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Up-regulated microRNAs in blastocoel fluid of human implanted embryos could control circuits of pluripotency and be related to embryo competence

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JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 2025年 1-15页

作者： Battaglia, Rosalia Caponnetto, Angela Ferrara, Carmen Fazzio, Anna Barbagallo, Cristina Stella, Michele Barbagallo, Davide Ragusa, Marco Vento, Maria Elena Borzi, Placido Scollo, Paolo Carli, Luca Feichtinger, Michael Kasapi, Evangelia Tsakos, Elias Palini, Simone Sierka, Wojciech Pecorino, Basilio Campitiello, Maria Rosaria Ronsini, Carlo Purrello, Michele Valerio, Domenico Longobardi, Salvatore D'Hooghe, Thomas Di Pietro, Cinzia Univ Catania Dept Biomed & Biotechnol Sci Sect Biol & Genet G Sichel I-95123 Catania Italy Univ Enna Kore Dept Med & Surg I-94100 Enna Italy Cannizzaro Hosp IVF Unit Catania Italy Wunschbaby Inst Feichtinger Vienna Austria EmbryoClin IVF Thessaloniki Greece Cervesi Hosp IVF Unit Cattolica Italy Gyncentrum Sp Zelazna 1 PL-40851 Katowice Poland ASL Salerno Dept Obstet & Gynecol & Physiopathol Human Reprod Salerno Italy Univ Campania Luigi Vanvitelli Dept Woman Child & Gen & Specialized Surg Naples Italy Inst Genet Res IRG I-80143 Naples Italy Merck Serono SpA Global Clin Dev Rome Italy Merck KGaA Darmstadt Germany KU Leuven Univ Leuven Dept Dev & Regenerat Biomed Sci Grp Leuven Belgium

Purpose The paper aims to investigate the biological role of microRNAs secreted by preimplantation embryo into the blastocoel fluid and to detect a distinctive molecular signature for identifying embryos with the highest implantation potential. Methods We carried on a multicenter retrospective study involving five European IVF centers. We collected 112 blastocoel fluid samples from embryos on day 5 post-fertilization, cultured individually, along with data on blastocyst grade and embryo transfer outcomes. Using a custom TLDA Array, we compared the expression levels of 89 miRNAs between 33 fluids from high-quality implanted embryos and 30 fluids from high-quality not-implanted embryos. Expression differences were assessed using SAM and t-test. Additionally, correlation and function enrichment analysis and network construction were conducted to identify the biological roles of deregulated microRNAs. Results We identified six up-regulated microRNAs in the blastocoel fluid from implanted embryos, significantly and positively correlated across all samples (r >= 0.7;P <= 0.05). They could take part in pluripotency circuits, regulating and being regulated by transcription factors associated with stemness, cell growth, and embryo development. The ROC curve analysis confirmed the potential of these miRNAs as implantation classifiers. Conclusion The six miRNAs up-regulated in blastocoel fluid from implanted embryos may represent a functional molecular signature for evaluating blastocyst quality and identifying the most competent embryos. Their evaluation associated with non-invasive preimplantation genetic testing, integrating epigenetic and genomic analyses, could enhance implantation grade and allow for identification of the euploid embryo not able to implant.

关键词： Blastocoel fluid Embryo development Embryo implantation Human blastocyst MicroRNAs

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EP09.50: Third trimester echocardiography in gyncentrum IVF and prenatal diagnosis clinic Poland

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Ultrasound in Obstetrics & Gynecology 2024年第S1期64卷 209-209页

作者： W. Rozmus Warcholinska A. Warcholinski Gyncentrum IVF and Prenatal Diagnosis Gyncentrum Clinic Poland Katowice Poland Atemida Software Company Sp z.o.o. Katowice Poland

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Evaluation of the Concentration of Selected Elements in the Serum of Patients with Degenerative Stenosis of the Lumbosacral spine

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BIOLOGICAL TRACE ELEMENT RESEARCH 2024年第11期202卷 4945-4960页

作者： Sobanski, Dawid Staszkiewicz, Rafal Filipowicz, Michal Holinski, Mateusz Jedrocha, Maciej Migdal, Marek Grabarek, Beniamin Oskar Szpital Sw Rafala Krakow Dept Neurosurg PL-30693 Krakow Poland WSB Univ Coll Med PL-41300 Dabrowa Gornicza Poland 5th Mil Clin Hosp Dept Neurosurg SP ZOZ Polyclin Krakow PL-30901 Krakow Poland Acad Silesia Fac Med Zabrze Dept Neurosurg PL-40555 Katowice Poland Gyncentrum Lab Mol Biol & Virol PL-40851 Katowice Poland

In humans, 23 elements have been shown to have biological activity. The purpose of this study was to evaluate the concentrations of iron (Fe), zinc (Zn), sodium (Na), potassium (K), magnesium (Mg), phosphorus (P), and calcium (Ca) in the serum of patients diagnosed with lumbar degenerative stenosis when compared to the concentrations of those elements in the serum of healthy volunteers. The study group consisted of 60 patients who were diagnosed with degenerative stenosis of the lumbosacral spine and who qualified for hemilaminectomy. The control group included 60 healthy volunteers without degenerative spinal stenosis. The clinical specimens studied had sera collected from both groups. The quantitative analysis of the selected elements revealed statistically significant (p < 0.05) lower concentrations of Zn (740 110 mu g/L vs. 880 +/- 160 mu g/L) and Mg (22,091 +/- 4256 mu g/L vs. 24,100 +/- 4210 mu g/L) in the serum of the patients from the study group when compared to the controls. By contrast, K (16,230 mu g/L +/- 1210 mu g/L vs. 13,210 mu g/L +/- 1060 mu g/L) and Fe (141.87 mu g/L +/- 11.22 mu g/L vs. 109.1 mu g/L +/- 26.43 mu g/L) levels were significantly higher in the study group compared to the controls (p < 0.05). No statistically significant changes were detected in the concentrations of the assessed micronutrients and macronutrients in both sexes in either the study group, the control group, or those based on body mass index (p > 0.05). In the serum samples from the study group, the strongest correlations were noted between the concentrations. In the study group, we showed a significant relationship between the levels of Fe/Zn (r = 0.41), Fe/Na (r = 0.41), Fe/P (r = 0.55), Zn/P (r = 0.68), Zn/K (r = 0.48), Zn/Ca (r = 0.94), Mg/Ca (r = 0.79), and Na/K (r = 0.67). We showed that only Mg concentration varied statistically significantly with the severity of pain (p < 0.05). These findings suggest that the assessment of Fe, Zn, Mg, and K concentr

关键词： spinal stenosis Micronutrients Macronutrients Trace elements Pain Body mass index

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The impact of wound-healing assay, phorbol myristate acetate (PMA) stimulation and siRNA-mediated FURIN gene silencing on endogenous retroviral ERVW-1 expression level in U87-MG astrocytoma cells

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ADVANCES IN MEDICAL SCIENCES 2024年第1期69卷 113-124页

作者： Machnik, Grzegorz Buldak, Lukasz Zapletal-Pudelko, Karolina Grabarek, Beniamin Oskar Staszkiewicz, Rafal Sobanski, Dawid Okopien, Bogus law Med Univ Silesia Fac Med Sci Katowice Dept Internal Med & Clin Pharmacol Medykow 18 PL-40752 Katowice Poland WSB Univ Coll Med Dabrowa Gornicza Poland Dept Mol Biol Gyncentrum Fertil Clin Katowice Poland SP ZOZ Polyclin Krakow 5th Mil Clin Hosp Dept Neurosurg Krakow Poland Szpital Sw Rafala Dept Neurosurg Krakow Poland Acad Silesia Fac Med Dept Neurosurg Katowice Poland

