F&S science最新文献

{"title":"A biomechanical assessment of tissue-engineered polymer neo-uteri after orthotopic implantation","authors":"Rachel C. Nordberg Ph.D. ,&nbsp;Renata S. Magalhaes M.D., Ph.D. ,&nbsp;Irene Cervelló Ph.D. ,&nbsp;J.Koudy Williams D.V.M. ,&nbsp;Anthony Atala M.D. ,&nbsp;Elizabeth G. Loboa Ph.D.","doi":"10.1016/j.xfss.2023.12.005","DOIUrl":"10.1016/j.xfss.2023.12.005","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the <em>in vivo</em><span> biomechanical maturation of tissue-engineered neo-uteri that have previously supported live births in a rabbit model.</span></p></div><div><h3>Design</h3><p>Nonclinical animal study.</p></div><div><h3>Setting</h3><p>University-based research laboratory.</p></div><div><h3>Animals</h3><p>Eighteen adult female rabbits.</p></div><div><h3>Intervention</h3><p><span>Biodegradable poly-DL-lactide-co-glycolide-coated polyglycolic acid scaffolds seeded with autologous uterine-derived endometrial and myometrial cells. Nonseeded scaffolds and seeded, tissue-engineered neo-uteri were implanted into one </span>uterine horn of rabbits for 1, 3, or 6 months, excised, and biomechanically assessed in comparison to native uterine tissue.</p></div><div><h3>Main Outcome Measures</h3><p>Tensile stress-relaxation testing, strain-to-failure testing, and viscoelastic modeling.</p></div><div><h3>Results</h3><p>By evaluating the biomechanical data with several viscoelastic models, it was revealed that tissue-engineered uteri were more mechanically robust than nonseeded scaffolds. For example, the 10% instantaneous stress of the tissue-engineered neo-uteri was 2.1 times higher than the nonseeded scaffolds at the 1-month time point, 1.6 times higher at the 3-month time point, and 1.5 times higher at the 6-month time point. Additionally, as the duration of implantation increased, the engineered constructs became more mechanically robust (e.g., 10% instantaneous stress of the tissue-engineered neo-uteri increased from 22 kPa at 1 month to 42 kPa at 6 months). Compared with native tissue values, tissue-engineered neo-uteri achieved or surpassed native tissue values by the 6-month time point.</p></div><div><h3>Conclusion</h3><p>The present study evaluated the mechanical characteristics of novel tissue-engineered neo-uteri that have previously been reported to support live births in the rabbit model. We demonstrate that the biomechanics of these implants closely resemble those of native tissue, giving further credence to their development as a clinical solution to uterine factor infertility.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 58-68"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity","authors":"Zoran Jason Pavlovic M.D. ,&nbsp;Angel Hsin-Yu Pai M.D. ,&nbsp;Tzu-Ti Hsiao M.S. ,&nbsp;Chih-Feng Yen M.D., Ph.D. ,&nbsp;Hasan Alhasan M.D. ,&nbsp;Asli Ozmen Ph.D. ,&nbsp;Erika P. New M.D. M.P.H. ,&nbsp;Xiaofang Guo M.D. ,&nbsp;Anthony N. Imudia M.D. ,&nbsp;Ozlem Guzeloglu-Kayisli Ph.D. ,&nbsp;Charles J. Lockwood M.D. ,&nbsp;Umit A. Kayisli Ph.D.","doi":"10.1016/j.xfss.2023.11.003","DOIUrl":"10.1016/j.xfss.2023.11.003","url":null,"abstract":"<div><h3>Objective</h3><p><span>To study the effect of adenomyosis<span> on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine </span></span>cell lineages<span>, cell differentiation, and organogenesis, potentially leading to impaired endometrial implantation.</span></p></div><div><h3>Design</h3><p>Laboratory based experimental study.</p></div><div><h3>Setting</h3><p>Academic hospital and laboratory.</p></div><div><h3>Patients</h3><p><span>Human endometrial stromal cells (HESCs) of reproductive age patients, 18–45 years of age, with adenomyosis were compared with patients with no pathology and leiomyomatous uteri as controls (n = 4 in each group, respectively). Additionally, midsecretory phase endometrial sections were obtained from patients with adenomyosis and control patients with </span>leiomyoma (n = 8 in each group, respectively).