Chondroitin Sulfate-Based Nanocapsules as Nanocarriers for Drugs and Nutraceutical Supplements.

Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as drugs. Here, we reported for the first time the preparation and characterization of NCs consisting of chondroitin sulfate (CS)-based shells and liquid oil cores. For this purpose, two amphiphilic CS derivatives (AmCSs) were obtained by grafting the polysaccharide chain with octadecyl or oleyl groups.

Hypoxia enhances anti-fibrotic properties of extracellular vesicles derived from hiPSCs via the miR302b-3p/TGFβ/SMAD2 axis.

Background: Cardiac fibrosis is one of the top killers among fibrotic diseases and continues to be a global unaddressed health problem. The lack of effective treatment combined with the considerable socioeconomic burden highlights the urgent need for innovative therapeutic options. Here, we evaluated the anti-fibrotic properties of extracellular vesicles (EVs) derived from human induced pluripotent stem cells (hiPSCs) that were cultured under various oxygen concentrations.

Bronchial Fibroblasts from Asthmatic Patients Display Impaired Responsiveness to Direct Current Electric Fields (dcEFs).

Accumulating evidence suggests that an important role is played by electric signals in modifying cell behaviour during developmental, regenerative and pathological processes. However, their role in asthma has not yet been addressed. Bronchial fibroblasts have recently been identified having important roles in asthma development.

Can l-ascorbic acid and trans-resveratrol protect HaCaT cells from fine particulate matter toxicity?

Continuous exposure of human skin to air pollution can result in a range of undesirable skin conditions. In our recent study, UV and visible light were found to increase cytotoxicity of fine particulate matter (PM ) against human keratinocytes. Since it is impossible to avoid exposure of human skin to PM , effective strategies are needed to reduce their damaging effects.

Saponin Fraction CIL1 from L. Enhances the Effect of a Targeted Toxin on Cancer Cells.

Saponins are plant metabolites that possess multidirectional biological activities, among these is antitumor potential. The mechanisms of anticancer activity of saponins are very complex and depend on various factors, including the chemical structure of saponins and the type of cell they target. The ability of saponins to enhance the efficacy of various chemotherapeutics has opened new perspectives for using them in combined anticancer chemotherapy.

PPARδ Agonist GW501516 Suppresses the TGF-β-Induced Profibrotic Response of Human Bronchial Fibroblasts from Asthmatic Patients.

The airway wall remodeling observed in asthma is associated with subepithelial fibrosis and enhanced activation of human bronchial fibroblasts (HBFs) in the fibroblast to myofibroblast transition (FMT), induced mainly by transforming growth factor-β (TGF-β). The relationships between asthma severity, obesity, and hyperlipidemia suggest the involvement of peroxisome proliferator-activated receptors (PPARs) in the remodeling of asthmatic bronchi. In this study, we investigated the effect of PPARδ ligands (GW501516 as an agonist, and GSK0660 as an antagonist) on the FMT potential of HBFs derived from asthmatic patients cultured in vitro.

[The basis of cell cryopreservation].

Cryopreservation (banking) techniques have been known to nature for centuries. Many species of insects, amphibians, fish and even reptiles use natural cryopreservation methods to survive the harsh conditions of winter or to live in extremely cold temperatures. Cryopreservation and dreams of immortality have intrigued humanity for years.

When healing turns into killing - the pathophysiology of pancreatic and hepatic fibrosis.

Disorders such as pancreatic or hepatic fibrosis are a cruel reminder that disruption of the delicate physiological balance could result in severe pathological consequences. Fibrosis is usually associated with chronic diseases and manifests itself as excessive deposition of the extracellular matrix, which gradually leads to the replacement of the cellular components by fibrotic lesions, significantly compromising normal tissue functions. The main cellular mediators of fibrosis are different populations of tissue fibroblasts, predominantly hepatic and pancreatic stellate cells in the liver and pancreas, respectively.

Discrimination between NSIP- and IPF-Derived Fibroblasts Based on Multi-Parameter Characterization of Their Growth, Morphology and Physic-Chemical Properties.

Background: The aim of the research presented here was to find a set of parameters enabling discrimination between three types of fibroblasts, i.e., healthy ones and those derived from two disorders mimicking each other: idiopathic pulmonary fibrosis (IPF), and nonspecific interstitial pneumonia (NSIP).

SB203580-A Potent p38 MAPK Inhibitor Reduces the Profibrotic Bronchial Fibroblasts Transition Associated with Asthma.

Subepithelial fibrosis is a component of the remodeling observed in the bronchial wall of patients diagnosed with asthma. In this process, human bronchial fibroblasts (HBFs) drive the fibroblast-to-myofibroblast transition (FMT) in response to transforming growth factor-β (TGF-β), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-β also promote the activation of non-canonical signaling pathways which can affect the FMT.

In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers.

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool.

Encapsulation of Curcumin in Polystyrene-Based Nanoparticles-Drug Loading Capacity and Cytotoxicity.

Nanoparticles made of amphiphilic block copolymers are commonly used in the preparation of nano-sized drug delivery systems. Poly(styrene)- poly(acrylic acid) (PS-PAA) copolymers have been proposed for drug delivery purposes; however, the drug loading capacity and cytotoxicity of PS-PAA nanoparticles are still not fully recognized. Herein, we investigated the accumulation of a model hydrophobic drug, curcumin, and its spatial distribution inside the PS-PAA nanoparticles.

Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β in epithelial-mesenchymal trophic unit model.

Background: The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis.

Asthma-derived fibroblast to myofibroblast transition is enhanced in comparison to fibroblasts derived from non-asthmatic patients in 3D in vitro culture due to Smad2/3 signalling.

The basic hallmarks of bronchial asthma, one of the most common chronic diseases occurring in the world, are chronic inflammation, remodelling of the bronchial wall and its hyperresponsiveness to environmental stimuli. It was found out that the fibroblast to myofibroblast transition (FMT), a key phenomenon in subepithelial fibrosis of the bronchial wall, was crucial for the development of asthma. Our previous studies showed that HBFs derived from asthmatic patients cultured in vitro display some inherent features which facilitate their TGF-b-induced FMT.

The Effect of Antioxidants on Photoreactivity and Phototoxic Potential of RPE Melanolipofuscin Granules from Human Donors of Different Age.

One of the most prominent age-related changes of retinal pigment epithelium (RPE) is the accumulation of melanolipofuscin granules, which could contribute to oxidative stress in the retina. The purpose of this study was to determine the ability of melanolipofuscin granules from younger and older donors to photogenerate reactive oxygen species, and to examine if natural antioxidants could modify the phototoxic potential of this age pigment. Electron paramagnetic resonance (EPR) oximetry, EPR-spin trapping, and time-resolved detection of near-infrared phosphorescence were employed for measuring photogeneration of superoxide anion and singlet oxygen by melanolipofuscin isolated from younger and older human donors.

Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment.

Airway remodelling with subepithelial fibrosis, which abolishes the physiological functions of the bronchial wall, is a major issue in bronchial asthma. Human bronchial fibroblasts (HBFs) derived from patients diagnosed with asthma display in vitro predestination towards TGF-β-induced fibroblast-to-myofibroblast transition (FMT), a key event in subepithelial fibrosis. As commonly used anti-asthmatic drugs do not reverse the structural changes of the airways, and the molecular mechanism of enhanced asthma-related TGF-β-induced FMT is poorly understood, we investigated the balance between the profibrotic TGF-β/Smad2/3 and the antifibrotic TGF-β/Smad1/5/9 signalling pathways and its role in the myofibroblast formation of HBF populations derived from asthmatic and non-asthmatic donors.

IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes.

Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, the expression of which is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes.

MCPIP1 overexpression in human neuroblastoma cell lines causes cell-cycle arrest by G1/S checkpoint block.

Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) has a multidomain structure, which assures its pleiotropic activity. The physiological functions of this protein include repression of inflammatory processes and the prevention of immune disorders. The influence of MCPIP1 on the cell cycle of cancer cells has not been sufficiently elucidated.

Synergistic anticancer activity of doxorubicin and piperlongumine on DU-145 prostate cancer cells - The involvement of carbonyl reductase 1 inhibition.

One of the causes of therapeutic failure of chemotherapy is cancer cell resistance. In the case of anthracyclines, many resistance mechanisms have been described. One of them assumes the role of carbonyl reductase 1 (CBR1), a cytosolic enzyme that is responsible for the biotransformation process of anthracyclines to less active, undesirable metabolites.

Lipofuscin-mediated photodynamic stress induces adverse changes in nanomechanical properties of retinal pigment epithelium cells.

Retinal pigment epithelium (RPE) is an important part of the blood-retina barrier (BRB) that separates the retina from the choroid. Although melanin granules contribute to the mechanical stability of the BRB complex, it is unknown if the age pigment lipofuscin affects mechanical properties of the tissue. To address this issue the effect of sub-lethal photic stress mediated by phagocytized lipofuscin granules, isolated from RPE of human donors, on morphology and mechanical properties of ARPE-19 cells was investigated.

Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization.

The activation of human bronchial fibroblasts by transforming growth factor-β₁ (TGF-β₁) leads to the formation of highly contractile myofibroblasts in the process of the fibroblast⁻myofibroblast transition (FMT). This process is crucial for subepithelial fibrosis and bronchial wall remodeling in asthma. However, this process evades current therapeutic asthma treatment strategies.

Correction to: Fibroblast-to-myofibroblast transition in bronchial asthma.

In the original publication, funding information was inadvertently omitted.

Fibroblast-to-myofibroblast transition in bronchial asthma.

Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue.

Polyion complex vesicles (PICsomes) from strong copolyelectrolytes. Stability and in vitro studies.

Polymer vesicles formed by a pair of oppositely charged diblock copolyelectrolytes (PICsomes) are considered as a good alternative to polymersomes formed by amphiphilic copolymers. Here, we report on inherent stability and in vitro biocompatibility of PICsomes prepared from a pair of oppositely charged zwitterionic-ionic copolymers, in which the ionic block is a strong polyelectrolyte. Our results demonstrated that the PICsomes are highly stable over a wide range of pH and temperatures.

Connexin43 Controls the Myofibroblastic Differentiation of Bronchial Fibroblasts from Patients with Asthma.

Pathologic accumulation of myofibroblasts in asthmatic bronchi is regulated by extrinsic stimuli and by the intrinsic susceptibility of bronchial fibroblasts to transforming growth factor-β (TGF-β). The specific function of gap junctions and connexins in this process has remained unknown. Here, we investigated the role of connexin43 (Cx43) in TGF-β-induced myofibroblastic differentiation of fibroblasts derived from bronchoscopic biopsy specimens of patients with asthma and donors without asthma.