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  • 1
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    Online Resource
    Role of IL-33/ST2 Axis in Chronic Inflammatory Neurological Disorderss
    Walter de Gruyter GmbH ; 2021
    In:  Serbian Journal of Experimental and Clinical Research Vol. 0, No. 0 ( 2021-12-08)
    Details
    In: Serbian Journal of Experimental and Clinical Research, Walter de Gruyter GmbH, Vol. 0, No. 0 ( 2021-12-08)
    Abstract: Interleukin-33 (IL-33) is a member of IL-1 family of cytokines, produced constitutively by fibroblasts, endothelial cells, and epithelial cells. IL-33 can be released passively from cells during tissue damage and cell necrosis, suggesting that it may act as an alarmin. Function of IL-33 is mediated by its interaction with ST2 molecule that is expressed on many immune cells: Th2 lymphocytes, NK, NKT and mast cells, monocytes, dendritic cells and granulocytes. IL-33/ST2 pathway plays, often dual, roles in different physiological and inflammatory processes, mediating both, pathological immune responses and tissue repair. Expression of IL-33 in the central nervous system (CNS) is significantly enhanced during various pathological processes, indicating its important role in the pathogenesis of neurological inflammatory and degenerative diseases. In this review the biological features, expression of IL-33 and its ligand ST2 in CNS, and the role of IL- 33/ST2 pathway in development of Alzheimer’s disease and multiple sclerosis are discussed.
    Type of Medium: Online Resource
    ISSN: 2335-075X , 1820-8665
    URL: Article
    DOI: 10.2478/sjecr-2020-0038
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2021
    detail.hit.zdb_id: 2710266-X
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  • 2
    Online Resource
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    Shikonin Derivatives from Onsoma visianii Decrease Expression of Phosphorylated STAT3 in Leukemia Cells and Exert Antitumor Activity
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 4 ( 2021-03-31), p. 1147-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 4 ( 2021-03-31), p. 1147-
    Abstract: Antitumor effects of shikonins on chronic lymphocytic leukemia (CLL) and B-cell prolymphocytic leukemia (B-PLL) are mostly unexplored. The antitumor activity of shikonins, isolated from Onosma visianii Clem (Boraginaceae), in BCL1, mouse CLL cells and JVM-13, human B-PLL cells was explored in this study. The cytotoxicity of shikonin derivatives was measured by an MTT test. Cell death, proliferation, cell cycle, and expression of molecules that control these processes were analyzed by flow cytometry. Expression of STAT3-regulated genes was analyzed by real-time q-RT-PCR (Quantitative Real-Time Polymerase Chain Reaction). The antitumor effects of shikonin derivatives in vivo were analyzed, using flow cytometry, by detection of leukemia cells in the peripheral blood and spleens of mice intravenously injected with BCL1 cells. The two most potent derivatives, isobutyrylshikonin (IBS) and α-methylbutyrylshikonin (MBS), induced cell cycle disturbances and apoptosis, inhibited proliferation, and decreased expression of phospho-STAT3 and downstream-regulated molecules in BCL1 and JVM-13 cells. IBS and MBS decreased the percentage of leukemia cells in vivo. The link between the decrease in phosphorylated STAT3 by MBS and IBS and BCL1 cell death was confirmed by detection of enhanced cell death after addition of AG490, an inhibitor of Jak2 kinase. It seems that IBS and MBS, by decreasing STAT3 phosphorylation, trigger apoptosis, inhibit cell proliferation, and attenuate leukemia cell stemness.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13041147
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 3
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    Galectin-3, Possible Role in Pathogenesis of Periodontal Diseases and Potential Therapeutic Target
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-3-19)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-3-19)
    Abstract: Periodontal diseases are chronic inflammatory diseases that occur due to the imbalance between microbial communities in the oral cavity and the immune response of the host that lead to destruction of tooth supporting structures and finally to alveolar bone loss. Galectin-3 is a β-galactoside-binding lectin with important roles in numerous biological processes. By direct binding to microbes and modulation of their clearence, Galectin-3 can affect the composition of microbial community in the oral cavity. Galectin-3 also modulates the function of many immune cells in the gingiva and gingival sulcus and thus can affect immune homeostasis. Few clinical studies demonstrated increased expression of Galectin-3 in different forms of periodontal diseases. Therefore, the objective of this mini review is to discuss the possible effects of Galectin-3 on the process of immune homeostasis and the balance between oral microbial community and host response and to provide insights into the potential therapeutic targeting of Gal-3 in periodontal disease.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.638258
