T/A polymorphism of the FTO gene and lifestyle are associated with fat accumulation in different age groups of men

BACKGROUND: Adiposity development and its complications are determined by lifestyle, genetic mechanisms and their interactions. Among the obesity-related genes, polymorphisms in the fat mass and obesity associated (FTO) gene are strongly associated with body fat estimates in different populations. AIMS: to examine the association between the FTO polymorphism (T/A, rs9939609) and fat accumulation in adult russian males. MATERIALS AND METHODS: The study engaged 205 participants; the age ranged from 17 to 52 years. Samples of buccal smears were collected and genomic DNA was isolated for T/A polymorphism genotyping. Anthropometric measurements were conducted with caliperometry and body composition was estimated by bioimpedance analysis. RESULTS: Genotype frequencies in the whole studied sample were as follows FTO*TT 14%, FTO*AT 52,6%, FTO*AA 33,4% (χ2HW = 1,65 p=0,193). The minor A allele was significantly associated with increased fat accumulation and abdominal adiposity. CONCLUSIONS: Among different lifestyle modifications regular and consistent programmes of exercise are most efficient strategy to reduce abdominal fat deposits significantly, independent of FTO genotype

Analysis of Polymorphism of Uniparental Markers in Reindeer-Herding Populations: The Tozhu Tuvans of Russia and The Tsaatans Of Mongolia

We analyzed the data on the variability of the Y chromosome and mitochondrial DNA (mtDNA) in populations of the Tsaatans of Mongolia and the Tozhu Tuvans of Russia. The populations studied are characterized by low genetic diver¬sity for both marker systems. The analysis of Y chromosome haplogroups in the Tsaatan and Tozhu revealed three hap¬logroups in the Tsaatan and seven haplogroups in the Tozhu. The composition of the haplogroups is coherent to literature data on the Tuvans, which is explained by common origin. According to the data on mitochondrial DNA variability, 12 haplogroups were determined in 46 Tozhus, of which C4b (30.43%) and F1b1b (23.91%) are major haplogroups. According to the HVS–1 (HyperVariable Segment) data, 15 haplotypes were found in the Tozhu Tuvans and the diversity coefficient of 0.8677 turned out to be much lower than among the Torghut of Mongolia (0.9857). In 23 Tsaatans, 14 haplogroups were determined; the most common of which are C4b (22.73%) and C5a1 (18.18%). According to HVS-1, 14 haplotypes were revealed in the Tsaatan, the diversity is 0.9486. The data obtained on uniparental marker systems in the Tozhus and Tsaatans are due to the isolated and inaccessible taiga region and the manifestation of the “founder effect”. The Tsaatans are less polymorphic in terms of the variety of Y chromosome haplogroups, while the Tozhus are less polymorphic in terms of mitochondrial DNA, which is probably a consequence of a high rate of endogamic marriages in the populations studied

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Ethnic differences in risk factors and prevalence of type 2 diabetes in the adult population of the Russian Federation (a sub-analysis of the NATION study)

A retrospective analysis of the database of the NATION nation-wide epidemiological cross-sectional study was carried out. Depending on the self-declared ethnicity and anthropological characteristics, the following ethnic groups were identified: “Mongoloid population”, “Peoples of the Volga region”, “Peoples of the North Caucasus”, “Peoples of Transcaucasia”, “Russians”. The analysis consisted of several stages and included: analysis of the selected groups’ anthropometrics, analysis of the prevalence of carbohydrate metabolism disorders in the selected ethnic groups, analysis of ethnic-specific T2D risk factors, and analysis of region-specific factors affecting the prevalence of carbohydrate metabolism disorders in various ethnic groups. We defined carbohydrate metabolism disorders as diabetes and/or a prediabetes condition. In accordance with the WHO criteria, HbA1c≥6.5% was interpreted as diabetes, whereas values ​​in the range of 5.7%≤HbA1c<6.5% as prediabetes.RESULTS: The highest prevalence of carbohydrate metabolism disorders was observed among the “Peoples of the Volga region” group (31.2%), the lowest – among the “Peoples of the North Caucasus” group (15.6%). The “Peoples of the Volga region” group had a significantly lower BMI vs. the “Peoples of the North Caucasus” group. Carbohydrate metabolism disorders occurred more often in patients with abdominal obesity / 1st-stage obesity or aged over 45 among the “Mongoloid population” and the “Peoples of the Volga region” groups vs. the “Peoples of the Northern Caucasus” and the “Peoples of Transcaucasia” groups. Prevalence of carbohydrate metabolism disorders among the “Peoples of the Volga region” group residing in their native lands was higher than among Russians residing in the same regions: 32.5% vs. 24.3% (p<0.001 χ2 test) and also higher than among Russians residing in the Central Federal District: 32.5% vs. 27.4%, respectively (p=0.001, χ2 test). Prevalence of carbohydrate metabolism disorders among the “Peoples of the North Caucasus” group was lower than among the “Russians” group: 13.9% vs. 27.36%, respectively (p<0.001, χ2 test). Prevalence of carbohydrate metabolism disorders among the “Peoples of the North Caucasus” group living in their native lands (n=598) was lower than among the same group residing elsewhere in Russia (n=164) (13.9% vs. 21.95%, p=0.012, χ2 test

