Multiomics Picture of Obesity in Young Adults.

Obesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications. By comparing the genetic, proteomic, and metabolomic profiles of individuals categorized as underweight, normal, overweight, and obese, we aimed to determine which omics layer most accurately reflects the phenotypic changes in an organism that result from obesity. We profiled blood plasma samples by employing three omics methodologies. The untargeted GC×GC-MS metabolomics approach identified 313 metabolites. To augment the metabolomic dataset, we integrated a label-free HPLC-MS/MS proteomics method, leading to the identification of 708 proteins. The genomic layer encompassed the genotyping of 647,250 SNPs. Utilizing omics data, we trained sparse Partial Least Squares models to predict body mass index. Molecular features exhibiting frequently non-zero coefficients were selected as potential biomarkers, and we further explored enriched biological pathways. Proteomics was the most effective in single-omics analyses, with a median absolute error (MAE) of 5.44 ± 0.31 kg/m2, incorporating an average of 24 proteins per model. Metabolomics showed slightly lower performance (MAE = 6.06 ± 0.33 kg/m2), followed by genomics (MAE = 6.20 ± 0.34 kg/m2). As expected, multiomic models demonstrated better accuracy, particularly the combination of proteomics and metabolomics (MAE = 4.77 ± 0.33 kg/m2), while including genomics data did not enhance the results. This manuscript is the first multiomics study of obesity in a gender-balanced cohort of young adults profiled by genomic, proteomic, and metabolomic methods. The comprehensive approach provides novel insights into the molecular mechanisms of obesity, opening avenues for more targeted interventions.

Linking Clinical Blood Metabogram and Gut Microbiota.

Recently, a clinical blood metabogram was developed as a fast, low-cost and reproducible test that allows the implementation of metabolomics in clinical practice. The components of the metabogram are functionally related groups of blood metabolites associated with humoral regulation, the metabolism of lipids, carbohydrates and amines, lipid intake into the organism, and liver function, thereby providing clinically relevant information. It is known that the gut microbiota affects the blood metabolome, and the components of the blood metabolome may affect the composition of the gut microbiota. Therefore, before using the metabogram in the clinic, the link between the metabogram components and the level of gut microorganisms should be established. For this purpose, the metabogram and microbiota data were obtained in this work for the same individuals. Metabograms of blood plasma were obtained by direct mass spectrometry of blood plasma, and the gut microbiome was determined by a culture-based method and real-time polymerase chain reaction (PCR). This study involved healthy volunteers and individuals with varying degrees of deviation in body weight (n = 44). A correlation analysis determined which metabogram components are linked to which gut microorganisms and the strength of this link. Moreover, diagnostic parameters (sensitivity, specificity and accuracy) confirmed the capacity of metabogram components to be used for diagnosing gut microbiota alterations. Therefore, the obtained results allow the use of the metabogram in a clinical setting, taking into account its relationship with gut microbiota.

Clinical Blood Metabogram: Application to Overweight and Obese Patients.

Recently, the concept of a mass spectrometric blood metabogram was introduced, which allows the analysis of the blood metabolome in terms of the time, cost, and reproducibility of clinical laboratory tests. It was demonstrated that the components of the metabogram are related groups of the blood metabolites associated with humoral regulation; the metabolism of lipids, carbohydrates, and amines; lipid intake into the organism; and liver function, thereby providing clinically relevant information. The purpose of this work was to evaluate the relevance of using the metabogram in a disease. To do this, the metabogram was used to analyze patients with various degrees of metabolic alterations associated with obesity. The study involved 20 healthy individuals, 20 overweight individuals, and 60 individuals with class 1, 2, or 3 obesity. The results showed that the metabogram revealed obesity-associated metabolic alterations, including changes in the blood levels of steroids, amino acids, fatty acids, and phospholipids, which are consistent with the available scientific data to date. Therefore, the metabogram allows testing of metabolically unhealthy overweight or obese patients, providing both a general overview of their metabolic alterations and detailing their individual characteristics. It was concluded that the metabogram is an accurate and clinically applicable test for assessing an individual's metabolic status in disease.

Lipoic Acid Exacerbates Oxidative Stress and Lipid Accumulation in the Liver of Wistar Rats Fed a Hypercaloric Choline-Deficient Diet.

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.

Does Proteomic Mirror Reflect Clinical Characteristics of Obesity?

