Особенности функционирования малого и среднего предпринимательства на современном этапе экономического развития

A significant reserve for ensuring the socio-economic development of the Republic of Belarus is the rational use of the entrepreneurial potential of business entities as an important component of the economic policy of the state. The paper analyzes the main theoretical approaches to the definition of entrepreneurial activity. The versatility of approaches creates difficulties in formulating a universal term due to the change in the content of this category in the process of development of economic science. The paper proposes the author's definition of entrepreneurial activity, taking into account the modern features of its development. The value added indicator has been introduced into the concept, which will allow taking into account a part of the cost of goods (works, services) incremented by the organization, as well as assessing the efficiency of the regional economy. The development of integration processes and the fragmentation of production activities increase the number of participants in the production chain from different countries that create intermediate imports, which include the added value segmented by them. Consequently, the country's gain from foreign trade, its export and technological potential will be largely determined by the added value it creates. This kind of assessment becomes the most demanded in the analysis of trade indicators of business entities, including their foreign trade. The main criteria for classifying enterprises as large, medium and small have been analyzed in the paper. In different countries, quantitative criteria are not the same, the initial criterion is the number of employees. The difficulty in determining the criteria lies in the fact that they cannot be equivalent for all sectors of the economy and for individual countries, since there is a dependence on established practice and the goals of state policy in relation to small and medium-sized businesses. An accurate description of business entities in terms of size will make it possible to identify their features, patterns of development, advantages and disadvantages. An additional quantitative criterion for referring to business entities in the Republic of Belarus is proposed – gross revenue.Существенным резервом обеспечения социально-экономического развития Республики Беларусь является рациональное использование предпринимательского потенциала субъектов хозяйствования как важной составляющей экономической политики государства. В статье проанализированы основные теоретические подходы к определению предпринимательской деятельности. Многогранность подходов создает сложности в формулировании универсального термина ввиду изменения содержания данной категории в процессе развития экономической науки. Предложено авторское определение предпринимательской деятельности, учитывающее современные особенности ее развития. В понятие введен показатель добавленной стоимости (созданной организацией), который позволит учесть часть стоимости товаров (работ, услуг), а также оценить эффективность региональной экономики. Развитие интеграционных процессов и фрагментация производственной деятельности увеличивают количество участников в производственной цепочке из разных стран, создающих промежуточный импорт, в состав которого входит сегментированная ими добавленная стоимость. Следовательно, выигрыш страны от внешней торговли, ее экспортный и технологический потенциалы во многом будут определяться тем, какую добавленную стоимость она создает. Такого рода оценка становится наиболее востребованной в анализе показателей торговли субъектов предпринимательства, включая их внешнюю торговлю. Проанализированы основные критерии отнесения предприятий к крупным, средним и малым. В разных странах количественные критерии неодинаковы, начальным критерием является численность работников. Сложность определения критериев заключается в том, что они не могут быть равнозначны для всех сфер экономики и для отдельных стран, так как существует зависимость от сложившейся практики и целей государственной политики в отношении к малому и среднему предпринимательству. Точная характеристика субъектов предпринимательства по размеру позволит выявить их особенности, закономерности развития, преимущества и недостатки. Предложен дополнительный количественный критерий отнесения к субъектам предпринимательства в Республике Беларусь – валовая выручка.

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

A Common Model for Cytokine Receptor Activation: Combined Scissor-Like Rotation and Self-Rotation of Receptor Dimer Induced by Class I Cytokine

The precise mechanism by which the binding of a class I cytokine to the extracellular domain of its corresponding receptor transmits a signal through the cell membrane remains unclear. Receptor activation involves a cytokine-receptor complex with a 1∶2 stoichiometry. Previously we used our transient-complex theory to calculate the rate constant of the initial cytokine-receptor binding to form a 1∶1 complex. Here we computed the binding pathway leading to the 1∶2 activation complex. Three cytokine systems (growth hormone, erythropoietin, and prolactin) were studied, and the focus was on the binding of the extracellular domain of the second receptor molecule after forming the 1∶1 complex. According to the transient-complex theory, translational and rotation diffusion of the binding entities bring them together to form a transient complex, which has near-native relative separation and orientation but not the short-range specific native interactions. Subsequently conformational rearrangement leads to the formation of the native complex. We found that the changes in relative orientations between the two receptor molecules from the transient complex to the 1∶2 native complex are similar for the three cytokine-receptor systems. We thus propose a common model for receptor activation by class I cytokines, involving combined scissor-like rotation and self-rotation of the two receptor molecules. Both types of rotations seem essential: the scissor-like rotation separates the intracellular domains of the two receptor molecules to make room for the associated Janus kinase molecules, while the self-rotation allows them to orient properly for transphosphorylation. This activation model explains a host of experimental observations. The transient-complex based approach presented here may provide a strategy for designing antagonists and prove useful for elucidating activation mechanisms of other receptors