Purpose: Human endogenous retroviruses (HERVs) are ubiquitous genomic sequences. Normally dormant HERVs, undergo reactivation by environmental factors. This deregulation of HERVs' transcriptional equilibrium correlates with medical conditions such as multiple sclerosis (MS). Here we sought to explore whether exposing the U-87 MG astrocytoma cells to traumatic injury deregulates the expression of HERV-W family member ERVW-1 encoding syncytin-1. We also examined the expression of FURIN gene that is crucial in syncytin-1 synthesis. Material and methods: Scratch assay was used as a model of cells injury in U-87 MG cells. Reverse transcriptionquantitative polymerase chain reaction (RT-qPCR), western blot (WB) and migration assay using Boyden chamber were used. Phorbol 12-myristate 13-acetate (PMA) and small interfering RNA (siRNA) were used for cell stimulation and gene expression inhibition, respectively. Results: Results revealed reduced ERVW-1 expression in cells exposed to injury (p < 0.05) while GFAP gene - a marker of active astrocytes, was upregulated (p < 0.01). These findings were confirmed by both WB and RT-qPCR. Expression of FURIN gene was not altered after injury, but cell stimulation by PMA strongly increased FURIN expression, simultaneously downregulating ERVW-1 (p < 0.01). SiRNA-mediated expression inhibition of ERVW-1 and FURIN influenced the mRNA level for SLC1A5 (ASCT2) - primary syncytin-1 receptor, that was significantly lower. FURIN inhibition by siRNA caused strong upregulation of ERVW-1 expression (p < 0.01). Conclusion: Results showed that mechanical impact affects the expression of endogenous retroviruses in U-87 MG astrocytoma cells by scratch assay. Regulation of FURIN, a crucial enzyme in ERVW-1 turnover may support the therapy of some neurological conditions.

关键词： Human endogenous retroviruses FURIN Astrocytes Central nervous system diseases Wounds and injuries

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HspA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines

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Cell Death and Disease 2025年第1期16卷 1-15页

作者： Gogler, Agnieszka Wilk, Agata Małgorzata Sojka, Damian Robert Adamiec-Organiściok, Małgorzata Matysiak, Natalia Kania, Daria Wiecha, Klaudia Małusecka, Ewa Cortez, Alexander Jorge Zamojski, Dawid Marczyk, Michał Mazurek, Agnieszka Maria Oziębło, Sylwia Scieglinska, Dorota Center for Translational Research and Molecular Biology of Cancer Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland Department of Biostatistics and Bioinformatics Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland Department of Systems Biology and Engineering Silesian University of Technology Akademicka 16 Gliwice 44-100 Poland Department of Histology and Cell Pathology Faculty of Medical Sciences in Zabrze Medical University of Silesia in Katowice Jordana 19 Zabrze 41-808 Poland Department of Data Science and Engineering Silesian University of Technology Akademicka 16 Gliwice 44-100 Poland Genetic Laboratory Gyncentrum Sp. z o.o. Sosnowiec 41-208 Poland Yale Cancer Center Yale School of Medicine New Haven CT United States

Chaperone proteins constitute a molecular machinery that controls proteostasis. HspA2 is a heat shock-non-inducible member of the human HspA/Hsp70 family, which includes several highly homologous chaperone proteins. HspA2 exhibits a cell type-specific expression pattern in the testis, brain, and multilayered epithelia. It is a crucial male fertility-related factor, but its role in somatic cells is poorly understood. Previously, we found that HspA2 deficiency can impair epidermal keratinocyte differentiation. In this study, we confirmed the crucial role of HspA2 in keratinocyte differentiation by investigating immortalized keratinocytes cultured in a reconstructed human epidermis model. Moreover, we uncovered the influence of HspA2 on immunomodulation. Transcriptomic analysis revealed that the total loss of HspA2 affected the expression of genes related to keratinocyte differentiation and interleukin- and interferon-mediated signaling. The functional analysis confirmed bidirectional changes associated with the loss of HspA2. The HspA2 knockout in HaCaT and Ker-CT keratinocytes, but not HspA2 overproduction, impaired granular layer development as evidenced by reduced levels of late keratinocyte differentiation markers, filaggrin and involucrin, along with structural abnormalities in the upper epidermal layer. Differentiation defects were accompanied by increased mRNA expression and extracellular secretion of keratinocyte-derived pro-inflammatory IL-6 cytokine and CCL2, CCL8, CXCL1, CXCL6, and CXCL10 chemokines. The loss of HspA2 also led to increased expression of extracellular HspA1 and interferon-stimulated genes and secretion of immune cell modulator SLAMF7. Knocking down HspA1 expression in keratinocytes decreased the secretion of IL-6 and CCL5 release, suggesting extracellular HspA1’s role in the HspA2-regulated molecular network. To summarize, we uncovered the complex homeostatic role of HspA2 in epidermal keratinocytes. Our results suggest that dysfunction in H

