Дослідження впливу екстрактів з листя стевії та чорниці на показники розвитку експериментального цукрового діабету, індукованого високофруктозною дієтою з додаванням ін’єкцій дексаметазону

The study of the investigation of influence of extract from leaves of stevia and vaccinum on the expression of insulin resistance. Keeping animals on high-calorie diet with the additoin of fructose causes complex metabolic disordes specific to metabolic syndrome anf type 2 diabetes. It was found that the antioxidation action and hypoglycemic effect of the extract from of stevia leaves, while the use of extract from vaccinum under idential experimental condition, is manifested in more antioxidation action. Recommended joint use of the studied extracts in the complex treatment of diabetes 2-type.Исследовано влияние  экстрактов  из листьев  стевии и черники на развитие инсулинорезистентности. Содержание лабораторных животных на высокофруктозной диете вызывает кимплекс метаболических нарушений, характериных для СД 2-го типа. Виявлено вираженное гипогликемическое  и слабое антиоксидатное действие экстракта из листьев стевии, в то время как применение экстракта из листьев черники при одинаковых экспериментальных условиях проявляется в более вираженном антиоксидатном действии. Рекомендовано совместное применение исследованных экстрактов в комплексном лечении СД 2-го типа.Досліджено вплив екстрактів з листя стевії і чорниці на розвиток інсулінорезистентності. Зміст лабораторних тварин на високофруктозной дієті викликає кімплекс метаболічних порушень, характеріних для СД 2-го типу. Виявлено виражену гіпоглікемічну і слабку антиоксидатну дію екстракту з листя стевії, в той час як застосування екстракту з листя чорниці при однакових експериментальних умовах проявляється в більш виражену антиоксидатну дію. Рекомендовано спільне застосування досліджених екстрактів в комплексному лікуванні ЦД 2-го типу

Дослідження впливу сухих екстрактів з листя брусниці і чорниці з додаванням L-аргініну на розвиток метаболічних порушень за умов експериментального цукрового діабету ІІ типу

Investigated the pharmacological properties of dry extractof cranberries and blueberries with the addition of L-arginine in experimental metabolic syndrome in rats induced vsokoprotocnah diet. Revealed more pronounced antiatherogenic properties of extracts of bilberry, compared with an extract of bilberry. Conclusions prospects for the use of extracts of the investigated plants as potential substrates for the treatment and prevention of metabolic syndrome.Исследованы фармакологические свойства сухих екстрактов брусники и черники с добавлением L-аргинина в условиях экспериментального метаболического синдрома у крыс, индуцированного високофруктозной диетой. Выявлено более выраженные антиатерогенные свойства экстрактов черники по сравнению с экстрактом брусники. Сделаны выводы перспективы применения экстрактов исследованных растений в качестве потенциальных субстратов для лечения и профилактики метаболического синдрома.  Досліджено фармакологічні властивості сухих екстрактів брусниці та чорниці з додаванням з L-аргініну за умов експериментального  метаболічного синдрому у щурів, індукованому високофруктозною дієтою. Виявлено більш виразні антиатерогенні властивості екстрактів чорниці порівняно з екстрактом брусниці.  Зроблено висновки щодо перспективи застосування екстрактів досліджених рослин в якості потенційних субстратів для лікування та профілактики метаболічного синдрому. 

The Hsc/Hsp70 Co-Chaperone Network Controls Antigen Aggregation and Presentation during Maturation of Professional Antigen Presenting Cells

The maturation of mouse macrophages and dendritic cells involves the transient deposition of ubiquitylated proteins in the form of dendritic cell aggresome-like induced structures (DALIS). Transient DALIS formation was used here as a paradigm to study how mammalian cells influence the formation and disassembly of protein aggregates through alterations of their proteostasis machinery. Co-chaperones that modulate the interplay of Hsc70 and Hsp70 with the ubiquitin-proteasome system (UPS) and the autophagosome-lysosome pathway emerged as key regulators of this process. The chaperone-associated ubiquitin ligase CHIP and the ubiquitin-domain protein BAG-1 are essential for DALIS formation in mouse macrophages and bone-marrow derived dendritic cells (BMDCs). CHIP also cooperates with BAG-3 and the autophagic ubiquitin adaptor p62 in the clearance of DALIS through chaperone-assisted selective autophagy (CASA). On the other hand, the co-chaperone HspBP1 inhibits the activity of CHIP and thereby attenuates antigen sequestration. Through a modulation of DALIS formation CHIP, BAG-1 and HspBP1 alter MHC class I mediated antigen presentation in mouse BMDCs. Our data show that the Hsc/Hsp70 co-chaperone network controls transient protein aggregation during maturation of professional antigen presenting cells and in this way regulates the immune response. Similar mechanisms may modulate the formation of aggresomes and aggresome-like induced structures (ALIS) in other mammalian cell types

Granulovacuolar Degenerations Appear in Relation to Hippocampal Phosphorylated Tau Accumulation in Various Neurodegenerative Disorders

BACKGROUND: Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders. METHODS: An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized. RESULTS: The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs. CONCLUSIONS: Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation

Viral Mediated Redirection of NEMO/IKKγ to Autophagosomes Curtails the Inflammatory Cascade

The early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF)-κB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-κB (IκB) proteins and the IκB kinase (IKK) complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR) and IL-1 receptor-dependent NF-κB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-κB essential modulator (NEMO), the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response

Programmed cell death and its role in inflammation

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases