Antibacterial and cytotoxic activities of naphthoquinone pigments from Onosma visianii Clem

In this study, the antibacterial and cytotoxic activities of isolated compounds from the roots of Onosma visianii were investigated. By using different chromatographic techniques and appropriate spectroscopic methods, the seven naphthoquinones were described: deoxyshikonin (1), isobutyrylshikonin (2), α-methylbutyrylshikonin (3), acetylshikonin (4), ß-hydroxyisovalerylshikonin (5), 5,8-O-dimethyl isobutyrylshikonin (6) and 5,8-O-dimethyl deoxyshikonin (7). Among the tested compounds, 3 and 4 exhibited the highest antibacterial activities toward all tested bacterial species (MIC50 and MIC90 for gram positive bacteria: 6.40 µg/mL-12.79 µg/mL and 6.82 µg/mL-13.60 µg/mL, respectively; for gram negative bacteria: 4.27 µg/mL-8.53 µg/mL and 4.77 µg/mL-9.54 µg/mL, respectively). Also, naphthoquinones 3 and 4 exhibited strong cytotoxic activity against MDA-MB-231 cells (IC50 values 86.0 µg/mL and 80.2 µg/mL, respectively), while compounds 1, 3, 4 and 5 significantly decreased viability of HCT116 cells (IC50 values of 97.8 µg/mL, 15.2 µg/mL, 24.6 µg/mL and 30.9 µg/mL, respectively). Our results indicated that all tested naphthoquinone pigments are potential candidates for clinical uses as antibacterial and cytotoxic agents

Melatonin Alters Age-Related Changes in Transcription Factors and Kinase Activation

Male mice were fed 40 ppm melatonin for 2 months prior to sacrifice at age 26 months, and compared with both 26 and 4 month-old untreated controls. The nuclear translocation of NF-κB increased with age in both brain and spleen and this was reversed by melatonin only in brain. Another transcription factor, AP-1 was increased with age in the spleen and not in brain and this could be blocked by melatonin treatment. The fraction of the active relative to the inactive form of several enabling kinases was compared. The proportion of activated ERK was elevated with age in brain and spleen but this change was unresponsive to melatonin. A similar age-related increase in glial fibrillary acidic protein (GFAP) was also refractory to melatonin treatment. The cerebral melatonin M1 receptor decreased with age in brain but increased in spleen. The potentially beneficial nature of melatonin for the preservation of brain function with aging was suggested by the finding that an age-related decline in cortical synaptophysin levels was prevented by dietary melatonin

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Supplementary data for the article: Stojković, D. L. J.; Bacchi, A.; Capucci, D.; Milenković, M. R.; Čobeljić, B.; Trifunović, S. R.; Andelković, K.; Jevtić, V. V.; Vuković, N.; Vukić, M.; et al. Synthesis and Characterization of Palladium(II) Complexes with Glycine Coumarin Derivatives. Journal of the Serbian Chemical Society 2016, 81 (12), 1383–1392. https://doi.org/10.2298/JSC160915087S

Supplementary material for: [https://doi.org/10.2298/JSC160915087S]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2392

Experimental and Analytical Research of the Heat Transfer Process in the Package of Perforated Plates

The need for compact heat exchangers has led to the development of many types of surfaces that enhance the rate of heat transfer, among them the perforated plate heat exchangers, also known as matrix heat exchangers. The perforated plate heat exchangers consist of a series of perforated plates that are separated by a series of spacers. The present study investigates the heat transfer characteristics of the package of perforated plates. Perforated plates were 2 mm thick, with holes with 2 mm in diameter and porosity of 25.6%. The package of one, two, and three perforated plates was set in the channel of the experimental chamber at which entrance was a thrust fan with the ability to control the flow rate. The fluid flow rates, the temperatures of the fluids at the inlet and outlet of the chamber and the temperature of the air between the plates, were measured at the pre-defined locations in the package and the experimental chamber. Based on the measurements, heat transfer coefficients for the individual plates, as well as for the packages of perforated plates were determined. In further research, an iterative analytical procedure for investigation of the heat transfer process and the overall heat transfer coefficient for the package of perforated plates were developed. Based on these analytical and experimental results, conclusions were drawn about the heat transfer in a package of perforated plates.17th Symposium of the Society-of-Thermal-Engineers-of-Serbia (SIMTERM), Oct 20-23, 2015, Sokobanja, Serbi

Synthesis and characterization of palladium(II) complexes with glycine coumarin derivatives

A Pd(II) complex with methyl 2-([1-{2,4-dioxochroman-3-ylidene}ethyl]amino)acetate was synthesized. The structures of both the ligand and its Pd(II) complex were determined by elemental analysis, and IR and NMR spectroscopy. Recrystallization of the Pd(II) complex from DMF/water solution resulted in its hydrolysis and the formation of the dimethylamine (2-[{1-(2,4-dioxochroman-3-ylidene) ethyl} amino] acetato) palladium(II) complex, the structure of which was determined by elemental analysis, IR, H-1- and C-13-NMR spectroscopy and X-ray analysis.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3626

Supplementary data for the article: Stojković, D. L. J.; Bacchi, A.; Capucci, D.; Milenković, M. R.; Čobeljić, B.; Trifunović, S. R.; Andelković, K.; Jevtić, V. V.; Vuković, N.; Vukić, M.; et al. Synthesis and Characterization of Palladium(II) Complexes with Glycine Coumarin Derivatives. Journal of the Serbian Chemical Society 2016, 81 (12), 1383–1392. https://doi.org/10.2298/JSC160915087S

Supplementary material for: [https://doi.org/10.2298/JSC160915087S]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2392

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination

The Rippling Effect of Non-linearities

Non-linearities can lead to unexpected dynamic behaviours in supply chain systems that could then either trigger disruptions or make the response and recovery process more difficult. In this chapter, we take a control-theoretic perspective to discuss the impact of non-linearities on the ripple effect. This chapter is particularly relevant for researchers wanting to learn more about the different types of non-linearities that can be found in supply chain systems, the existing analytical methods to deal with each type of non-linearity and future scope for research based on the current knowledge in this field

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondria! numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1(-/-) animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of I immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.Molecular Technology and Informatics for Personalised Medicine and Healt