Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer

Myeloid-derived suppressor cells (MDSCs) expansion is a hallmark of cancer. Three major MDSC subsets defined as monocytic (M)-MDSCs, polymorphonuclear (PMN)-MDSCs and early stage (e)MDSCs can be revealed in human diseases. However, the clinical relevance and immunosupressive pattern of these cells in epithelial ovarian cancer (EOC) are unknown. Therefore, we performed a comprehensive analysis of each MDSC subset and immunosupressive factors in the peripheral blood (PB), peritoneal fluid (PF), and the tumor tissue (TT) samples from EOC and integrated this data with the patients' clinicopathological characteristic. MDSCs were analyzed using multicolor flow cytometry. Immunosuppressive factors analysis was performed with ELISA and qRT-PCR. The level of M-MDSCs in the PB/PF/TT of EOC was significantly higher than in healthy donors (HD); frequency of PMN-MDSCs was significantly greater in the TT than in the PB/PF and HD; while the level of eMDSCs was greater in the PB compared with the PF and HD. Elevated abundance of tumor-infiltrating M-MDSCs was associated with advanced stage and high grade of EOC. An analysis of immunosuppressive pattern showed significantly increased blood-circulating ARG/IDO/IL-10-expressing M- and PMN-MDSCs in the EOC patients compared with HD and differences in the accumulation of these subsets in the three tumor immune microenvironments (TIME). This accumulation was positively correlated with levels of TGF-β and ARG1 in the plasma and PF. Low level of blood-circulating and tumor-infiltrating M-MDSCs, but neither PMN-MDSCs nor eMDSCs was strongly associated with prolonged survival in ovarian cancer patients. Our results highlight M-MDSCs as the subset with potential the highest clinical significance

A comprehensive approach to transdermal drug delivery through the skin: Ibuprofen derivatives in semi-solid formulations

Abstract. This article presents a comprehensive study on the formulation and evaluation of pharmaceutical emulsions for topical drug delivery. The research focused on emulsions containing ibuprofen and its derivatives (sodium and L-lysine propyl ester salts), investigating their solubility, consistency, stability, and skin permeation. The study offers valuable insights into the development of effective pharmaceutical products. Background. Transdermal and topical drug delivery is a promising approach for the treatment of various medical conditions. Pharmaceutical emulsions provide an ideal platform for delivering active substances through the skin. The selection of emulsion ingredients, consistency, and stability play a critical role in determining the suitability of these formulations. Aim of the study. The primary aim of this study was to formulate and evaluate pharmaceutical emulsions containing ibuprofen and other active substances. Key objectives included assessing solubility, consistency, stability, and skin permeation characteristics of the emulsions. The study aimed to provide insights into the development of effective topical drug delivery systems. Material and methods. Solubility tests were conducted to select suitable emulsion ingredients. Various emulsions were prepared with different water-to-oil phase ratios. Rheology modifiers were added to enhance consistency. Quality control assessments were performed, including uniformity, consistency, stability, density, viscosity, and particle size analysis. The release of active substances from the formulations and their penetration and accumulation in the skin were determined. Results. The results revealed variations in viscosity, consistency, and stability among different formulations. Emulsion-based preparations demonstrated the highest accumulation of active substances in the skin, with formulation F1 (5294.617 μg/g skin) exhibiting the most promising results. The highest release of ibuprofen was observed from the formulation based on Celugel with the addition of [LysOPr][IBU] (F6) - approximately 7750 μg IBU/cm2, and the highest penetration of the active substance was obtained for the emulsion with the addition of IBU∙Na (F2) - 3300 μg IBU/cm2 after 24 hours of testing. Conclusion. This comprehensive study on pharmaceutical emulsions for topical drug delivery provides critical insights into the formulation and evaluation of cosmetic and pharmaceutical products. The findings highlight the importance of ingredient selection, consistency, and stability in the development of effective emulsion-based formulations. Furthermore, the study suggests that emulsion-based preparations have potential for topical applications, especially for more hydrophilic active substances. Future research can build on these results to enhance drug delivery systems and improve patient outcomes

Morphological and environmental aspects of biological diversity, using Trama troglodytes (Hemiptera, Aphididae) as an example

tekst w j. pol. i ang.Celem pracy było określenie morfologicznych adaptacji T. troglodytes do żerowania na korzeniach Asteraceae z zastosowaniem elektronowej mikroskopii skaningowej

Differences in the Clinical Picture in Women with a Depressive Episode in the Course of Unipolar and Bipolar Disorder

Due to current depression prevalence, it is crucial to make the correct diagnosis as soon as possible. The study aimed to identify commonly available, easy to apply, and quick to interpret tools allowing for a differential diagnosis between unipolar and bipolar disorder. The study group includes women with long duration of unipolar (UP, N = 34) and bipolar (BP, N = 43) affective disorder. The diagnosis was established according to the DSM criteria using SCID questionnaire. Additional questionnaires were used to differentiate between UP and BP. BP patients had an earlier age of onset, were hospitalized more times, and more often had a family history of psychiatric disorders than UP (p-value < 0.05). Moreover, BP achieved a higher impulsiveness score and more frequently had experienced severe problems with close individuals. To our knowledge, this is the first publication presenting results of numerous questionnaires applied simultaneously in patients on clinical group. Several of them suggest the direction of clinical assessment, such as: the age of onset, family psychiatric burdens, history of stressful life events, learning problems, social and job relations. Further studies are necessary to confirm the utility of this approach

