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Drawing lines in the sand: The growing threat of obesity in type 1 diabetes
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作者 Theocharis Koufakis Dimitrios Patoulias +2 位作者 Ioanna Zografou Nikolaos Papanas Djordje S Popovic 《World Journal of Diabetes》 SCIE 2024年第5期823-827,共5页
In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesit... In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule.Chronic exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in T1DM.As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes.Stereotypes regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes care.In this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM. 展开更多
关键词 OBESITY OVERWEIGHT Type 1 diabetes Metabolic syndrome
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Food contaminants and potential risk of diabetes development:A narrative review
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作者 Maja Milanovic Natasa Milosevic +3 位作者 Natasa Milic Milica Medic Stojanoska Edward Petri Jelena Markovic Filipovic 《World Journal of Diabetes》 SCIE 2023年第6期705-723,共19页
The number of people diagnosed with diabetes continues to increase,especially among younger populations.Apart from genetic predisposition and lifestyle,there is increasing scientific and public concern that environmen... The number of people diagnosed with diabetes continues to increase,especially among younger populations.Apart from genetic predisposition and lifestyle,there is increasing scientific and public concern that environmental agents may also contribute to diabetes.Food contamination by chemical substances that originate from packaging materials,or are the result of chemical reactions during food processing,is generally recognized as a worldwide problem with potential health hazards.Phthalates,bisphenol A(BPA)and acrylamide(AA)have been the focus of attention in recent years,due to the numerous adverse health effects associated with their exposure.This paper summarizes the available data about the association between phthalates,BPA and AA exposure and diabetes.Although their mechanism of action has not been fully clarified,in vitro,in vivo and epidemiological studies have made significant progress toward identifying the potential roles of phthalates,BPA and AA in diabetes development and progression.These chemicals interfere with multiple signaling pathways involved in glucose and lipid homeostasis and can aggravate the symptoms of diabetes.Especially concerning are the effects of exposure during early stages and the gestational period.Well-designed prospective studies are needed in order to better establish prevention strategies against the harmful effects of these food contaminants. 展开更多
关键词 ACRYLAMIDE Bisphenol A PHTHALATES Endocrine disrupting chemicals β-cell DIABETES
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Ikaros isoforms:The saga continues 被引量:1
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作者 Laura A Perez-Casellas Aleksandar Savic Sinisa Dovat 《World Journal of Biological Chemistry》 CAS 2011年第6期140-145,共6页
Through alternate splicing,the Ikaros gene produces multiple proteins.Ikaros is essential for normal hematopoiesis and possesses tumor suppressor activity.Ikaros isoforms interact to form dimers and potentially multim... Through alternate splicing,the Ikaros gene produces multiple proteins.Ikaros is essential for normal hematopoiesis and possesses tumor suppressor activity.Ikaros isoforms interact to form dimers and potentially multimeric complexes.Diverse Ikaros complexes produced by the presence of different Ikaros isoforms are hypothesized to confer distinct functions.Small dominantnegative Ikaros isoforms have been shown to inhibit the tumor suppressor activity of full-length Ikaros.Here,we describe how Ikaros activity is regulated by the coordinated expression of the largest Ikaros isoforms IK-1 and IK-H.Although IK-1 is described as full-length Ikaros,IK-H is the longest Ikaros isoform.IK-H,which includes residues coded by exon 3B (60 bp that lie between exons 3 and 4),is abundant in human but not murine hematopoietic cells.Specific residues that lie within the 20 amino acids encoded by exon 3B give IK-H DNA-binding characteristics that are distinct from those of IK-1.Moreover,IK-H can potentiate or inhibit the ability of IK-1 to bind DNA.IK-H binds to the regulatory regions of genes that are upregulated by Ikaros,but not genes that are repressed by Ikaros.Although IK-1 localizes to pericentromeric heterochromatin,IK-H can be found in both pericentromeric and non-pericentromeric locations.Anti-silencing activity of gamma satellite DNA has been shown to depend on the binding of IK-H,but not other Ikaros isoforms.The unique features of IK-H,its influence on Ikaros activity,and the lack of IK-H expression in mice suggest that Ikaros function in humans may be more complex and possibly distinct from that in mice. 展开更多
关键词 IKAROS Chromatin Pericentromeric TRANSCRIPTION IK-H LEUKEMIA γ satellite
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High dose chemotherapy with stem cell support in the treatment of testicular cancer
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作者 Lazar Popovic Gorana Matovina-Brko +4 位作者 Milica Popovic Dragana Petrovic Ana Cvetanovic Jelena Vukojevic Darjana Jovanovic 《World Journal of Stem Cells》 SCIE CAS 2015年第11期1222-1232,共11页
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. ... 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. 展开更多
关键词 High DOSE chemotherapy Germ-cell cancer Stem cell TRANSPLANTATION PLERIXAFOR