The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis

Under physiological conditions, intracellular and tissue levels of reactive oxygen species (ROS) are carefully controlled and employed as fine modulators of signal transduction, gene expression and cell functional responses (redox signaling). A significant derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, plays a role in the pathogenesis of human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis, including chronic liver diseases. In this chapter major concepts and mechanisms in redox signaling will be briefly recalled to introduce a number of selected examples of redox-related mechanisms that can actively contribute to critical events in the natural history of a chronic liver diseases, including induction of cell death, perpetuation of chronic inflammatory responses and fibrogenesis. A major focus will be on redox-dependent mechanisms involved in the modulation of phenotypic responses of activated, myofibroblast-like, hepatic stellate cells (HSC/MFs), still considered as the most relevant pro-fibrogenic cells operating in chronic liver diseases

Transplanted Human Amniotic Membrane-Derived Mesenchymal Stem Cells Ameliorate Carbon Tetrachloride-Induced Liver Cirrhosis in Mouse

BACKGROUND: Human amniotic membrane-derived mesenchymal stem cells (hAMCs) have the potential to reduce heart and lung fibrosis, but whether could reduce liver fibrosis remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Hepatic cirrhosis model was established by infusion of CCl₄ (1 ml/kg body weight twice a week for 8 weeks) in immunocompetent C57Bl/6J mice. hAMCs, isolated from term delivered placenta, were infused into the spleen at 4 weeks after mice were challenged with CCl₄. Control mice received only saline infusion. Animals were sacrificed at 4 weeks post-transplantation. Blood analysis was performed to evaluate alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histological analysis of the livers for fibrosis, hepatic stellate cells activation, hepatocyte apoptosis, proliferation and senescence were performed. The donor cell engraftment was assessed using immunofluorescence and polymerase chain reaction. The areas of hepatic fibrosis were reduced (6.2%±2.1 vs. control 9.6%±1.7, p<0.05) and liver function parameters (ALT 539.6±545.1 U/dl, AST 589.7±342.8 U/dl,vs. control ALT 139.1±138.3 U/dl, p<0.05 and AST 212.3±110.7 U/dl, p<0.01) were markedly ameliorated in the hAMCs group compared to control group. The transplantation of hAMCs into liver-fibrotic mice suppressed activation of hepatic stellate cells, decreased hepatocyte apoptosis and promoted liver regeneration. More interesting, hepatocyte senescence was depressed significantly in hAMCs group compared to control group. Immunofluorescence and polymerase chain reaction revealed that hAMCs engraftment into host livers and expressed the hepatocyte-specific markers, human albumin and α-fetoproteinran. CONCLUSIONS/SIGNIFICANCE: The transplantation of hAMCs significantly decreased the fibrosis formation and progression of CCl₄-induced cirrhosis, providing a new approach for the treatment of fibrotic liver disease

Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting survivin independent of JAK2/STAT3 phosphorylation

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Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis

Objectives: Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HK) is catalyze the first step in glucose metabolism and HK2 constitutes the principal HK inducible isoform. We hypothesize that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage. Methods: HK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of WT mice. K/BxN serum-transfer arthritis was induced in HK2F/F mice harboring Col1a1-Cre (HK2Col1), to delete HK2 in non-hematopoietic cells. Results: HK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and co-localizes with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.Conclusion: HK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts

Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

<p>Abstract</p> <p>Background</p> <p>To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue.</p> <p>Results</p> <p>By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific <it>G</it>ene <it>E</it>xpression <it>T</it>emplates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.</p> <p>Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity.</p> <p>Conclusions</p> <p>These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.</p