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1دورية أكاديمية
المؤلفون: Ekaterina Tolmacheva, Anna S. Bolshakova, Jekaterina Shubina, Margarita S. Rogacheva, Alexey N. Ekimov, Julia L. Podurovskaya, Artem A. Burov, Denis V. Rebrikov, Vladimir G. Bychenko, Dmitry Yu. Trofimov, Gennady T. Sukhikh
المصدر: BMC Medical Genomics, Vol 17, Iss 1, Pp 1-8 (2024)
مصطلحات موضوعية: Whole exome sequencing, MED13, De novo variant, Expanding phenotype, Internal medicine, RC31-1245, Genetics, QH426-470
الوصف: Abstract Background Whole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients. Results Here we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients. Conclusions Therefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/1755-8794
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2دورية أكاديمية
المؤلفون: Leila V. Adamyan, Irina V. Menzhinskaya, Alena A. Antonova, Narine M. Tonoyan, Gennady T. Sukhikh
المصدر: International Journal of Molecular Sciences, Vol 25, Iss 12, p 6545 (2024)
مصطلحات موضوعية: premature ovarian insufficiency, infertility, diminished ovarian reserve, autoimmunity, autoantibodies against steroidogenic enzymes, cholesterol side-chain cleavage enzyme, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4–76.9%), specificity (83.3–89.9%), and AUC values (0.842–0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75–79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Aleksey M. Krasnyi, Lyubov T. Gadzhieva, Diana N. Kokoeva, Mark G. Kosenko, Ekaterina L. Yarotskaya, Stanislav V. Pavlovich, Levon A. Ashrafyan, Gennady T. Sukhikh
المصدر: International Journal of Molecular Sciences, Vol 25, Iss 9, p 4892 (2024)
مصطلحات موضوعية: methylation, atypical endometrial hyperplasia, endometrial cancer stage IA, organ-preserving treatment, MS-HRM, CDO1, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). Conclusion: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Elena P. Khashchenko, Mikhail Yu. Vysokikh, Maria V. Marey, Ksenia O. Sidorova, Ludmila A. Manukhova, Natalya N. Shkavro, Elena V. Uvarova, Vladimir D. Chuprynin, Timur Kh. Fatkhudinov, Leila V. Adamyan, Gennady T. Sukhikh
المصدر: International Journal of Molecular Sciences, Vol 25, Iss 8, p 4238 (2024)
مصطلحات موضوعية: peritoneal endometriosis, mitochondrial biogenesis, glycolysis, apoptosis, Bcl-2, autophagy, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Energy metabolism plays a pivotal role in the pathogenesis of endometriosis. For the initial stages of the disease in adolescents, this aspect remains unexplored. The objective of this paper was to analyze the association of cellular and endosomal profiles of markers of glycolysis, mitochondrial biogenesis, apoptosis, autophagy and estrogen signaling in peritoneal endometriosis (PE) in adolescents. We included 60 girls aged 13–17 years in a case–control study: 45 with laparoscopically confirmed PE (main group) and 15 with paramesonephric cysts (comparison group). Samples of plasma and peritoneal fluid exosomes, endometrioid foci and non-affected peritoneum were tested for estrogen receptor (Erα/β), hexokinase (Hex2), pyruvate dehydrogenase kinase (PDK1), glucose transporter (Glut1), monocarboxylate transporters (MCT1 and MCT2), optic atrophy 1 (OPA1, mitochondrial fusion protein), dynamin-related protein 1 (DRP1, mitochondrial fission protein), Bax, Bcl2, Beclin1, Bnip3, P38 mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (Hif-1α), mitochondrial voltage-dependent anion channel (VDAC) and transforming growth factor (TGFβ) proteins as markers of estrogen signaling, glycolysis rates, mitochondrial biogenesis and damage, apoptosis and autophagy (Western-Blot and PCR). The analysis identified higher levels of molecules associated with proliferation (ERβ), glycolysis (MCT2, PDK1, Glut1, Hex2, TGFβ and Hif-1α), mitochondrial biogenesis (OPA1, DRP1) and autophagy (P38, Beclin1 and Bnip3) and decreased levels of apoptosis markers (Bcl2/Bax) in endometrioid foci compared to non-affected peritoneum and that in the comparison group (p < 0.05). Patients with PE had altered profiles of ERβ in plasma and peritoneal fluid exosomes and higher levels of Glut1, MCT2 and Bnip3 in plasma exosomes (p < 0.05). The results of the differential expression profiles indicate microenvironment modification, mitochondrial biogenesis, estrogen reception activation and glycolytic switch along with apoptosis suppression in peritoneal endometrioid foci already in adolescents.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Ljubava D. Zorova, Polina A. Abramicheva, Nadezda V. Andrianova, Valentina A. Babenko, Savva D. Zorov, Irina B. Pevzner, Vasily A. Popkov, Dmitry S. Semenovich, Elmira I. Yakupova, Denis N. Silachev, Egor Y. Plotnikov, Gennady T. Sukhikh, Dmitry B. Zorov
المصدر: Pharmaceutics, Vol 16, Iss 4, p 444 (2024)
مصطلحات موضوعية: mitochondria, cancer, tumor, energetics, hypoxia, fumarate reductase, Pharmacy and materia medica, RS1-441
الوصف: There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of mitochondria. This analytical review examines three specific features of adaptive mitochondrial changes in several malignant tumors. The first feature is characteristic of solid tumors, whose cells are forced to rebuild their energetics due to the absence of oxygen, namely, to activate the fumarate reductase pathway instead of the traditional succinate oxidase pathway that exists in aerobic conditions. For such a restructuring, the presence of a low-potential quinone is necessary, which cannot ensure the conventional conversion of succinate into fumarate but rather enables the reverse reaction, that is, the conversion of fumarate into succinate. In this scenario, complex I becomes the only generator of energy in mitochondria. The second feature is the increased proliferation in aggressive tumors of the so-called mitochondrial (peripheral) benzodiazepine receptor, also called translocator protein (TSPO) residing in the outer mitochondrial membrane, the function of which in oncogenic transformation stays mysterious. The third feature of tumor cells is the enhanced retention of certain molecules, in particular mitochondrially directed cations similar to rhodamine 123, which allows for the selective accumulation of anticancer drugs in mitochondria. These three features of mitochondria can be targets for the development of an anti-cancer strategy.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Angelika V. Timofeeva, Ivan S. Fedorov, Yuliya V. Suhova, Alla M. Tarasova, Larisa S. Ezhova, Tatyana M. Zabelina, Oksana N. Vasilchenko, Tatyana Y. Ivanets, Gennady T. Sukhikh
