Search

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating the underlying mechanisms of the disease has facilitated the identification of new potential therapeutic targets and promising drug candidates. In this review, we summarize the newest data, considering multiple connections between IL-22 and AD. The presence of circulating IL-22 has been found to correlate with the severity of AD and is identified as a critical factor driving the inflammatory response associated with the condition. Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD.

Asthma and chronic obstructive pulmonary disease (COPD) represent chronic inflammatory respiratory disorders that, despite having distinct pathophysiological underpinnings, both feature airflow obstruction and respiratory symptoms. A critical component in the pathogenesis of each condition is the transforming growth factor-β (TGF-β), a multifunctional cytokine that exerts varying influences across these diseases. In asthma, TGF-β is significantly involved in airway remodeling, a key aspect marked by subepithelial fibrosis, hypertrophy of the smooth muscle, enhanced mucus production, and suppression of emphysema development. The cytokine facilitates collagen deposition and the proliferation of fibroblasts, which are crucial in the structural modifications within the airways. In contrast, the role of TGF-β in COPD is more ambiguous. It initially acts as a protective agent, fostering tissue repair and curbing inflammation. However, prolonged exposure to environmental factors such as cigarette smoke causes TGF-β signaling malfunction. Such dysregulation leads to abnormal tissue remodeling, marked by excessive collagen deposition, enlargement of airspaces, and, thus, accelerated development of emphysema. Additionally, TGF-β facilitates the epithelial-to-mesenchymal transition (EMT), a process contributing to the phenotypic alterations observed in COPD. A thorough comprehension of the multifaceted role of TGF-β in asthma and COPD is imperative for elaborating precise therapeutic interventions. We review several promising approaches that alter TGF-β signaling. Nevertheless, additional studies are essential to delineate further the specific mechanisms of TGF-β dysregulation and its potential therapeutic impacts in these chronic respiratory diseases.

The immunological pathogenesis of atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) has not been fully elucidated yet. The aim of our research was to assess the serum concentration of interleukin-5 receptor (IL-5R) in relation to the disease activity and pruritus intensity in adult patients with AD and CSU. This pilot study included 45 participants (15 patients with AD, 15 patients with CSU, and 15 healthy controls). Blood samples were taken to examine the serum levels of IL-5R using the enzyme-linked immunosorbent assay (ELISA) test. The Scoring Atopic Dermatitis (SCORAD) index, the Urticaria Activity Score (UAS7), and the Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that the IL-5R concentration was significantly higher in patients with CSU than in patients with AD and in the controls ( p = 0.038). There was a positive correlation between the IL-5R level and the SCORAD index in patients with AD (r = -0.9, p = 0.047), which was not found for the CSU activity by UAS7 and with the pruritus severity by VAS in both examined groups of patients. Our findings underscore higher serum levels of IL-5R among CSU and AD patients, which may highlight its functional role in the pathogenesis of these diseases. In contrast, IL-5R might not be fully useful in reflecting the severity of symptoms. Although our results are promising, this study should be conducted on a larger cohort of patients.

Asthma is a chronic complex pulmonary disease characterized by airway inflammation, remodeling, and hyperresponsiveness. Vascular endothelial growth factor (VEGF) and eosinophil-derived neurotoxin (EDN) are two significant mediators involved in the pathophysiology of asthma. In asthma, VEGF and EDN levels are elevated and correlate with disease severity and airway hyperresponsiveness. Diversity in VEGF polymorphisms results in the variability of responses to glucocorticosteroids and leukotriene antagonist treatment. Targeting VEGF and eosinophils is a promising therapeutic approach for asthma. We identified lichochalcone A, bevacizumab, azithromycin (AZT), vitamin D, diosmetin, epigallocatechin gallate, IGFBP-3, Neovastat (AE-941), endostatin, PEDF, and melatonin as putative add-on drugs in asthma with anti-VEGF properties. Further studies and clinical trials are needed to evaluate the efficacy of those drugs. AZT reduces the exacerbation rate and may be considered in adults with persistent symptomatic asthma. However, the long-term effects of AZT on community microbial resistance require further investigation. Vitamin D supplementation may enhance corticosteroid responsiveness. Herein, anti-eosinophil drugs are reviewed. Among them are, e.g., anti-IL-5 (mepolizumab, reslizumab, and benralizumab), anti-IL-13 (lebrikizumab and tralokinumab), anti-IL-4 and anti-IL-13 (dupilumab), and anti-IgE (omalizumab) drugs. EDN over peripheral blood eosinophil count is recommended to monitor the asthma control status and to assess the efficacy of anti-IL-5 therapy in asthma.

