Comparative assessment of subsipopulations of tumor-associated macrophages in breast cancer depending on the response to chemotherapy

The key cells of the immune system that determine the relationship between tumor cells and the microenvironment, beginning with early stages of tumor growth, including regulation of neoangiogenesis and the terminal stage of malignant process, are tumor-associated macrophages (TAM). In the present study, identification of TAM markers in breast tumors in patients with neoadjuvant chemotherapy and a comparative assessment of the differences in the macrophages subpopulation in tumors with different response to chemotherapy were carried out. The data we obtained indicate the functional differences between TAM subpopulations that have various phenotypes, that are confirmed at the level of associative links with the effectiveness of chemotherapy

Combining benzo[d]isoselenazol-3-ones with sterically hindered alicyclic amines and nitroxides: enhanced activity as glutathione peroxidase mimics

Benzo[d] isoselenazol-3-ones N-substituted with sterically hindered diamagnetic and paramagnetic five-or six-membered nitroxides or their precursors, including ring-opened diselenides, exhibit synergism in glutathione peroxidase (GPx) activity

Методы контроля социальной адаптации

Методам стабилографии определены биомеханические характеристики статического равновесия у спортсменов занимающихся спортивными бальными танцами. Показано, что высококвалифицированные спортсмены способны лучше поддерживать равновесие, что проявляется в больших показателях отклонения амплитуды колебаний в сравнении со спортсменами низкой квалификации. При этом у девушек танцоров с повышением спортивной квалификации происходит увеличение показателя отклонения вправо, а у их партнеров - отклонение влево. Динамика основных характеристики стабилограммы может использоваться в качестве индикатора уровня технической подготовленности спортсменов и их адаптации к окружающему социуму

Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases

Hydroximic Acid Derivatives:Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness

According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy.</p

Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness

According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy