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14 pages, 223 KiB  
Article
Dante and the Ecclesial Paradox: Rebuke, Reverence, and Redemption
by Jonathan Farrugia
Religions 2025, 16(8), 951; https://doi.org/10.3390/rel16080951 - 22 Jul 2025
Viewed by 283
Abstract
In the past hundred years, three pontiffs have written apostolic letters to commemorate anniversaries relating to Dante: in 1921, Benedict XV marked the sixth centenary of the death of the great poet; in 1965, Paul VI judged it opportune to write on the [...] Read more.
In the past hundred years, three pontiffs have written apostolic letters to commemorate anniversaries relating to Dante: in 1921, Benedict XV marked the sixth centenary of the death of the great poet; in 1965, Paul VI judged it opportune to write on the occasion of the seventh centenary of his birth; and in 2021, Pope Francis added his voice to the numerous others wishing to honour the memory of the supreme Florentine poet on the seventh centenary of his death. Each letter is a product of its time: one hundred years ago, the Pope—still confined within the Vatican and refusing to recognise the Kingdom of Italy due to the Roman Question—addressed his text “to the beloved sons, professors and pupils of literary institutes and centres of higher learning within the Catholic world”; Paul VI, in full accord with the spirit of the Second Vatican Council and its vision of a Church seeking collaboration with the world, addressed his writing to Dante scholars more broadly, and within the same letter, together with other academic authorities, established the Chair of Dante Studies at the Catholic University of the Sacred Heart in Milan; Pope Francis today, in his outward-facing style of evangelisation, challenges everyone to (re)read Dante, whose teaching remains relevant seven hundred years after his death. Despite the differing political contexts and ecclesial agendas, Benedict XV, Paul VI, and Pope Francis are united on one point: Dante is a Christian poet—critical of the Church, certainly, but loyal to his faith and desirous of a religious institution that is more serious and less corrupt. This brief study presents the homage which the Church, today, seven centuries later, renders to this Poet—now widely recognised as a passionate witness of an arduous and active faith, in pursuit of justice and freedom. Full article
(This article belongs to the Special Issue Casta Meretrix: The Paradox of the Christian Church Through History)
19 pages, 42627 KiB  
Article
Molecular Remodeling of the Sperm Proteome Following Varicocele Sclero-Embolization: Implications for Semen Quality Improvement
by Domenico Milardi, Edoardo Vergani, Francesca Mancini, Fiorella Di Nicuolo, Emanuela Teveroni, Emanuele Pierpaolo Vodola, Alessandro Oliva, Giuseppe Grande, Alessandro Cina, Roberto Iezzi, Michela Cicchinelli, Federica Iavarone, Silvia Baroni, Alberto Ferlin, Andrea Urbani and Alfredo Pontecorvi
Proteomes 2025, 13(3), 34; https://doi.org/10.3390/proteomes13030034 - 15 Jul 2025
Viewed by 393
Abstract
Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem [...] Read more.
Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies. Full article
(This article belongs to the Section Proteomics of Human Diseases and Their Treatments)
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16 pages, 2021 KiB  
Article
Exploring OR2H1-Mediated Sperm Chemotaxis: Development and Application of a Novel Microfluidic Device
by Fiorella Di Nicuolo, Emanuela Teveroni, Alessandro Devigili, Clelia Gasparini, Andrea Urbani, Tullio Ghi, Alfredo Pontecorvi, Domenico Milardi and Francesca Mancini
Cells 2025, 14(13), 944; https://doi.org/10.3390/cells14130944 - 20 Jun 2025
Viewed by 509
Abstract
Microfluidic platforms have emerged as critical technologies for exploring sperm chemotaxis, providing precise gradient control, and facilitating in-depth behavioral assessment. We designed a novel, user-friendly microfluidic device that is optimized for human sperm morphology and motility. The device was validated using two well-established [...] Read more.