The aim of the work was to design and construct a microscopic stage that enables the observation of biological cells in a magnetic field with a constant magnetic force. Regarding the requirements for biological observations in the magnetic field, construction was based on the standard automatic stage of an optical microscope ZEISS Axio Observer, and the main challenge was to design a set of magnets which were the source of a field in which the magnetic force was constant in the observation zone. Another challenge was to design a magnet arrangement producing a weak magnetic field to manipulate the cells without harming them. The Halbach array of magnets was constructed using permanent cubic neodymium magnets mounted on a 3D printed polymer ring. Four sets of magnets were used, differing in their dimensions, namely, 20, 15, 12, and 10 mm. The polymer rings were designed to resist magnetic forces and to keep their shape undisturbed when working under biological conditions. To check the usability of the constructs, experiments with magnetic microparticles were executed. Magnetic microparticles were placed under the microscope and their movement was observed to find the acting magnetic force.

Polylactide and aliphatic polyurethane are biodegradable synthetic polymers which are broadly used as biomaterials in regenerative medicine for implants and scaffolds for tissue engineering. In this paper, the detailed studies of the fabrication of the electrospun fibers of polyurethane/polylactide mixtures were described. The influence of the used solvent (dimethylformamide (DMF)) and diluents (acetone and dichloromethane (DCM)) on the rheological parameters and electrospinning of the described mixtures was examined. Rheological studies showed that polyure-thane/polylactide mixtures have mostly non-Newtonian character, strongly influenced by the diluent. Solutions containing 50 wt.% or more of polyurethane became less viscous after the addition of DCM or acetone, whereas those with bigger amount of polylactide showed higher viscosity after the addition of DCM and lower viscosity after the addition of acetone. Optimized electrospinning process has been elaborated. Fibers with diameters from 250 nm up to 1 µm have been produced and compared. Pure acetone worsened the electrospinning process, but the more DCM was in the mixture, the thinner and more aligned fibers were produced.

Highly porous, elastic, and degradable polyurethane and polyurethane/polylactide (PU/PLDL) sponges, in various shapes and sizes, with open interconnected pores, and porosity up to 90% have been manufactured. They have been intended for gap filling in the injured spinal cord. The porosity of the sponges depended on the content of polylactide, i.e., it decreased with the increase of polylactide content. The rise of polylactide content caused an increase of Young modulus and rigidity as well as a more complex morphology of the polyurethane/polylactide blends. The mechanical properties, in vitro toxicity, and degradation in artificial cerebrospinal fluid were tested. Sponges underwent continuous degradation with varying degradation rates depending on the polymer composition. In vitro cell studies with fibroblast cultures proved the biocompatibility of the polymers. Based on the obtained results, the designed PU/PLDL sponges appeared to be promising candidates for bridging gaps within injured spinal cord in further in vitro and in vivo studies.

