Analysis of cancer incidence and mortality in Bosnia and Herzegovina and comparison with Slovenia, Croatia and Serbia

Electricity demand forecasting is one of the most important components in the power system analysis. Furthermore, it is difficult and complicated process to forecast energy consumption. This study deals with modeling of the electrical energy consumption in Bosnia and Herzegovina in order to forecast future consumption of electrical loads based on temperature variables using machine learning methods. We used three different  machine learning methods for analyzing short term forecasting. The methods were trained using historical load data, collected from JP Elektroprivreda electrical power utility in BiH, and also considering weather data which is known to have a big impact on the use of electric power. Comparing the results it was seen that prediction for 500 hours is pretty good in range from 92,92% for reactive power till 98.84% for active power. Four different parameters were analyzed mean absolute error, root mean squared error, relative absolute error and root relative square error. The best results for apparent power were gotten with linear regression and are presented as for mean absolute error 9.84, root mean squared error 13.62, relative absolute error 14.06%, root relative squared error 14.39%. It is also seen from the results that,  the short term power consumption can be predicted which is important for maintaining of the voltage at the consumer side

Adverse drug reaction reporting and development of pharmacovigilance systems in Bosnia and Herzegovina, Croatia, Serbia, and Montenegro: a retrospective pharmacoepidemiological study

Aim To compare individual case safety reports (ICSR) rates and characteristics between Croatia, Serbia, Montenegro, and Bosnia and Herzegovina (B&H). Methods This retrospective pharmacoepidemiological study used the data from ICSR received by the Agency for Medicines and Medical Devices in B&H in 2011-2016. The number, characteristics, and sources of reports, suspected drugs, and patient characteristics were analyzed. The results were compared with the publicly available data from Croatia, Serbia, and Montenegro. Results The number of reported adverse drug reactions per one million of inhabitants was lowest in B&H and highest in Croatia. There were significant differences in reporter characteristics, sources of reports, and the percentage of missing data in ICSR, while the Anatomical Therapeutic Chemical product classes, patient’s sex, and adverse drug reaction System Organ Classes were similar. Conclusion Despite the historical and geographical vicinity of B&H and its neighboring countries, there were significant differences in indicators of pharmacovigilance development

Helminth-derived product(s): Source for potential therapeutic

Helminth parasites that inhabit mammalian body surfaces have a highly evolved relationship with the immune system. Many of these resident helminths carry out functions to ensure their survival in the hosts. To attain this objective helminth parasites adopt immunoregulatory mechanisms to counter host’s hostile immune response. Indeed, immunomodulatory molecules have been discovered in the worm’s extracts and in their excretion/secretion. In this review, we discuss the state of our understanding of the interplay between helminths and immune pathways. We also highlight the key challenges that must be confronted in identification of the helminth-derived molecules involved in immune modulation.  We consider whether helminth-derived signaling hold promise for the design of novel therapeutic approaches for the treatment of inflammatory disorders (inflammatory bowel disease, allergies, and autoimmune diseases)

Analysis of Antitumor Potential of Xanthene Compounds in Lymphoma Cells

Antitumor activity of two newly and sixteen previously synthesized 9-arylsubstituted 2,6,7-trihydroxyxanthene-3-ones on diffuse large B-cell lymphoma cells were analyzed in this study. Xanthene derivatives are characterized with numerous therapeutic applications, including anticancer, antioxidant, anti-inflammatory and other activities. In silico molecular docking analysis suggests significant binding affinities of certain compounds toward Akt and NF-κB proteins as two major players of cell proliferation and differentiation. Results of WST-8 assay indicate mild or no activity of xanthene compounds on cell viability of HBL-1 and DHL-4 cell lines belonging to ABC and GCB DLBCL subtypes, respectively. Western blotting showed stimulatory activity of certain compounds, with increased expression of Akt in HBL-1 and DHL-4 cells. Our results provide an insight into activation of compensatory Akt mechanism in DLBCL models that could be an important step for further approaches in application of dual inhibitors for cancer treatment to achieve greater therapeutic effectiveness and drug resistance escape

