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The primary objective of the current study was to assess the influence of early high-fat feeding on tissue trace element content in young male Wistar rats. Twenty weanling male Wistar rats were divided into two groups fed standard (STD) or high-fat diet (HFD) containing 10 and 31.6 % of total calories from fat, respectively, for 1 month. Serum lipid spectrum, apolipoproteins, glucose, insulin, adiponectin, and leptin levels were assessed. The level of trace elements was estimated using inductively coupled plasma mass spectrometry. High-fat feeding significantly increased epidydimal (EDAT) and retroperitoneal adipose tissue (RPAT), as well as total adipose tissue mass by 34, 103, and 59 %, respectively. Serum leptin levels in HFD animals were twofold higher than those in the control rats. No significant difference in serum lipid spectrum, apolipoproteins, glucose, adiponectin, and insulin was detected between the groups. HFD significantly altered tissue trace element content. In particular, HFD-fed animals were characterized by significantly lower levels of Cu, I, Mn, Se, and Zn in the liver; Cr, V, Co, Cu, Fe, and I content of EDAT; Co, Cu, I, Cr, V, Fe, and Zn concentration in RPAT samples. At the same time, only serum Cu was significantly depressed in HFD-fed animals as compared to the control ones. Hair Co, Mn, Si, and V levels were significantly increased in comparison to the control values, whereas Se and I content was decreased. HFD feeding induced excessive adiposity and altered tissue trace element content in rats without insulin resistance, adiponectin deficiency, and proatherogenic state. Hypothetically, trace element disbalance may precede obesity-associated metabolic disturbances.

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Disturbed cervicovaginal-microbiome (CVM) structure promotes human papillomavirus (HPV) persistence and reflects risks of cervical lesions and cancer onset and recurrence. Therefore, microbiomic biomarkers may be useful for cervical disease screening and patient management. Here, by 16S rRNA gene sequencing and commercial PCR-based diagnostic kits, we profiled CVM in cytological preparations from 140 HPV-tested women (from Novosibirsk, Russia) with normal cytological findings, cervical lesions, or cancer and from 101 women who had recently received different cancer therapies. An increase in lesion severity was accompanied by higher HPV prevalence and elevated CVM biodiversity. Post-treatment CVM was found to be enriched with well-known microbial biomarkers of dysbiosis, just as in cervical disease. Nonetheless, concentrations of some skin-borne and environmental species (which gradually increased with increasing lesion severity)—especially Cutibacterium spp., Achromobacter spp., and Ralstonia pickettii—was low in post-treatment patients and depended on treatment types. Frequency of Lactobacillus iners dominance was high in all groups and depended on treatment types in post-treatment patients. Microbiome analysis via PCR-based kits revealed statistically significant differences among all groups of patients. Thus, microbiome profiling may help to find diagnostic and prognostic markers for management of cervical lesions; quantitative PCR-based kits may be suitable for these purposes.

Purpose: This research is devoted to designing the synthesis of sulfanyl-substituted 3,5-dimethylisoxazoles, which contain structural analogues of the SAM drug in the molecule. SAM (S-adenosyl-L-methionine), formed in the biosynthetic process, is used as an effective hepatoprotective drug. Complexation and hepatoprotective properties of the combinatorial series of bis(isoxazolylsulfanyl)ethane have been studied.Methods: Bis(isoxazol-4-ylmethylsulfanyl)alkanes were synthesized using the one-pot method. The structures of compounds were established by one-dimensional (1H,13C) and two-dimensional (COSY, HCQS, HMBC) NMR spectroscopy, mass-spectrometry and X-ray diffraction. The biological activity of the combinatorial series of sulfanyl derivatives of diketones, azoles and their metal complexes has been studied by in vivo method. Simulation of the animal associated processes was carried out in accordance with the principles of bioethics. Screening studies of hepatoprotective activity were carried out in a model of acute CC14 intoxication after a single injection intraperitoneally as a 50% solution in olive oil. The pharmacologically known hepatoprotective drug SAM served as a control.Results: Two-step synthesis of novel α,ω-bis(isoxazol-4-ylmethylsulfanyl)alkanes was carried out via the multicomponent reaction between 2,4-pentandione, CH2O and α,ω-dithiols, then the resulting α,ω-bis(1,3-diketone-2-ylmethylsulfanyl)alkanes were transformed by hydroxyl amine to obtain bis-isoxasole derivatives. Promising precursor 1,2-bis(isoxazol-4-ylmethylsulfanyl)ethane was converted to metal complexes by interaction with PdCl2 or CuCl. The obtained compounds were found to be practically non-toxic compounds (1001 – 3000 mg/kg) according to the classification of K.K. Sidorov, but copper complex refers to low-toxic compounds substances (165 mg/kg). Compounds of sulfanyl ethane series demonstrate hepatoprotective activity.Conclusion: Palladium(II) complex being almost non-toxic possesses hepatoprotective activity comparable to the drug like SAM.