Publications by authors named "Jelena Tosic"

Anterior mesoderm (AM) and definitive endoderm (DE) progenitors represent the earliest embryonic cell types that are specified during germ layer formation at the primitive streak (PS) of the mouse embryo. Genetic experiments indicate that both lineages segregate from -expressing progenitors in response to different Nodal signaling levels. However, the precise spatiotemporal pattern of the emergence of these cell types and molecular details of lineage segregation remain unexplored.

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Objective: The aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall.

Methods: Using MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI.

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The first lineage specification of pluripotent mouse epiblast segregates neuroectoderm (NE) from mesoderm and definitive endoderm (ME) by mechanisms that are not well understood. Here we demonstrate that the induction of ME gene programs critically relies on the T-box transcription factors Eomesodermin (also known as Eomes) and Brachyury, which concomitantly repress pluripotency and NE gene programs. Cells deficient in these T-box transcription factors retain pluripotency and differentiate to NE lineages despite the presence of ME-inducing signals transforming growth factor β (TGF-β)/Nodal and Wnt.

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Article Synopsis
  • The study investigates the relationship between genetic polymorphisms of the angiotensin-converting enzyme (ACE) and matrix metalloproteinase-3 (MMP3) genes and the risk of vascular access failure in hemodialysis patients.
  • 200 hemodialysis patients were analyzed retrospectively, comparing those with and without vascular access failures, with no significant differences in demographics or genetic genotype frequencies found between the two groups.
  • Although not statistically significant, results suggested that homozygotes for the I allele of ACE may have a higher risk (2 times) of vascular access failure, while those with the 5A allele of MMP3 also showed an increased risk (1.7 times) compared
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Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens.

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We examined the effects of betaine, an endogenous and dietary methyl donor essential for the methionine-homocysteine cycle, on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet (MCD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice received standard chow (control), standard chow and betaine (1.5% w/v in drinking water), MCD, or MCD and betaine.

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The protective activity of dry olive leaf extract (DOLE) in carbon tetrachloride (CCl)-induced liver damage and possible mechanisms involved in this protection were investigated in rats. Acute CCl intoxication resulted in a massive hepatic necrosis, in increased serum transaminases, and in a perturbation of oxidative stress parameters in liver tissue [malondyaldehide, glutathione (GSH), catalase]. CCl did not affect the expression of caspase-3 and cytochrome c as markers of apoptosis; however, CCl increased the AMP-activated protein kinase (AMPK) activity and the expression of autophagy-related protein LC3II and decreased the expression of p62 protein.

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We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0-32), while the protection was less pronounced if the treatment was limited to the induction (day 0-7 post-immunization) or effector (from day 8 onwards) phase of the disease.

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Pluripotency can be induced in vitro from adult somatic mammalian cells by enforced expression of defined transcription factors regulating and initiating the pluripotency network. Despite the substantial advances over the last decade to improve the efficiency of direct reprogramming, exact mechanisms underlying the conversion into the pluripotent stem cell state are still vaguely understood. Several studies suggested that induced pluripotency follows reversed embryonic development.

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The immunoglobulin superfamily adhesion molecule close homolog of L1 (CHL1) plays important roles during nervous system development. Here, we identified the hedgehog receptor patched-1 (PTCH1) as a novel CHL1-binding protein and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Colocalization and co-immunoprecipitation of CHL1 with PTCH1 suggest an association of CHL1 with this major component of the hedgehog signaling pathway.

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Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules.

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We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and GM cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis.

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Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge.

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Introduction: The use of non-steroidal anti-inflammatory drugs may lead to stricture of the small intestine and less frequently of the colon. Colonic strictures have not been described in patients on dialysis and the aim of this report is to show the case of dialysis patient who was followed for recurrent and prolonged diarrhea.

Case Report: We present the patient on chronic dialysis for 15 years who used non-steroidal anti-inflammatory drugs due to chronic pain and who developed recurrent diarrhea.

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Introduction: Retrospective studies showed that hemodiafiltration was associated with a reduced risk of mortality compared with standard hemodialysis in the patients with end-stage renal disease. Recently, a few prospective randomized clinical trials found no advantage in survival with hemodiafiltration as compared with high-flux hemodialysis and low-flux hemodialysis. The aim of this study was to compare the parameters of hemodialysis adequacy and two-year survival of patients depending on the modality of hemodialysis.

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Article Synopsis
  • Arylpiperazine compounds showed neuroprotective effects in a model of neuroinflammation (EAE) by reducing clinical symptoms in treated rats.
  • The compound 6b was more effective than 6a in delaying disease onset and reducing symptoms due to its higher affinity for specific receptors (D2 and 5-HT1A).
  • Treatment with 6b reduced harmful immune cell infiltration and proinflammatory cytokine expression in the CNS, while enhancing protective pathways, indicating its potential for treating neuroinflammatory diseases.
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The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor.

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Introduction: The optimal length of dialysis is still under debate and current regimen of 12 hours a week is medically acceptable. The aim of this observational study was to confirm the relationship between different length of dialysis per week and the parameters of dialysis adequacy and cardiovascular morbidity.

Material And Methods: The study included 206 patients (128 man and 78 females) who were on maintenance hemodialysis for more than 6 months.

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Introduction: Cardiovascular morbidity and mortality are the major concern in dialysis patients and many risk factors are thought to be involved in its pathogenesis. Apart from traditional and non-traditional risk factors, the genetic susceptibility may be of importance, including renin-angiotensin system gene polymorphism. The aim of this study was to analyse renin-angiotensin system polymorphism in our group of hemodialysis patients and to correlate the findings with cardiovascular morbidity.

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