Obesity is a frightening chronic disease, which has tripled since 1975. It is not expected to slow down staying one of the leading cases of preventable death and resulting in an increased clinical and economic burden. Poor lifestyle choices and excessive intake of "cheap calories" are major contributors to obesity, triggering type 2 diabetes, cardiovascular diseases, and other comorbidities. Understanding the molecular mechanisms responsible for development of obesity is essential as it might result in the introducing of anti-obesity targets and early-stage obesity biomarkers, allowing the distinction between metabolic syndromes. The complex nature of this disease, coupled with the phenomenon of metabolically healthy obesity, inspired us to perform data-centric, hypothesis-generating pilot research, aimed to find correlations between parameters of classic clinical blood tests and proteomic profiles of 104 lean and obese subjects. As the result, we assembled patterns of proteins, which presence or absence allows predicting the weight of the patient fairly well. We believe that such proteomic patterns with high prediction power should facilitate the translation of potential candidates into biomarkers of clinical use for early-stage stratification of obesity therapy.

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare.

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non-COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

A new threat from an old enemy: Re­emergence of coronavirus (Review).

The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus­associated disease, the spread and lethality of the 2019 outbreak (COVID­19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

The effect of chronic vitamin deficiency and long term very low dose exposure to 6 pesticides mixture on neurological outcomes - A real-life risk simulation approach.

We investigate the long-term effect of very-low dose exposure to a mixture of six pesticides associated with hydrophilic vitamin deficiency on the neurobehavioral outcomes of rats. Two hundred Wistar rats were divided into four groups, two control groups, a vitamin sufficient control group and a vitamin deficiency control group and 2 test groups, a vitamin sufficient test group, and a vitamin deficiency group. The test groups were exposed for 9 months to a mixture of diquat, imazamox, imazethapyr, tepraloxydin, bentazone and acifluorfen in doses of 0.01xNOAEL (mg/kg bw/day). After 9 months of exposure, the behavior changes were evaluated by open field test and elevated plus maze test and the memory was assessed by passive avoidance test. Chronic vitamin deficiency decreased locomotor and special orientation activity and increased anxiety-like behavior in rats. Exposure to very low doses of a mixture of 6 pesticides caused central nervous effects, manifested as decreased locomotor activity, and increased anxiety levels. Vitamin deficiency and low dose chronic pesticides mixture exposure thus affected the central nervous system, especially long-term memory.

Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study.

The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40-70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of ß-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (-3.97 ± 10.09 µmol/L; -1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population.

Impact on environment, ecosystem, diversity and health from culturing and using GMOs as feed and food.

Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible environmental, ecological, and health risks. Scientific-and-political debates can even influence legislation and prospective risk assessment procedure. Currently, the scientifically-assessed direct hazardous impacts of GM food and feed on fauna and flora are conflicting; indeed, a review of literature available data provides some evidence of GM environmental and health risks. Although the consequences of gene flow and risks to biodiversity are debatable. Risks to the environment and ecosystems can exist, such as the evolution of weed herbicide resistance during GM cultivation. A matter of high importance is to provide precise knowledge and adequate current information to regulatory agencies, governments, policy makers, researchers, and commercial GMO-releasing companies to enable them to thoroughly investigate the possible risks.

Biocompatible Colloidal Suspensions Based on Magnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicological Profile.

The use of magnetic iron oxide nanoparticles in biomedicine has evolved intensely in the recent years due to the multiple applications of these nanomaterials, mainly in domains like cancer. The aim of the present study was: (i) to develop biocompatible colloidal suspensions based on magnetic iron oxide nanoparticles as future theranostic tools for skin pathology and (ii) to test their effects in vitro on human keratinocytes (HaCat cells) and in vivo by employing an animal model of acute dermal toxicity. Biocompatible colloidal suspensions were obtained by coating the magnetic iron oxide nanoparticles resulted during the solution combustion synthesis with a double layer of oleic acid, as innovative procedure in increasing bioavailability. The colloidal suspensions were characterized in terms of dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro effects of these suspensions were tested by means of Alamar blue assay and the noxious effects at skin level were measured using non-invasive methods. The in vitro results indicated a lack of toxicity on normal human cells induced by the iron oxide nanoparticles colloidal suspensions after an exposure of 24 h to different concentrations (5, 10, and 25 µg·mL-1). The dermal acute toxicity test showed that the topical applications of the colloidal suspensions on female and male SKH-1 hairless mice were not associated with significant changes in the quality of barrier skin function.

Environmental impacts of genetically modified plants: A review.