</p></div><div><h3>Interventions</h3><p><span>GATA2<span><span> and GATA6 </span>immunohistochemistry and H-SCORE were performed on the midsecretory phase endometrial sections from adenomyosis and leiomyoma control patients (n = 8 each, respectively). Control and adenomyosis patient HESC cultures were treated with placebo or 10</span></span>^-8<span> M estradiol (E2), or decidualization media (EMC) containing 10</span>^-8 M E2, 10^-7<span> M medroxyprogesterone acetate, and 5 × 10</span>^-5<span> M cAMP for 6 and 10 days. Additionally, control HESC cultures (n = 4) were transfected with scrambled small interfering RNA (siRNA) (control) or </span><em>GATA2</em>-specific siRNAs for 6 days while adenomyosis HESC cultures (n = 4) were transfected with human <em>GATA2</em><span> expression vectors to silence or induce </span><em>GATA2</em> overexpression.</p></div><div><h3>Main Outcome Measures</h3><p><span><span>Immunohistochemistry was performed to obtain GATA2 and GATA6 H-SCORES in adenomyosis vs. control patient endometrial tissue. Expression of GATA2, GATA6, insulin-like growth factor-binding protein 1 (IGFBP1), prolactin (PRL), progesterone receptor (PGR), </span>estrogen receptor 1 (ESR1), leukemia inhibitory factor (LIF), and Interleukin receptor 11 (IL11R) messenger RNA (mRNA) levels were analyzed using by qPCR with normalization to </span><em>ACTB</em><span>. Silencing and overexpression experiments also had the corresponding mRNA levels of the above factors analyzed. Western blot analysis was performed on isolated proteins from transfection experiments.</span></p></div><div><h3>Results</h3><p><span><span>Immunohistochemistry revealed an overall fourfold lower GATA2 and fourfold higher GATA6 H-SCORE level in the endometrial stromal cells of patients with adenomyosis vs. controls. Decidual induction with EMC resulted in significantly lower GATA2, PGR, PRL and IGFBP1 mRNA levels in HESC cultures from patients with adenomyosis patient vs. controls","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 92-103"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135764119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An assessment of alterations to human sperm methylation patterns in coronavirus disease 2019 infected and healthy control males","authors":"Isaac Stirland B.S. ,&nbsp;Murilo Racy Soares Ph.D. ,&nbsp;Cristiana Libardi Miranda Furtado Ph.D. ,&nbsp;Rosana Maria Dos Reis Ph.D. ,&nbsp;Kenneth I. Aston Ph.D. ,&nbsp;R. Parker Smith ,&nbsp;Timothy G. Jenkins Ph.D.","doi":"10.1016/j.xfss.2023.12.003","DOIUrl":"10.1016/j.xfss.2023.12.003","url":null,"abstract":"<div><h3>Objective</h3><p><span>To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects </span>male reproductive health<span>, considering the many potential factors that contribute to declines in male fertility on a semiglobal scale.</span></p></div><div><h3>Design</h3><p><span><span>In total, 64 human semen samples—32 treatment and 32 control—were laboratory processed and bioinformatically analyzed to assess differences in DNA </span>methylation patterns. Implementing multiple bioinformatic tools, the analyses conducted will elicit between-group differences with respect to </span>epigenetic age, epigenetic instability, semiglobal, and regional methylation, in addition to methylation patterns as a function of time since infection.</p></div><div><h3>Setting</h3><p>University hospital.</p></div><div><h3>Patients</h3><p>The study cohort of 64 individuals was drawn from a larger population of 94 volunteer participants recruited at the Human Reproduction Center at the Clinical Hospital of the Ribeirao Preto Medical School—University of São Paulo between June 2021 and January 2022 as well as in accordance with the ethical guidelines established by the Declaration of Helsinki.</p></div><div><h3>Intervention</h3><p>Exposure to SARS-CoV-2.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>Effects on male reproductive health were reported as differences in DNA methylation measured using an array. Mean β values at key regulatory loci for human </span>spermatocytes were analyzed and compared between groups. Further analysis of β values using epigenetic age, instability, semiglobal, and regional methylation tools provided an analysis with substantial breadth and depth.