MicroRNAs (miRNAs) represent endogenous small RNAs that post-transcriptionally regulate gene expression and, thus they are involved in the onset and progression of various diseases and conditions (Bader et al., 2010) such as for overweight and obesity. Antiadipogenic miRNA-27a is a negative regulator in fat metabolism, which inhibits adipocyte differentiation through downregulation of adipogenic marker genes (e.g. PPARγ) (Kim et al., 2010). Reduced miRNA-27a levels are often associated with the development of obesity and, therefore, this miRNA might represent a promising candidate for miRNA mimic replacement therapy (Lin et al., 2009). However, the application of naked RNAs has shown low membrane permeability, cellular uptake, and rapid degradation in the circulation. The present study aimed to develop a cationic, lipid-based nanoparticle system for targeting adipose tissue and delivering miRNA-27a. These systems are composed of positively charged nanostructured lipid carriers (cNLCs) and negatively charged miRNAs, which results in complex formation based on electrostatic interactions between these components. Materials and methods

Omeprazole is a proton pump inhibitor commonly used in pediatric patients (Wensel, 2009). Pediatric patients are usually unable to swallow solid dosage forms and they need dose adjustment. Therefore, the dosage form of choice for this population is compounded liquid preparation. Since pharmacies don't usually dispose of pure active substances, compounded liquid preparations are most commonly prepared from commercially available solid dosage forms, in a way that tablets are simply pulverized or capsule contents emptied, adding water or one of the commercially available vehicles (Haywood and Glass, 2013). Considering the risks associated with the preparation and use of compounded preparations, the Chapter <795> of the US Pharmacopoeia states that the beyond-use date is 14 days for non-preserved aqueous oral formulations, if stored in the refrigerator. Preserved aqueous preparations can be stored for 35 days at controlled room temperature or in the refrigerator (USP, 2015).

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).

Lead ions removal from aqueous solutions onto bean shells is presented in this paper. The experiments were conducted in a batch system. The bean shells samples were rinsed with distilled water before the adsorption experiments. The analysis of the rinsed water showed that a significant amount of alkali and alkaline-earth metal ions are transferred from the adsorbent structure into the rinsed solution during the rinsing process. The COD analysis showed that these waters should be treated before being discharged into the surrounding watercourses. The influence of different process parameters (the pH value of the solution, the initial metal ions concentration, and the initial mass of the adsorbent) on the adsorption capacity was investigated. The adsorption capacity was higher at higher pH values of the solution. The adsorption capacity showed a decrease with the increase in the mass of the adsorbent. The increase in the initial metal ions concentration was shown to lead to an increase in the adsorption capacity until 0.8 g dm-3, after which a slight decrease was noted. Characterization of the adsorbent was performed by SEM-EDX, DTA-TGA, and FTIR analysis. The SEM-EDX analysis indicates a change in the morphology of the sample after the adsorption, as well as that K and Mg are possibly exchanged with lead ions during the adsorption process. The results obtained by the DTA-TGA analysis showed a weight loss of 77.8 % in the temperature range from 20oC to 900oC. The FTIR analysis indicated that the amide group is involved in the adsorption process. The pseudo-second order kinetic model was shown to be the best fit for the analyzed data, which led to the conclusion that chemisorption was a possible way of binding lead ions onto the surface of the bean shells. The Hill isotherm model was the best model for the analyzed adsorption equilibrium data. Obtained thermodynamic data indicated that the adsorption process was spontaneous, endothermic, and disordered, in which lead ions are bound to the surface of the bean shells by chemisorption. The maximum achieved adsorption capacity was 46.36 mg g-1.

Aflatoksin M1 ve M2, aflatoksin B1 ve B2'nin hidroksile metabolitleri olup, sut ve sut urunlerinde bulunabilir. Bu calismanin amaci, Bosna-Hersek'in farkli bolgelerinden farkli donemlere ait test sonuclarini kullanarak cig sutteki bu toksine maruz kalma ve saglik riski degerlendirmesi yapmaktir. AFM1 alim degerlendirmesi icin, Bosna-Hersek'te Tarim ve Kirsal Kalkinmaya Yonelik Katilim Oncesi Yardim Sektor Analizleri raporundaki veriler kullanilmistir. Aflatoksin M1'in cig sutteki konsantrasyonu icin, Saraybosna Eczacilik Universitesi Toksikolojik Kimya Fakultesi Laboratuvari'ndan alinan onceki calismalarin verileri ile yayinlanmamis veriler kullanilmistir. Dort maruziyet senaryosu icin yillik hepatoseluler karsinom riski (HCC) insidansi hesaplanarak risk karakterizasyonu yapilmistir. Sonuclar, ortalama tahmini gunluk aflatoksin M1 aliminin gunde 0.049 ng/kg vucut agirligi oldugunu gostermistir. Hepatoseluler karsinom riski (vaka/yil/100.000 kisi), HBsAg prevalansina bagli olarak nispeten dusuk bulunmustur (ortalama 0.000064-0.000074 vaka/yil/100.000). Son yillarda, aflatoksin M1'in kanserojen riskinin dusuk oldugu ve Bosna Hersek'te kritik olmadigi sonucuna varilmistir.

Plant peptide protease inhibitors are important molecules in seed storage metabolism and to fight insect pests. Commonly they contain multiple disulfide bonds and are exceptionally stable molecules. In this study, a novel peptide protease inhibitor from beetroot (Beta vulgaris) termed bevuTI-I was isolated, and its primary structure was determined via mass spectrometry-based amino acid sequencing. By sequence homology analysis a few peptides with high similarity to bevuTI-I, also known as the Mirabilis jalapa trypsin inhibitor subfamily of knottin-type protease inhibitors, were discovered. Hence, we assessed bevuTI-I for inhibitory activity toward trypsin (IC50 = 471 nM) and human prolyl oligopeptidase (IC50 = 11 μM), which is an emerging drug target for neurodegenerative and inflammatory disorders. Interestingly, using a customized bioinformatics approach, bevuTI-I was found to be the missing link to annotate 243 novel sequences of M. jalapa trypsin inhibitor-like peptides. According to their phylogenetic distribution they appear to be common in several plant families. Therefore, the presented approach and our results may help to discover and classify other plant-derived cystine knot peptides, a class of plant molecules that play important functions in plant physiology and are currently being explored as lead molecules and scaffolds in drug development.

Cancer and heart diseases are the leading causes of morbidity and mortality in many countries worldwide. Using chemotherapy and targeted therapies has led to an improvement in cancer survival rates and, unfortunately, higher cardiac adverse side effects – cardiotoxicity (Leong et al., 2019). Antineoplastic medicines have improved overall survival and progression-free survival to the oncological patients (Jemal et al., 2011; Varricchi et al., 2019). Mentioned medicines can be associated with several side effects, including cardiovascular toxicity. The National Cancer Institute defines cardiotoxicity in very general terms as “toxicity that affects the heart” (www.cancer.gov/dictionary/). Cardiotoxicity can develop in a subacute, acute, or chronic manner (Albini et al., 2018). Mitochondria are central targets for antineoplastic medicineinduced cardiovascular toxicity (Varricchi et al., 2019). Antineoplastic-related cardiovascular toxicities have been presented in many countries especially North American and European (Leong et al., 2019). Reported results from western countries are showed that the incidence rate of cancer treatment-induced cardiotoxicity is related with several chemotherapy and targeted therapies: anthracycline (0.9%–57%), cyclophosphamide (2%–28%), trastuzumab (0%– 28%) and bevacizumab (1.7%–10.9%) (Leong et al., 2019). The Agency for medicines and medical devices of Bosnia and Herzegovina (ALMBIH) was established by the Law on Drugs and Medical Devices ("Official Gazette of B&H, No. 58/08") as an authorized body for medicines and medical devices produced and used in B&H. In 2019. ALMBIH has become full member of Uppsala Monitoring Centre – World Health Organization. The aim of this work was to investigate the cardiovascular toxicity of antineoplastic medicines in Bosnia and Herzegovina.