REALIZATION OF DISTRIBUTED MEDICAL DATA REPOSITORY IN AN ENVIRONMENT WITH HETEROGENOUS MIS

The introduction of centralized registers of medical data after a long time from the implementation of medical information systems and their long-term daily operation is a very challenging and demanding process. In this paper, three ways for the realization of centralized repositories of medical data are considered, and on that occasion, the advantages and limitations of these solutions are emphasized. Due to the heterogeneity of medical information systems in terms of technologies used and implementation, the construction of a distributed centralized national register of medical data emerges as a good solution. A proposal of architecture for the realization of the distributed central republic register of medical data is given. As an example of the proposed solution, the realized collaboration of the central republic radiological information system and its implementation with the medical information system MEDIS.NET is presented

Dental mesenchymal stromal/stem cells in different microenvironments — implications in regenerative therapy

Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells

Tumorigenic Aspects of MSC Senescence—Implication in Cancer Development and Therapy

As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered to be the root of many diseases of the elderly, as infections, autoimmune and chronic inflammatory diseases, degenerative diseases, and cancer. The role of mesenchymal stromal/stem cells (MSCs) in the inflammaging process and the age-related diseases is not completely established, although numerous features of aging MSCs, including altered immunomodulatory properties, impeded MSC niche supporting functions, and senescent MSC secretory repertoire are consistent with inflammaging development. Although senescence has its physiological function and can represent a mechanism of tumor prevention, in most cases it eventually transforms into a deleterious (para-)inflammatory process that promotes tumor growth. In this review we are going through current literature, trying to explore the role of senescent MSCs in making and/or sustaining a microenvironment permissive to tumor development and to analyze the therapeutic options that could target this process

The Role of Doxycycline and IL-17 in Regenerative Potential of Periodontal Ligament Stem Cells: Implications in Periodontitis

Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed

Uticaj Doksiciklina na regenerativni potencijal mezenhimskih matičnih ćelija periodoncijuma

Parodontopatija je hronično progresivno inflamatorno oboljenje tkiva parodoncijuma uzrokovano bakterijama zubnog plaka. Destrukcija parodoncijuma je posledica prekomerne aktivacije inflamatornog odgovora domaćina na bakterijsku infekciju i posledične produkcije citokina uključujući Interleukin-17 (IL-17). Lečenje parodontopatije podrazumeva i sistemsku primenu oralnih antibiotika poput doksociklina. Ovaj antibiotik iz klase tetraciklina ispoljava kako antibakterijska, tako i antiinflamatorna svojstva, a poznato je da utiče i na reparaciju tkiva i metabolizam alveolarnih kostiju. Cilj ove studije je bio da utvrdimo da li doksociklin utiče na regenerativni potencijal mezenhimskih matičnih ćelija periodoncijuma (PDL-MMĆ) tretiranih sa IL-17. Naši rezultati su pokazali da doksociklin značajno smanjuje stimulativni efekat IL-17 na migraciju i ekspresiju matriksne metaloproteinaze 2 u PDL-MMĆ. Pored toga, doksociklin stimuliše osteogenu diferencijaciju PDL-MMĆ poništavajući inhibitorni efekat IL-17 na osteogenezu ovih ćelija. Analize ćelijske respiracije su otkrile da doksociklin smanjuje stopu potrošnje kiseonika i mitohondrijalnu biogenezu u IL-17-tretiranim PDL-MMĆ. Pokazana pro-regenerativna svojstva doksociklina u inflamatornom okruženju ukazuju na potencijal njegove primene u razvoju novih pristupa za terapiju parodontopatije

Supplementary data for the article: Đurašević, S.; Stojković, M.; Sopta, J.; Pavlović, S.; Borković-Mitić, S.; Ivanović, A.; Jasnić, N.; Tosti, T.; Đurović, S.; Đorđević, J.; Todorović, Z. The Effects of Meldonium on the Acute Ischemia/Reperfusion Liver Injury in Rats. Sci Rep 2021, 11 (1), 1305. https://doi.org/10.1038/s41598-020-80011-y.

Supplementary material for: [https://doi.org/10.1038/s41598-020-80011-y]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4458

Interleukin-17 modulates uPA and MMP2 expression in human periodontal ligament mesenchymal stem cells: Involvement of the ERK1/2 MAPK pathway

Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various proinflammatory cytokines, including interleukin (IL)-17. Successful regeneration of damaged periodontal tissues depends on the proper functionality of periodontal ligament mesenchymal stem cells (PDLMSCs), especially the production of extracellular matrix proteases. We investigated the influence of IL-17 on ECM remodeling through modulation of urokinasetype plasminogen activator (uPA) and MMP2/MMP9 expression in human PDLMSCs at mRNA, protein and activity levels using by RT-PCR, Western blotting and zymography, respectively. Investigation of the involvement of MAPKs in these processes in PDLMSCs was determined by Western blotting, as well as by utilizing specific p38 and MEK1/2 inhibitors. Our results show that IL-17 activates MAPK signaling in PDLMSCs. Moreover, IL-17 had no effect on MMP9 expression, but it stimulated uPA and MMP2 gene and protein expression in PDLMSCs through the activation of the ERK1/2 MAPK signaling pathway. The obtained data suggest that IL-17 contributes to ECM degradation in the periodontal ligament by stimulating uPA and MMP2 expression and activity in PDLMSCs. This information is important for understanding periodontal disease development and defining future directions of its treatment