</p></div><div><h3>Results</h3><p>In all analyses, there were no differences between groups. Considering these results, it can be inferred that infection with SARS-CoV-2 does not alter the epigenome of human spermatocytes in significant and/or persistent ways. Tangentially, these data also suggest that human male reproductive health is minimally altered by the virus, or that it is altered in a way that is independent of epigenetic programming.</p></div><div><h3>Conclusion</h3><p>Infection with SARS-CoV-2 has been reportedly associated with alterations in male fertility. This study asserts that such alterations do not have an epigenetic basis but are likely a result of concomitant symptomatology<span>, i.e., fever and inflammation. Across the multiple bioinformatic analyses conducted, the results of this test did not detect any differences in DNA methylation patterns between coronavirus disease 2019 and noncoronavirus disease semen donor groups.</span></p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 2-15"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138614077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of tenascin C in lesion formation in early peritoneal endometriosis","authors":"Maako Moriyama M.D. ,&nbsp;Kazuomi Nakamura Ph.D. ,&nbsp;Hiroki Nagata M.D. ,&nbsp;Ikumi Wada M.D. ,&nbsp;Kei Nagira M.D., Ph.D. ,&nbsp;Yukihiro Azuma M.D., Ph.D. ,&nbsp;Eri Sato M.D., Ph.D. ,&nbsp;Tasuku Harada M.D., Ph.D. ,&nbsp;Fuminori Taniguchi M.D., Ph.D.","doi":"10.1016/j.xfss.2023.12.004","DOIUrl":"10.1016/j.xfss.2023.12.004","url":null,"abstract":"<div><h3>Objective</h3><p><span>To identify cytokines or extracellular matrix<span> components that contribute to adhesion to, and invasion of, the peritoneum, proximal to lesions in the early phase of </span></span>endometriosis.</p></div><div><h3>Design</h3><p>Laboratory-based study.</p></div><div><h3>Setting</h3><p>University Hospital and Laboratory of Animal Science.</p></div><div><h3>Patients and Animals</h3><p><span>Five women with ovarian endometrioma, 138 wild-type (WT) C57BL/6N mice, and 48 </span><span><em>Tenascin</em><em> C</em></span> (<em>Tnc</em>) knockout (TncKO) mice.</p></div><div><h3>Interventions</h3><p><span><span>To establish a murine endometriosis model, 20 pieces of minced uterine tissue fragments from each horn were administered intraperitoneally to syngeneic mice. Three days later, endometriotic lesions and peritoneal tissues were collected. Separately, we transfected human peritoneal </span>mesothelial cells<span> (HMrSV5) or human endometrial stromal cells (hESCs) with </span></span><em>Tnc</em><span> small interfering ribonucleic acid.</span></p></div><div><h3>Main Outcome Measures</h3><p><span>We employed a polymerase chain reaction<span> array to profile gene expression in the murine peritoneum, in both peritoneum distal to lesions and peritoneum surrounding lesions (PSL). The expression of upregulated genes in the PSL was verified in the peritoneal samples by real-time reverse transcription-polymerase chain reaction. TncKO mice were used to investigate the role of Tnc in the development of endometriosis. We evaluated the proliferative activity or inflammatory state of lesions by Ki67 or CD3 immunostaining. Intraperitoneal distribution of macrophages was assessed by fluorescence-activated cell sorting. Using </span></span><em>Tnc</em> small interfering ribonucleic acid, we examined the invasive capacity of hESCs in a coculture system with HMrSV5.</p></div><div><h3>Results</h3><p><em>Tnc</em> gene expression was significantly higher in PSL than in peritoneum distal to lesions. The weight and number of TncKO lesions in TncKO hosts were lower than those of WT lesions in WT hosts. In contrast, the weight and number of nonattached TncKO lesions in TncKO hosts were higher than those of nonattached WT lesions in WT hosts. We observed decreased Ki67-positive cells or H-scores for CD3, a lower proportion of M1 macrophages, and a higher proportion of M2 macrophages in TncKO lesions in TncKO recipients. Silencing of <em>Tnc</em> expression in hESCs and HMrSV5 diminished the invasivity of hESCs.