ABSTRACT
Background: Obesity is one of the most common metabolic disorders in the world, which develops due to an imbalance in energy consumption and expenditure, and both genetic and environmental factors are of great importance. We investigated the potential interactions of single nucleotide polymorphisms that might contribute to the development of polygenic obesity in children. Objective: The study involved 367 children and adolescents of both sexes aged from 4 to 18 years. The control group (normal weight) and the overweight groups included 65 and 302 children respectively. Methods: DNA for analysis was isolated from peripheral blood lymphocytes, then allelic variants rs99305069 of the FTO gene (chr16:53786615), Gln192Arg of the PON1 gene (chr7: 95308134), -250G>A of the LIPC gene (chr15: 58431740), and Ser447Ter of the LPL gene (chr8:19957678) were studied using the SNP-Express reagent kit. The results of allelic interactions were analyzed using the multifactor dimensionality reduction method. Results and Discussion: Among overweight children, the distribution of genotype and allele frequencies for the studied single nucleotide polymorphisms of the four genes corresponded to those of the control group (p > 0.05). It was found that in obese children SerSer homozygotes at the Ser447Ter polymorphism of the LPL gene, had serum triglyceride (TG) levels 2.3 times higher than in children with the same genotype from the control group. In overweight Ser447Ter heterozygotes (p < 0.0001), the TG level exceeded the control values by only 13% (p = 0.044). A two-locus genotype FTO AT/LPL SerTer, was associated with a reduced risk of childhood obesity.
Subject(s)
Genetic Predisposition to Disease , Lipid Metabolism/genetics , Pediatric Obesity/genetics , Adolescent , Body Mass Index , Case-Control Studies , Child , Child, Preschool , Female , Gene Frequency , Humans , Male , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology , Polymorphism, Single Nucleotide , Risk Assessment/methodsABSTRACT
Bats are potential natural reservoirs for emerging viruses, causing deadly human diseases, such as COVID-19, MERS, SARS, Nipah, Hendra, and Ebola infections. The fundamental mechanisms by which bats are considered "living bioreactors" for emerging viruses are not fully understood. Some studies suggest that tolerance to viruses is linked to suppressing antiviral immune and inflammatory responses due to DNA damage by energy generated to fly. Our study reveals that bats' gut bacteria could also be involved in the host and its microbiota's DNA damage. We performed screening of lactic acid bacteria and bacilli isolated from bats' feces for mutagenic and oxidative activity by lux-biosensors. The pro-mutagenic activity was determined when expression of recA increased with the appearance of double-strand breaks in the cell DNA, while an increase of katG expression in the presence of hydroxyl radicals indicated antioxidant activity. We identified that most of the isolated bacteria have pro-mutagenic and antioxidant properties at the same time. This study reveals new insights into bat gut microbiota's potential involvement in antiviral response and opens new frontiers in preventing emerging diseases originating from bats.
Subject(s)
Chiroptera/virology , Gastrointestinal Microbiome , Mutagens , Animals , Antioxidants/metabolism , Antiviral Agents , Bacillus , Bacterial Proteins/genetics , Biosensing Techniques , COVID-19 , DNA , DNA Damage , Disease Reservoirs/virology , Escherichia coli/metabolism , Feces , Immune System , Inflammation , Lactic Acid/metabolism , Mass Spectrometry , Mutagenesis , Oxidative Stress , Rec A Recombinases/metabolism , SARS-CoV-2 , Viruses/isolation & purification , Zoonoses/virologyABSTRACT
BACKGROUND: Current assessment methods of penile cavernous fibrosis in animal models have limitations due to the inability to provide complex and volume analysis of fibrotic alterations. OBJECTIVE: The aim was to evaluate micro-computed tomography for assessment of cavernous fibrosis and compare it with histological, histochemical, immunohistochemical, and RT-PCR analysis. MATERIALS AND METHODS: A controlled trial was performed involving 25 New Zealand male rabbits with induced testosterone deficiency by orchidectomy. Penile samples were obtained before and after 7, 14, 21, and 84 days from orchidectomy. We consistently performed (a) gray value analysis of corpora cavernosa 3D models reconstructed after micro-computed tomography, (b) morphometry of smooth muscles/connective tissue ratio, collagen type I/III ratio, and area of TGF-beta-1 expression in corpora cavernosa, and (c) RT-PCR of TGF-beta-1 expression. RESULTS: Micro-computed tomography allowed visualization of penile structures at a resolution comparable to light microscopy. Gray values of corpora cavernosa decreased from 1673 (1512-1773) on the initial day to 1184 (1089-1232) on the 21st day (p < 0.005). However, on the 84th day, it increased to 1610 (1551-1768). On 21st and 84th days, there was observed a significant decrease in smooth muscle/connective tissue ratio and a significant increase in collagen type I/III ratio (p < 0.05). TGF-beta1 expression increased on the 84th day according to immunohistochemistry (p < 0.005). RT-PCR was impossible to conduct due to the absence of RNA in obtained samples after micro-CT. DISCUSSION AND CONCLUSIONS: Micro-computed tomography provided 3D visualization of entire corpora cavernosa and assessment of radiodensity alterations by gray value analysis in fibrosis progression. We speculate that gray value changes at early and late fibrosis stages could be related to tissue reorganization. RT-PCR is impossible to conduct on tissue samples studied by micro-CT due to RNA destruction. We also suggest that micro-computed tomography could negatively affect the immunohistochemical outcome, as a significant increase of TGF-beta-1 expression occurs later than histological fibrotic signs.