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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.

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Cervical cancer screening is based on cytologic analysis and high-risk human papillomavirus (HR-HPV) testing, each having their drawbacks. Implementation of new biomarker-based methods may improve screening accuracy. Here, the levels of 25 microRNAs (miRNAs, miRs) and 12 mRNAs involved in cervical carcinogenesis in 327 air-dried Papanicolaou-stained cervical smears from patients with cervical precancerous lesions, cancer, or without the disease were estimated by real-time PCR. Using logistic regression analysis, small-scale miRNA-based, mRNA-based, and combined molecular classifiers were built based on paired ratios of miRNA or mRNA concentrations; their ability to detect high-grade cervical lesions and cancer was then compared. Combined mRNA-miRNA classifiers manifested a better combination of sensitivity and specificity than miRNA- and mRNA-based classifiers. The best classifier, combining miR-375, miR-20, miR-96, CDKN2A, TSP4, and ECM1, predicted high-grade lesions with diagnostic sensitivity of 89.0%, specificity of 84.2%, and a receiver-operating characteristic area under the curve of 0.913. Additionally, in a subsample of the same specimens, the levels of MIR124-2 and MAL promoter methylation, HR-HPV genotypes, and viral loads were analyzed. The relative high-grade lesion risk estimated by the classifier correlated with the frequency of MAL and MIR124-2 methylation but not with the HR-HPV genotype or viral load. The results support the feasibility of cellular biomarker-based methods for cervical screening and patient management.

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The present study aimed to assess the effect of Zn supplementation on trace element levels in the liver, serum, and hair of rats with dietary-induced non-alcoholic fatty liver disease (NAFLD). A total of 26 3-month-old female Wistar rats were divided into four groups: control, NAFLD, Zn-supplemented (227 mg/L zinc as Zn sulfate Zn(SO)4 dissolved in a drinking water), and NAFLD-Zn-supplemented. NAFLD was verified by histological assessment of liver samples. The serum was examined for routine biochemical parameters. Trace elements content was assessed using inductively coupled plasma mass spectrometry (ICP-MS). Zn treatment resulted in an improvement in liver weight and morphology. Dietary supplementation with Zn prevented NAFLD-induced decrease liver Co. The tendency to increase liver Fe in the Zn-treated group was observed. Zn treatment decreased hepatic Al and serum V levels. However, Zn administration did not affect NAFLD-induced I, Mn, and Se depletion in the liver. Hair Zn levels raised in Zn-supplemented groups. Conclusively, the results of the study indicate that Zn supplementation could have a beneficial effect in modulation of the altered trace element status and liver morphology. HIGHLIGHTS: •Zn treatment improved liver weight and morphology in rats with NAFLD. •Zn supplementation decreased liver Al in NAFLD. •Treatment by Zn prevented depletion of liver Co. •Zn decreased serum V and increased hair Zn levels. •No effect of Zn on NAFLD-induced hepatic I, Mn and Se depletion was observed.

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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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The primary objective of the study was to assess the level of metals and trace elements in liver, serum, and hair of rats with diet-induced non-alcoholic fatty liver disease (NAFLD) using inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS). 56 female 3-months-old Wistar rats divided into two equal groups were fed either standard (10% calories from fat) or high-fat high-carbohydrate diet (60% calories from fat in chow and 10% sucrose solution) for 6 weeks. Serum was examined for insulin resistance markers, lipid profile, and alanine aminotransferase (ALT) activity. Liver histology was assessed after hematoxylin and eosin staining. Metal and trace element concentrations were assessed by means of ICP-DRC-MS. Overfed animals were characterized by higher values of morphometric parameters. Liver examination revealed large and small droplet steatosis, hepatocyte ballooning and necrosis, being characteristic for NAFLD. Animals with NAFLD were characterized by insulin resistance, atherogenic changes of lipid profile and increased ALT activity. Significantly decreased hepatic Co, Cu, I, Li, Mn, Se, Zn levels were observed in rats with NAFLD. At the same time, only hepatic Mn and Se levels remained decreased after adjustment for total protein. Overfed animals were characterized by significantly lower I, Li, and Mn levels in blood serum, whereas concentration of Co, Se, V, and Sr exceeded the control values. In general, the results of the study demonstrate that NAFLD significantly affects metal and trace element status in experimental animals.

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