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Linzagolix provides rapid, significant reduction of heavy menstrual bleeding in women with uterine fibroids

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EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY 2024年 293卷 300-300页

作者： Olejek, A. Ciebiera, M. Skrzypulec-Plinta, V. Boolell, M. Bestel, E. GynCentrum Clin Sp Zoo Katowice Poland Ctr Postgrad Med Educ Dept Obstet & Gynecol 2 Warsaw Poland Med Univ Silesia Fac Hlth Sci Katowice Dept Reprod Hlth & Sexol Dept Womens Hlth Silesia Poland Theramex London England Theramex Zurich Switzerland

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O-211 A comparative analysis of non-invasive preimplantation genetic testing for aneuploidies using next-generation sequencing on day 5 and day 6 spent culture media versus trophectoderm

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Human Reproduction 2023年第SUPPLEMENT_1期38卷

作者： Strychalska, A Sierka, W Kokot, A Jodlowec-Lubanska, N Wroblewska, U Mermer, P Simka-Lampa, K Morawiec, E Pudelko, A Bednarska-Czerwinska, A Gyncentrum Sp. z o. o. Genetic Laboratory Sosnowiec Poland Gyncentrum Sp. z o. o. Embryology Katowice Poland University of Technology Faculty of Medicine Katowice Poland Medical university of Silesia Clinical Biochemistry Sosnowiec Poland

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Expression profile of Tripartite motif family (TRIM) in human fibroblasts (NHDF) infected with porcine endogenous retrovirus (PERV)

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XENOTRANspLANTATION 2021年第1期28卷 e12650-e12650页

作者： Emilia, Morawiec Roman, Nowak Barbara, Strzalka-Mrozik Urszula, Mazurek Krzysztof, Lopata Pawel, Olczyk Univ Technol Katowice Fac Med Zabrze Dept Microbiol Ul Pk Hutniczy 3-5 PL-41800 Katowice Poland Med Univ Silesia Fac Pharmaceut Sci Sosnowiec Dept Mol Biol Katowice Poland Gyncentrum Lab Mol Biol & Virol Katowice Poland Med Univ Silesia Fac Pharmaceut Sci Sosnowiec Dept Community Pharm Katowice Poland Silesian Med Univ Sosnowiec Orthopaed Clin Unit 5 Sosnowiec Sosnowiec Poland Jozef Tyszkiewicz Higher Sch Bielsko Biala Bielsko Biala Poland Karol Godula Upper Silesian Acad Entrepreneurship Chorzow Poland HYDREX DIAGNOST Sp Zoo Spk Warsaw Poland

Background Understanding the interactions between the microRNA (miRNA) and mRNA of genes encoding restriction factors (RFs) can lead to the development of new antiretroviral strategies aimed at providing the resistance and reducing susceptibility of human cells to potential PERV infection. Among RFs TRIM family play an important role in shaping the immune response during various stages of infection. The aim of the study was to evaluate in vitro the transcriptional profile of TRIM family genes and identify complementary miRNAs in NHDF cells infected with PERVs and induced by gram negative lipopolysacharide (LPS). Methods Human dermal fibroblasts cells were cultured in four separate conditions- 2 monocultures: control (N), treated with LPS (NL) and 2 co-cultures with porcine PK15 cells: without LPS (NP) and treated with LPS (NLP). Bacterial LPS was used in this study as an inducer of inflammation in NHDF cells. After extraction of DNA and RNA from cells PERV infection was confirmed in co-cultures by qPCR and RTqPCR. RNA extracts served as a matrix for HGU 133A 2.0 and miRNA 2.0 microarrays to evaluate the expression profile of the selected TRIM family genes and miRNAs *** 2,14,22, and28were selected for the validation of HGU 133A 2.0 results. Statistical analyses were performed with the use of REST (c) 2009 and Genespring GX 13.0. Transcriptome Analysis Console 4.0 program (Affymetrix) was used to identify miRNAs that differentiate the studied genes in all conditions. Results Porcine endogenous retrovirus infection at DNA and RNA level was confirmed in NHDF cells in each of the tested groups (NP and NLP). Contamination was excluded in N and NL groups. Based on the analysis of HGU 133A 2.0 results 93 mRNA IDs of TRIM family genes differentiating analyzed conditions were selectedP < .05. HGU 133A 2.0 mRNA fluorescence profile was confirmed with RTqPCR of TRIM2, TRIM14, TRIM22 and TRIM28P < .05. TRIM14 down regulation was specific only in PERV monoinfection (

