Assessment of plastic flows and stocks in Serbia using material flow analysis

Material flow analysis was used to assess the amounts of plastic materials flows and stocks that are annually produced, consumed, imported, exported, collected, recycled, and disposed in the landfills in Serbia. The analysis revealed that approximately 269,000 tons of plastic materials are directly disposed in uncontrolled landfills in Serbia without any pretreatment, and that significant amounts of these materials have already accumulated in the landfills. The substantial amounts of land-filled plastics represent not only a loss of valuable recourses, but also pose a serious treat to the environment and human health, and if the trend of direct plastic land-filling is continued, Serbia will face with grave consequences

Povezanost reklamnih poruka i korišćenja bankarskih usluga

U savremenim uslovima poslovanja teško je rešavati ekonomske probleme na tržištu bez implementacije znanja drugih naučnih disciplina, posebno marketinga. Značaj i interdisciplinarnost marketinga, za konkretna istraživanja u radu, osim njegovog oslanjanja na dostignuća i otkrića drugih nauka, disciplina, koncepcija, metoda i tehnika, ogleda se u značaju ekonomske propagande. Cilj ovog istraživanja je ispitivanje stepena i prirode povezanosti između načina, učestalosti i razumevanja korišćenja bankarskih usluga i poverenja u reklamne poruke, kao i značaja koji ispitanici pridaju reklamnim porukama. Shodno definisanom cilju, u istraživanju dominira teorijska razrada rezultata istraživanja. Tokom istraživanja i obrade rezultata rada korišćene su sledeće metode: Likertova skala, T-test, jednofaktorska analiza varijanse, Pirsonov koeficijent korelacije, logistička regresija i višestruka regresija

Research of the influence of socio-demographic characteristics of population to develop tourism (example: Serbian case)

Dominance of the free time and free money as basic factors of tourism development is confirmed by the synthesis of relevant economic and theoretical concepts and empirical studies, from the earliest, to the modern stage of tourism. Both of these factors imply consumption as the main outcome of the economic process. Also, these two factors as final objectives of the economic activity are characteristic only for the individual. A human with all its characteristics - both positive and negative, has a crucial influence on development of tourism. In order to confirm the set hypothesis, a research entitled "The impact of socio-demographic characteristics of the population to develop tourism in Serbia" has started. Theoretical elaboration is dominant in the research results according to the defined purpose of the research. During the research process and results, the following methods were used: Likert Scale, T-test, ANOVA, Pearson correlation coefficient, Logistic regression and Multiple regression

Frequency of balanitis xerotica obliterans among boys with phimosis

Introduction: Balanitis xerotica obliterans (BXO) is an inflammatory disease of unknown etiology and pathogenesis, that represents genital form of lichen sclerosus. Disease is located on foreskin, glans of penis and on urethra. It was discovered that BXO is common cause of phimosis. There is evidence of connections between balanitis xerotica obliterans and appearance of squamous cell carcinoma. The diagnosis of the disease can be clinical and pathohistological. Therapy can be conservative and surgical. The Aim: Determining the frequency of BXO among the boys with phimosis in the light of increasing number of evidence about importance of this clinical entity in development of many complications of urogenital system. Material and methods: Our research contained 470 male patients aged from 1 to 18 years. All the patients who were included in the study were surgically treated in period from 1. January 2014. till 1. January 2017. in University Children's Hospital and all of them had diagnosed phimosis. All the patients underwent circumcision. Foreskins that were suspicious of BXO diagnosis, but could not be diagnosed clinically, were sent to pathohistological analysis. Statistical methods used for measuring central tendency and for determining frequency of BXO were methods of descriptive statistics, or frequency analysis in IBM SPSS Statistics 22 program. Results: Patients with phimosis were in average age of 9.12 ± 4.46 (1-18) years. After data analysis, it was established that in the group of 470 patients there are 48 with BXO diagnosis (10.21%). Patients with BXO were in average age of 10.33 ± 3.14 (6-18) years. Conclusion: Our research has shown that the frequency of BXO among boys with phimosis population is coherent with results of other studies. We concluded that pathohistological analysis of the foreskin is necessary to avoid false negative results after clinical examination

