Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome–brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed

Plasma Profile of Inflamatory Mediators in NHL Patients

Both cancer and inflammation are almost invariably accompanied by lipidome dysregulation. Hence, various lipid species have been reported as candidate markers for many solid tumours 1-3 .However, neitherthe globallipidome norsub-lipidome ofinflammatory pathways in Non-Hodgkin lymphoma (NHL) has been studied. In order to fill this gap and shed light on the inflammatory pathways accompanying NHL, we designed a targeted liquid chromatography – Multiple Reaction Monitoring of bioactive lipids/lipid mediators in plasma of female patients with Diffuse Large B-cell Lymphoma (DLBCL), the most often type of NHL. We chose to quantify lipids known or hypothesized to be involved in inflammation and cancer progression along with theirmembrane precursors. In a pilot study encompassing plasma samples from 17 DLBCL patients and 21 BMI-matched controls, we analysed levels of pro-inlammatory arachidonic acid (AA)-derived oxylipins, focusing on lipoxygenase (LOX) and cytochrome P450 monooxygenase products: hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids; several AA-containing phospholipids (PLs); specificlysophospholipid subclasses; sphingomyelins (SMs), sphingosine 1-phosphate (S1P) and polyunsaturated fatty acids. Data were subjected to classical statistics and multivariate unsupervised and supervised machine learning (ML) algorithms. The DLBCL status was profoundly associated with altered S1P, SM 34:1, SM 36:1 and phosphatidylinositol PI 34:1 abundance. On the other hand, eicosanoids 12(S)-HETE, 15(S)-HETE and thromboxane B2 were major lipid species discriminating between DLBCL and healthy status, as well as lysophosphatidylinositol LPI 20:4. The correlations between lipid species varied considerably between the cancer and controls, reflecting significant changes in lipid metabolic and/or signalling pathways, particularly those within LOX pathway and cell membrane PL remodelling. We suggest S1P, SM 36:1, SM 34:1 and PI 34:1 may beviewed as lipid signatures of DLBCL. Furthermore, these four lipid species could serve asa basis for the prospective validation in larger DLBCL/NHL clinical studies. As far as we know, this is the first plasma lipid profiling in DLBCL/NHL and, as such, brings new knowledge on the metabolic basis of inflammation in this cancer. The added value of our plasma lipid profiling in DLBCL is a deeper understanding of particulate lipid dysregulations in this tumourSePA : 6th Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“; June 2, Rektorat Univerziteta u Kragujevc

Plasma Profile of Inflamatory Mediators in NHL Patients

Both cancer and inflammation are almost invariably accompanied by lipidome dysregulation. Hence, various lipid species have been reported as candidate markers for many solid tumours1-3. However, neither the global lipidome nor sub-lipidome of inflammatory pathways in Non-Hodgkin lymphoma (NHL) has been studied. In order to fill this gap and shed light on the inflammatory pathways accompanying NHL, we designed a targeted liquid chromatography – Multiple Reaction Monitoring of bioactive lipids/lipid mediators in plasma of female patients with Diffuse Large B-cell Lymphoma (DLBCL), the most often type of NHL. We chose to quantify lipids known or hypothesized to be involved in inflammation and cancer progression along with their membrane precursors. In a pilot study encompassing plasma samples from 17 DLBCL patients and 21 BMI-matched controls, we analysed levels of pro-inlammatory arachidonic acid (AA)-derived oxylipins, focusing on lipoxygenase (LOX) and cytochrome P450 monooxygenase products: hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids; several AA-containing phospholipids (PLs); specificlysophospholipid subclasses; sphingomyelins (SMs), sphingosine 1-phosphate (S1P) and polyunsaturated fatty acids. Data were subjected to classical statistics and multivariate unsupervised and supervised machine learning (ML) algorithms. The DLBCL status was profoundly associated with altered S1P, SM 34:1, SM 36:1 and phosphatidylinositol PI 34:1 abundance. On the other hand, eicosanoids 12(S)-HETE, 15(S)-HETE and thromboxane B2 were major lipid species dis criminating between DLBCL and healthy status, as well as lysophosphatidylinositol LPI 20:4. The correlations between lipid species varied considerably between the cancer and controls, reflecting significant changes in lipid metabolic and/or signalling pathways, particularly those within LOX pathway and cell membrane PL remodelling. We suggest S1P, SM 36:1, SM 34:1 and PI 34:1 may beviewed as lipid signatures of DLBCL. Furthermore, these four lipid species could serve as a basis for the prospective validation in larger DLBCL/NHL clinical studies. As far as we know, this is the first plasma lipid profiling in DLBCL/NHL and, as such, brings new knowledge on the metabolic basis of inflammation in this cancer. The added value of our plasma lipid profiling in DLBCL is a deeper understanding of particulate lipid dysregulations in this tumour.SePA : 6th Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“; June 2, Kragujevac

Effect of genotype x environment interactions of grapevine hybrids characteristics

