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  • 1
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    COVID-19 Infection during Pregnancy: Disruptions in Lipid Metabolism and Implications for Newborn Health
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-07), p. 13787-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-07), p. 13787-
    Abstract: The COVID-19 pandemic has raised questions about indirect impact in pregnant women on the development of their future children. Investigating the characteristics of lipid metabolism in the “mother–placenta–fetus” system can give information about the pathophysiology of COVID-19 infection during pregnancy. A total of 234 women were included in study. Maternal plasma, cord blood, and amniotic fluid lipidome were analyzed using HPLC-MS/MS. Differences in lipid profile were searched by Mann–Whitney and Kruskall–Wallis test, and diagnostic model based on logistic regression were built by AIC. Elevated levels of lysophospholipids, triglycerides, sphingomyelins, and oxidized lipids were registered in patients’ maternal and cord plasma after COVID-19 infection. An increase in maternal plasma sphingomyelins and oxidized lipids was observed in cases of infection during the second trimester. In amniotic fluid, compared to the control group, nine lipids were reduced and six were elevated. Levels of phosphoglycerides, lysophosphoglycerides, and phosphatidylinositols decreased during infection in the second and third trimesters of pregnancy. A health diagnostic model for newborns based on maternal plasma was developed for each group and exhibited good diagnostic value (AUC 〉 0.85). Maternal and cord plasma’s lipidome changes during delivery, which are associated with COVID-19 infection during pregnancy, are synergistic. The most significant disturbances occur with infections in the second trimester of pregnancy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241813787
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
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  • 2
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    The Impact of Maternal SARS-CoV-2 Infection Next to Pre-Immunization with Gam-COVID-Vac (Sputnik V) Vaccine on the 1-Day-Neonate’s Blood Plasma Small Non-Coding RNA Profile: A Pilot Study
    MDPI AG ; 2022
    In:  COVID Vol. 2, No. 7 ( 2022-06-24), p. 837-857
    Details
    In: COVID, MDPI AG, Vol. 2, No. 7 ( 2022-06-24), p. 837-857
    Abstract: The antenatal and postnatal effects of maternal SARS-CoV-2 on the fetus outcomes, especially in the case of maternal pre-vaccination against this infection, are still under investigation. Such effects may be due to placental insufficiency caused by maternal hypoxia and inflammatory response associated with SARS-CoV-2, and/or be a direct cytopathic effect of the virus. In this work, we studied the profile of small non-coding RNAs (sncRNAs) in the blood plasma of a newborn from a mother who had SARS-CoV-2 at the 22nd week of gestation after immunization with Gam-COVID-Vac (Sputnik V). The fetus had ultrasound signs of hypertrophy of the right heart and hydropericardium 4 weeks after infection of the mother with SARS-CoV-2, as well as cysts of the cerebral vascular plexuses by the time of birth. Taking this into account, we compared the sncRNA profile of this newborn on the first postpartum day with that of neonates born to COVID-19-negative women with different perinatal outcomes: severe cardiovascular and/or neurological disorders, or absence of any perinatal complications. According to next-generation sequencing data, we found that the fetus born to a COVID-19-affected mother pre-immunized with Gam-COVID-Vac (Sputnik V) vaccine differs from newborns with severe cardiovascular and/or nervous system abnormalities either in multidirectional changes in circulating sncRNAs or in less pronounced unidirectional changes in the level of sncRNAs relative to control samples. Considering this, it can be concluded that maternal vaccination against SARS-CoV-2 before pregnancy has a protective effect in preventing antenatal development of pathological processes in the cardiovascular and nervous systems of the neonate associated with COVID-19.
