Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts

Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1111]This is the peer reviewed version of the paper: Aleksić, I., Ristivojević, P., Pavić, A., Radojević, I., Comić, L. R., Vasiljević, B., Opsenica, D., Milojkovic-Opsenica, D., & Šenerović, L. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. Journal of Ethnopharmacology, 222, 148–158. [https://doi.org/10.1016/j.jep.2018.05.005]Supplementary data: [https://imagine.imgge.bg.ac.rs/handle/123456789/1768

Supplementary data for the article: Aleksić, I., Ristivojević, P., Pavić, A., Radojević, I., Comić, L. R., Vasiljević, B., Opsenica, D., Milojkovic-Opsenica, D., & Šenerović, L. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. Journal of Ethnopharmacology, 222, 148–158. https://doi.org/10.1016/j.jep.2018.05.005

Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1111]Related to accepted version:[https://imagine.imgge.bg.ac.rs/handle/123456789/1762]Supplementary material for: [https://doi.org/10.1016/j.jep.2018.05.005

A comparative antimicrobial and toxicological study of gold(III) and silver(I) complexes with aromatic nitrogen-containing heterocycles: synergistic activity and improved selectivity index of Au(III)/Ag(I) complexes mixture

Five aromatic nitrogen-containing heterocycles, pyridazine (pydz, 1), pyrimidine (pm, 2), pyrazine (pz, 3), quinoxaline (qx, 4) and phenazine (phz, 5) have been used for the synthesis of gold(III) and silver(I) complexes. In contrast to the mononuclear Au1-5 complexes all having square-planar geometry, the corresponding Ag1-5 complexes have been found to be polynuclear and of different geometries. Complexes Au1-5 and Ag1-5, along with K[AuCl4], AgNO3 and N-heterocyclic ligands used for their synthesis, were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. All tested complexes exhibited excellent to good antibacterial activity with minimal inhibitory (MIC) values in the range of 2.5 to 100 mu g mL(-1) against the investigated strains. The complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC = 2.5-30 mu g mL(-1)) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. Moreover, the Au1-4 and Ag1-5 complexes exhibited pronounced ability to competitively intercalate double stranded genomic DNA of P. aeruginosa, which was demonstrated by gel electrophoresis techniques and supported by molecular docking into the DNA major groove. Antiproliferative effect on the normal human lung fibroblast cell line MRC5 has also been evaluated in order to determine therapeutic potential of Au1-5 and Ag1-5 complexes. Since the investigated gold(III) complexes showed much lower negative effects on the viability of the MRC5 cell line than their silver(I) analogues and slightly lower antimicrobial activity against the investigated strains, the combination approach to improve their pharmacological profiles was applied. Synergistic antimicrobial effect and the selectivity index of 10 were achieved for the selected gold(III)/silver(I) complexes mixtures, as well as higher P. aeruginosa PAO1 biofilm disruption activity, and improved toxicity profile towards zebrafish embryos, in comparison to the single complexes. To the best of our knowledge, this is the first report on synergistic activity of gold(III)/silver(I) complexes mixtures and it could have an impact on development of new combination therapy methods for the treatment of multi-resistant bacterial infections.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3334

Supplementary data for the article: Savić, N. D.; Milivojevic, D. R.; Glišić, B. D.; Ilic-Tomic, T.; Veselinovic, J.; Pavic, A.; Vasiljevic, B.; Nikodinovic-Runic, J.; Djuran, M. I. A Comparative Antimicrobial and Toxicological Study of Gold(III) and Silver(i) Complexes with Aromatic Nitrogen-Containing Heterocycles: Synergistic Activity and Improved Selectivity Index of Au(III)/Ag(i) Complexes Mixture. RSC Advances 2016, 6 (16), 13193–13206. https://doi.org/10.1039/c5ra26002g

Supplementary material for: [https://doi.org/10.1039/c5ra26002g]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2041

Supplementary data for the article: Savić, N. D.; Milivojevic, D. R.; Glišić, B. D.; Ilic-Tomic, T.; Veselinovic, J.; Pavic, A.; Vasiljevic, B.; Nikodinovic-Runic, J.; Djuran, M. I. A Comparative Antimicrobial and Toxicological Study of Gold(III) and Silver(i) Complexes with Aromatic Nitrogen-Containing Heterocycles: Synergistic Activity and Improved Selectivity Index of Au(III)/Ag(i) Complexes Mixture. RSC Advances 2016, 6 (16), 13193–13206. https://doi.org/10.1039/c5ra26002g

Supplementary material for: [https://doi.org/10.1039/c5ra26002g]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2041