</p></div><div><h3>Conclusion</h3><p><em>Tnc</em> may be a crucial factor in the development of early peritoneal endometriosis.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 69-79"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oocyte-derived growth differentiation factor 9 suppresses the expression of CYP17A1 and androgen production in human theca cells","authors":"Xi Guo Ph.D. ,&nbsp;Yiping Zhong M.Phil. ,&nbsp;Yang Liu M.Phil. ,&nbsp;Rihan Wu M.Phil. ,&nbsp;Ling Huang Ph.D. ,&nbsp;Chuan Huang M.Phil. ,&nbsp;Minghui Chen Ph.D.","doi":"10.1016/j.xfss.2023.10.005","DOIUrl":"10.1016/j.xfss.2023.10.005","url":null,"abstract":"<div><h3>Objective</h3><p><span>To investigate the direct effect of growth differentiation factor 9<span> (GDF9) on androgen production in human </span></span>theca cells.</p></div><div><h3>Design</h3><p>Experimental study.</p></div><div><h3>Setting</h3><p>Tertiary hospital-based research laboratory.</p></div><div><h3>Patient(s)</h3><p>Women who underwent in vitro fertilization and intracytoplasmic sperm injections at our clinic were included in this study.</p></div><div><h3>Intervention(s)</h3><p>Primary cultured human theca cells from women undergoing in vitro fertilization and intracytoplasmic sperm injection treatment were treated with GDF9, an activin receptor-like kinase 5 (ALK5) inhibitor, and a SMAD4 agonist.</p></div><div><h3>Main Outcome Measure(s)</h3><p>The expression of androgen synthesis-related genes <em>StAR</em>, <span><em>CYP17A1</em></span>, and <span><em>LHCGR</em></span><span>, levels of androstenedione<span> and testosterone, phosphorylation of SMAD2/3, and the interaction between bone morphogenic protein-activated type II receptor and ALK5 were evaluated using reverse transcription-quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assays, and coimmunoprecipitation assays, respectively.</span></span></p></div><div><h3>Result(s)</h3><p>Growth differentiation factor 9 decreased <em>StAR, CYP17A1</em>, and <em>LHCGR</em> expression levels in human theca cells, which was prevented by treatment with the ALK5 inhibitor, and suppressed production of androgen in human theca cells. Growth differentiation factor 9 increased SMAD2/3 phosphorylation, and the ALK5 inhibitor also suppressed this effect. Bone morphogenic protein-activated type II receptor and ALK5 bound to each other after GDF9 stimulation. The SMAD4 agonist kartogenin also decreased messenger RNA levels of <em>StAR</em> and <em>CYP17A1</em> and protein levels of StAR in human theca cells.</p></div><div><h3>Conclusion(s)</h3><p><span>Growth differentiation factor 9 can activate the bone morphogenic protein-activated type II receptor-ALK5-SMAD2/3 signaling pathway, suppress </span><em>CYP17A1</em> expression, and decrease androgen production in human theca cells.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 16-23"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136152846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryo ranking agreement between embryologists and artificial intelligence algorithms","authors":"Nikica Zaninovic M.S., Ph.D. ,&nbsp;Jose T. Sierra Ph.D. ,&nbsp;Jonas E. Malmsten D.P.S. ,&nbsp;Zev Rosenwaks M.D.","doi":"10.1016/j.xfss.2023.10.002","DOIUrl":"10.1016/j.xfss.2023.10.002","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate the degree of agreement of embryo ranking between embryologists and eight artificial intelligence (AI) algorithms.</p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Patient(s)</h3><p>A total of 100 cycles with at least eight embryos were selected from the Weill Cornell Medicine database. For each embryo, the full-length time-lapse (TL) videos, as well as a single embryo image at 120 hours, were given to five embryologists and eight AI algorithms for ranking.</p></div><div><h3>Intervention(s)</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Kendall rank correlation coefficient (Kendall’s τ).