Ascorbic Acid—The Little-Known Antioxidant in Woody Plants

Reactive oxygen species (ROS) are constantly produced by metabolically active plant cells. The concentration of ROS may determine their role, e.g., they may participate in signal transduction or cause oxidative damage to various cellular components. To ensure cellular homeostasis and minimize the negative effects of excess ROS, plant cells have evolved a complex antioxidant system, which includes ascorbic acid (AsA). AsA is a multifunctional metabolite with strong reducing properties that allows the neutralization of ROS and the reduction of molecules oxidized by ROS in cooperation with glutathione in the Foyer-Halliwell-Asada cycle. Antioxidant enzymes involved in AsA oxidation and reduction switches evolved uniquely in plants. Most experiments concerning the role of AsA have been performed on herbaceous plants. In addition to extending our understanding of this role in additional taxa, fundamental knowledge of the complex life cycle stages of woody plants, including their development and response to environmental factors, will enhance their breeding and amend their protection. Thus, the role of AsA in woody plants compared to that in nonwoody plants is the focus of this paper. The role of AsA in woody plants has been studied for nearly 20 years. Studies have demonstrated that AsA is important for the growth and development of woody plants. Substantial changes in AsA levels, as well as reduction and oxidation switches, have been reported in various physiological processes and transitions described mainly in leaves, fruits, buds, and seeds. Evidently, AsA exhibits a dual role in the photoprotection of the photosynthetic apparatus in woody plants, which are the most important scavengers of ozone. AsA is associated with proper seed production and, thus, woody plant reproduction. Similarly, an important function of AsA is described under drought, salinity, temperature, light stress, and biotic stress. This report emphasizes the involvement of AsA in the ecological advantages, such as nutrition recycling due to leaf senescence, of trees and shrubs compared to nonwoody plants

Nicotinamide adenine dinucleotides are associated with distinct redox control of germination in Acer seeds with contrasting physiology.

Seed germination is a complex process enabling plant reproduction. Germination was found to be regulated at the proteome, metabolome and hormonal levels as well as via discrete post-translational modification of proteins including phosphorylation and carbonylation. Redox balance is also involved but less studied. Acer seeds displaying orthodox and recalcitrant characteristics were investigated to determine the levels of redox couples of nicotinamide adenine dinucleotide (NAD) phosphate (NADP) and integrated with the levels of ascorbate and glutathione. NAD and NADP concentrations were higher in Norway maple seeds and exceptionally high at the germinated stage, being the most contrasting parameter between germinating Acer seeds. In contrast, NAD(P)H/NAD(P)+ ratios were higher in sycamore seeds, thus exhibiting higher reducing power. Despite distinct concentrations of ascorbate and glutathione, both seed types attained in embryonic axes and cotyledons had similar ratios of reduced/oxidized forms of ascorbate and half-cell reduction potential of glutathione at the germinated stage. Both species accomplished germination displaying different strategies to modulate redox status. Sycamore produced higher amounts of ascorbate and maintained pyridine nucleotides in reduced forms. Interestingly, lower NAD(P) concentrations limited the regeneration of ascorbate and glutathione but dynamically drove metabolic reactions, particularly in this species, and contributed to faster germination. We suggest that NAD(P) is an important player in regulating redox status during germination in a distinct manner in Norway maple and sycamore seeds

Dried fruits as a source of ingredients with antioxidant potential and the possibility of their use to stabilize fat in meat products such as liver pâté

Celem pracy była ocena wpływu owoców suszonych z aronii, aceroli, borówki i dzikiej róży na zmiany zawartości pierwotnych i wtórnych produktów utleniania tłuszczu oraz wartości pH, aw, potencjału redox w przechowywanych wędlinach podrobowych typu pasztetowa, otrzymanych z częściową wymianą tłuszczu zwierzęcego tłuszczem roślinnym. Dodatek suszonych owoców pozytywnie wpłynął na spowolnienie procesu powstawania produktów utleniania tłuszczu. Stwierdzono, że wybrane dodatki wpłynęły istotnie na badane parametry i spowodowały m.in. podwyższenie potencjału oksydacyjno-redukcyjnego w analizowanych produktach. Dodatkami, które wywarły największy wpływ na parametry fizyczne badanych produktów mięsnych były acerola (Malpighia emarginata) oraz dzika róża (Rosa canina L.).The aim of the study was to evaluate the effect of dried fruits from chokeberry, acerola, blueberry and rosehip on storage changes of primary and secondary products of fat oxidation as well as the pH value, aw, redox potential in of liver pâté, obtained with partial replacement of animal fat with vegetable fat. The addition of dried fruit had a positive effect on slowing down the formation of fat oxidation products. It was found that the selected additives had a significant effect on the tested parameters and caused, among others, increasing the oxidation-reduction potential in the analyzed products. Acerola (Malpighia emarginata) and wild rose (Rosa canina L.) turned out to be the additive that had the greatest impact on the physical parameters of the meat products tested