Material engineering for atopic dermatitis treatment

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a prevalence of 30% for children and to 17% for adults. There is observed an increasing trend of occurring AD over time in the world. Many factors contribute to the development of the disease, such as environmental, genetic and psychological factors. The proper AD treatment should be complexed and consists of skin care with emollients and pharmacological treatment. Most of the topical corticosteroids and other drugs have unpleasant side effects, therefore, developing new therapies is very useful. To minimalize side effects with a simultaneous reduction in the duration, a NPs (nanoparticles) therapy application is highly proposed. On the other hand, hydrogels and their shielding properties with high hydrating level and drug delivery capability are also widely studied. Some works report on the combination of these two solutions with promising results. Material engineering for biomedical applications is a dynamically growing field which offers new drug delivery systems (DDS). In this paper, based on the literature we discuss the new methods of AD treatment using hydrogels and nanotechnology

Comparison of Losartan and Furosemide Interaction with HSA and Their Influence on HSA Antioxidant Potential

Serum albumin (HSA) is the most important protein in human body. Due to the antioxidant activity, HSA influences homeostasis maintenance and transport of drugs as well as other substances. It is noteworthy that ligands, such as popular drugs, modulate the antioxidant activity of HSA. The aim of this study was to analyze the influence of losartan (LOS) and furosemide (FUR) on HSA antioxidant properties as well as the interaction between these drugs and protein using calorimetric and spectroscopic methods. LOS and FUR showed the high affinity for human serum albumin, and the binding reactions between them were spontaneous and exothermic. LOS and FUR, separately and together in the system, have no significant impact on the secondary HSA structure; however they have significant impact on the tertiary HSA structure. LOS and FUR mixed with HSA have the ability to scavenge free radicals, and the ligand(s)–HSA interactions were synergistic

The differences between the antioxidant activity of vitamin products

Antioxidants are compounds naturally found in many products i.e. fruits, vegetables, and herbs. Antioxidants naturally occurring in plants include vitamins A, C, and E, polyphenols, and mineral compounds. These compounds are also found in many dietary supplements. This study aimed to determine the total antioxidant capacity (TAC) and total polyphenol content (TPC) of selected juices and dietary supplements. 1.1-diphenyl-2-picrylhydrazyl (DPPH) assay is a research method that allows antioxidant activity analysis. The TPC in test samples was measured by the Folin-Ciocalteu method. The study showed that all selected for the analysis products have antioxidant properties. The values of TAC corresponded to TPC with 0.94 (juices) and 0.98 (diet supplements) correlation coefficients. The highest value of TAC was obtained for juice consisting of apples, beets, cherries, and the lowest for juice containing only carrots and products containing vitamin C composition. The tested juices have higher values of TAC compared to dietary supplements, and therefore juices should be the basic prevention of civilization diseases

Collagen - structure, properties and application

Collagen is the dominant component of the extracellular matrix of mammals. It occurs almost in all animal tissues. Collagen is a highly heterogeneous protein. The collagen protein family is characterized by great diversity in terms of structure, occurrence, and function. Up till now, 29 types of collagens proteins have been classified. The representation of individual types of collagen has certain common features. The most important property is the above-average mechanical strength that results directly from the spatial structure. Collagen is a building material for most tissues and organs. It also plays an important role in the process of cell growth and differentiation, which results from the specific structure of collagen fibers as well as their ability to adhere. The development of research techniques allowed to study in detail the molecular structure and properties of collagen. Therefore, collagen has become a subject of interest in many branches of science. Synthetic recombinant collagen fibers were developed as the basis of collagen biomaterials for medical applications, including implantology or gynecology. The specific structure of collagen also makes it applicable as a protein carrier in drug delivery systems (DDS), particularly in the treatment of cancer and genetic diseases. The use of tissue regenerative abilities and an interdisciplinary look at the properties of collagen and collagen-based biomaterials may constitute the future of medical development

Spectroscopic Studies of Quinobenzothiazine Derivative in Terms of the In Vitro Interaction with Selected Human Plasma Proteins: Part 2