</p></div><div><h3>Result(s)</h3><p>Embryologists had a high degree of agreement in the overall ranking of 100 cycles with an average Kendall’s tau (K-τ) of 0.70, slightly lower than the interembryologist agreement when using a single image or video (average K-τ = 0.78). Overall agreement between embryologists and the AI algorithms was significantly lower (average K-τ = 0.53) and similar to the observed low inter-AI algorithm agreement (average K-τ = 0.47). Notably, two of the eight algorithms had a very low agreement with other ranking methodologies (average K-τ = 0.05) and between each other (K-τ = 0.01). The average agreement in selecting the best-quality embryo (1/8 in 100 cycles with an expected agreement by random chance of 12.5%; confidence interval [CI]95: 6%–19%) was 59.5% among embryologists and 40.3% for six AI algorithms. The incidence of the agreement for the two algorithms with the low overall agreement was 11.7%. Agreement on selecting the same top two embryos/cycle (expected agreement by random chance corresponds to 25.0%; CI95: 17%–32%) was 73.5% among embryologists and 56.0% among AI methods excluding two discordant algorithms, which had an average agreement of 24.4%, the expected range of agreement by random chance. Intraembryologist ranking agreement (single image vs. video) was 71.7% and 77.8% for single and top two embryos, respectively. Analysis of average raw scores indicated that cycles with low diversity of embryo quality generally resulted in a lower overall agreement between the methods (embryologists and AI models).</p></div><div><h3>Conclusion(s)</h3><p>To our knowledge, this is the first study that evaluates the level of agreement in ranking embryo quality between different AI algorithms and embryologists. The different concordance methods were consistent and indicated that the highest agreement was intraembryologist agreement, followed by interembryologist agreement. In contrast, the agreement between some of the AI algorithms and embryologists was similar to the inter-AI algorithm agreement, which also showed a wide range of pairwise concordance. Specifically, two AI models showed intra- and interagreement at the level expected from random selection.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 50-57"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From the Editor-in-Chief","authors":"William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2024.01.001","DOIUrl":"10.1016/j.xfss.2024.01.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Page 1"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin induces degradation of the extracellular matrix in human leiomyomata: novel in vitro, in vivo, and patient level evidence of matrix metalloproteinase involvement","authors":"Joy Britten M.D. ,&nbsp;Jaime A. Roura-Monllor M.D., M.S. ,&nbsp;Minnie Malik Ph.D. ,&nbsp;Sean Moran Ph.D. ,&nbsp;Anthony DeAngelis M.D., Ph.D. ,&nbsp;Paul Driggers Ph.D. ,&nbsp;Sadia Afrin Ph.D. ,&nbsp;Mostafa Borahay M.D., Ph.D. ,&nbsp;William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2023.11.005","DOIUrl":"10.1016/j.xfss.2023.11.005","url":null,"abstract":"<div><h3>Objectives</h3><p>To assess the effect of simvastatin<span> on uterine leiomyoma<span> growth and extracellular matrix (ECM) deposition.</span></span></p></div><div><h3>Design</h3><p><span>Laboratory analysis of human leiomyoma<span> cell culture, xenograft in a mouse model, and patient tissue from a </span></span>clinical trial.</p></div><div><h3>Setting</h3><p>Academic research center.</p></div><div><h3>Patient(s)</h3><p>Tissue culture from human leiomyoma tissue and surgical leiomyoma tissue sections from a placebo-controlled randomized clinical trial.</p></div><div><h3>Intervention(s)</h3><p>Simvastatin treatment.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Serum concentrations, xenograft volumes, and protein expression.</p></div><div><h3>Results</h3><p><span>Mice xenografted with 3-dimensional human leiomyoma cultures were divided as follows: 7 untreated controls; 12 treated with activated simvastatin at 10 mg/kg body weight; and 15 at 20 mg/kg body weight. Simvastatin was detected in the serum of mice injected at the highest dose. Xenograft volumes were significantly smaller (mean 53% smaller at the highest concentration). There was dissolution of compact ECM, decreased ECM formation, and lower collagen protein expression in xenografts. </span>Membrane type 1 matrix metalloproteinase<span> was increased in vitro and in vivo. Matrix metalloproteinase 2 and low-density lipoprotein receptor-related protein 1 were increased in vitro.