Cell migration is an important biological phenomenon which depends on a number of internal and external factors. One of such factors can be the mechanical properties of the environment which can have an impact on the cell's regulatory pathways through so-called mechanotransduction. Ultimately, these properties can also influence the process of cell migration. The goal of this work is to investigate how substrate stiffness (elasticity) changes basic migration parameters of migrating cells. Fish keratocytes migrating on polyacrylamide hydrogels have been used as a model of fast migrating cells. Cell migration have been tracked with optical microscopy, employing a time-lapse technique. Migration parameters have been determined from image analysis. This study has shown a systematic decrease of some of the key migration parameters-average cell speed and angular persistence-with a simultaneous increase of substrate elasticity. The results demonstrate that the elasticity of the substrate is the key factor in cell migration. It determines speed and angular persistence, which proves that mechanical parameters of the environment can affect cellular processes. A detailed knowledge of mechanotransduction processes can have major implications for tissue engineering and for the understanding of metastasis.

Polymeric biomaterials based on polyurethane and polylactide blends are promising candidates for regenerative medicine applications as biocompatible, bioresorbable carriers. In current research we showed that 80/20 polyurethane/polylactide blends (PU/PLDL) with confirmed biological properties in vitro may be further improved by the addition of ZnO nanoparticles for the delivery of bioactive zinc oxide for cells. The PU/PLDL blends were doped with different concentrations of ZnO (0.001%, 0.01%, 0.05%) and undertaken for in vitro biological evaluation using human adipose stromal stem cells (ASCs) and olfactory ensheathing cells (OECs). The addition of 0.001% of ZnO to the biomaterials positively influenced the morphology, proliferation, and phenotype of cells cultured on the scaffolds. Moreover, the analysis of oxidative stress markers revealed that 0.001% of ZnO added to the material decreased the stress level in both cell lines. In addition, the levels of neural-specific genes were upregulated in OECs when cultured on sample 0.001 ZnO, while the apoptosis-related genes were downregulated in OECs and ASCs in the same group. Therefore, we showed that PU/PLDL blends doped with 0.001% of ZnO exert beneficial influence on ASCs and OECs in vitro and they may be considered for future applications in the field of regenerative medicine.

Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of the experimental conditions and testing techniques are provided.-Szarek, D., Marycz, K., Lis, A., Zawada, Z., Tabakow, P., Laska, J., Jarmundowicz, W. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis., (© FASEB.)

Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells., (Copyright © 2015. Published by Elsevier B.V.)

Recently, we described the influence of sodium alginate on the inflammatory infiltrate during neuroregeneration in tube nerve grafts. It was noticeable that there was the coexistence of inflammatory cells, including neutrophils, plasma cells, and macrophages with Schwann cells and axons. This may indicate a beneficial interaction between alginates and the infiltrate and the additional beneficial effect of the cells on the neuroregeneration process in the inflammatory infiltrates. In this study, we have performed in vivo evaluation of our novel tubular implant prepared by a polyurethane/polylactide blend filled with alginate fibers. The influence of filling the lumen of the tubes with sodium and calcium alginates on the regeneration process of the rat sciatic nerve was investigated. The neuroregeneration process was assessed by detailed histomorphometric studies, axon counting, and calculating the regenerative indexes. It was observed that calcium alginate had a supportive effect on nerve regeneration similar to nerve autotransplant., (© 2013 International Union of Biochemistry and Molecular Biology, Inc.)

Neurological disorders and injuries such as ischemic or haemorrhagic strokes or traumatic brain injuries result in the damage of cerebral parenchyma structures and in consequence, the loss of neurological functions. The current clinical strategies for the treatment of the brain nervous tissue disruptions are limited. The aforementioned methods can reduce the tissue degeneration or mitigate the subsequent symptoms, but do not alter the fact that many of the affected people are incapable of returning to the condition before the accident and they need long-lasting rehabilitation. Regenerative strategies based on the cell therapies and the use of polymeric scaffolds seem to be very promising for many patients. Polymer scaffolds may provide an opportunity to enhance the probability of cell therapy success by creating an artificial extracellular matrix which further facilitates cell survival, proliferation, differentiation, and promotes integrity of transplanted as well as endogenous cells. This paper presents selected forms of the polymeric scaffolds, which have been tested for the restoration processes within brain tissue and their potential clinical applications of scaffolds in both the treatment of posttraumatic neuronal loss and the neurodegenerative disorders.