Powerful scientific techniques have caused dramatic expansion of genetically modified crops leading to altered agricultural practices posing direct and indirect environmental implications. Despite the enhanced yield potential, risks and biosafety concerns associated with such GM crops are the fundamental issues to be addressed. An increasing interest can be noted among the researchers and policy makers in exploring unintended effects of transgenes associated with gene flow, flow of naked DNA, weediness and chemical toxicity. The current state of knowledge reveals that GM crops impart damaging impacts on the environment such as modification in crop pervasiveness or invasiveness, the emergence of herbicide and insecticide tolerance, transgene stacking and disturbed biodiversity, but these impacts require a more in-depth view and critical research so as to unveil further facts. Most of the reviewed scientific resources provide similar conclusions and currently there is an insufficient amount of data available and up until today, the consumption of GM plant products are safe for consumption to a greater extent with few exceptions. This paper updates the undesirable impacts of GM crops and their products on target and non-target species and attempts to shed light on the emerging challenges and threats associated with it. Underpinning research also realizes the influence of GM crops on a disturbance in biodiversity, development of resistance and evolution slightly resembles with the effects of non-GM cultivation. Future prospects are also discussed.

Activity of xenobiotic-metabolizing enzymes in the liver of rats with multi-vitamin deficiency.

The purpose of the study was to determine how multi-vitamin deficiency affects xenobiotic-metabolizing enzyme (XME) activities in the rat liver. Vitamin levels and XME activities were studied in the livers of male Wistar rats who were fed for 4 weeks with semi-synthetic diets containing either adequate (100 % of recommended vitamin intake) levels of vitamins (control), or decreased vitamin levels (50 % or 20 % of recommended vitamin intake). The study results have shown that moderate vitamin deficiency (50 %) leads to a decrease of vitamin A levels only, and to a slight increase, as compared with the control, in the following enzyme activities: methoxyresorufin O-dealkylase (MROD) activity of CYP1 A2 - by 34 % (p < 0.05), UDP-glucuronosyl transferase - by 26 % (p < 0.05), and quinone reductase - by 55 % (p < 0.05). Profound vitamin deficiency (20 %) led to a decrease of vitamins A, E, B1, B2, and C, and enzyme activities in the liver: MROD - to 78 % of the control level (p < 0.05), 4-nitrophenol hydroxylase - to 74 % (p < 0.05), heme oxygenase-1 - to 83 % (p < 0.05), and quinone reductase - to 60 % (p < 0.05). At the same time, the UDP-glucuronosyl transferase activity and ethoxyresorufin O-dealkylase activity of CYP1A1, pentoxyresorufin O-dealkylase activity of CYP2B1/2 and 6ß-testosterone hydroxylase, as well as the total activity of glutathione transferase did not differ from the control levels. The study has demonstrated that profound multi-vitamin deficiency is associated with a decrease in the expression of CYP1A2 and CYP3A1 mRNAs to 62 % and 79 %, respectively. These data indicated that a short-term but profound multi-vitamin deficiency in rats leads to a decrease in the activities and expression of the some XME that play an important role in detoxification of xenobiotics and metabolism of drugs and antioxidant protection.

Safety assessment of genetically modified organisms of plant origin in the Russian Federation.

The beginning of the 21st century is characterized by growing interest in the problems of biosafety, which are determined, on the one hand, by the wide use of novel biotechnologies and the necessity to develop the adequate precautionary measures, and, on the other hand, by the objective threat of bioterrorism. Therefore, improvement of the estimation system for genetically modified (GM) sources of food and strengthening the control of their circulation are the urgent problems of modern biology and medicine. Russia is one of the countries where the estimation system of food products obtained from the GM sources is rather efficient. The key features of this system are the complex toxicological and epidemiological examinations. One of the main parts of GM food safety assessment is based upon detection of their potentially toxic properties, which could provoke unintended effects of the genetic modification.

Deoxynivalenol in cereals in Russia.

A survey of the occurrence of deoxynivalenol (DON) and zearalenone (ZEN) in wheat, rye, barley and maize harvested in 1989-2001 in several regions of Russia has been conducted. A total of 5652 samples of cereals were analysed for DON and ZEN by using TLC and normal-phase HPLC with UV-detector. DON was detected in 69% of 2166 samples from Krasnodar region which is considered to be the major Fusarium endemic region of Russia. The contamination levels ranged from 0.1 till 8.6 ppm, MTEL was exceeded in 37% of these samples. The positive correlation between DON concentration and a percentage of Fusaria-damaged wheat kernels has been shown. DON occurrence and contamination levels were much lower that for wheat. Based on the results of monitoring and the data of average actual consumption of wheat products in Russia, the estimated daily intake of DON per 1 kg of body weight (EDI)was calculated. EDI varied from 0.07 ug in 1990-1991 till 1.40 ug in 1992. Although average EDI were lower than adopted tolerable daily intake (TDI, 3 ug/kg body weight) EDIs for the North-Caucasian region in some cases exceeded TDI.