المصدر: International Journal of Molecular Sciences, Vol 25, Iss 2, p 871 (2024)
مصطلحات موضوعية: miRNA, NGS, real-time PCR, peripheral blood, placenta, myometrium, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial–myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening. miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profiles in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or pre-eclampsia, were obtained using deep sequencing. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p, quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset pre-eclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to data from the literature, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for first-trimester screening of pregnant women, subject to validation with independent test samples.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Evgenia I. Deryusheva, Alexander N. Panin, Irina O. Chikileva, Tatiana N. Abashina, Vyacheslav G. Melnikov, Nataliya E. Suzina, Ilia N. Nikonov, Anna A. Akhmetzyanova, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh, Vladimir N. Uversky, Andrey V. Karlyshev
المصدر: Biomolecules, Vol 13, Iss 12, p 1740 (2023)
مصطلحات موضوعية: S-layer protein 2, Lactobacillus crispatus, Candida albicans, probiotic bacteria, anti-pathogenic potential, anti-adhesive effect, Microbiology, QR1-502
الوصف: Previously, the protective role of the S-layer protein 2 (Slp2) of the vaginal Lactobacillus crispatus 2029 (LC2029) strain against foodborne pathogens Campylobacter jejuni, Salmonella enterica serovar Enteritidis, and Escherichia coli O157:H was demonstrated. We demonstrate the new roles of the Slp2-positive LC2029 strain and soluble Slp2 against C. albicans infections. We show that LC2029 bacteria can adhere to the surface of the cervical epithelial HeLa cells, prevent their contact with C. albicans, and block yeast transition to a pathogenic hyphal form. Surface-bound Slp2 provides the ability for LC2029 to co-aggregate with various C. albicans strains, including clinical isolates. C. albicans-induced necrotizing epithelial damage is reduced by colonization with the Slp2-positive LC2029 strain. Slp2 inhibits the adhesion of various strains of C. albicans to different human epithelial cells, blocks yeast transition to a pathogenic hyphal form, and prevents the colonization and pathogenic infiltration of mucosal barriers. Only Slp2 and LC2029 bacteria stimulate the production of protective human β-defensin 3 in various epithelial cells. These findings support the anti-Candida albicans potential of the probiotic LC2029 strain and Slp2 and form the basis for further research on their ability to prevent and manage invasive Candida infections.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Evgenia I. Deryusheva, Tatiana V. Priputnevich, Alexander N. Panin, Irina O. Chikileva, Tatiana N. Abashina, Ashot M. Manoyan, Anna A. Akhmetzyanova, Dmitriy A. Blumenkrants, Olga E. Ivanova, Tigran T. Papazyan, Ilia N. Nikonov, Nataliya E. Suzina, Vyacheslav G. Melnikov, Valentin S. Khlebnikov, Vadim K. Sakulin, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh, Vladimir N. Uversky, Andrey V. Karlyshev
المصدر: Antibiotics, Vol 13, Iss 1, p 30 (2023)
مصطلحات موضوعية: Salmonella enteritidis, multi-drug resistance, gene expression, Therapeutics. Pharmacology, RM1-950
الوصف: Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. Ligilactobacillus salivarius strain 7247 (LS7247) was isolated at the same time from the intestines and reproductive system of a healthy woman. The genomes of these strains contain genes responsible for the production of peptidoglycan-degrading enzymes and factors that increase the permeability of the outer membrane of Gram-negative pathogens. In this work, the anti-Salmonella and intestinal homeostatic features of the LF3872 and LS7247 consortium were studied. A multi-drug resistant (MDR) strain of Salmonella enteritidis (SE) was used in the experiments. The consortium effectively inhibited the adhesion of SE to intact and activated human, porcine, and chicken enterocytes and reduced invasion. The consortium had a bactericidal effect on SE in 6 h of co-culturing. A gene expression analysis of SE showed that the cell-free supernatant (CFS) of the consortium inhibited the expression of virulence genes critical for the colonization of human and animal enterocytes. The CFS stimulated the production of an intestinal homeostatic factor—intestinal alkaline phosphatase (IAP)—in Caco-2 and HT-29 enterocytes. The consortium decreased the production of pro-inflammatory cytokines IL-8, TNF-α, and IL-1β, and TLR4 mRNA expression in human and animal enterocytes. It stimulated the expression of TLR9 in human and porcine enterocytes and stimulated the expression of TLR21 in chicken enterocytes. The consortium also protected the intestinal barrier functions through the increase of transepithelial electrical resistance (TEER) and the inhibition of paracellular permeability in the monolayers of human and animal enterocytes. The results obtained suggest that a LF3872 and LS7247 consortium can be used as an innovative feed additive to reduce the spread of MDR SE among the population and farm animals.