Synthesis, biological evaluation and docking studies of benzoxazoles derived from thymoquinone

Thymoquinone (TQ), a natural compound with antimicrobial and antitumor activity, was used as the starting molecule for the preparation of 3-aminothymoquinone (ATQ) from which ten novel benzoxazole derivatives were prepared and characterized by elemental analysis, IR spectroscopy, mass spectrometry and NMR (1H,13C) spectroscopy in solution. The crystal structure of 4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazole-5-ol (1a) has been determined by X-ray diffraction. All compounds were tested for their antibacterial, antifungal and antitumor activities. TQ and ATQ showed better antibacterial activity against tested Gram-positive and Gram-negative bacterial strains than benzoxazoles. ATQ had the most potent antifungal effect against Candida albicans, Saccharomyces cerevisiae and Aspergillus brasiliensis. Three benzoxazole derivatives and ATQ showed the highest antitumor activities. The most potent was 2-(4-fluorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1f). Western blot analyses have shown that this compound inhibited phosphorylation of protein kinase B (Akt) and Insulin-like Growth Factor-1 Receptor (IGF1R β) in HeLa and HepG2 cells. The least toxic compound against normal fibroblast cells, which maintains similar antitumor activities as TQ, was 2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1e). Docking studies indicated that 1e and 1f have significant effects against selected receptors playing important roles in tumour survival.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3004

Supplementary material for the article: Glamočlija, U.; Padhye, S.; Špirtović-Halilović, S.; Osmanović, A.; Veljović, E.; Roca, S.; Novaković, I.; Mandić, B.; Turel, I.; Kljun, J.; et al. Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone. Molecules 2018, 23 (12). https://doi.org/10.3390/molecules23123297

Supplementary material for: [https://www.mdpi.com/1420-3049/23/12/3297]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2807

Genetički polimorfizmi u dijabetesu: Utjecaj na terapiju oralnim antidijabeticima