In this study, scanning electron microscopy (SEM) has been applied for instantaneous assessment of processes occurring at the site of regenerating nerve. The technique proved to be especially useful when an artificial implant should have been observed but have not yet been extensively investigated before for assessment of nerve tissue. For in vivo studies, evaluation of implant's morphology and its neuroregenerative properties is of great importance when new prototype is developed. However, the usually applied histological techniques require separate and differently prepared samples, and therefore, the results are never a 100% comparable. In our research, we found SEM as a technique providing detailed data both on an implant behavior and the nerve regeneration process inside the implant. Observations were carried out during 12-week period on rat sciatic nerve injury model reconstructed with nerve autografts and different tube nerve grafts. Samples were analyzed with haematoxylin-eosin (HE), immunocytochemical staining for neurofillament and S-100 protein, SEM, TEM, and the results were compared. SEM studies enabled to obtain characteristic pictures of the regeneration process similarly to TEM and histological studies. Schwann cell transformation and communication as well as axonal outgrowth were identified, newly created and matured axons could be recognized. Concurrent analysis of biomaterial changes in the implant (degradation, collapsing of the tube wall, migration of alginate gel) was possible. This study provides the groundwork for further use of the described technique in the nerve regeneration studies., (© Wiley Periodicals, Inc.)

Traumatic spinal cord injuries are very serious burden for the organism of affected human population, and are more critical because mostly touching the young cluster of population. Physical, emotional and economic problems caused by traumatic spinal cord injuries as a general rule significantly limit the individual patient functionality and are burden for the society. The spinal cord has considerable lack of ability for spontaneous and functional regeneration, hence the spinal cord injury cause a solemn and frequently permanent disabilities. The pathophysiology of spinal cord injury is the results of sequential two phenomena, primary physical and biochemical secondary mechanisms of injury. After physical injury, the spinal cord undergoes a sequential progression in biochemical pathologic deviations increasing after injury, that are mutually deteriorating and cause further damage in the spinal cord. Consequently series of pathological processes lead to haemorrhage, oedema, neuronal necrosis, axonal fragmentation, demyelination of the remaining axons, and formation of ultimately cyst. Furthermore spinal cord injuries can immediately result in neural cells death and cause disruption of the blood supply to the site of the injury. The most important difference between peripheral and central nervous system is the fact that in the spinal cord the neuronal cell bodies are damaged, while in the peripheral nervous system only axons are injured. In the surroundings of the spinal cord, one of the major factors hampering regeneration is the glial scar expansion. The spreading of densely packed astrocytes on the site of injuries effectively inhibit axon growth through the nerve grow blocking. Glial scar, which consists mainly of overactive astrocytes and fibroblasts, as well as the presence of growth-inhibitor molecules such as chondroitin sulphate proteoglycans (derived from the breakdown of damaged nerve cells) form a physicochemical barrier for effective regenerating axons. The recent scientific progress in medicine, biology and biomaterials engineering, and predominantly in the fields of neurosurgery, cell culture and tissue engineering, creates the opportunity for the development of new therapies, which support healing of the effects of traumatic spinal cord injuries and prevent further neurodegenerative processes. The most promising effects so far have been obtained using well-designed polymer scaffold as structural support for axon regeneration combined with drug delivery system or therapeutic cell line and neurotrophic factors. This review article focuses on the application of selected biomaterials for the regeneration of traumatic spinal cord injuries. First, the basic anatomical structure of the spinal cord has been described. Then the injury and neurodegenerative mechanisms within the peripheral and central nervous system have been compared. The pathophysiology of the spinal cord damage has been referred to the current strategy of biomaterials engineering in experimental therapies supporting neuroregeneration processes. In the summary, the promising interdisciplinary therapeutic strategies aimed at the regeneration of the spinal cord have been highlighted.