Synthesis of anticancer substances and studying their binding abilities towards human serum proteins as carriers are important parts of pharmaceutical and medical sciences development. The presented work is a continuation of studies of quinobenzothiazine derivatives binding with serum proteins. The main aim of this work was a spectroscopic analysis of second from benzothiazinium derivatives salt, 9-fluoro-5-alkyl-12(H)-quino [3,4-b][1,4]benzothiazinium chloride (Salt2), its interaction with carrier proteins, i.e., human serum albumin (HSA), α1-acid glycoprotein (AGP), human gamma globulin (HGG), and the study of protein secondary and tertiary structure changes using spectroscopic techniques (spectrofluorescence, UV-Vis and circular dichroism CD spectroscopy). In order to mimic in vivo conditions, control normal serum (CNS) was used. Using the Klotz method, both binding constants (Ka [M−1]) and the number of binding classes (n) were calculated. In addition, the percentage of displacement of binding site markers from HSA and AGP molecules has been defined. Based on the obtained data, it can be concluded that the main binding protein for Salt2 is AGP. HSA and HGG are also involved in the distribution of the studied substance in the bloodstream. Moreover, Salt2 very slightly interacts with CNS, which can cause strong therapeutic as well as toxic effects. The analysis of CD spectra confirms that there are no changes in the secondary structure of the main binding proteins in the presence of Salt2

Ocena właściwości przeciwproliferacyjnych, cytotoksycznych i proapoptotycznych wybranych flawonoidów w stosunku do nowotworów wątroby w badaniach in vitro

INTRODUCTION: Flavonoids belong to phytotherapeutics with a wide spectrum of pharmacological activity. It has been proven that flavonoids possess properties that can inhibit the development of cancer by inducing cells into the programmed cell death process. The aim of the work was to demonstrate the apoptotic, antiproliferative and cytotoxic properties of selected flavonoids. MATERIAL AND METHODS: The test material was the human primary hepatocellular carcinoma SK Hep-1 cell line. The tested compounds were assessed for cytotoxicity with the MTT assay. The next step was to evaluate the level of protein expression from the Bcl-2 family using the human Bcl-2 ELISA test. RESULTS: The compound with the strongest cytotoxic properties confirmed by the MTT test is chrysin, the IC50 value of which was 316.67 μM/L. In the case of all the tested compounds, apoptotic processes were confirmed by the human Bcl-2 ELISA test. The highest level of Bcl-2 protein expression occurred after 48 hours after the administration of chrysin, hesperidin, naringin and kaempferol. CONCLUSIONS: On the basis of the obtained research results, it can be concluded that the studied flavonoids (chrysin, hesperidin, naringin, kaempferol) exhibit cytotoxic, proapoptotic and antiproliferative properties in relation to SK Hep-1 hepatoma cells.WSTĘP: Flawonoidy należą do fitoterapeutyków o szerokim spektrum działania farmakologicznego. Udowodniono, że flawonoidy posiadają właściwości mogące hamować rozwój choroby nowotworowej poprzez wywoływanie w komórkach procesu programowanej śmierci komórki. Celem pracy było wykazanie właściwości apoptotycznych, antyproliferacyjnych oraz cytotoksycznych wybranych flawonoidów. MATERIAŁ I METODY: Materiał do badań stanowiła ludzka linia komórkowa pierwotnego raka wątrobowokomórkowego. Badane związki poddano ocenie cytotoksyczności za pomocą testu MTT. Kolejnym etapem była ocena poziomu ekspresji białek z rodziny Bcl-2 testem Human Bcl-2. WYNIKI: Związkiem posiadającym najsilniejsze właściwości cytotoksyczne, potwierdzone testem MTT, jest chryzyna, której wartość IC50 wyniosła 316,67 μM/L. W przypadku wszystkich badanych związków stwierdzono zainicjowanie procesów apoptotycznych potwierdzone testem Human Bcl-2 ELISA. Najwyższy poziom ekspresji białek Bcl-2 miał miejsce po upływie 48 godzin od podania chryzyny, hesperydyny, narynginy i kemferolu. WNIOSKI: Na podstawie uzyskanych wyników badań można wnioskować, że badane flawonoidy (chryzyna, hesperydyna, naryngina, kemferol) wykazują właściwości cytotoksyczne, proapoptotyczne i antyproliferacyjne w stosunku do komórek raka wątrobowokomórkowego SK Hep-1

Changes in Glycated Human Serum Albumin Binding Affinity for Losartan in the Presence of Fatty Acids In Vitro Spectroscopic Analysis

Conformational changes in human serum albumin due to numerous modifications that affect its stability and biological activity should be constantly monitored, especially in elderly patients and those suffering from chronic diseases (which include diabetes, obesity, and hypertension). The main goal of this study was to evaluate the effect of a mixture of fatty acids (FA) on the affinity of losartan (LOS, an angiotensin II receptor (AT1) blocker used in hypertension, a first-line treatment with coexisting diabetes) for glycated albumin—simulating the state of diabetes in the body. Individual fatty acid mixtures corresponded to the FA content in the physiological state and in various clinical states proceeding with increased concentrations of saturated (FAS) and unsaturated (FAUS) acids. Based on fluorescence studies, we conclude that LOS interacts with glycated human serum albumin (af)gHSA in the absence and in the presence of fatty acids ((af)gHSAphys, (af)gHSA4S, (af)gHSA8S, (af)gHSA4US, and (af)gHSA8US) and quenches the albumin fluorescence intensity via a static quenching mechanism. LOS not only binds to its specific binding sites in albumins but also non-specifically interacts with the hydrophobic fragments of its surface. Incorrect contents of fatty acids in the body affect the drug pharmacokinetics. A higher concentration of both FAS and FAUS acids in glycated albumin reduces the stability of the complex formed with losartan. The systematic study of FA and albumin interactions using an experimental model mimicking pathological conditions in the body may result in new tools for personalized pharmacotherapy

