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TG-interacting Factor(TGIF) Downregulates SOX3 Gene Expression in the NT2/D1 Cell Line

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Journal of Genetics and Genomics 2012年第1期39卷 19-27页

作者： Marija Mojsin jelena popovic Natasa Kovacevic Grujicic Milena Stevanovic Laboratory for Human Molecular Genetics Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeVojvode Stepe 444aPO Box 2311010 BelgradeSerbia

SOX3 is a member of the Sox gene family implicated in brain formation and cognitive function. It is considered to be one of the earliest neural markers in vertebrates, playing a role in specifying neuronal fate. Recently, we have established the first link between TALE （three- amino-acid loop extension） proteins, PBX1 （pre-B-cell leukemia homeobox 1） and MEIS1 （myeloid ecotropic viral integration site 1 homologue）, and the expression of the human SOX3 gene. Here we present the evidence that TGIF （TG-interacting factor） is an additional TALE superfamily member involved in the regulation of human SOX3 gene expression in NT2/D1 cells by direct interaction with the consensus binding site that is conserved in primate orthologue promoters. Functional analysis demonstrated that mutation of the TGIF binding site resulted in the activation of SOX3 promoter. TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and retinoic acid （RA）-induced NT2/D1 ceils. Up to now, this is the first transcription factor identified as a negative regulator of SOX3 gene expression. The obtained results further underscore the significance of TALE proteins as important transcriptional regulators of SOX3 gene expression.

关键词： NT2/D1 cells TGIF Retinoic acid SOX3

Design and Optimization of a GaN GIT Based PFC Boost Converter

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Chinese Journal of Electrical Engineering 2017年第3期3卷 34-43页

作者： Wenbo Wang Frans Pansier jelena popovic J.A.Ferreira Delft University of Technology DelftThe Netherlands

The advent of GaN power devices brings the possibility of pushing up frequencies of power electronics system beyond the capacity of conventional Si *** harvest the high frequency operation benefits of GaN technology,not only GaN devices should be used optimally by providing proper switching and conduction conditions to best accommodate parasitic elements inherent with the devices,other components should also be capable of facilitating high frequency *** this paper,PFC boost converter is used as a platform to harvest the benefits of GaN technology and,at the same time,to uncover the limitations in pushing power electronics systems up.A 600W PFC boost converter with a maximum switching frequency of 3MHz is designed and implemented,which reached an average efficiency of 98.5%.The results indicate that,when properly used,a GaN PFC boost converter could operate at a frequency that is beyond the reach of conventional Si *** well,with availability of GaN devices,high frequency operation of power electronics systems is no longer limited by the lack of switching devices but by practical issues *** frequency magnetic materials,high frequency controllers,etc.

关键词： GaN GIT boost converter PFC high frequency design optimization

Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

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BIOCELL 2021年第5期45卷 1355-1367页

作者： ISIDORA PETROVIC MILENA MILIVOJEVIC ANA ARSENIJEVIC ANDRIJANA LAZIC NATASA KOVACEVIC GRUJICIC MARIJA SCHWIRTLICH jelena popovic MILENA STEVANOVIC Institute of Molecular Genetics and Genetic Engineering University of BelgradeBelgradeSerbia Institute of Cell Biology School of Biological SciencesThe University of EdinburghEdinburghUK Department of Radiation Oncology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Faculty of Biology University of BelgradeBelgradeSerbia Serbian Academy of Sciences and Arts BelgradeSerbia

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast *** evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy *** SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor *** aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 *** applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell *** have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle *** effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular *** have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell *** functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of *** ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from ***,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

关键词： Breast carcinoma Anti-proliferative activity Transcription factors MCF7 cell line SK-BR-3 cell line

Effect of special types of bread with select herbal components on postprandial glucose levels in diabetic patients

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World Journal of Diabetes 2024年第4期15卷 664-674页

作者： Drasko M Gostiljac Srdjan S popovic Vesna Dimitrijevic-Sreckovic Sasa M Ilic jelena A Jevtovic Dragan M Nikolic Ivan A Soldatovic Clinic for Endocrinology Diabetes and Metabolic DiseasesUniversity Clinical Centre of SerbiaBelgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia Clinic for Gastroenterology and Hepatology University Clinical Centre of SerbiaBelgrade 11000Serbia Clinic for Endocrinology Diabetes and Metabolic Diseases-Laboratory for Human Pancreatic Islets CultureUniversity Clinical Centre of SerbiaBelgrade 11000Serbia

BACKGROUND Nutrition recommendations in patients with type 2 diabetes mellitus(T2DM)are to consume rye or integral bread instead of white bread.A positive effect on glucoregulation has been achieved by enriching food with various biologically active substances of herbal origin,so we formulated an herbal mixture that can be used as a supplement for a special type of bread(STB)to achieve better effects on postprandial glucose and insulin levels in patients with *** To compare organoleptic characteristics and effects of two types of bread on postprandial glucose and insulin levels in T2DM *** This trial included 97 patients with T2DM.A parallel group of 16 healthy subjects was also *** participants were given 50 g of rye bread and the same amount of a STB with an herbal mixture on 2 consecutive *** blood glucose and insulin levels were compared at the 30^(th),60^(th),90^(th) and 120th min.A questionnaire was used for subjective estimation of the organoleptic and satiety features of the two types of *** Compared to patients who consumed rye bread,significantly lower postprandial blood glucose and insulin concentrations were found in T2DM patients who consumed *** relevant differences were found among the healthy *** estimated organoleptic and satiety characteristics are better for STB than for rye *** STB have better effects than rye bread on postprandial glucoregulation in T2DM *** estimated organoleptic and satiety characteristics are better for STB than for rye ***,STB can be recommended for nutrition in T2DM patients.

