Nicotinamide adenine dinucleotide biosynthesis and consumption in dysfunctional white adipocytes

In addition to its role in storage of dietary energy in a highly concentrated form, the white adipose tissue (WAT) is an active endocrine organ that regulates various physiological processes in the body. It plays a central role in insulin responsiveness and energy homeostasis, which is mediated by the action of a wide range of biologically active molecules - adipokines. During its “remodeling”, the obese WAT becomes inflamed and dysfunctional, which causes insulin resistance. Dysfunctional WAT in obesity exhibits increased production of reactive oxygen species (ROS) and decreased activity of some of the key antioxidant enzymes, which leads to oxidative stress. Indeed, protein carbonyls in the visceral adipose tissue are considered as a reliable biomarker of the level of oxidative stress in this tissue. Their negative correlation with serum adiponectin is indicative of systemic effects of oxidative stress in the visceral WAT. Glutathione S-transferase isoform A4 (GSTA4) has an important role in protection of the white adipocytes from oxidative stress and protein carbonylation. However, GstA4 is downregulated in adipocytes treated with tumor necrosis factor α (TNFα), as well as in adipose tissue from obese mice, suggesting the link between oxidative stress, inflammation and insulin resistance. GstA4 silenced 3T3L1s are a good experimental model to study the consequences of oxidative stress in dysfunctional adipocytes in obesity induced insulin resistance. Among other findings, it has been shown that the expression of Sirtuin 3 (Sirt3) is decreased in GstA4 silenced 3T3-L1 adipocytes (Bernlohr lab., unpublished results). Sirtuins are enzymes that deacetylate lysine residues on both histone and nonhistone proteins. Mammals have seven sirtuins with different subcellular localization. SIRT3 is located in mitochondria. There is evidence that SIRT3 can delay the onset of a number of oxidative stress- and age-related pathologies. Sirtuin activity is nicotinamide adenine dinucleotide (NAD+) dependent and is directly linked to the energetic and redox status of the cell. We explored the expression of some of the key genes involved in NAD+ biosynthesis and consumption in a model of inflamed white adipocytes. Our experiments demonstrated a significant disturbance of NAD+ metabolism, and decreased Sirt3 expression. These findings indicate that Sirt3 and NAD+ pathway can be considered as potential therapeutic targets in obesity induced insulin resistance

Molecular bioinformatic analyses for systematic reviews

This Summer school is organized by INRAE within the framework of European Twinning Project PhenolAcTwin coordinated by the Tubitak Institute (Turkey) and in which INRAE is partner. PhenolAcTwin aims to Enhance Research and Innovation Capacity of TUBITAK MRC Food Institute in the field of Dietary Polyphenols and Bioavailability / Bioefficacy (https://phenolactwin.eu/en/#). The Human Nutrition Unit of INRAE (Clermont-Ferrand, France) has built this training school with the aim to enhance the research capacity of young scientists interested in research on Polyphenols & Health and to help bridging opportunities for further collaborations between delegates. In this training, a diversity of innovative approaches to develop research on polyphenols and health will be addressed by international experts, including meta-analysis, microbiome analysis, nutrigenomics and in silico docking. This training aims to maintain tight connections between trainees and trainers in order to provide an appropriate support to young scientists in their future research and favor the development of collaborative projects. This training is dedicated to Master Students, PhD students and Early Career Scientists, from European Universities and Institutes with a priority given to partners of the PhenolAcTwin Consortium

1. Fulbright International Education Exchange – Fostering Science and Mutual Understanding between Nations and Cultures. 2. NAD – a Rediscovered ‘Old’ Molecule.

Fulbright Scholar at UND Katie Haines, Staff writer • February 5, 2015 UND Biology department introduced seminar speaker Tatjana Ruskovska, Fulbright Scholar and Associate Professor of Clinical Chemistry and Biochemistry at Goce Delcev University in Macedonia on Friday, where students received an opportunity to meet with and hear her speak about what it’s like to “do” science in the Republic of Macedonia

Molecular aspects of nutrition - scientific achievements and perspectives

This is the keynote lecture at the seminar "Molecular aspects of nutrition" and also an introduction to the small grant titled "Scientific club in molecular nutrition," which is being implemented within the project of the Macedonian American Alumni Association (MAAA), titled "Alumni encouraging community services and extracurricular activities" and supported by the American Embassy in Skopje. From MDA as one of the products of lipid peroxidation and the atherogenic potential of oxidized LDL particles, through oxidative stress and dysfunction of obese adipose tissue, to the vasculoprotective role of plant food bioactives and the application of multi-omics technologies in nutrition science, this lecture provides an excellent foundation for the seminar itself and for future activities within this small grant

Bioinformatic analysis of nutrigenomics data of plant food bioactives extracted from in-vitro and in-vivo studies

It was my great pleasure and honor to be invited at INRA, Centre de Clermont Ferrand/Theix, Unite de Nutrition Humaine, to conduct the STSM “Bioinformatic analysis of nutrigenomics data of plant food bioactives extracted from in-vitro and in-vivo studies”. This STSM was related to the upcoming activities of the WG2 of the COST Action POSITIVe, more specifically to the subgroup Cell and Molecular Targets. During my stay at INRA, I conducted a pilot bioinformatics analysis of nutrigenomic data of plant food bioactives. For in-vitro studies, extracted data were grouped according to the cell type and bioactives used for treatment. Some of the gene symbols were transformed to official gene symbols using the database GeneCards. Differentially expressed genes were analyzed using the software GeneTrail2. Pathways which were significantly associated with these genes (p<0.05) were identified in BioCarta and KEGG databases. Common genes and pathways for different cell types were identified with the software Venny 2.1.0. During this STSM I tested various approaches for data analysis. In consultation with my host, Dr. Dragan Milenkovic, we were able to identify the workflow and critical points to be addressed in the upcoming analysis of extracted data from in-vitro and in-vivo studies