Immunogenicity and safety of a recombinant adenovirus type-5 COVID-19 vaccine in adults: Data from a randomised, double-blind, placebo-controlled, single-dose, phase 3 trial in Russia.

BackgroundTo determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV:placebo), phase 3 trial (Prometheus).MethodsFrom 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsSeroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59.0% (95% CI: 53.3; 64.6) seroconversion of neutralising antibodies against SARS-CoV-2 at 28 days post-vaccination were observed. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405 [95% CI: 366; 449]) and S protein (677 [95% CI: 608; 753]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.7 [95% CI: 15.3; 18.3]). Using an IFN-γ ELISpot assay after stimulating the cells with recombinant S protein ectodomain we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically significant compared with the placebo (рConclusionA single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.Trial registrationTrial registration: ClinicalTrials.gov: NCT04540419

Highly Sensitive Nanomagnetic Quantification of Extracellular Vesicles by Immunochromatographic Strips: A Tool for Liquid Biopsy

Extracellular vesicles (EVs) are promising agents for liquid biopsy—a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification. The tool is demonstrated by detection of EVs isolated from cell culture supernatants and various body fluids using characteristic biomarkers, CD9 and CD81, and a tumor-associated marker—epithelial cell adhesion molecules. The detection limit of 3.7 × 105 EV/µL is one to two orders better than the most sensitive traditional lateral flow system and commercial ELISA kits. The detection specificity is ensured by an isotype control line on the test strip. The tool’s advantages are due to the spatial quantification of EV-bound magnetic nanolabels within the strip volume by an original electronic technique. The inexpensive tool, promising for liquid biopsy in daily clinical routines, can be extended to other relevant biomarkers

Establishing Normative Values to Determine the Prevalence of Biochemical Hyperandrogenism in Premenopausal Women of Different Ethnicities from Eastern Siberia

Androgen assessment is a key element for diagnosing polycystic ovary syndrome (PCOS), and defining a “normal” level of circulating androgens is critical for epidemiological studies. We determined the upper normal limits (UNLs) for androgens in a population-based group of premenopausal “healthy control” women, overall and by ethnicity (Caucasian and Asian), in the cross-sectional Eastern Siberia PCOS Epidemiology and Phenotype (ESPEP) Study (ClinicalTrials.gov ID: NCT05194384) conducted in 2016–2019. Overall, we identified a “healthy control” group consisting of 143 healthy premenopausal women without menstrual dysfunction, hirsutism, polycystic ovaries, or medical disorders. We analyzed serum total testosterone (TT) by using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and DHEAS, sex-hormone-binding globulin (SHBG), TSH, prolactin, and 17-hydroxyprogesterone (17OHP) were assessed with an enzyme-linked immunosorbent assay (ELISA). The UNLs for the entire population for the TT, free androgen index (FAI), and DHEAS were determined as the 98th percentiles in healthy controls as follows: 67.3 (95% confidence interval (CI): 48.1, 76.5) ng/dl, 5.4 (3.5, 14.0), and 355 (289, 371) μg/dl, respectively. The study results demonstrated that the UNLs for TT and FAI varied by ethnicity, whereas the DHEAS UNLs were comparable in the ethnicities studied