</span></p></div><div><h3>Conclusions</h3><p>Simvastatin exhibited antitumoral activity with ECM degradation and decreased leiomyoma tumor volume in vivo. Activation of the matrix metalloproteinase 2, membrane type 1 matrix metalloproteinase, and low-density lipoprotein receptor-related protein 1 pathway may explain these findings.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 80-91"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone-primed cycles result in slower embryos without compromising implantation potential and with the advantages of oral administration and potential cost reduction","authors":"Daniela Paes de Almeida Ferreira Braga D.V.M., Ph.D. ,&nbsp;Amanda Setti M.Sc. ,&nbsp;Edward Carrilho M.D. ,&nbsp;Patrícia Guilherme M.Sc. ,&nbsp;Assumpto Iaconelli Jr. M.D. ,&nbsp;Edson Borges Jr. M.D., Ph.D.","doi":"10.1016/j.xfss.2023.12.001","DOIUrl":"10.1016/j.xfss.2023.12.001","url":null,"abstract":"<div><h3>Objective</h3><p>To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles.</p></div><div><h3>Design</h3><p>Cohort study.</p></div><div><h3>Setting</h3><p>Private university–affiliated in vitro fertilization center.</p></div><div><h3>Patient(s)</h3><p>This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups.</p></div><div><h3>Intervention(s)</h3><p>The kinetic recorded markers were time to pronuclear appearance and fading, time to 2–8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Embryo morphokinetics and clinical outcomes.</p></div><div><h3>Results</h3><p>Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively.</p></div><div><h3>Conclusions</h3><p>Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 43-49"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138621879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of natural compounds Crila and epigallocatechin gallate showed enhanced antiproliferative effects on human uterine fibroid cells compared with single treatments","authors":"Tao Bai Ph.D. ,&nbsp;Mohamed Ali Ph.D. ,&nbsp;Bernard Somers B.S. ,&nbsp;Qiwei Yang Ph.D. ,&nbsp;Sue McKinney J.D. ,&nbsp;Ayman Al-Hendy M.D., Ph.D.","doi":"10.1016/j.xfss.2023.09.004","DOIUrl":"10.1016/j.xfss.2023.09.004","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the combined effects of Crila and green tea extract, epigallocatechin gallate (EGCG), compared with single treatments, on human uterine fibroid cells.</p></div><div><h3>Design</h3><p>Human uterine leiomyoma (HuLM) cells were treated with different concentrations of Crila, alone or in combination with EGCG, and several experiments were employed.</p></div><div><h3>Setting</h3><p>A laboratory study.</p></div><div><h3>Patientss</h3><p>N/A.</p></div><div><h3>Interventions</h3><p>Crila, EGCG.</p></div><div><h3>Main Outcome Measures</h3><p>Cell proliferation assay, drug synergy using combination index, protein and gene expression analysis of proliferation marker proliferating cell nuclear antigen, and apoptosis marker BAX using western blotting and quantitative polymerase chain reaction, respectively.</p></div><div><h3>Results</h3><p>Results showed that tested Crila concentrations, when combined with 25 and 50 μM EGCG, exerted synergistic growth inhibitory effects on HuLM viability. This inhibitory effect on HuLM cell viability was because of decreased cell proliferation, as shown by a decrease in the proliferation marker proliferating cell nuclear antigen at messenger RNA and protein levels, rather than inducing apoptosis.</p></div><div><h3>Conclusion</h3><p>Our study concludes that the utility of natural compounds may provide a safe and cost-effective alternative to currently used short-term hormonal therapies against uterine fibroids.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 4","pages":"Pages 341-349"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666335X23000526/pdfft?md5=16ad7e27860baaa5dca2d9ad106e25e0&pid=1-s2.0-S2666335X23000526-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}