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
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    The Role of IL-17 in the Pathogenesis of Oral Squamous Cell Carcinoma
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-08), p. 9874-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-08), p. 9874-
    Abstract: Elucidating the inflammatory mechanisms underlying formation and progression of oral squamous cell carcinoma (OSCC) is crucial for discovering new targeted therapeutics. The proinflammatory cytokine IL-17 has proven roles in tumor formation, growth, and metastasis. The presence of IL-17 is demonstrated in both in vitro and in vivo models, and in OSCC patients, is mostly accompanied by enhanced proliferation and invasiveness of cancer cells. Here we review the known facts regarding the role of IL-17 in OSCC pathogenesis, namely the IL-17 mediated production of proinflammatory mediators that mobilize and activate myeloid cells with suppressive and proangiogenic activities and proliferative signals that directly induce proliferation of cancer cells and stem cells. The possibility of a potential IL-17 blockade in OSCC therapy is also discussed.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24129874
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Interleukin-17 in Chronic Inflammatory Neurological Diseases
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-6-3)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-6-3)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2020.00947
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 6
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    Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 14 ( 2020-07-19), p. 5097-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 14 ( 2020-07-19), p. 5097-
    Abstract: Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune liver disease characterized by inflammation and damage of small bile ducts. The NLRP3 inflammasome is a multimeric complex of proteins that after activation with various stimuli initiates an inflammatory process. Increasing data obtained from animal studies implicate the role of NLRP3 inflammasome in the pathogenesis of various diseases. Galectin-3 is a β-galactoside-binding lectin that plays important roles in various biological processes including cell proliferation, differentiation, transformation and apoptosis, pre-mRNA splicing, inflammation, fibrosis and host defense. The multilineage immune response at various stages of PBC development includes the involvement of Gal-3 in the pathogenesis of this disease. The role of Galectin-3 in the specific binding to NLRP3, and inflammasome activation in models of primary biliary cholangitis has been recently described. This review provides a brief pathogenesis of PBC and discusses the current knowledge about the role of Gal-3 in NLRP3 activation and PBC development.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21145097
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 3 ( 2021-03-22), p. 1022-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 3 ( 2021-03-22), p. 1022-
    Abstract: The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13031022
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 8
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    Antitumor Activity of Ruthenium(II) Terpyridine Complexes towards Colon Cancer Cells In Vitro and In Vivo
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 20 ( 2020-10-14), p. 4699-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 20 ( 2020-10-14), p. 4699-
    Abstract: Ruthenium complexes have attracted considerable interest as potential antitumor agents. Therefore, antitumor activity and systemic toxicity of ruthenium(II) terpyridine complexes were evaluated in heterotopic mouse colon carcinoma. In the present study, cytotoxic effects of recently synthesized ruthenium(II) terpyridine complexes [Ru(Cl-tpy)(en)Cl] [Cl] (en = ethylenediamine, tpy = terpyridine, Ru-1) and [Ru(Cl-tpy)(dach)Cl] [Cl] (dach = 1,2-diaminocyclohexane, Ru-2) towards human and murine colon carcinoma cells were tested in vitro and in vivo and compared with oxaliplatin, the most commonly used chemotherapeutic agent against colorectal carcinoma. Ruthenium(II) complexes showed moderate cytotoxicity with IC50 values ranging between 19.1 to 167.3 μM against two human, HCT116 and SW480, and one mouse colon carcinoma cell line, CT26. Both ruthenium(II) terpyridine complexes exerted a moderate apoptotic effect in colon carcinoma cells, but induced significant necrotic death. Additionally, both complexes induced cell cycle