Оценка влияния метформина и терапии другими сахароснижающими препаратами на исходы заболевания при остром коронарном синдроме у пациентов с сахарным диабетом второго типа

Aim. To study the influence of hypoglycemic therapy on hospital and long-term prognosis in patients with acute coronary syndrome (ACS) and diabetes type 2.Methods. The study included 63 patients with ACS and type 2 diabetes. All patients had a clinical examination, assessment of mortality risk and myocardial infarction on GRACE scale (Global Registry of Acute Coronary Events) and TIMI (Thrombolisis In Myocardial Infarction) in-hospital and six months after hospitalization.Results. Metformin is associated with a lower estimated risk of in-hospital mortality and within 6 months after discharge in patients with acute coronary syndrome on the background of type 2 diabetes and with less risk of adverse cardiovascular events within 14 days of their occurrence in patients with unstable angina pectoris on the background of diabetes. High daily doses of metformin have also been associated with a decrease in the estimated risk of in-hospital mortality and within 6 months after discharge in patients with ACS associated with diabetes. The inverse association between the daily dosage of metformin and the presence of angina pectoris in patients with ACS and diabetes type 2 indicates a protective effect of metformin high daily dosages in relation to the risk of complications within six months after the discharge from hospital.Conclusion. One of the important aspects of ACS treatment, along with effective therapy, is the impact on concomitant risk factors, including blood glucose control. The main groups of hypoglycemic drugs have currently been identified; their effect on cardiovascular events, long-term effects and long-term prognosis are being investigated.Цель. Оценить влияние метформина и других сахароснижающих препаратов на госпитальный и долгосрочный прогноз у пациентов с острым коронарным синдромом (ОКС) на фоне сахарного диабета 2-го типа (СД 2).Материалы и методы. В исследование включены 63 пациента с ОКС и СД 2. Всем больным проведено клиническое обследование, оценка риска летальности и развития инфаркта миокарда по шкалам GRACE (Global Registry of Acute Coronary Events), TIMI (Thrombolisis In Myocardial Infarction) на госпитальном этапе и через 6 мес. после госпитализации.Результаты. Прием метформина ассоциирован с меньшим расчетным риском внутригоспитальной летальности и летальности в течение 6 мес. после выписки среди больных ОКС на фоне СД 2, а также меньшим риском наступления неблагоприятных сердечно-сосудистых событий в течение 14 дней после их возникновения у пациентов с нестабильной стенокардией на фоне СД 2. Высокие суточные дозировки метформина также показали ассоциацию со снижением расчетного риска внутригоспитальной летальности и летальности в течение 6 мес. после выписки среди пациентов с ОКС на фоне СД 2. Обратная ассоциация между суточной дозировкой метформина и стенокардией (боль в груди, одышка) у больных ОКС и СД 2 свидетельствует о протективном эффекте высоких суточных дозировок метформина в отношении риска осложнений в течение полугода после выписки.Заключение. Наряду с эффективной терапией одним из важных аспектов лечения ОКС является воздействие на сопутствующие факторы риска, в том числе контроль уровня глюкозы крови. В настоящее время определены основные группы сахароснижающих препаратов, исследуют их влияние на сердечно-сосудистые события, отдаленные эффекты и долгосрочный прогноз. Результаты представленной работы свидетельствуют о наличии кардиопротективных эффектов метформина и указывают на необходимость дальнейшего изучения метформина для подтверждения преимущества применения препарата с целью вторичной профилактики среди пациентов с ОКС и СД 2

Systematic Identification of Cell-Cell Communication Networks in the Developing Brain