Microfluidic platforms have emerged as critical technologies for exploring sperm chemotaxis, providing precise gradient control, and facilitating in-depth behavioral assessment. We designed a novel, user-friendly microfluidic device that is optimized for human sperm morphology and motility. The device was validated using two well-established sperm chemoattractants, progesterone and bourgeonal, demonstrating its reliability and reproducibility. Given the key role of olfactory receptors (ORs) in mediating sperm chemotaxis, the newly developed device was employed to identify additional receptors that may contribute to sperm behavior. Using the Atlas database, we identified OR2H1 as a candidate receptor. It is enriched in testis-derived cells, particularly in early and late spermatids, and it is broadly expressed across human spermatozoa. We demonstrated that OR2H1’s ligand, methional, a sulfur-containing aldehyde naturally found in vaginal fluid and biosynthesized by Lactococcus lactis, significantly enhances sperm migration and progressive motility. Methional stimulation also triggered increased intracellular calcium levels, indicating receptor activation. Computer-assisted sperm analysis revealed that methional treatment improved sperm linearity, straightness, and wobble without affecting the average velocity, suggesting enhanced directional movement. These findings provide evidence that methional promotes sperm chemotaxis via OR2H1 and highlight the potential role of the vaginal microbiome in influencing human fertility. Full article
(This article belongs to the Section Reproductive Cells and Development)
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11 pages, 312 KiB  
Article
Descending to Bring Up “The Knowledge of the Son of God”: The Descent–Ascent Use of Psalm 68:18 in Ephesians 4:8–10, Compared with Romans 10:6–8’s Use of Deuteronomy 30
by Benjamin D. Giffone
Religions 2025, 16(5), 578; https://doi.org/10.3390/rel16050578 - 30 Apr 2025
Viewed by 452
Abstract
This paper offers a new explanation for the quotation of Psalm 68:18 in Ephesians 4:8. There are at least three puzzles in this text: (1) the significance of the quotation within the argument in the Ephesians passage (and why the apparent interruption between [...] Read more.
This paper offers a new explanation for the quotation of Psalm 68:18 in Ephesians 4:8. There are at least three puzzles in this text: (1) the significance of the quotation within the argument in the Ephesians passage (and why the apparent interruption between 4:7 and 4:11); (2) the divergent form of the quotation from the MT and LXX vis-a-vis the giving of gifts versus receiving; (3) why is only one set of gifts—proclaiming/verbal gifts, not gifts of service or discernment—mentioned in 4:11–12? This paper argues three points. First, diversity of spiritual gifts is not the focus of Eph 4:7–16, but rather, the same gift given to many: the word of truth about Jesus’s identity as Messiah and Son of God and his resurrection. Second, Ephesians 4:8–10 is comprehensible in context if viewed through another lens: Romans 10:6–8, the motif of “Messiah ascending victorious after having previously descended”. Third, the invocation of Psalm 68:18 in Ephesians 4:8–10 matches the Aramaic textual tradition, over-against the MT and the LXX. Paul’s use of the verse mirrors the proto-Targumic understanding of the “gifts given to the sons of mankind” as the Law of Moses. Paul is adopting this motif of “ascending with the Law-truth”, but with his own implied substitution of “the truth about Jesus”. Full article
(This article belongs to the Special Issue Resurrection and New Creation in Ephesians)
25 pages, 2236 KiB  
Article
Secretory Profile Analysis of Human Granulosa Cell Line Following Gonadotropin Stimulation
by Francesca Mancini, Emanuela Teveroni, Michela Cicchinelli, Federica Iavarone, Anna Laura Astorri, Giuseppe Maulucci, Cassandra Serantoni, Duaa Hatem, Daniela Gallo, Carla Di Nardo, Andrea Urbani, Alfredo Pontecorvi, Domenico Milardi and Fiorella Di Nicuolo
Int. J. Mol. Sci. 2025, 26(9), 4108; https://doi.org/10.3390/ijms26094108 - 25 Apr 2025
Viewed by 749
Abstract
Granulosa cell (GC) differentiation, stimulated by FSH and LH, drives oocyte maturation and follicle development. FSH promotes GC proliferation, and LH triggers ovulation. In clinical practice, hCG is used to mimic LH. Despite various controlled ovarian stimulation (COS) protocols employing exogenous gonadotropins and [...] Read more.