Due to new genetic insights, etiologic classification of diabetes is under constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2 diabetes. Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies. Individually, each of these polymorphisms is only moderately predisposed to type 2 diabetes. On the other hand, monogenic forms of diabetes such as MODY and neonatal diabetes are characterized by unique clinical features and the possibility of applying a tailored treatment. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of a number of medications. Mutations in genes important in drug absorption, distribution, metabolism and excretion (ADME) play a critical role in pharmacogenetics of diabetes. There are currently five major classes of oral pharmacological agents available to treat type 2 diabetes: sulfonylureas, meglitinides, metformin (a biguanide), thiazolidinediones, and α-glucosidase inhibitors. Other classes are also mentioned in literature. In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1, HNF1ß and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed.Dijabetes tipa 2 dosegao je proporcije epidemije u SAD (> 18 milijuna) i cijelom svijetu (170 milijuna oboljelih osoba) te ima tendenciju daljnjeg dramatičnog rasta. Stoga se u posljednje vrijeme ulažu napori da se otkriju i razviju novi farmakološki agensi za liječenje ove bolesti. Klasifikacija šećerne bolesti proširena je uspjesima istraživača na području genetike. Da bismo razumjeli farmakogenetiku antidijabetika neophodno je razumjeti genetiku samog dijabetesa. Kao što će biti prikazano u ovom radu veliki broj gena koji su povezani s razvojem dijabetesa takođe utječu i na odgovor na terapiju antidijabeticima. S druge strane, mutacije gena koji utječu na ADME (apsorpcija, distribucija, metabolizam i ekskrecija) lijeka imaju značajan utjecaj na farmakogenetiku oralnih antidijabetika. Utvrđeno je da je dijabetes genetički heterogena bolest. Uobičajeni oblici dijabetesa su gotovo uvijek poligenski i za razvoj same bolesti vrlo su značajne snažne interakcije među različitim genima kao i između gena i okoliša. Zbog toga mutacije ili polimorfizmi koji u manjoj mjeri utječu na funkciju gena mogu postati klinički značajni samo u slučaju kada se kombiniraju s drugim faktorima odnosno genima. Smatra se da u razvoju dijabetesa mogu sudjelovati stotine pa čak i tisuće gena. Do 2006. identificirano je nekoliko uobičajenih alela koji povećavaju rizik za razvoj dijabetesa, od kojih su najznačajniji PPARG (Pro12), KCNJ11 (Lys23) i TCF7L2 (T na rs7903146). Do danas je najveći uspjeh postignut u identifikaciji gena odgovornih za razmjerno rijetke oblike ove bolesti poput ”Maturity-onset diabetes of the young” (MODY) i neonatalnog dijabetesa. Monogenske oblike dijabetesa odlikuju jedinstvene kliničke karakteristike i mogućnost primjene individualnog tretmana. Genetički polimorfizmi enzima koji utječu na metabolizam lijekova, transportera, receptora i drugih ciljeva djelovanja lijekova povezani su s interindividualnim razlikama u efikasnosti i toksičnosti mnogih lijekova. Vrlo je važno da se na temelju farmakogenetičkih istraživanja mogu predvidjeti neki neželjeni efekti lijekova. Trenutačno postoji pet glavnih klasa oralnih antidijabetika: sulfoniluree, meglitinidi, metformin (bigvanid), tiazolidindioni i inhibitori α-glukozidaze. U literaturi se također spominju inhibitori dipeptidil peptidaze IV (DPP-IV), selektivni antagonisti kanabinoidnog receptora 1 (CB-1), glukagonu slični peptid 1 mimetici i amilin mimetici. Razumijevanje mehanizama koji rezultiraju disfunkcijom β stanica na fiziološkom i molekularnom nivou neophodno je za napredak u razumijevanju tretmana dijabetesa. U ovom radu dat je pregled različitih genetičkih mutacija (mutacije gena za glukokinazu, HNF 1, HNF1ß, Kir6.2 i SUR 1 podjedinicu KATP kanala ß stanica, PPAR-γ, OCT1 i OCT2, citohrome, KCNJ11, faktore koji utječu na razvoj bolesti (TCF7L2) i varijante gena koji dovode do hepatosteatoze uzrokovane tiazolidindionima) te njihov utjecaj na odgovor na terapiju oralnim antidijabeticima

In vitro propagation of Lilium martagon L. var. cattaniae Vis. and evaluation of genotoxic potential of its leaves and bulbs extracts

Lilium martagon L. var. cattaniae Vis. (Liliaceae) is endemic plant of Dinaridi mountain. In this work we established protocol for fast in vitro propagation and multiplication of Lilium martagon var. cattaniae. The aim was to enable fast production of plant material as potential source of pharmaceutically valuable secondary metabolites. Seeds of L.martagon var. cattaniae were germinated on a Murashige and Skoog basal medium with a supplement of 0.15 mg/l gibberellic acid (GA3), and multiplication was performed on MS medium supplemented with 0.1 mg/l gibberellic acid (GA3), 0.2 mg/l indole-3-butyric acid (IBA) and 0.5 mg/l 6-ben- zylaminopurine (BAP). We used ultrasound assisted extraction to prepare extracts of leaves and bulbs of Lilium martagon var. cattaniae, which were evaluated for their genotoxic potential using Allium test and cytokinesis-block micronucleus test in human lymphocytes culture. There was statistically significant difference between all used concentrations of lilium extracts and control on proliferation of cells of root tip of onion (Allium cepa). In cytokinesis-block micronucleus test no statistically significant difference between frequencies of analyzed parameters in samples treated with tested concentrations of extracts and control was obtained