Uloga testova otpuštanja interferona gama u nadzoru nad tuberkulozom

Tuberculosis is still one of the major global public health threats. Countries with low incidence must focus on exhausting the reservoir of future cases by preventing reactivation. Therefore, it is important to identify and effectively treat those individuals who have latent tuberculosis infection and who may develop active disease. The tuberculin skin test has been the standard for detection of immune response against M. tuberculosis since the beginning of the 20th century. The new millennium has brought advancement in the diagnosis of latent tuberculosis infection. The name of the new blood test is interferon-gamma release assay (IGRA). Croatia is a middle-incidence country with a long decreasing trend and developed tuberculosis control. To reach low incidence and finally eliminate tuberculosis, its tuberculosis programme needs a more aggressive approach that would include intensive contact investigation and treatment of persons with latent tuberculosis infection. This article discusses the current uses of IGRA and its role in tuberculosis control.Tuberkuloza je i danas jedan od vodećih javnozdravstvenih problema. Zemlje s niskom incidencijom fokusiraju se na iscrpljivanje rezervoara budućih slučajeva sprječavanjem reaktivacije bolesti. To se odnosi na traženje i učinkovito liječenje infi ciranih osoba, primarno onih koje su u riziku od obolijevanja nakon infekcije. Tuberkulinski test je od početka 20. stoljeća bio standard u otkrivanju imunosnog odgovora na kontakt s Mycobacterium tuberculosis. Novo tisućljeće donijelo je određeni napredak u obliku novih testova za dijagnozu latentne tuberkulozne infekcije, krvne testove otpuštanja interferona gama. Hrvatska je zemlja srednje incidencije tuberkuloze s dugogodišnjim silaznim trendom i razvijenim protutuberkuloznim aktivnostima. U težnji prema niskoj incidenciji i u konačnici eliminaciji tuberkuloze potrebne su opsežnije aktivnosti unutar državnog programa nadzora nad tuberkulozom, uključujući intenzivnu obradu kontakata i probir na postojanje latentne tuberkulozne infekcije. Ovaj rad razmatra trenutačnu uporabu IGRE (engl. interferon - gamma release assay) i njezinu ulogu u nadzoru nad tuberkulozom

Forest fire analysis and classification based on a Serbian case study

A recent forest fire in the Republic of Serbia is discussed concerning classification, legislative framework and fire management, giving a detailed analysis of the forest fire occurrence. Analysing past and predicting future fires are crucial for policy development and forest management practices to prevent and mitigate fires. Fire hazard is discussed through several fire protection and prevention legislative documents. The nonparametric Mann-Kendall test was used to analyse resent forest fire data in an attempt to find causality in occurrences and frequency. The meteorological data and fire statistics provided by the Serbian Hydro-meteorological Service and the Ministry of Interior/Sector for Emergency Management of the Republic of Serbia were used to calculate the Forest Fire Weather Indices, along with deficit or surplus of precipitation for the case study of Tara Mountain. The paper highlights the need for better hierarchical classification of fire hazards and its harmonisation along with standardisations presented by leading international research institutions. A significant correlation between meteorological parameters and forest fire occurrence was found. This opens a possibility for further investigation and analysis of geophysical and anthropogenic driven factors that can influence disaster occurrence

Supplementary data for article: Selaković, Ž.; Tran, J. P.; Kota, K. P.; Lazić, M.; Retterer, C.; Besh, R.; Panchal, R. G.; Soloveva, V.; Sean, V. A.; Jay, W. B.; et al. Second Generation of Diazachrysenes: Protection of Ebola Virus Infected Mice and Mechanism of Action. European Journal of Medicinal Chemistry 2019, 162, 32–50. https://doi.org/10.1016/j.ejmech.2018.10.061

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S0223523418309383?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/360]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2966

Plasma fucosylated glycans and C-reactive protein as biomarkers of HNF1A-MODY in young adult–onset nonautoimmune diabetes

OBJECTIVE Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the commonest type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and hs-CRP are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes. RESEARCH DESIGN AND METHODS We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed. RESULTS We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L). CONCLUSIONS Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele

Recommendations for the diagnosis of pediatric tuberculosis

Tuberculosis (TB) is still the world's second most frequent cause of death due to infectious diseases after HIV infection, and this has aroused greater interest in identifying and managing exposed subjects, whether they are simply infected or have developed one of the clinical variants of the disease. Unfortunately, not even the latest laboratory techniques are always successful in identifying affected children because they are more likely to have negative cultures and tuberculin skin test results, equivocal chest X-ray findings, and atypical clinical manifestations than adults. Furthermore, they are at greater risk of progressing from infection to active disease, particularly if they are very young. Consequently, pediatricians have to use different diagnostic strategies that specifically address the needs of children. This document describes the recommendations of a group of scientific societies concerning the signs and symptoms suggesting pediatric TB, and the diagnostic approach towards children with suspected disease