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Immunotherapy in the treatment of lymphoma
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作者 Lazar S Popovic Gorana Matovina-Brko +5 位作者 Maja Popovic Milica Popovic Ana Cvetanovic Ivan Nikolic Biljana Kukic Dragana Petrovic 《World Journal of Stem Cells》 SCIE 2021年第6期503-520,共18页
Relapsed or refractory non-Hodgkin’s lymphomas,especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases.Patients who do not respond to initial therapy or... Relapsed or refractory non-Hodgkin’s lymphomas,especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases.Patients who do not respond to initial therapy or experience relapse are treated with salvage regimens,and if eligible for aggressive therapy,treatment is continued with high-dose chemotherapy and autologous stem cell transplantation.Current therapy options can cure substantial numbers of patients,however for some it is still an uncurable disease.Numerous new drugs and cell therapies are being investigated for the treatment of relapsed or refractory lymphomas.Different types of immunotherapy options have shown promising results,and some have already become the standard of care.Here,we review immunotherapy options for the treatment of lymphoma and discuss the results,positions,practical aspects,and future directions of different drugs and cellular therapies for the treatment of this disease. 展开更多
关键词 IMMUNOTHERAPY Receptors Chimeric antigen Antibodies MONOCLONAL IMMUNOCONJUGATES Hodgkin disease LYMPHOMA Large B-cell Diffuse
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Regulation of Ikaros function by casein kinase 2 and protein phosphatase 1
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作者 Amy K Erbe Aleksandar Savic Sinisa Dovat 《World Journal of Biological Chemistry》 CAS 2011年第6期126-131,共6页
The Ikaros gene encodes a zinc finger,DNA-binding protein that regulates gene transcription and chromatin remodeling.Ikaros is a master regulator of hematopoiesis and an established tumor suppressor.Moderate alteratio... The Ikaros gene encodes a zinc finger,DNA-binding protein that regulates gene transcription and chromatin remodeling.Ikaros is a master regulator of hematopoiesis and an established tumor suppressor.Moderate alteration of Ikaros activity (e.g.haploinsufficiency) appears to be sufficient to promote malignant transformation in human hematopoietic cells.This raises questions about the mechanisms that normally regulate Ikaros function and the potential of these mechanisms to contribute to the development of leukemia.The focus of this review is the regulation of Ikaros function by phosphorylation/dephosphorylation.Site-specific phosphorylation of Ikaros by casein kinase 2 (CK2) controls Ikaros DNA-binding ability and subcellular localization.As a consequence,the ability of Ikaros to regulate cell cycle progression,chromatin remodeling,target gene expression,and thymocyte differentiation are controlled by CK2.In addition,hyperphosphorylation of Ikaros by CK2 leads to decreased Ikaros levels due to ubiquitinmediated degradation.Dephosphorylation of Ikaros by protein phosphatase 1 (PP1) acts in opposition to CK2 to increase Ikaros stability and restore Ikaros DNA binding ability and pericentromeric localization.Thus,the CK2 and PP1 pathways act in concert to regulate Ikaros activity in hematopoiesis and as a tumor suppressor.This highlights the importance of these signal transduction pathways as potential mediators of leukemogenesis via their role in regulating the activities of Ikaros. 展开更多
关键词 IKAROS LEUKEMIA Zinc FINGER Transcription factor CASEIN kinase 2 Protein PHOSPHATASE 1 PHOSPHORYLATION
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Spleen:Histomorphological Changes of the White Pulp during Fetal Development
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作者 Jovana Rajković Branko Baljak +1 位作者 MatildaĐolai Jelena Amidžić 《Journal of Pharmacy and Pharmacology》 CAS 2021年第10期320-332,共13页
For a long time spleen has been an important field of study for researchers.However,details about changes of microscopic structure in spleen during the fetal period are far less available in literature.Our goals were ... For a long time spleen has been an important field of study for researchers.However,details about changes of microscopic structure in spleen during the fetal period are far less available in literature.Our goals were to determine distribution of white pulp as well as its relationship with blood vessels and to observe development and distribution of blood vessels and arrangement of CD4+and CD8+lymphocytes.The study was carried out on 16 specimens of fetal spleens.After standard histological hematoxylin and eosin(H&E)staining,the specimens were stained with immunohistochemical methods.Antibodies for CD4+,CD8+and vascular endothelial cells were used.Qualitative,semi-quantitative and quantitative analyses were performed.The results were statistically analyzed and graphically presented.By the 19th week of gestation lymphocytes can be found in spleen.The 24th week of gestation is the period of the formation of a white pulp of the spleen with centrally placed blood vessels in the follicles.Also,during this week the arterioles were completely surrounded by the CD4+lymphocytes.The number of arterioles in spleen increases during fetal development.With the increase of gestational age of the fetus,lymphatic tissue in the parenchyma of the spleen increases,as well as the number of the arterioles,while the number of capillary blood vessels decreases. 展开更多
关键词 SPLEEN development white pulp T lymphocytes.
