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. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon.

Cinnamic acid derivatives are widely used in cosmetics and possess various functions. This group of compounds includes both naturally occurring and synthetic substances. On the basis of the Cosmetic Ingredient Database (CosIng) and available literature, this review summarizes their functions in cosmetics, including their physicochemical and biological properties as well as reported adverse effects. A perfuming function is typical of many derivatives of cinnamaldehyde, cinnamyl alcohol, dihydrocinnamyl alcohol and cinnamic acid itself; these substances are commonly used in cosmetics all over the world. Some of them show allergic and photoallergic potential, resulting in restrictions in maximum concentrations and/or a requirement to indicate the presence of some substances in the list of ingredients when their concentrations exceed certain fixed values in a cosmetic product. Another important function of cinnamic acid derivatives in cosmetics is UV protection. Ester derivatives such as ethylhexyl methoxycinnamate (octinoxate), isoamyl p-methoxycinnamte (amiloxiate), octocrylene and cinoxate are used in cosmetics all over the world as UV filters. However, their maximum concentrations in cosmetic products are restricted due to their adverse effects, which include contact and a photocontact allergies, phototoxic contact dermatitis, contact dermatitis, estrogenic modulation and generation of reactive oxygen species. Other rarely utilized functions of cinnamic acid derivatives are as an antioxidant, in skin conditioning, hair conditioning, as a tonic and in antimicrobial activities. Moreover, some currently investigated natural and synthetic derivatives of cinnamic acid have shown skin lightening and anti-ageing properties. Some of them may become new cosmetic ingredients in the future. In particular, 4-hydroxycinnamic acid, which is currently indexed as a skin-conditioning cosmetics ingredient, has been widely tested in vitro and in vivo as a new drug candidate for the treatment of hyperpigmentation.

Determination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds. One of the main challenges of medicinal chemistry is not only to design compounds demonstrating beneficial activity, but also molecules exhibiting favourable pharmacokinetic parameters. Chemical compounds can be divided into those which are metabolized relatively fast and those which undergo slow biotransformation. Rapid biotransformation reduces exposure to the maternal compound and may lead to the generation of active, non-active or toxic metabolites. In contrast, high metabolic stability may promote interactions between drugs and lead to parent compound toxicity. In the present paper, issues of compound metabolic stability will be discussed, with special emphasis on its significance, in vitro metabolic stability testing, dilemmas regarding in vitro-in vivo extrapolation of the results and some aspects relating to different preclinical species used in in vitro metabolic stability assessment of compounds.

No abstract

No abstract

Poly(allylamine hydrochloride) (PAH) has found many applications both in biotechnology and biomedical fields. However, its high toxicity toward various mammalian cells significantly limits its effective usage. This study focuses on improving the biological properties of PAH by its modification to strong polyelectrolytes. The strong polycations were prepared by the direct quaternization of PAH amino groups or by the attachment of glycidyltrimethylammonium chloride to these groups. The biological properties, such as cytotoxicity toward human skin fibroblasts (HSFs), proliferation and migration of the cells on a polymeric surface, and antibacterial activities against two pathogenic bacteria, Staphylococcus aureus and Escherichia coli, were determined. All the modified polyelectrolytes are considerably less toxic to HSFs as compared to PAH. Moreover, the directly quaternized polycations are stronger biocides against S. aureus than the parent polymer. Contrary to PAH, thin films of the modified polyelectrolytes improve or do not affect HSFs proliferation and can stimulate cell migration into the wound, as was demonstrated using an in vitro model. The relationship between the structure of the modified polymers (amount and localization of the quaternary ammonium groups) and the biological activity is discussed. Due to the improved biological properties, the obtained polycations may be potentially useful for a variety of biotechnological and biomedical applications.

Triterpene saponins (saponosides) are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflamatory, vasoprotective, gastroprotective and antimicrobial properties. Recently, a potential anticancer activity of saponins has been suggested by their cytotoxic, cytostatic, pro-apoptotic and anti-invasive effects. At high concentrations (more than 100 µM) saponins exert cytotoxic and haemolytic effects via permeabilization of the cell membranes. Noteworthy, the inhibition of cancer cell proliferation, the induction of apoptosis and attenuation of cell invasiveness is observed in the presence of low saponin concentrations. Saponins might affect the expression of genes associated with malignancy. These alterations are directly related to the invasive phenotype of cancer cells and depend on "cellular context". It illustrates the relationships between the action of saponins, and the momentary genomic/proteomic status of cancer cells. Here, we discuss the hallmarks of anti-cancer activity of saponins with the particular emphasis on anti-invasive effect of diverse groups of saponins that have been investigated in relation to tumor therapy.

SummaryAnthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds. Moreover, overexpression of ANT-reducing enzymes (CBR and AKR) are found in many ANT-resistant cancers. The secondary metabolites show decreased cytotoxic properties and are more susceptible to ABC-mediated efflux than their parent compounds; thus, metabolite formation is considered one of the mechanisms of cancer resistance. Inhibitors of CBR and AKR were found to reduce the cardiotoxicity of ANT and the resistance of cancer cells, and therefore are being investigated as prospective cardioprotective and chemosensitizing drug candidates. In this review, the significance of a two-electron reduction of ANT, including daunorubicin, epirubicin, idarubicin, valrubicin, amrubicin, aclarubicin, and especially doxorubicin, is described with respect to toxicity and efficacy of therapy. Additionally, CBR and AKR inhibitors, including monoHER, curcumin, (−)-epigallocatechin gallate, resveratrol, berberine or pixantrone, and their modulating effect on the activity of ANT is characterized and discussed as potential mechanism of action for novel therapeutics in cancer treatment.