关键词： miRNA PERVs restriction factors TRIM

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The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study

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ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS 2023年第1期71卷 1-13页

作者： Sadeghdoust, Mohammadamin Aligolighasemabadi, Farnaz Dehesh, Tania Taefehshokr, Nima Sadeghdoust, Adel Kotfis, Katarzyna Hashemiattar, Amirhossein Ravandi, Amir Aligolighasemabadi, Neda Vakili, Omid Grabarek, Beniamin Staszkiewicz, Rafal Los, Marek J. J. Mokarram, Pooneh Ghavami, Saeid Islamic Azad Univ Dept Internal Med Mashhad Med Sci Branch Mashhad Iran Kerman Univ Med Sci Sch Publ Hlth Dept Biostat & Epidemiol Kerman Iran Univ Western Ontario Ctr Human Immunol Dept Microbiol & Immunol London ON Canada Hormozgan Univ Med Sci Sch Med Dept Internal Med Bandar Abbas Iran Pomeranian Med Univ Dept Anesthesiol Intens Therapy & Acute Intoxicat Szczecin Poland Islamic Azad Univ Dept Radiol Mashhad Med Sci Branch Mashhad Iran Univ Manitoba Inst Cardiovasc Sci Sr Boniface Res Ctr Winnipeg MB Canada Guilan Univ Med Sci Razi Hosp Sch Med Dept Internal Med Rasht Iran Isfahan Univ Med Sci Sch Pharm & Pharmaceut Sci Dept Clin Biochem Esfahan Iran Acad Silesia Katowice Fac Med Zabrze Dept Histol Cytophysiol & Embryol Zabrze Poland Acad Silesia Katowice Fac Med Zabrze Dept Gynaecol & Obstet Zabrze Poland GynCentrum Lab Mol Biol & Virol Katowice Poland 5Th Mil Clin Hosp Dept Neurosurg SP ZOZ Polyclin Krakow Krakow Poland Silesian Tech Univ Biotechnol Ctr Gliwice Poland Shiraz Univ Med Sci Autophagy Res Ctr Dept Biochem Shiraz Iran Univ Manitoba Max Rady Coll Med Rady Fac Hlth Sci Dept Human Anat & Cell Sci Winnipeg MB Canada Univ Technol Katowice Acad Silesia Fac Med Zabrze Zabrze Poland Manitoba Univ Manitoba Res Inst Oncol & Hematol Canc Care Winnipeg MB Canada Univ Manitoba Children Hosp Res Inst Manitoba Biol Breathing Theme Winnipeg MB Canada

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM. [Graphics]

关键词： COVID-19 Diabetes mellitus Statins Post-acute COVID-19 syndrome Pulmonary fibrosis

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O-062 MicroRNAs in Blastocoel Fluid: a molecular signature for predicting human embryo implantation potential

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Human Reproduction 2023年第SUPPLEMENT_1期38卷

作者： Battaglia, R Caponnetto, A Ferrara, C Fazzio, A Barbagallo, C Barbagallo, D Vento, M E Carli, L Kasapi, E Palini, S Sierka, W Valerio, D Longobardi, S D’Hooghe, T Di Pietro, C University of Catania Biomedical and Biotechnological Sciences Catania Italy Cannizzaro Hospital IVF Unit Catania Italy Wunschbaby Institut Feichtinger Infertility clinic Vienna Austria EmbryoClinic - Hellenic Medical Research Institute IVF center Thessaloniki Greece Cervesi Hospital Cattolica IVF Unit Cattolica Italy Gyncentrum Sp. z o.o. IVF Center Katowice Poland Institute Genetic Research IRG Napoli Italy Global Clinical Development Merck Serono SpA Roma Italy Merck KGaA- Darmstadt- Germany Development and Regeneration- Biomedical Sciences Group- KU Leuven University of Leuven Leuven Belgium

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