The Effect of Smoking on Biomarkers of (Anti) oxidant Status

The influence of smoking on the levels of several biomarkers of oxidative stress, antioxidant status and redox status have been investigated in 48 healthy men with a mean age of 25 y. The biomarkers of oxidative stress are the reactive oxygen metabolytes (ROM) and the total oxidant status (TOS). The biomarkers for the antioxidant activity are the biological antioxidant potential (BAP), the ferric reducing ability of plasma (FRAP), the total antioxidant status (TAS), the assay for the defense against the oxidation by hypochlorous acid (OXY) and uric acid (UA). The total thiol levels (TTL) have been measured as a biomarker for the redox status. The average concentration of ROM was 14% higher in smokers compared with non-smokers (p<0.05), whereas TOS was 4.9% higher (not statistically significant).The average concentrations of BAP, FRAP and TAS decreased with smoking with 3.6 (p<0.025), 3.6 (non-significant) and 6.1% (p<0.025), respectively. Alsouric acid, the main antioxidant in serum and a major contributor to the antioxidant status in serum, decreased by 10.6 % (p<0.025) in smokers. The biomarker of the redox status (TTL) was not influenced by smoking. From these results, it is concluded that in epidemiological studies the effect of smoking should be taken in account when using oxidative stress and antioxidant biomarkers

Molecular bioinformatic analyses for systematic reviews on polyphenols and cardiometabolic health

On November 28th and 29th, 2023, Prof. Dr. Tatjana Ruskovska, full professor at the Faculty of Medical Sciences, Goce Delcev University in Stip, organized a workshop entitled "The use of molecular and bioinformatic analyses in studying the health-promoting effects of polyphenols”. The workshop was part of the project activities led by Prof. Dr. Tatjana Ruskovska, member of the Macedonian American Alumni Association (MAAA), within the larger project entitled "Alumni encouraging community services and extracurricular activities", supported by the U.S. Embassy in Skopje. The workshop was organized in the form of a Scientific Club for Molecular Nutrition for students from the Faculty of Medical Sciences at Goce Delcev University in Stip. It was supported by the Faculty Student Assembly (FSA) of the Faculty of Medical Sciences and the Student Organized Medical Association (SOMA)

The Effect of Smoking on Biomarkers of (Anti) oxidant Status

The influence of smoking on the levels of several biomarkers of oxidative stress, antioxidant status and redox status have been investigated in 48 healthy men with a mean age of 25 y. The biomarkers of oxidative stress are the reactive oxygen metabolytes (ROM) and the total oxidant status (TOS). The biomarkers for the antioxidant activity are the biological antioxidant potential (BAP), the ferric reducing ability of plasma (FRAP), the total antioxidant status (TAS), the assay for the defense against the oxidation by hypochlorous acid (OXY) and uric acid (UA). The total thiol levels (TTL) have been measured as a biomarker for the redox status. The average concentration of ROM was 14% higher in smokers compared with non-smokers (p<0.05), whereas TOS was 4.9% higher (not statistically significant).The average concentrations of BAP, FRAP and TAS decreased with smoking with 3.6 (p<0.025), 3.6 (non-significant) and 6.1% (p<0.025), respectively. Alsouric acid, the main antioxidant in serum and a major contributor to the antioxidant status in serum, decreased by 10.6 % (p<0.025) in smokers. The biomarker of the redox status (TTL) was not influenced by smoking. From these results, it is concluded that in epidemiological studies the effect of smoking should be taken in account when using oxidative stress and antioxidant biomarkers

Biological and genotoxic monitoring as integral part of predictive and preventive medical surveillance of children living in polluted area

Introduction: Presence of many elements and their compounds in the environment pose a significant health risks to the exposed individuals and contributesto the burden of disease in society. An example for one of these black points wich destroyed the health of the people is lead and tine smelter in Veles (city in R of Macedonia). It is obvious that there is environmental-health risk with enough evidence for the pollution of the environment, as well as impact of higher blood level of lead in selected children. Objective: To registred and define the environmental health risk on children in Veles.Method: In this study we compare two groups of 100 children (average 10years old). Exposed group comprised children living in Veles (contaminated area),and control group were children who live in village Ivankovci. Results: Student’s t-test indicates statistically significant differences(t=15.14; p<0.001), between average concentration of lead in the air in Veles (0.94mg/m3) and Ivankovci (0.03 mg/m3); statistically significant differences (t=5.74;p<0.001), between average concentrations of BLL (37.27 μg/ml) in exposed group and control group (18.20 μg/ml); statistically significant differences (t=2.35;p<0.05), between average concentrations of hemoglobin in exposed group (children who live in Veles) and control group and the other hematological parameters between two groups. Discussion: The significance of these results show that children are exposed to mixtures rather than single chemicals. This complexity is a major reason why mixtures are not well studied. In this study are illustrated some of the principles and approaches that can be used to study the effects of mixtures. The multidisciplinary elaboration of the topic, suggests the need for a more serious approach to this important phenomenon(genotoxicological impact of heavy metals) and also is a specific model that is capable of application in other related research. Conclusion: Registered changes had reversible character. Manifested signs of disease were not registered, because of yet successful compensatory mechanisms in the examined children