Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet.

Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels.

In the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous ligands and an unknown role in the central nervous system and periphery. In this study, we generated two new TAAR9 knockout (TAAR9-KO) rat strains by CRISPR-Cas9 technology as in vivo models to evaluate the role of TAAR9 in mammalian physiology. In these mutant rats, we performed a comparative analysis of a number of hematological and biochemical parameters in the blood. Particularly, we carried out a complete blood count, erythrocyte osmotic fragility test, and screening of a panel of basic biochemical parameters. No significant alterations in any of the hematological and most biochemical parameters were found between mutant and WT rats. However, biochemical studies revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of both strains of TAAR9-KO rats. Such role of TAAR9 in cholesterol regulation not only brings a new understanding of mechanisms and biological pathways of lipid exchange but also provides a new potential drug target for disorders involving cholesterol-related pathology, such as atherosclerosis.

Prevalence of high-risk human papillomavirus types and cervical squamous intraepithelial lesions in women over 30 years of age in St. Petersburg, Russia.

BACKGROUND: Cytology-based screening has significantly decreased incidence of and mortality from cervical cancer. High sensitivity of high-risk human papillomavirus (hrHPV) test for the detection of high-grade cervical intraepithelial neoplasia (CIN) makes it a useful screening tool, especially in settings where cytology is not available or not quality assured. The study aimed to determine the prevalence of hrHPV and associated cervical lesions in Russian women over 30 years of age and to assess usefulness of HPV test for cervical screening in Russia. METHODS: Consecutive women aged 30-65 years (n=823) receiving routine gynaecological care, not pregnant and not treated for high-grade CIN, were recruited. Oncogenic HPV types were detected using Hybrid Capture 2 (HC2) assay and genotyped with direct DNA sequencing. Women with cytological abnormalities higher than atypical squamous cells of undetermined significance (ASCUS) and women positive for hrHPV were referred to colposcopy. RESULTS: HPV infection was present in 107 (13%) women. Cytological abnormalities were found in 81 (9.8%) patients, including 59 (7.2%) with ASCUS, 21 (2.5%) with low-grade squamous intraepithelial lesions (LSIL), and one (0.1%) with high-grade SIL. Only 11 (18.6%) patients with ASCUS were positive for hrHPV. Histological diagnoses were obtained for 63 women. Relative sensitivities and positive predictive values of the HPV test and cytology for the detection of high-grade CIN were 100% (6/6) and 9.5% (6/63), and 83.3% (5/6) and 27.8% (5/18), respectively. The most prevalent hrHPV types were 16 (3.9%), 31 (2.8%), 52 (1.7%), and 33 (1.3%). Cytological abnormalities and symptoms of a urogenital infection were strongly associated with hrHPV infection. CONCLUSIONS: The study provides data on the prevalence of hrHPV types in association with cervical lesions, as well as on hrHPV determinants, in an unvaccinated population of Russian women. Our results indicate that HPV test might be a useful screening tool in Russia.