AAA formation. Until now, no pharmacological treatment has been implemented to prevent the formation of AAA or to cure the disease. Therefore, it is important that patients are diagnosed at a very early stage of the disease. Biomarkers contribute to the assessment of the concentration level, which will help to determine the level and rate of AAA development. The potential biomarkers today include homocysteine, cathepsins, osteopontin, and osteoprotegerin. In this review, we describe the major aspects of molecular processes that take place in the aortic wall during AAA formation. In addition, biomarkers, the monitoring of which will contribute to the prompt diagnosis of AAA patients over the age of 55 years, are described.
Osteogenesis Imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes characterized primarily by bone fragility. The prevalence of OI ranges from about 1:15,000 to 1:20,000 births. Five types of the disease are commonly distinguished, ranging from a mild (type I) to a lethal one (type II). Types III and IV are severe forms allowing survival after the neonatal period, while type V is characterized by a mild to moderate phenotype with calcification of interosseous membranes. In most cases, there is a reduction in the production of normal type I collagen (col I) or the synthesis of abnormal collagen as a result of mutations in col I genes. Moreover, mutations in genes involved in col I synthesis and processing as well as in osteoblast differentiation have been reported. The currently available treatments try to prevent fractures, control symptoms and increase bone mass. Commonly used medications in OI treatment are bisphosphonates, Denosumab, synthetic parathyroid hormone and growth hormone for children therapy. The main disadvantages of these therapies are their relatively weak effectiveness, lack of effects in some patients or cytotoxic side effects. Experimental approaches, particularly those based on stem cell transplantation and genetic engineering, seem to be promising to improve the therapeutic effects of OI.
Novel, nontoxic star copolymers of N,N-dimethylaminoethyl methacrylate (DMAEMA) and hydroxyl-bearing oligo(ethylene glycol) methacrylate (OEGMA-OH) were synthesized via atom transfer radical polymerization (ATRP) using hyperbranched poly(arylene oxindole) as the macroinitiator. Stars with molar masses from 100,000 g/mol to 257,000 g/mol and with various amounts of OEGMA-OH in the arms were prepared. As these polymers can find applications, e.g., as carriers of nucleic acids, drugs or antibacterial or antifouling agents, in this work, much attention has been devoted to exploring their solution behavior and their stimuli-responsive properties. The behavior of the stars was studied in aqueous solutions under various pH and temperature conditions, as well as in PBS buffer, in Dulbecco’s modified Eagle’s medium (DMEM) and in organic solvents for comparison. The results indicated that increasing the content of hydrophilic OEGMA-OH units in the arms up to 10 mol% increased the cloud point temperature. For the stars with an OEGMA-OH content of 10 mol%, the thermo- and pH-responsivity was switched off. Since cytotoxicity experiments have shown that the obtained stars are less toxic than homopolymer DMAEMA stars, the presented studies confirmed that the prepared polymers are great candidates for the design of various nanosystems for biomedical applications.
Induced pluripotent stem cells (iPSCs) are defined as reprogrammed somatic cells exhibiting embryonic stem cell characteristics. Since their discovery in 2006, efforts have been made to utilize iPSCs in clinical settings. One of the promising fields of medicine, in which genetically patient-specific stem cells may prove themselves useful, is gene therapy. iPSCs technology holds potential in both creating models of genetic diseases and delivering therapeutic agents into the organism via auto-transplants, which reduces the risk of rejection compared to allotransplants. However, in order to safely administer genetically corrected stem cells into patients’ tissues, efforts must be made to establish stably pluripotent stem cells and reduce the risk of insertional tumorigenesis. In order to achieve this, optimal reprogramming factors and vectors must be considered. Therefore, in this review, the molecular bases of reprogramming safe iPSCs for clinical applications and recent attempts to translate iPSCs technology into the clinical setting are discussed.
21 January 2020 in International Journal of Polymeric Materials and Polymeric Biomaterials
Star polymers of N,N′-dimethylaminoethyl methacrylate (DMAEMA) and hydroxyl-bearing oligo(ethylene glycol) methacrylate (OEGMA-OH) were used as pDNA and mRNA carriers. To the best of our knowledge, this is the first report of stars in the formation of polyplexes with mRNA. Polyplexes efficiently delivered nucleic acids into HT-1080 cells, while their cytotoxicity was kept significantly low due to the presence of OEGMA-OH units in the star. Hydroxyl functionalities were used for the introduction of fluorophore moieties for monitoring of the complex location after the cell uptake. Thus, versatile gene delivery vectors based upon functional star polymers were developed.
19 December 2017 in Journal of Materials Chemistry B
In this study, we describe novel thermoresponsive star copolymer surfaces used for the first time for the culture of fibroblast sheets, followed by their detachment, controlled by a change in temperature. To date, no star polymers, or their layers, have been used for this purpose. A “grafting to” strategy was applied to obtain poly[oligo(ethylene glycol) methacrylate] star layers on functionalized solid supports. Atom transfer radical polymerization of oligo(ethylene glycol) methacrylates and glycidyl methacrylate initiated with modified poly(arylene oxindole) yielded stars with molar masses up to Mn = 380 000 g mol−1. Stars were attached to a glass substrate via the reaction between the functional epoxy groups of the stars with the amine groups of the functionalized substrate. The thickness of the layer was related to the dimensions of isolated stars in solution, which showed that multilayers were obtained. Above the phase transition temperature, polymer nanolayers were hydrophobic, thus enabling the growth of fibroblasts on their surfaces and the formation of a cell sheet. Decreasing the temperature below the phase transition temperature made the star surfaces hydrophilic. This eliminated the affinity of the surface for cells and led to detachment of the intact fibroblast sheet. These observations have shown for the first time that the star polymer architecture favors the detachment of cell sheets as compared to linear polymer analogues grafted onto supports, thus reducing the time of this process. Knowledge of the influence of the polymer topology on layer properties and cell growth and detachment can aid in the development of polymeric materials for tissue culture applications.