Since the generation of cell-type specific knockout models, the importance of inter-cellular communication between neural, vascular, and microglial cells during neural development has been increasingly appreciated. However, the extent of communication between these major cell populations remains to be systematically mapped. Here, we describe EMBRACE (embryonic brain cell extraction using FACS), a method to simultaneously isolate neural, mural, endothelial, and microglial cells to more than 94% purity in ∼4 h. Utilizing EMBRACE we isolate, transcriptionally analyze, and build a cell-cell communication map of the developing mouse brain. We identify 1,710 unique ligand-receptor interactions between neural, endothelial, mural, and microglial cells in silico and experimentally confirm the APOE-LDLR, APOE-LRP1, VTN-KDR, and LAMA4-ITGB1 interactions in the E14.5 brain. We provide our data via the searchable “Brain interactome explorer”, available at https://mpi-ie.shinyapps.io/braininteractomeexplorer/. Together, this study provides a comprehensive map that reveals the richness of communication within the developing brain

Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed

Findings to the flora of Russia and adjacent countries: New national and regional vascular plant records, 4

With this paper we continue a new annual series, the main purpose of which is to make significant floristic findings from Russia and neighboring countries more visible in Russia and abroad. In total, this paper presents new records for 48 vascular plant species from 6 Eurasian countries, obtained during field explorations, as well as during taxonomic revisions of herbarium materials. For the first time, a new locality of Leontopodium leiolepis is recorded for Russia, Rheum uzengukuushi for China, Rorippa prolifera for Lithuania, Lappula marginata for Kyrgyzstan and Tajikistan, Anthriscus caucalis, Chenopodium ficifolium, Euphorbia prostrata for Uzbekistan, Adonis × hybrida, Potamogeton × franconicus, Solidago × niederederi for the Asian part of Russia, Echinochloa esculenta, Poa jamalinensis, Puccinellia poecilantha for Siberia, Potentilla intermedia for the Caucasus, Rhynchospora alba for the Russian part of Altai, Poa sphondylodes, Veronica beccabunga for Eastern Siberia, Asclepias syriaca for the Republic of Altai, Chimaphila umbellata, Orobanche korshinskyi, Veronica scutellata for the Republic of Buryatia, Cirsium alatum, Thalictrum simplex for the Republic of Crimea, Thymus rariflorus, Th. terekensis for the Republic of Ingushetia, Berberis thunbergii, Crataegus maximowiczii, Prunus serotina for the Republic of Mordovia, Oenothera villosa for the Republic of Tatarstan, Astragalus sulcatus, Galium mollugo for the Republic of Tyva, Phragmites altissimus for the Chelyabinsk Region, Senecio dubitabilis for the Magadan Region, Asclepias syriaca, Galatella villosa, Potentilla recta for the Novosibirsk Region, Dodartia orientalis for the Omsk Region, Viola hultenii for the Sakhalin Region, Phragmites tzvelevii for the Samara Region and the Middle Volga, Jacobaea ferganensis for the Samara Region, Carex media, Impatiens parviflora for the Tyumen Region. There are some more findings which are not new for the region but they contribute significantly to the understanding of species distribution

Circulating tumour cells demonstrate an altered response to hypoxia and an aggressive phenotype

BACKGROUND: Tumours contain hypoxic regions that select for an aggressive cell phenotype; tumour hypoxia induces metastasis-associated genes. Treatment refractory patients with metastatic cancer show increased numbers of circulating tumour cells (CTCs), which are also associated with disease progression. The aim of this study was to examine the as yet unknown relationship between hypoxia and CTCs. METHODS: We generated human MDA-MB-231 orthotopic xenografts and, using a new technology, isolated viable human CTCs from murine blood. The CTCs and parental MDA-MB-231 cells were incubated at 21 and 0.2% (hypoxia) oxygen, respectively. Colony formation was assayed and levels of hypoxia- and anoxia-inducible factors were measured. Xenografts generated from CTCs and parental cells were compared. RESULTS: MDA-MB-231 xenografts used to generate CTCs were hypoxic, expressing hypoxia factors: hypoxia-inducible factor1 alpha (HIF1alpha) and glucose transporter protein type 1 (GLUT1), and anoxia-induced factors: activating transcription factor 3 and 4 (ATF3 and ATF4). Parental MDA-MB-231 cells induced ATF3 in hypoxia, whereas CTCs expressed it constitutively. Asparagine synthetase (ASNS) expression was also higher in CTCs. Hypoxia induced ATF4 and the HIF1alpha target gene apelin in CTCs, but not in parental cells. Hypoxia induced lower levels of carbonic anhydrase IX (CAIX), GLUT1 and BCL2/adenovirus E1B 19-KD protein-interacting protein 3 (BNIP3) proteins in CTCs than in parental cells, supporting an altered hypoxia response. In chronic hypoxia, CTCs demonstrated greater colony formation than parental cells. Xenografts generated from CTCs were larger and heavier, and metastasised faster than MDA-MB-231 xenografts. CONCLUSION: CTCs show an altered hypoxia response and an enhanced aggressive phenotype in vitro and in vivo

Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts

Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations

The Features of West Nile Fever Epidemiological Situation in the World and Russia in 2013 and Prognosis of Its Development in 2014

Epidemiological situation on West Nile Fever (WNF) in Europe in 2013 was characterized by a notable rise of morbidity rate primarily due to the outbreak of WNF in Serbia (302 cases registered). In the North America, in the United States and Canada, WNF manifestations in 2013 were characterized by the lower intensity compared to previous epidemic season. 192 cases were registered in 16 constituent entities of the Russian Federation in 2013. It was revealed, that genotype 2 West Nile Virus (WNV) circulated in the territory of the Volgograd and Saratov regions, the same as in Serbia, Greece and Italy, and genotype 1 WNV in the Astrakhan region. According to the data obtained from the Reference Center for monitoring over WNV pathogen, WNV markers were detected in the territory of 61 constituent entities of the Russian Federation throughout the period of observation in 1999-2013 which testified to the existence of potential risk of human exposure during epidemic season in most of the parts of country. According to Federal Service for Hydrometeorology and Environmental Monitoring forecast, climatic conditions in Russia for the next 5-10 years will stick to global warming trend which will contribute to further spread of WNV onto the northern areas

Testis-specific glyceraldehyde-3-phosphate dehydrogenase: origin and evolution

<p>Abstract</p> <p>Background</p> <p>Glyceraldehyde-3-phosphate dehydrogenase (GAPD) catalyses one of the glycolytic reactions and is also involved in a number of non-glycolytic processes, such as endocytosis, DNA excision repair, and induction of apoptosis. Mammals are known to possess two homologous GAPD isoenzymes: GAPD-1, a well-studied protein found in all somatic cells, and GAPD-2, which is expressed solely in testis. GAPD-2 supplies energy required for the movement of spermatozoa and is tightly bound to the sperm tail cytoskeleton by the additional N-terminal proline-rich domain absent in GAPD-1. In this study we investigate the evolutionary history of GAPD and gain some insights into specialization of GAPD-2 as a testis-specific protein.</p> <p>Results</p> <p>A dataset of GAPD sequences was assembled from public databases and used for phylogeny reconstruction by means of the Bayesian method. Since resolution in some clades of the obtained tree was too low, syntenic analysis was carried out to define the evolutionary history of GAPD more precisely. The performed selection tests showed that selective pressure varies across lineages and isoenzymes, as well as across different regions of the same sequences.</p> <p>Conclusions</p> <p>The obtained results suggest that GAPD-1 and GAPD-2 emerged after duplication during the early evolution of chordates. GAPD-2 was subsequently lost by most lineages except lizards, mammals, as well as cartilaginous and bony fishes. In reptilians and mammals, GAPD-2 specialized to a testis-specific protein and acquired the novel N-terminal proline-rich domain anchoring the protein in the sperm tail cytoskeleton. This domain is likely to have originated by exonization of a microsatellite genomic region. Recognition of the proline-rich domain by cytoskeletal proteins seems to be unspecific. Besides testis, GAPD-2 of lizards was also found in some regenerating tissues, but it lacks the proline-rich domain due to tissue-specific alternative splicing.</p