Lipid antioxidants: free radical scavenging versus regulation of enzymatic lipid peroxidation

The essentiality of polyunsaturated lipids makes membranes susceptible to peroxidative modifications. One of the most contemporary examples includes selective peroxidation of cardiolipin in mitochondria of cells undergoing apoptosis. Cardiolipin peroxidation products are required for the mitochondrial membrane permeabilization, release of pro-apoptotic factors and completion of the cell death program. Therefore, search for effective inhibitors of cardiolipin peroxidation is critical to discovery and development of anti-apoptotic antioxidants. Mitochondria contain significant amounts of α-tocopherol, a well known scavenger of reactive free radicals. In the present study, we used an oxidative lipidomics approach to evaluate the effect of α-tocopherol and its homologues with different lengths of the side-chain such as 2,5,7,8,-tetramethyl-2(4-methylpentyl)-6-chromanol and 2,2,5,7,8-pentamethyl-6-chromanol, on oxidation of tetralinoleoyl cardiolipin induced by cytochrome c in the presence of hydrogen peroxide. Our data indicate that vitamin E homologues inhibit not only accumulation of tetralinoleoyl cardiolipin hydroperoxides but also hydroxy-derivatives of tetralinoleoyl cardiolipin formed in the enzymatic peroxidase half-reaction catalyzed by cytochrome c. This suggests that protective effects of vitamin E homologues against tetralinoleoyl cardiolipin peroxidation catalyzed by cytochrome c/hydrogen peroxide are realized largely due to their effects on the peroxidase activity of cytochrome c towards tetralinoleoyl cardiolipin rather than via their scavenging activity

A class action in various legal systems

The article is devoted to the application of the class action institution in different countries and legal systems. The article deals with questions about the meaning of the institute of class action, interests protected with the help of it, positive and negative aspects of this institution are estimated. In addition, the article analyses characteristics and conditions of presentation of the class actio

Functional States of Myeloid Cells in Cancer

Myeloid cells, comprised of macrophages, dendritic cells, monocytes, and granulocytes, represent a major component of the tumor microenvironment (TME) and are critically involved in regulation of tumor progression and metastasis. In recent years, single-cell omics technologies have identified multiple phenotypically distinct subpopulations. In this review, we discuss recent data and concepts suggesting that the biology of myeloid cells is largely defined by a very limited number of functional states that transcend the narrowly defined cell populations. These functional states are primarily centered around classical and pathological states of activation, with the latter state commonly defined as myeloid-derived suppressor cells. We discuss the concept that lipid peroxidation of myeloid cells represents a major mechanism that governs their pathological state of activation in the TME. Lipid peroxidation is associated with ferroptosis mediating suppressive activity of these cells and thus could be considered an attractive target for therapeutic intervention

Business administration as a basis for development of global entrepreneurship

The purpose of the article is to determine the role and meaning of business administration in development of global entrepreneurship. The work uses the proprietary methodology of evaluation of global competitiveness of enterprise and the proprietary methodology of evaluation of efficiency of business administration of enterprise, as well as method of correlation analysis. The authors determine the role of business administration in management of factors of development of global enterprise and offer the proprietary structural and logical model of organization of the process of business administration of global enterprise as a perspective tool for provision of global competitiveness of business and development of global entrepreneurship on the whole. The authors come to the conclusion that business administration is a basis for development of global entrepreneurship and plays an important role in this process, which consists in managing other internal and external factors of functioning of global business.peer-reviewe

Polymorphonuclear myeloid-derived suppressor cells limit antigen crosspresentation by dendritic cells in cancer

DCs are a critical component of immune responses in cancer primarily due to their ability to cross-present tumor-associated antigens. Cross-presentation by DCs in cancer is impaired, which may represent one of the obstacles for the success of cancer immunotherapies. Here, we report that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) blocked crosspresentation by DCs without affecting direct presentation of antigens by these cells. This effect did not require direct cell-cell contact and was associated with transfer of lipids. Neutrophils (PMN) and PMN-MDSC transferred lipid to DCs equally well; however, PMN did not affect DC cross-presentation. PMN-MDSC generate oxidatively truncated lipids previously shown to be involved in impaired cross-presentation by DCs. Accumulation of oxidized lipids in PMN-MDSC was dependent on myeloperoxidase (MPO). MPO-deficient PMN-MDSC did not affect cross-presentation by DCs. Cross-presentation of tumor-associated antigens in vivo by DCs was improved in MDSC-depleted or tumor-bearing MPO-KO mice. Pharmacological inhibition of MPO in combination with checkpoint blockade reduced tumor progression in different tumor models. These data suggest MPO-driven lipid peroxidation in PMN-MDSC as a possible non–cell autonomous mechanism of inhibition of antigen cross-presentation by DCs and propose MPO as potential therapeutic target to enhance the efficacy of current immunotherapies for patients with cancer

Excessive phospholipid peroxidation distinguishes ferroptosis from other cell death modes including pyroptosis

Lipid peroxidation (LPO) drives ferroptosis execution. However, LPO has been shown to contribute also to other modes of regulated cell death (RCD). To clarify the role of LPO in different modes of RCD, we studied in a comprehensive approach the differential involvement of reactive oxygen species (ROS), phospholipid peroxidation products, and lipid ROS flux in the major prototype modes of RCD viz. apoptosis, necroptosis, ferroptosis, and pyroptosis. LC-MS oxidative lipidomics revealed robust peroxidation of three classes of phospholipids during ferroptosis with quantitative predominance of phosphatidylethanolamine species. Incomparably lower amounts of phospholipid peroxidation products were found in any of the other modes of RCD. Nonetheless, a strong increase in lipid ROS levels was detected in non-canonical pyroptosis, but only during cell membrane rupture. In contrast to ferroptosis, lipid ROS apparently was not involved in non-canonical pyroptosis execution nor in the release of IL-1 beta and IL-18, while clear dependency on CASP11 and GSDMD was observed. Our data demonstrate that ferroptosis is the only mode of RCD that depends on excessive phospholipid peroxidation for its cytotoxicity. In addition, our results also highlight the importance of performing kinetics and using different methods to monitor the occurrence of LPO. This should open the discussion on the implication of particular LPO events in relation to different modes of RCD

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death

High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these “partial” intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented

Lipid homeostasis and inflammatory activation are disturbed in classically activated macrophages with peroxisomal β-oxidation deficiency

Macrophage activation is characterized by pronounced metabolic adaptation. Classically activated macrophages show decreased rates of mitochondrial fatty acid oxidation and oxidative phosphorylation and acquire a glycolytic state together with their pro-inflammatory phenotype. In contrast, alternatively activated macrophages require oxidative phosphorylation and mitochondrial fatty acid oxidation for their anti-inflammatoryfunction. Although it is evident that mitochondrial metabolism is regulated during macrophage polarization and essential for macrophagefunction, little is known on the regulation and role of peroxisomal -oxidation during macrophage activation. In this study, we show that peroxisomal -oxidation is strongly decreased in classically activated bone-marrow-derived macrophages (BMDM) and mildly induced in alternatively activated BMDM. To examine the role of peroxisomal -oxidation in macrophages, we used Mfp2(-/-) BMDM lacking the key enzyme of this pathway. Impairment of peroxisomal -oxidation in Mfp2(-/-) BMDM did not cause lipid accumulation but rather an altered distribution of lipid species with very-long-chain fatty acids accumulating in the triglyceride and phospholipid fraction. These lipid alterations in Mfp2(-/-) macrophages led to decreased inflammatory activation of Mfp2(-/-) BMDM and peritoneal macrophages evidenced by impaired production of several inflammatory cytokines and chemokines, but did not affect anti-inflammatory polarization. The disturbed inflammatory responses of Mfp2(-/-) macrophages did not affect immune cell infiltration, as mice with selective elimination of MFP2 from myeloid cells showed normal monocyte and neutrophil influx upon challenge with zymosan. Together, these data demonstrate that peroxisomal -oxidation is involved in fine-tuning the phenotype of macrophages, probably by influencing the dynamic lipid profile during macrophage polarization

El impacto del método de proyectos en el desarrollo de habilidades de liderazgo en los estudiantes

The impact of the project method on the development of leadership skills in students / Valentyna O. Tyurina, Hanna Y. Shevchuk, Yuliya D. Kriukova and ot/ // Revista de Investigación Apuntes Universitarios. - 2022. - Vol. 12, Issue 2. – P. 179-197. -DOI: https://doi.org/10.17162/au.v12i2.1045.Досліджено вплив методу проектів на розвиток лідерських якостей у студентів. Проаналізовано розвиток особистості у студентському віці. Використовано комплекс методів дослідження: педагогічний експеримент, тест, спостереження. У дослідженні взяли участь 292 людини. Виявлено переважання середніх показників лідерських якостей у респондентів. Найменш розвиненими виявилися такі компоненти, як мотивація успіху та вольовий самоконтроль. Метод групових проектів довів ефективність для розвитку всіх вивчених навичок, крім вольового самоконтролю. Достовірність усіх виявлених змін знаходиться на рівні p = 0,05, що визначає необхідність подальшої модифікації використовуваного методу. Отримані дані можуть бути використані в практичній діяльності викладачів і психологів вищих навчальних закладів для розвитку лідерських якостей учнів.The article examines the influence of the project method on the development of students' leadership skills. Information on the use of the project method in high school and the details of the leader's personality development at the student's age are analyzed. A set of research methods was used: pedagogical experiment, test, observation, Student's t-test. The study involved 292 people. The predominance of average indicators of leadership skills of the respondents was revealed. Components such as motivation for success and volitional self-control were the least developed. The method of group projects has proven effective for the development of all the skills studied, except volitional self-control. The significance of all the changes detected is at the level of p = 0.05, which determines the need for further modification of the method used. The data obtained can be used in the practice of teachers and psychologists of higher education institutions (HEIs) in the development of students' leadership skills. Other perspectives for scientific research include studying the leadership competence of students and finding the correlation of leadership skills with structural components of personality.Рассматривается влияние метода проектов на развитие лидерских качеств у студентов. Проанализировано развитие личности в студенческом возрасте. Был использован комплекс методов исследования: педагогический эксперимент, тест, наблюдение. В исследовании приняли участие 292 человека. Выявлено преобладание средних показателей лидерских качеств у респондентов. Наименее развиты такие компоненты, как мотивация на успех и волевой самоконтроль. Метод групповых проектов доказал свою эффективность для развития всех изучаемых навыков, кроме волевого самоконтроля. Значимость всех выявленных изменений находится на уровне p = 0,05, что определяет необходимость дальнейшей модификации используемого метода. Полученные данные могут быть использованы в практике преподавателей и психологов высших учебных заведений в развитие лидерских качеств учащихся