Spectroscopic Studies of Quinobenzothiazine Derivative in Terms of the In Vitro Interaction with Selected Human Plasma Proteins. Part 1

Plasma proteins play a fundamental role in living organisms. They participate in the transport of endogenous and exogenous substances, especially drugs. 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts, have been synthesized as potential anticancer substances used for cancer treatment. Most anticancer substances generate a toxic effect on the human body. In order to check the toxicity and therapeutic dosage of these chemicals, the study of ligand binding to plasma proteins is very relevant. The present work presents the first comparative analysis of the binding of one of the 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium derivatives (Salt1) with human serum albumin (HSA), α-1-acid glycoprotein (AGP) and human gamma globulin (HGG), assessed using fluorescence, UV-Vis and CD spectroscopy. In order to mimic in vivo ligand–protein binding, control normal serum (CNS) was used. Based on the obtained data, the Salt1 binding sites in the tertiary structure of all plasma proteins and control normal serum were identified. Both the association constants (Ka) and the number of binding site classes (n) were calculated using the Klotz method. The strongest complex formed was Salt1–AGPcomplex (Ka = 7.35·104 and 7.86·104 mol·L−1 at excitation wavelengths λex of 275 and 295 nm, respectively). Lower values were obtained for Salt1–HSAcomplex (Ka = 2.45·104 and 2.71·104 mol·L−1) and Salt1–HGGcomplex (Ka = 1.41·104 and 1.33·104 mol·L−1) at excitation wavelengths λex of 275 and 295 nm, respectively, which is a positive phenomenon and contributes to the prolonged action of the drug. Salt1 probably binds to the HSA molecule in Sudlow sites I and II; for the remaining plasma proteins studied, only one binding site was observed. Moreover, using circular dichroism (CD), fluorescence and UV-Vis spectroscopy, no effect on the secondary and tertiary structures of proteins in the absence or presence of Salt1 has been demonstrated. Despite the fact that the conducted studies are basic, from the scientific point of view they are novel and encourage further in vitro and in vivo investigations. As a next part of the study (Part 2), the second new synthetized quinobenzothiazine derivative (Salt2) will be analyzed and published

Spectroscopic Analysis of an Antimalarial Drug’s (Quinine) Influence on Human Serum Albumin Reduction and Antioxidant Potential

Quinine (Qi) is a well-known drug used in malaria therapy; it is also a potential anti-arrhythmic drug used in the treatment of calf cramps, rheumatoid arthritis, colds, and photodermatitis. Moreover, it is used in the food industry for the production of tonics. This study aimed to analyze the interaction between quinine and a transporting protein—human serum albumin (HSA)—as well as the influence of Qi on both protein reduction and antioxidant potential. It was found that Qi (via spectrofluorometric measurements and circular dichroism spectroscopy) binds to HSA with a low affinity and slightly affects the secondary structure of albumin. As demonstrated by the use of ABTS and FRAP assays, HSA has a higher antioxidant and reduction potential than Qi, while their mutual interaction results in a synergistic effect in antioxidant activity and reduction potential

The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure. One such reaction is albumin oxidation. Chloramine T is a strong oxidant. Solutions of human serum albumin, both non-modified and modified by chloramine T, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. 10H-3,6-diazaphenothiazine (DAPT) has anticancer activity and it has been studied for the first time in terms of binding with human serum albumin—its potential as a transporting protein. Using fluorescence spectroscopy, in the presence of dansylated amino acids, dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), DAPT binding with two main albumin sites—in subdomain IIA and IIIA—has been evaluated. Based on the conducted data, in order to measure the stability of DAPT complexes with human (HSA) and oxidized (oHSA) serum albumin, association constant (Ka) for ligand-HSA and ligand-oHSA complexes were calculated. It has been presumed that oxidation is not an important issue in terms of 10H-3,6-diazaphenothiazine binding to albumin. It means that the distribution of this substance is similar regardless of changes in albumin structure caused by oxidation, natural occurring in the organism