41 research outputs found
E-learning and AMRES in teaching architecture
The paper is a result of a scientific research projects: Spatial, ecological, energy efficient and social aspects of settlement development and climate change – interrelationships, financed by Ministry of education and science, Republic of Serbia, TR36035 and project III-44009 Development of embedded systems with
connected services and digital technology.ICT is not only the additional instrument of the Information Society, but also an important catalyst and tool for inducing educational reforms that change our students into productive knowledge workers. There are notions that students should be trained to learn more autonomously and to get access to and digest information more independently which could provide a good basis for life long learning. The research will discuss pros and cons of using AMRES as an e-learning academic platform in academic education in theoretical and practical courses at engineering and architectural studies. The hypothesis is that e-learning concept provides attitude change among students in knowledge development regarding the course subject.
The hypothesis will be tested inside main approaches and attitudes of using ICT in knowledge development, using case study using AMRES at the courses Design of
Open Public Spaces and Studio Project 3, both at Bachelor studies at the Faculty of Architecture, University of Belgrade
Variation of the cytokine profiles in gingival crevicular fluid between different groups of periodontally healthy teeth
© 2020, University of Kragujevac, Faculty of Science. All rights reserved. Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premolars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in proinflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in proinflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context
BMP axis in cancer cachexia
BACKGROUND
Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although cancer cachexia is responsible for about 25% of cancer deaths, no effective therapies are available, and the underlying mechanisms have not been fully elucidated.
Its occurrence complicates patients’ management, reduces tolerance to treatments and negatively affects patient quality of life. Muscle wasting, mainly due to increased protein breakdown rates, is one of the most prominent features of cachexia. Blocking muscle loss in cachexia mouse models dramatically prolongs survival even of animals in which tumor growth is not inhibited.
Recent observations showed that bone morphogenetic protein (BMP) signaling, acting through Smad1, Smad5 and Smad8 (Smad1/5/8), is a master regulator of muscle homeostasis. BMP-Smad1/5/8 axis negatively regulates a novel ubiquitin ligase (MUSA1) required for muscle loss induced by denervation.
MATERIALS AND METHODS
First aim of the present work was to test if alterations of the BMP signaling pathway occur in cancer-induced muscle wasting in patients. For this purpose we checked the state of activation of the BMP pathway in muscle of cachectic vs non–cachectic patients affected by colon, pancreatic and esophagus cancer and in control subjects. We checked by Western Blot the phosphorylation levels of Smad1/5/8 and of Smad3 and by quantitative Real-Time PCR (qRT-PCR) the expression levels of different atrophy-related genes The second aim was to evaluate the degree of muscle atrophy and distribution of muscle fibers in patients and control subjects using morphometric and immunohistochemical analyses. We also performed analysis on distribution of NCAM positive muscle fibers to assess the effect of denervation on muscle tropism.
RESULTS
From December 2014 we collected 95 rectus abdominis muscle biopsies of cancer patients and 11 from control subjects. In line with the results we obtained in C26 mice model (a well-established cancer cachexia experimental model) Smad1/5/8 phosphorylation, readout of the state of activation of the BMP pathway, was nearly completely abrogated in the muscles of cancer cachectic patients compared to cancer non-cachectic ones. Interestingly, the level of phosphorylation of Smad3 was not significantly affected suggesting specific effects of cancer growth on BMP pathway. The expression levels of different atrophy-related genes including MUSA1 were induced in the cachectic muscles. Interestingly, several BMP related genes are also changing the expression during cancer growth. We also found a correlation between suppression of BMP pathway, expression of atrophy related genes and Noggin, known to block BMP pathway.
Morphometric analysis shown that patients with cancer cachexia have smaller myofiber diameter (in particular fast type fibers) in comparison to age-matched controls. In skeletal muscle from cancer patients (either cachectic or non-cachectic) we detected a prevalence of flat shaped, angulated and severely atrophic myofibers (i.e. morphological features of denervated myofibers), big fiber-type grouping (i.e. typical hallmark of denervation/reinnervation events) and numerous NCAM positive myofibers (i.e. specific marker of denervation).
CONCLUSIONS
These findings are consistent with the hypothesis that BMP inhibition is permissive to cachexia onset. Since the reactivation of the BMP-dependent signaling and MUSA1 suppression was sufficient to prevent tumor-induced muscle atrophy in our C26 mouse model (data not shown), the present data suggest that the BMP axis can be an effective target for therapeutic approaches to counteract cachexia also in cancer patients.
The results of morphometric and immunohistochemical studies collected till now may suggest that denervation contributes to myofiber atrophy in cancer cachexia
Impact of the Financial Structure on the Efficiency of Entrepreneurs in Serbia
The development of entrepreneurship has been very important for
the economic growth of most countries in the world, in the recent
years. However, starting up new business and its development to a
successful stable organization is faced with a number of problems
and limitations. Financing is a very serious problem for the countries
in transitions. Surveys, conducted in Serbia by the National Agency
for Regional Development, have shown that Serbian entrepreneurs
have been faced with a number of financial problems which have
directly affected their efficiency. This paper investigated whether the
problems in financial management (especially problems that depend
on the changes to financial structure) had a major impact on
the efficiency of entrepreneurs in Serbia. The aim of this paper was
to identify the key financial problems that entrepreneurs in Serbia
were facing with in the previous period and propose actions whose
implementation may lead to their reduction or elimination in the
future. Using a sample of more than 13000 entrepreneurs in Serbia
(based on the data from the Serbian Business Registers Agency) in
the period from 2004 to 2014, we found that extremely large impact
on the efficiency of entrepreneurs in Serbia had big financial
expenses and a high level of financial risk. Applying the correlation
analysis we showed that the growth of long-term debt and related
financial expenses caused the reduction of efficiency of entrepreneurs
in Serbia. Regression analysis showed that the increase in
indebtedness significantly contributed to the increase in inefficiency
and bankruptcy of large number of entrepreneurs in Serbia
Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors
Multifunctional enzymes glutathione transferases (GSTs) are involved in the development of chemoresistance, thus representing a promising target for a novel approach in cancer treatment. This superfamily of polymorphic enzymes exhibits extraordinary substrate promiscuity responsible for detoxification of numerous conventional chemotherapeutics, at the same time regulating signaling pathways involved in cell proliferation and apoptosis. In addition to upregulated GST expression, different cancer cell types have a unique GST signature, enabling targeted selectivity for isoenzyme specific inhibitors and pro-drugs. As a result of extensive research, certain GST inhibitors are already tested in clinical trials. Catalytic properties of GST isoenzymes are also exploited in bio-activation of specific pro-drugs, enabling their targeted accumulation in cancer cells with upregulated expression of the appropriate GST isoenzyme. Moreover, the latest approach to increase specificity in treatment of solid tumors is development of GST pro-drugs that are derivatives of conventional anti-cancer drugs. A future perspective is based on the design of new drugs, which would selectively target GST overexpressing cancers more prone to developing chemoresistance, while decreasing side effects in off-target cells
Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness
Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease
Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth
Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premolars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in proinflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in proinflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context