Granulosa cell (GC) differentiation, stimulated by FSH and LH, drives oocyte maturation and follicle development. FSH promotes GC proliferation, and LH triggers ovulation. In clinical practice, hCG is used to mimic LH. Despite various controlled ovarian stimulation (COS) protocols employing exogenous gonadotropins and GnRH analogs to prevent premature ovulation, their effectiveness and safety remain debated. To identify markers predicting a positive treatment response, the secretome of gonadotropin-stimulated GC using the human granulosa-like tumor cell line (KGN) via proteomics was analyzed. Additionally, a novel 2D-FFT quantitative method was employed to assess cytoskeleton fiber aggregation and polymerization, which are critical processes for GC differentiation. Furthermore, the activation of key kinases, focal adhesion kinase (FAK), and Rho-associated coiled-coil-containing protein kinase 1 (ROCK-1), which are implicated in cytoskeleton dynamics and hormone signaling, was evaluated. The proteomic analysis revealed significant modulation of proteins involved in extracellular matrix organization, steroidogenesis, and cytoskeleton remodeling. Notably, the combined FSH/hCG treatment led to a dynamic upregulation of the semaphorin pathway, specifically semaphorin 7A. Finally, a significant reorganization of the cytoskeleton network and signaling was detected. These findings enhance our understanding of folliculogenesis and suggest potential novel molecular markers for predicting patient responses to gonadotropin stimulation. Full article
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18 pages, 285 KiB  
Article
Widening the Circles of Dialogue: Paul VI and Interreligious Dialogue After 60 Years of Ecclesiam suam
by Rafael Vázquez Jiménez
Religions 2025, 16(2), 246; https://doi.org/10.3390/rel16020246 - 17 Feb 2025
Viewed by 774
Abstract
On the 60th anniversary of the publication of Paul VI’s encyclical Ecclesiam suam, dedicated to the issue of dialogue, we propose an analysis of this document focused on interreligious dialogue. We will identify the relationship between the encyclical, the theology of religions [...] Read more.
On the 60th anniversary of the publication of Paul VI’s encyclical Ecclesiam suam, dedicated to the issue of dialogue, we propose an analysis of this document focused on interreligious dialogue. We will identify the relationship between the encyclical, the theology of religions and the documents of the Second Vatican Council, focusing especially on the declaration Nostra aetate. In addition, we will point out how this encyclical has indirectly influenced the evolution of interreligious dialogue in the post-council period until today. Full article
17 pages, 303 KiB  
Article
The Pact of the Catacombs as a Pathway for a Poor-Servant Church
by Valentine Ugochukwu Iheanacho
Religions 2025, 16(2), 208; https://doi.org/10.3390/rel16020208 - 8 Feb 2025
Cited by 1 | Viewed by 578
Abstract
On 16 November 1965, three weeks before the end of the Second Vatican Council, about forty conciliar bishops gathered to celebrate the Holy Eucharist in the Catacombs of St. Domitilla. The Mass was presided over by Msgr. Charles-Marie Himmer (1902–1994). At the end [...] Read more.
On 16 November 1965, three weeks before the end of the Second Vatican Council, about forty conciliar bishops gathered to celebrate the Holy Eucharist in the Catacombs of St. Domitilla. The Mass was presided over by Msgr. Charles-Marie Himmer (1902–1994). At the end of the Mass, the assembled bishops walked up to the altar and appended their signatures to what is now known as “The Pact of the Catacombs.” This document later went into oblivion and suffered obscurity for half a century. Nevertheless, its significance was never lost on some of the bishops who pledged themselves, among other things, to work for the emergence of a “poor and servant Church” with a commitment to justice and charity. The bishops seemed to have followed the example of Pope Paul VI, who on 12 September 1965, in the same Catacombs of St. Domitilla, had spoken about the lessons of simplicity, poverty, charity, and justice that are historically engraved in the Church’s memory of the catacombs. This research examines “The Pact of the Catacombs”, its recent coming to light, and its significance as a pathway for a possible poor-servant church. As a qualitative research, its approach is historical, and its analysis of primary and secondary sources will be both narrative and descriptive in connecting it to other important documents of the same milieu. Full article
15 pages, 324 KiB  
Article
Liturgy of the Hours and the Lectio Continua of the Psalter
by Dieter Böhler
Religions 2024, 15(12), 1511; https://doi.org/10.3390/rel15121511 - 11 Dec 2024
Viewed by 1461
Abstract
In the last 40 years, the exegesis of the Psalms has made it increasingly clear that the Psalms should be read as a coherent book, since the individual Psalms are linked together by iuxtapositio and concatenatio. They are not just isolated poems but [...] Read more.