Medicinska hemija inhibitora histon deacetilaza

Today, we are witnessing an explosion of scientific concepts in cancer chemotherapy. It has been considered for a long time that genetic instability in cancer should be treated with drugs that directly damage the DNA. Understanding the molecular basis of malignant diseases shed light on studying phenotypic plasticity. In the era of epigenetics, many efforts are being made to alter the aberrant homeostasis in cancer without modifying the DNA sequence. One such strategy is modulation of the lysine acetylome in human cancers. To remove the acetyl group from the histones, cells use the enzymes that are called histone deacetylases (HDACs). The disturbed equilibrium between acetylation and deacetylation on lysine residues of histones can be manipulated with histone deacetylase inhibitors (HDACi). Throughout the review, an effort will be made to present the mechanistic basis of targeting the HDAC isoforms, discovered selective HDAC inhibitors, and their therapeutical implications and expectations in modern drug discovery.Savremena hemoterapija kancera se bazira na velikom broju različitih naučnih pristupa. Dugo se smatralo da bi genetsku nestabilnost u kancerskim oboljenjima trebalo lečiti agensima koji direktno oštećuju DNK. Razumevanje molekularnih osnova malignih oboljenja rasvetlilo je značaj fenotipske plastičnosti. U eri epigenetike, učinjeni su mnogi napori da se izmeni aberantna homeostaza u kancerskom oboljenju bez modifikovanja sekvence DNK. Jedna od takvih strategija je modulacija lizinskog acetiloma u humanim kancerima. Da bi se acetil grupa uklonila sa histona, ćelije koriste enzime histon deacetilaze. Poremećena ravnoteža acetilacije i deacetilacije na lizinskim ostacima histona može biti regulisana inhibitorima histon deacetilaza. Kroz ovaj pregledni rad, biće prikazani mehanizmi inhibicije izoformi histon deacetilaza, različiti inhibitori histon deacetilaza, kao i njihove terapijske primene i očekivanja u modernom razvoju lekova

Patterns of herbivore damage, developmental stability, morphological and biochemical traits in female and male Mercurialis perennis in contrasting light habitats

Light environments can influence variation in plant morphology, development and susceptibility to herbivores. Our research interest was to investigate the patterns of herbivore damage and developmental stability in dioecious understory forb Mercurialis perennis in contrasting light habitats, located at 1700 m a.s.l. on Mt. Kopaonik. Male and female plants from two light habitats, open (a sun-exposed field) and shaded (a spruce forest) were examined with respect to: herbivore damage (percentage of leaf area loss), fluctuating asymetry (FA) as a measurement of developmental stability, plant morphological and, specifically, leaf size traits, as well as biochemical traits relating to nutritional quality and defence, taking into account the possible presence of intersexual differences. Our results show that herbivore damage was significantly higher in open habitat, as well as one out of four univariate FA indices and the multivariate index. Morphological and biochemical traits, apart from defensive compounds, had higher values in the shade, pointing to sun-exposed habitat being more stressful for this species. Intersexual differences were observed for foliar damage, defensive compounds (phenolics and tannins), all leaf size traits, total leaf area, and protein content. Contrasting light habitats affected most of the analysed traits. Both foliar damage and FA were higher in a more stressful habitat; within habitats, no positive correlations were found. Herbivore damage was significantly male biased in open habitat. The analysis of intersexual differences in developmental stability measured by leaf asymmetry levels provided no evidence that female plants were more sensitive to environmental stress.This is a post-peer-review, pre-copyedit version of an article published in Alpine Botany. The final authenticated version is available online at: [http://dx.doi.org/10.1007/s00035-018-0203-8

Halkoni potencijalni inhibitori HIV‐1 proteaze

The discovery of HIV and the study of molecular mechanisms crucial for the virus replication cycle have led to the identification of important protein structures - potential targets of drug action in AIDS therapy. One of the most significant discoveries is HIV-1 protease (PR), an enzyme that plays a key role in the HIV replication cycle (1). This study aimed to test and demonstrate the interactions of newly synthesized chalcones (1,3-diaryl-2- propen-1-one) as well as three commercial drugs (lopinavir, ritonavir and darunavir) in the active site of HIV-1 protease using in sillico methods. and that the results obtained correlate with the results of in vitro tests on the enzyme itself. The twenty structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Docking calculations were performed using the Autodock Wine program in the 3D structure of the enzime catalytic site (pdb code: 6B36). The inhibition of enzyme activity was monitored by fluorimetric method (2). The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC 50 values of 0.001 μM which is comparable with commercial product Darunavir. The results obtained indicate that the synthesized compounds can be classified as potential anti-HIV-1 protease inhibitors. Further research is focused on testing the ADMET properties of the synthesized compounds as well as the synthesis of their analogues for which in silico tests have shown satisfactory results.Otkrić e HIV-a i istraživanje molekularnih mehanizama ključnih za ciklus replikacije virusa dovelo je do identifikacije važnih proteinskih struktura - potencijalnih ciljnih mesta dejstva lekova u terapiji AIDS-a. Jedno od najznačajnijih otkrića je HIV-1 proteaza (PR), enzim koji ima ključnu ulogu u ciklusu replikacije HIV-a (1). Ova studija imala je za cilj da primenom in sillico metoda ispita i prikaže interakcije novosintetisanih halkona (1,3-diaril-2- propen-1-ona) kao i tri komercijalna leka (lopinavira, ritonavira i darunavira) u aktivnom mestu HIV-1 proteaze i da dobijene rezultate koreliše sa rezultatima in vitro testova na samom enzimu. Sintetisano je dvadeset strukturno sličnih derivata halkona i izvršena njihova fizičko-hemijska karakterizacija. Docking studije izvedene su u programu Autodock Vine u 3D strukturi enzimskog katalitičkog mesta (pdb kod: 6B36). Inhibicija enzimske aktivnosti određena je primenom fluorimetrijske metode (2). Dobijeni rezultati ukazuju da svih 20 jedinjenja ispoljava anti-HIV-1 proteaznu aktivnost. Jedinjenje HNT1 je pokazalo najveć u inhibitornu aktivnost sa vrednostima IC50 od 0,001 μM što je uporedivo sa komercijalnim proizvodom darunavirom. Dobijeni rezultati ukazuju da se sitetisana jedinjenja mogu klasifikovati kao potencijalni anti-HIV-1 proteazni inhibitori. Dalje istraživanje je usmereno na ispitivanju ADMET osobina sintetisanih jedinjenja kao i sintezi njihovih analoga za koje su in silico ispitivanja pokazala zadovoljavajuće rezultate.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Impaired Bile Acid Metabolism and Gut Dysbiosis in Mice Lacking Lysosomal Acid Lipase

Lysosomal acid lipase (LAL) is the sole enzyme known to be responsible for the hydrolysis of cholesteryl esters and triglycerides at an acidic pH in lysosomes, resulting in the release of unesterified cholesterol and free fatty acids. However, the role of LAL in diet-induced adaptations is largely unexplored. In this study, we demonstrate that feeding a Western-type diet to Lal-deficient (LAL-KO) mice triggers metabolic reprogramming that modulates gut-liver cholesterol homeostasis. Induction of ileal fibroblast growth factor 15 (three-fold), absence of hepatic cholesterol 7α-hydroxylase expression, and activation of the ERK phosphorylation cascade results in altered bile acid composition, substantial changes in the gut microbiome, reduced nutrient absorption by 40%, and two-fold increased fecal lipid excretion in LAL-KO mice. These metabolic adaptations lead to impaired bile acid synthesis, lipoprotein uptake, and cholesterol absorption and ultimately to the resistance of LAL-KO mice to diet-induced obesity. Our results indicate that LAL-derived lipolytic products might be important metabolic effectors in the maintenance of whole-body lipid homeostasis

Lysosomal acid lipase regulates VLDL synthesis and insulin sensitivity in mice

AIMS/HYPOTHESIS: Lysosomal acid lipase (LAL) hydrolyses cholesteryl esters and triacylglycerols (TG) within lysosomes to mobilise NEFA and cholesterol. Since LAL-deficient (Lal (-/-) ) mice suffer from progressive loss of adipose tissue and severe accumulation of lipids in hepatic lysosomes, we hypothesised that LAL deficiency triggers alternative energy pathway(s). METHODS: We studied metabolic adaptations in Lal (-/-) mice. RESULTS: Despite loss of adipose tissue, Lal (-/-) mice show enhanced glucose clearance during insulin and glucose tolerance tests and have increased uptake of [(3)H]2-deoxy-D-glucose into skeletal muscle compared with wild-type mice. In agreement, fasted Lal (-/-) mice exhibit reduced glucose and glycogen levels in skeletal muscle. We observed 84% decreased plasma leptin levels and significantly reduced hepatic ATP, glucose, glycogen and glutamine concentrations in fed Lal (-/-) mice. Markedly reduced hepatic acyl-CoA concentrations decrease the expression of peroxisome proliferator-activated receptor α (PPARα) target genes. However, treatment of Lal (-/-) mice with the PPARα agonist fenofibrate further decreased plasma TG (and hepatic glucose and glycogen) concentrations in Lal (-/-) mice. Depletion of hepatic nuclear factor 4α and forkhead box protein a2 in fasted Lal (-/-) mice might be responsible for reduced expression of microsomal TG transfer protein, defective VLDL synthesis and drastically reduced plasma TG levels. CONCLUSIONS/INTERPRETATION: Our findings indicate that neither activation nor inactivation of PPARα per se but rather the availability of hepatic acyl-CoA concentrations regulates VLDL synthesis and subsequent metabolic adaptations in Lal (-/-) mice. We conclude that decreased plasma VLDL production enhances glucose uptake into skeletal muscle to compensate for the lack of energy supply