关键词： Special types of bread Postprandial glucoregulation Insulin Nutrition Type 2 diabetes mellitus

Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium

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Biomedical and Environmental Sciences 2021年第3期34卷 192-202页

作者： KULAS jelena TUCOVIC Dina ZELJKOVIC Milica popovic Dusanka POPOV ALEKSANDROV Aleksandra KATARANOVSKI Milena MIRKOV Ivana Immunotoxicology Group Department of EcologyInstitute for Biological Research‘Sinisa Stankovic'-National Institute of Republic of SerbiaUniversity of Belgrade142 Bulevar despota StefanaBelgrade 11000Serbia

Objective To investigate involvement of the aryl hydrocarbon receptor(Ah R)in the immunomodulatory effects of cadmium(Cd).Methods The effect of Cd on Ah R activation(CYP1 A1 and CYP1 B1 m RNA expression)was examined in lung leukocytes of Cd-exposed rats(5 and 50 mg/L,30 d orally)and by in vitro leukocyte *** involvement of Ah R signaling in the effects of Cd on the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)lung leukocyte response was investigated in vitro using the receptor antagonist *** Cd increased CYP1 B1(in vivo and in vitro)and CYP1 A1(in vitro)m RNA,indicating Ah R involvement in the action of *** response to Cd,lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels,but decreased IL-1βproduction due to reduced *** Ah R antagonist CH-223191 abrogated the observed effects of Cd on the cytokine *** absence of Ah R reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high Ah R repressor m RNA *** Ah R signaling is involved in the lung leukocyte proinflammatory cytokine response to *** relevance of the Ah R to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.

关键词： Cadmium Lung leukocytes Aryl hydrocarbon receptor Cytokine(IL-6,TNF,IL-1β)response

Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats

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Biomedical and Environmental Sciences 2022年第11期35卷 1038-1050页

作者： Dina Tucovic jelena Kulas Ivana Mirkov Dusanka popovic Lidija Zolotarevski Marta Despotovic Milena Kataranovski Aleksandra Popov Aleksandrov Immunotoxicology Group Department of EcologyInstitute for Biological Research"Sinisa Stankovic"-National Institute of Republic of SerbiaUniversity of Belgrade142 Bulevar despota Stefana11060 BelgradeSerbia Medical College of Applied Sciences 254 Cara Dusana11080 BelgradeSerbia Centre of Research Excellence in Nutrition and Metabolism Institute for Medical ResearchUniversity of Belgrade11 Tadeusa Koscuska 111000 BelgradeSerbia

Objective The effect of oral cadmium(Cd)intake to influence contact skin allergies was examined,since it is known that Cd is a heavy metal that affects many tissues,including the skin,in which it disturbs homeostasis,thus resulting in inflammation and *** Male rats were evoked with experimental contact hypersensitivity reaction(CHS)to hapten dinitrochlorobenzene(DNCB),after prolonged(30 day)oral exposure to an environmentally relevant Cd dose(5 ppm).The ear cell population was analyzed with flow *** production by ear skin cells and the activity of skin-draining lymph node(DLN)cells were measured using enzyme-linked immunosorbent assay(ELISA).Results Orally acquired Cd(5 ppm)increased CHS intensity only in Dark Agouti(DA)rats by affecting inflammatory responses in both the sensitization(an increase of IFN-γ and IL-17 cytokine production)and challenge(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production)*** increased CHS reaction was seen in Albino Oxford(AO)rats only at a high Cd dose(50 ppm),during the challenge phase(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production).Conclusion These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.

关键词： Cadmium(Cd) Contact hypersensitivity reaction(CHS) Dinitrochlorobenzene(DNCB)

High dose chemotherapy with stem cell support in the treatment of testicular cancer

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World Journal of Stem Cells 2015年第11期7卷 1222-1232页

作者： Lazar popovic Gorana Matovina-Brko Milica popovic Dragana Petrovic Ana Cvetanovic jelena Vukojevic Darjana Jovanovic Medical School University of Novi Sad Department for Medical Oncology Oncology Institute of Vojvodina Department for Internal Medicine Clinical Center of Vojvodina Department for Oncology Clinical Center Nis

Testicular germ cell cancer(TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy(HDCT) approach was used for the first time during the 1980 s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.

关键词： High dose chemotherapy Germ-cell cancer Stem cell transplantation Plerixafor