Research in this paper was performed at two different locations: Radmilovac and Vrsac in Serbia. Four new interspecific hybrids (9846, 9896, 19574 and 20506) which are intended for table consumption were used as a material. Grape yield per unit area, the properties of the bunch (bunch weight, bunch length, bunch width and number of berries in bunch), the properties of berry (berry weight, berry length and berry width), as well as the characteristic of grape quality (sugar content and total acids in the must) were studied in selected hybrids. The highest yield per unit area in the localities Radmilovac and Vr. sac had a hybrid 9896 (14 998 kg/ha; 11 365 kg/ha). Analysis of variance results showed for the bunch weight, bunch width and number of berries in bunch, berry weight and berry length significant differences among the genotypes. Significant differences between investigated localities were determined for the bunch length and all the berry characters. The interaction between genotype and localities showed significant differences for bunch length, berry length and berry width. Since the genotypes in the initial yielding (third year after planting), they are showed satisfactory results in relation to the objectives of selection

Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies

Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed

The traveling salesman problem: The spectral radius and the length of an optimal tour

We consider the symmetric traveling salesman problem (TSP) with instances represented by complete graphs with distances between cities as edge weights. Computational experiments with randomly generated instances on 50 and 100 vertices with the uniform distribution of integer edge weights in interval [1, 100] show that there exists a correlation between the sequences of the spectral radii of the distance matrices and the lengths of optimal tours obtained by the well known TSP solver Concorde. In this paper we give a partial theoretical explanation of this correlation.Bulletin de l'Académie serbe des sciences. Classe des sciences mathématiques et naturelles. Sciences mathématiques. . - 43 , 151 (2018

Disturbed Plasma Lipidomic Profiles in Females with Diffuse Large B-Cell Lymphoma: A Pilot Study

Lipidome dysregulation is a hallmark of cancer and inflammation. The global plasma lipidome and sub-lipidome of inflammatory pathways have not been reported in diffuse large B-cell lymphoma (DLBCL). In a pilot study of plasma lipid variation in female DLBCL patients and BMI-matched disease-free controls, we performed targeted lipidomics using LC-MRM to quantify lipid mediators of inflammation and immunity, and those known or hypothesised to be involved in cancer progression: sphingolipids, resolvin D1, arachidonic acid (AA)-derived oxylipins, such as hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids, along with their membrane structural precursors. We report on the role of the eicosanoids in the separation of DLBCL from controls, along with lysophosphatidylinositol LPI 20:4, implying notable changes in lipid metabolic and/or signalling pathways, particularly pertaining to AA lipoxygenase pathway and glycerophospholipid remodelling in the cell membrane. We suggest here the set of S1P, SM 36:1, SM 34:1 and PI 34:1 as DLBCL lipid signatures which could serve as a basis for the prospective validation in larger DLBCL cohorts. Additionally, untargeted lipidomics indicates a substantial change in the overall lipid metabolism in DLBCL. The plasma lipid profiling of DLBCL patients helps to better understand the specific lipid dysregulations and pathways in this cancer

Chronic idiopathic portal vein thrombosis: A case study

Tromboza portne vene (TPV) je retko oboljenje splanhničke cirkulacije, koje najčešće nastaje sadejstvom više lokalnih i/ili sistemskih faktora. Ukoliko TPV komplikuje osnovnu bolest, ona pogoršava njenu prognozu, a konkomitantno se leče obe. Iako se najčešće javlja u sklopu ciroze jetre, malignih bolesti abdominalnih organa i nekih hemopatija, postoji i idiopatska TPV, koja se definiše ekskluzijom svih poznatih uzroka TPV. U ovom radu je prikazan slučaj hronične idioptaske TPV.Portal vein thrombosis (PVT) is a rare disorder of splanchnic circulation, frequently caused by concomitant presence of local and/or systemic factors. When portal vein thrombosis complicates causative diseases, it will worsen their prognosis, and in such a case, the causative disease and PVT are treated concomitantly. Despite the fact that PVT frequently complicates liver cirrhosis, intraabdominal malignancies, and some hematological diseases, after all causes are excluded, one can define idiopathic portal vein thrombosis. In this study we have described the case of idiopathic chronical portal vein thrombosis

Enhancing Capacity for Short-Term Climate Change Adaptations in Agriculture in Serbia: Development of Integrated Agrometeorological Prediction System

The Integrated Agrometeorological Prediction System (IAPS) was a two-year project for the development of the long term forecast (LRF) for agricultural producers. Using LRF in decision-making, to reduce the risks and seize the opportunities, represents short-term adaptation to climate change. High-resolution ensemble forecasts (51 forecasts) were made for a period of 7 months and were initiated on the first day of each month. For the initial testing of the capacity of LRF to provide useful information for producers, 2017 was chosen as the test year as it had a very hot summer and severe drought, which caused significant impacts on agricultural production. LRF was very useful in predicting the variables which bear the memory of the longer period, such are growing degree days for the prediction of dates of the phenophases’ occurrences and the soil moisture of deeper soil layers as an indicator for the drought. Other project activities included field observations, communication with producers, web portal development, etc. Our results showed that the selected priority forecasting products were also identified by the producers as being the highest weather-related risks, the operational forecast implementation with the products designed for the use in agricultural production is proven to be urgent and necessary for decision-making, and required investments are affordable. The total cost of the full upgrade of agrometeorological climate services to meet current needs (including monitoring, seamless forecasting system development and the development of tools for information dissemination) was found to be about three orders of magnitude lower than the assessed losses in agricultural production in the two extreme years over the past decade