    Type of Medium: Online Resource
    ISSN: 2673-8112
    URL: Article
    DOI: 10.3390/covid2070061
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3056217-X
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  • 3
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    Non-Invasive Differential Diagnosis of Cervical Neoplastic Lesions by the Lipid Profile Analysis of Cervical Scrapings
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 9 ( 2022-09-19), p. 883-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 9 ( 2022-09-19), p. 883-
    Abstract: Cervical cancer is one of the most common cancers in women with pronounced stages of precancerous lesions. Accurate differential diagnosis of such lesions is one of the primary challenges of medical specialists, which is vital to improving patient survival. The aim of this study was to develop and test an algorithm for the differential diagnosis of cervical lesions based on lipid levels in scrapings from the cervical epithelium and cervicovaginal canal. The lipid composition of the samples was analyzed by high-performance chromato-mass spectrometry. Lipid markers were selected using the Mann–Whitney test with a cutoff value of 0.05 and by projections to latent structures discriminant analysis, where a projection threshold of one was chosen. The final selection of variables for binomial logistic regressions was carried out using the Akaike information criterion. As a result, a final neoplasia classification method, based on 20 logistic regression sub-models, has an accuracy of 79% for discrimination NILM/cervicitis/LSIL/HSIL/cancer. The model has a sensitivity of 83% and a specificity of 88% for discrimination of several lesions (HSIL and cancer). This allows us to discuss the prospective viability of further validation of the developed non-invasive method of differential diagnosis.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12090883
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 4
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    miRNAs and Their Gene Targets—A Clue to Differentiate Pregnancies with Small for Gestational Age Newborns, Intrauterine Growth Restriction, and Preeclampsia
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 4 ( 2021-04-20), p. 729-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 4 ( 2021-04-20), p. 729-
    Abstract: Despite the differences in the clinical manifestations of major obstetric syndromes, such as preeclampsia (PE) and intrauterine growth restriction (IUGR), their pathogenesis is based on the dysregulation of proliferation, differentiation, and invasion of cytotrophoblast cells that occur in the developing placenta, decidual endometrium, and myometrial parts of the spiral arteries. To understand the similarities and differences in the molecular mechanisms of PE and IUGR, samples of the placental bed and placental tissue were analyzed using protein mass spectrometry and the deep sequencing of small RNAs, followed by validation of the data obtained by quantitative RT-PCR in real time. A comparison of the transcriptome and proteomic profiles in the samples made it possible to conclude that the main changes in the molecular profile in IUGR occur in the placental bed, in contrast to PE, in which the majority of molecular changes occurs in the placenta. In placental bed samples, significant changes in the ratio of miRNA and its potential target gene expression levels were revealed, which were unique for IUGR (miR-30c-5p/VIM, miR-28-3p/VIM, miR-1-3p/ANXA2, miR-30c-5p/FBN1; miR-15b-5p/MYL6), unique for PE (miR-185-3p/FLNA), common for IUGR and PE (miR-30c-5p/YWHAZ and miR-654-3p/FGA), but all associated with abnormality in the hemostatic and vascular systems as well as with an inflammatory process at the fetal‒maternal interface.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11040729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 5
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    Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 12 ( 2020-06-26), p. 4568-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 12 ( 2020-06-26), p. 4568-
    Abstract: Current methods for the intraoperative determination of breast cancer margins commonly suffer from the insufficient accuracy, specificity and/or low speed of analysis, increasing the time and cost of operation as well the risk of cancer recurrence. The purpose of this study is to develop a method for the rapid and accurate determination of breast cancer margins using direct molecular profiling by mass spectrometry (MS). Direct molecular fingerprinting of tiny pieces of breast tissue (approximately 1 × 1 × 1 mm) is performed using a home-built tissue spray ionization source installed on a Maxis Impact quadrupole time-of-flight mass spectrometer (qTOF MS) (Bruker Daltonics, Hamburg, Germany). Statistical analysis of MS data from 50 samples of both normal and cancer tissue (from 25 patients) was performed using orthogonal projections onto latent structures discriminant analysis (OPLS-DA). Additionally, the results of OPLS classification of new 19 pieces of two tissue samples were compared with the results of histological analysis performed on the same tissues samples. The average time of analysis for one sample was about 5 min. Positive and negative ionization modes are used to provide complementary information and to find out the most informative method for a breast tissue classification. The analysis provides information on 11 lipid classes. OPLS-DA models are created for the classification of normal and cancer tissue based on the various datasets: All mass spectrometric peaks over 300 counts; peaks with a statistically significant difference of intensity determined by the Mann–Whitney U-test (p 〈 0.05); peaks identified as lipids; both identified and significantly different peaks. The highest values of Q2 have models built on all MS peaks and on significantly different peaks. While such models are useful for classification itself, they are of less value for building explanatory mechanisms of pathophysiology and providing a pathway analysis. Models based on identified peaks are preferable from this point of view. Results obtained by OPLS-DA classification of the tissue spray MS data of a new sample set (n = 19) revealed 100% sensitivity and specificity when compared to histological analysis, the “gold” standard for tissue classification. “All peaks” and “significantly different peaks” datasets in the positive ion mode were ideal for breast cancer tissue classification. Our results indicate the potential of tissue spray mass spectrometry for rapid, accurate and intraoperative diagnostics of breast cancer tissue as a means to reduce surgical intervention.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21124568