disturbances, but these effects were specific for the cell line. Further, Ru-1 significantly reduced the growth of primary heterotopic tumor in mice, similarly to oxaliplatin. Renal damage in Ru-1 treated mice was lower in comparison with oxaliplatin treated mice, as evaluated by serum levels of urea and creatinine and histological evaluation, but Ru-1 induced higher liver damage than oxaliplatin, evaluated by the serum levels of alanine aminotransferase. Additionally, the interaction of these ruthenium(II) terpyridine complexes with the tripeptide glutathione (GSH) was investigated by proton nuclear magnetic resonance (1H NMR) spectroscopy. All reactions led to the formation of monofunctional thiolate adducts [Ru(Cl-tpy)(en)GS-S] (3) and [Ru(Cl-tpy)(dach)GS-S] (4). Our data highlight the significant cytotoxic activity of [Ru(Cl-tpy)(en)Cl] [Cl] against human and mouse colon carcinoma cells, as well as in vivo antitumor activity in CT26 tumor-bearing mice similar to standard chemotherapeutic oxaliplatin, accompanied with lower nephrotoxicity in comparison with oxaliplatin.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25204699
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 9
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    Xenobiotic Induced Model of Primary Biliary Cirrhosis
    Walter de Gruyter GmbH ; 2014
    In:  Serbian Journal of Experimental and Clinical Research Vol. 15, No. 3 ( 2014-10-1), p. 145-150
    Details
    In: Serbian Journal of Experimental and Clinical Research, Walter de Gruyter GmbH, Vol. 15, No. 3 ( 2014-10-1), p. 145-150
    Abstract: Primarna bilijarna ciroza (PBC) je autoimunska bolest jetre koju karakteriše destrukcija intrahepatičnih žučnih kanalića i prisistvo antimitohondrijalnih antitela (AMAs). Poslednjih godina je razvijeno nekoliko mišjih modela PBC koji imaju slične serološke, biohemijske i histološke karakteristike kao i humana PBC. Ovi animalni modeli su omogućili ispitivanje etiologije i mehanizama uključenih u patogenezu PBC. U PBC imunski odgovor je usmeren na E2 komponentu 2-okso-kiseline dehidrogenaza familije enzima koji su locirani u mitohondrijama, a imunodominantni epitop je peptidna sekvenca sa lipidima koja je zajednička za ove enzime. Imunizacija miševa 2-oktinoičnom kisleinom vezanom za goveđi serumski albumin (2-OA-BSA), antigenom koji je strukturno sličan E2 subjedinici kompleksa piruvat dehidrogenaze (PDC-E2), omogućava razvoj histoloških promena koje karakterišu PBC kod ljudi. Ovaj model PBC indukovan ksenobiotikom je pogodan za ispitivanje početnih događaja u patogenezi PBC i za razvoj novih lekova za PBC.
    Type of Medium: Online Resource
    ISSN: 2335-075X , 1820-8665
    URL: Article
    DOI: 10.2478/sjecr-2014-0019
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2014
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  • 10
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    Latent Murine Cytomegalovirus Infection Contributes to EAE Pathogenesis / Latentna Infekcija Mišjim Citomegalovirusom Ima Ulogu U Patogenezi Eksperimentalnog Autoimunskog Encefalomijelitisa
    Walter de Gruyter GmbH ; 2014
    In:  Serbian Journal of Experimental and Clinical Research Vol. 15, No. 4 ( 2014-12-1), p. 183-190
    Details
    In: Serbian Journal of Experimental and Clinical Research, Walter de Gruyter GmbH, Vol. 15, No. 4 ( 2014-12-1), p. 183-190
    Abstract: Virusna infekcija se navodi kao najverovatniji faktor okoline koji utiče na razvoj multiple skleroze (MS). Postoje konfliktni podaci o ulozi infekcije citomegalovirusom (CMV) u patogenezi multiple skleroze. Koristili smo BALB/c miševe, rezistentne na indukciju eksperimentalnog autoimunskog encefalomijelitisa (EAE), i mišji citomegalovirus (MCMV), mišji homolog humanom citomegalovirusu da ispitamo kako virusna infekcija može da utiče na razvoj autoimunske neuroinflamacije. Miševi sa latentnom neonatalnom infekcijom mišjim citomegalovirusom su razvili tipičan EAE. Slično kao u MS, MCMV EAE miševi su razvili infiltrate u centralnom nervnom sistemu (CNS) sa sličnom zastupljenošću CD4+ i CD8+ T limfocita. Uočen je influks i Th 1 i Th 17 ćelija u CNS MCMV EAE miševa. Interesantno je da razvoj autoimunske inflamacije nakon latentne MCMV infekcije prati značajan influks samo Tc17 (CD8+IL-17+ i CD8+RoRγt+), a ne i Tc1 ćelija. Naši rezultati ukazuju da latentna MCMV infekcija verovatno utiče na razvoj inflamatornih limfocita koji mogu da indukuju autoimunski proces u CNS-u, direktno pojačava razvoj patoloških procesa u CNS-u nakon indukcije EAE i ukazuje na CMV kao na mogući faktor okoline koji utiče na razvoj multiple skleroze i drugih autoimunskih bolesti.
    Type of Medium: Online Resource
    ISSN: 2335-075X , 1820-8665
    URL: Article
    DOI: 10.2478/sjecr-2014-0023
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2014
    detail.hit.zdb_id: 2710266-X
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