وصف الملف: electronic resource
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9دورية أكاديمية
المؤلفون: Olga S. Beznoshchenco, Andrey Yu. Romanov, Nataliya V. Dolgushina, Elena A. Gorodnova, Tatiana Yu. Ivanets, Ekaterina L. Yarotskaya, Aleksey V. Pyregov, Sergej V. Grachev, Gennady T. Sukhikh
المصدر: Biomedicines, Vol 12, Iss 1, p 42 (2023)
مصطلحات موضوعية: COVID-19, von Willebrand factor, ADAMTS-13, hypercoagulation, thrombosis, Biology (General), QH301-705.5
الوصف: SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) activates the immune system, causing thrombin dysregulation and tissue damage and reduces endothelium anticoagulant function, leading to excessive thrombin formation. Hypercoagulability, which causes multiple organ failure in critically ill COVID-19 (COronaVIrus Disease 2019) patients, can be detected by viscoelastic tests like thromboelastography and rotational thromboelastometry (ROTEM). We aimed to assess the coagulation system status and fibrinolytic activity using ROTEM thromboelastometry in patients with COVID-19 and convalescents. The observational prospective study included 141 patients with COVID-19: Group 1—patients with mild (n = 39), Group 2—patients with moderate (n = 65), and Group 3—patients with severe (n = 37) COVID-19. The coagulation status was assessed twice—during the disease and in convalescence. The male gender, age > 56 years, overweight, and obesity were risk factors for developing severe COVID-19. During the disease in patients with moderate and severe COVID-19, the hemostatic system was characterized by a procoagulant status, which persists during the period of convalescence. Fibrinolysis shutdown was detected in both moderate and severe patients with COVID-19. The procoagulant status of the coagulation system and the shutdown of fibrinolysis are typical for patients with moderate to severe COVID-19. In convalescents, activation of coagulation remains, which indicates the need to monitor the hemostatic system after Illness.
وصف الملف: electronic resource
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10دورية أكاديمية
المؤلفون: Tatiana M. Zavarykina, Polina K. Lomskova, Irina V. Pronina, Svetlana V. Khokhlova, Marina B. Stenina, Gennady T. Sukhikh
المصدر: International Journal of Molecular Sciences, Vol 24, Iss 23, p 17073 (2023)
مصطلحات موضوعية: breast cancer, circulating tumor DNA, liquid biopsy, digital PCR, next-generation sequencing, chemotherapy, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: This paper introduces the reader to the field of liquid biopsies and cell-free nucleic acids, focusing on circulating tumor DNA (ctDNA) in breast cancer (BC). BC is the most common type of cancer in women, and progress with regard to treatment has been made in recent years. Despite this, there remain a number of unresolved issues in the treatment of BC; in particular, early detection and diagnosis, reliable markers of response to treatment and for the prediction of recurrence and metastasis, especially for unfavorable subtypes, are needed. It is also important to identify biomarkers for the assessment of drug resistance and for disease monitoring. Our work is devoted to ctDNA, which may be such a marker. Here, we describe its main characteristics and potential applications in clinical oncology. This review considers the results of studies devoted to the analysis of the prognostic and predictive roles of various methods for the determination of ctDNA in BC patients. Currently known epigenetic changes in ctDNA with clinical significance are reviewed. The possibility of using ctDNA as a predictive and prognostic marker for monitoring BC and predicting the recurrence and metastasis of cancer is also discussed, which may become an important part of a precision approach to the treatment of BC.
وصف الملف: electronic resource
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