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 6
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    Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 15 ( 2023-07-30), p. 12214-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 15 ( 2023-07-30), p. 12214-
    Abstract: The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241512214
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 3 ( 2021-03-10), p. 447-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 3 ( 2021-03-10), p. 447-
    Abstract: The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13030447
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 8
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    Combination of Low-Temperature Electrosurgical Unit and Extractive Electrospray Ionization Mass Spectrometry for Molecular Profiling and Classification of Tissues
    MDPI AG ; 2019
    In:  Molecules Vol. 24, No. 16 ( 2019-08-15), p. 2957-
    Details
    In: Molecules, MDPI AG, Vol. 24, No. 16 ( 2019-08-15), p. 2957-
    Abstract: Real-time molecular navigation of tissue surgeries is an important goal at present. Combination of electrosurgical units and mass spectrometry (MS) to perform accurate molecular visualization of biological tissues has been pursued by many research groups. Determination of molecular tissue composition at a particular location by surgical smoke analysis is now of increasing interest for clinical use. However, molecular analysis of surgical smoke is commonly lacking molecular specificity and is associated with significant carbonization and chemical contamination, which are mainly related to the high temperature of smoke at which many molecules become unstable. Unlike traditional electrosurgical tools, low-temperature electrosurgical units allow tissue dissection without substantial heating. Here, we show that low-temperature electrosurgical units can be used for desorption of molecules from biological tissues without thermal degradation. The use of extractive electrospray ionization technique for the ionization of desorbed molecules allowed us to obtain mass spectra of healthy and pathological tissues with high degree of differentiation. Overall, the data indicate that the described approach has potential for intraoperative use.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules24162957
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2008644-1
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  • 9
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    SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 3 ( 2020-01-30), p. 914-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 3 ( 2020-01-30), p. 914-
    Abstract: Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitrypsin) in urine remain one of the most promising peptide markers of PE. In this study the diagnostic potential of urinary α1-antitrypsin peptides in PE was evaluated. The urinary peptidome composition of 79 pregnant women with preeclampsia (PE), chronic arterial hypertension (CAH), and a control group was investigated. Mann–Whitney U-test (p 〈 0.05) revealed seven PE specific SERPINA1 peptides demonstrating 52% sensitivity and 100% specificity. SERPINA1 in urine has been associated with the most severe forms of preeclampsia (p = 0.014), in terms of systolic hypertension (p = 0.01) and proteinuria (p = 0.006). According to Spearman correlation analysis, the normalized intensity of SERPINA1 urinary peptides has a similar diagnostic pattern with known diagnostic PE markers, such as sFLT/PLGF. SERPINA1 peptides were not urinary excreted in superimposed PE (PE with CAH), which is a milder form of PE. An increase in expression of SERPINA1 in the structural elements of the placenta during preeclampsia reflects a protective mechanism against hypoxia. Increased synthesis of SERPINA1 in the trophoblast leads to protein accumulation in fibrinoid deposits. It may block syncytial knots and placenta villi, decreasing trophoblast invasion. Excretion of PE specific SERPINA1 peptides is associated with syncytiotrophoblast membrane destruction degradation and increased SERPINA1 staining. It confirms that the placenta could be the origin of SERPINA1 peptides in urine. Significant correlation (p 〈 0.05) of SERPINA1 expression in syncytiotrophoblast membrane and cytoplasm with the main clinical parameters of severe PE proves the role of SERPINA1 in PE pathogenesis. Estimation of SERPINA1 peptides in urine can be used as a diagnostic test of the severity of the condition to determine further treatment, particularly the need for urgent surgical delivery.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21030914
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 10
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    The Effect of Bisphenol A on the IVF Outcomes Depending on the Polymorphism of the Detoxification System Genes
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 11 ( 2021-10-26), p. 1091-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 11 ( 2021-10-26), p. 1091-
    Abstract: The aim of the study was to analyze the relationship between the level of bisphenol A (BPA) in the blood and follicular fluid, the polymorphism of the detoxification system genes, and the outcomes of IVF cycles. The data of 300 infertile patients with fresh IVF-ET cycles were analyzed. The level of BPA in the blood and follicular fluid was determined by HPLC-MRM-MS/MS. Determination of genotypes of the detoxification system genes was carried out by the real-time PCR. The threshold level for determining BPA was 0.1 ng/mL. BPA was detected in 92.3% (277/300) blood and in 16.8% (49/292) follicular fluid (FF) samples. There was no correlation between BPA level in the blood and FF. In patients with the absence of the A allele of the SULT1A1 gene, BPA was detected in FF significantly more often (22.6% vs. 13.5%, p = 0.0341). There was an association (not statistically significant) between the level of BPA in the blood and the presence of the G allele of the GSTP1 gene (rs1695) and the C allele in the GSTP1 gene (rs1138272). Our data suggests the role of detoxification system genes in the metabolism of BPA in the human body. The influence of BPA and detoxification system genes on the IVF outcomes requires further research.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11111091
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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