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Fractal Dimension in Animal Model of Alzheimer’s Dementia
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作者 Ljiljana Martac Slobodan Sekulic 《Journal of Behavioral and Brain Science》 2018年第9期512-518,共7页
The aim of this study was to qualitatively described effect of the oxidative stress, neurotransmission change and the neurodegeneration in animal model of chronic intoxication by aluminum. Electrocortical brain activi... The aim of this study was to qualitatively described effect of the oxidative stress, neurotransmission change and the neurodegeneration in animal model of chronic intoxication by aluminum. Electrocortical brain activity of animal model of stress and neurodegeneration is comparable with Alzheimer’s Dementia (AD). We used adult animals, during 6 weeks intraperitoneally treated with aluminum. Both animals and patients with Alzheimer’s Dementia have increased relative spectral power in delta range. By fractal analysis we described changes in electrocortical activity of aluminum intoxication animals compare to physiological control. We used change in delta range to calculate fractal dimension for the pathophysiological state of disease. We evaluate effect of stress and neurodegeneration, oxidative stress and accumulation of beta amyloid and neurofibrillary tangles as change in fractal dimension (FD). We conclude that change in fractal dimension could be used for prognosis of AD. Results show that decrease in fractal dimension could be used for evaluation of changes in neural activity in occurrence of AD. 展开更多
关键词 NEUROTOXICITY Fractal Dimension Alzheimer’s Dementia
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A candidate identification questionnaire for postmenopausal osteoporosis patients switched from daily or weekly bisphosphonate to once-monthly ibandronate: An open, prospective, multicenter study—BONCURE study
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作者 Yesim Gokce Kutsal Nurten Eskiyurt +39 位作者 Jale Irdesel Vesile Sepici Hatice Ugurlu Yesim Kirazli Fusun Ardic Mirko Korsic Tonko Vlak Mane Grlickov Snezana Markovic Temelkova Miroslav Lazarov Nada Pilipovic Vera Popovic Aleksandar Dimic Branka Kovacev Dorina Ruci Argjend Tafaj Elma Kucukalic-Selimovic Dijana Avdic Hajrija Seleskovic Snjezana Pejicic Bulent Butun Gulseren Akyuz Lale Cerrahoglu Omer Faruk Sendur Peyman Yalcin Sema Oncel Merih Saridogan Tunay Sarpel Mehmet Tosun Kazim Senel Savas Gursoy Ferhan Canturk Huseyin Demir Blazenka Miskic Dalibor Krpan Franjo Skreb Simeon Grazio Zeljka Crncevic-Orlic Fatih Ozdener Hakan Oncel 《Health》 2013年第7期30-40,共11页
A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once... A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment. 展开更多
关键词 BISPHOSPHONATE Compliance IBANDRONATE POSTMENOPAUSAL Osteoporosis
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Leptospirosis distribution related to freshwater habitats in the Vojvodina region (Republic of Serbia)
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作者 Zorica SVIREV Slobodan B. MARKOVI +8 位作者 Jovan VUKADINOV Sandra STEFAN-MIKI Maja RUZI Radoslava DODER Milotka FABRI Grozdana ANAK Vesna TURKULOV Dejan B. STOJANOVI Mirko DRAGANI 《Science China(Life Sciences)》 SCIE CAS 2009年第10期965-971,共7页
The retrospective study (2002-2007) for human leptospirosis in Vojvodina was undertaken in order to describe the distribution of the disease in relation with some environmental factors. Regarding the presented results... The retrospective study (2002-2007) for human leptospirosis in Vojvodina was undertaken in order to describe the distribution of the disease in relation with some environmental factors. Regarding the presented results, the major detected number of leptospirosis cases concurs with stagnant waters, wetlands, fish pond areas and protected regions, which comprised the basis for mapping of the region in three risk zones: very high risk (incidence rate higher than 5.0), high risk (2.5-5.0) and medium risk of leptospirosis infection (1.0-2.5). During the investigated period, 97 cases were registered with an average of 13.85 cases per year: 2002, 32 cases; 2003, 7; 2004, 22; 2005, 16; 2006, 4 and 2007, 16. Out of these 97 cases only 5 were women. Serovars from 11 presumptive serogroups caused infection, with a predominance of Icterohaemorrhagiae and Bratislava, accounting for 72.72% of cases together. Icterohaemorrhagiae was the commonest infecting serogroup mostly connected with fish ponds. Case fatality ratio was 9.4%. 展开更多
关键词 LEPTOSPIROSIS risk zones fish PONDS protected areas WETLANDS VOJVODINA Serbia
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