In the last 40 years, the exegesis of the Psalms has made it increasingly clear that the Psalms should be read as a coherent book, since the individual Psalms are linked together by iuxtapositio and concatenatio. They are not just isolated poems but tell a story, the story of David, God’s anointed king who is persecuted and suffers, but ultimately is triumphant—a Christological story. This article examines how the principle of lectio continua of the Psalter is taken into account in the breviaries of Pius V, Pius X and Paul VI, and it shows what problems arise when it is disregarded. Full article
(This article belongs to the Special Issue Bible and Liturgy in Dialogue)
16 pages, 409 KiB  
Article
What Justification? Pauline Reception and the Interpretation of Phld. 8.2
by Jonathon Lookadoo
Religions 2024, 15(4), 405; https://doi.org/10.3390/rel15040405 - 26 Mar 2024
Viewed by 1419
Abstract
While studies of how Paul and the Pauline letters were received in early Christianity continue to appear at an ever-quickening rate, there are still corners of early Christian literature that remain underexplored with regard to Pauline reception. The letters of Ignatius of Antioch [...] Read more.
While studies of how Paul and the Pauline letters were received in early Christianity continue to appear at an ever-quickening rate, there are still corners of early Christian literature that remain underexplored with regard to Pauline reception. The letters of Ignatius of Antioch would not usually be included in the underexplored category, but this article argues that one statement within Ignatius’s letters is deserving of more careful attention vis-à-vis its relationship to Pauline themes and terminology. After showing that interpretations of Ignatius’s Philadelphians (Phld.) 8.2 have typically run along two opposing tracks, the article argues that both ways of interpreting Ignatius’s letter fail to do justice to his rhetoric in the letter. The article proposes an alternative way of reading Ignatius’s justification language in Phld. 8.2. Whereas Paul wrote about justification before God, Ignatius desires to be proven right in the eyes of his Philadelphian readers, with whom he has had a dispute. The article concludes by offering ways to account for the different meanings evidenced in the letters of Ignatius and Paul while also endeavouring to explain the purpose for which Ignatius employs terminology that is similar to that of Paul. In the final clause of Phld. 8.2, Pauline terminology provides Ignatius not with his doctrinal substance but rather with authoritative rhetoric that evokes the Apostle. Full article
(This article belongs to the Section Religions and Theologies)
17 pages, 3023 KiB  
Article
SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma
by Emanuela Teveroni, Fiorella Di Nicuolo, Edoardo Vergani, Alessandro Oliva, Emanuele Pierpaolo Vodola, Giada Bianchetti, Giuseppe Maulucci, Marco De Spirito, Tonia Cenci, Francesco Pierconti, Gaetano Gulino, Federica Iavarone, Andrea Urbani, Domenico Milardi, Alfredo Pontecorvi and Francesca Mancini
Int. J. Mol. Sci. 2023, 24(23), 16891; https://doi.org/10.3390/ijms242316891 - 29 Nov 2023
Cited by 2 | Viewed by 1706
Abstract
Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and [...] Read more.
Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and E-cadherin (CDH1). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma. Full article
(This article belongs to the Special Issue Molecular Biology of Testicular Germ Cell Tumours)
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13 pages, 836 KiB  
Article
Participation “In the Heavenlies” in Christ: Deification in Ephesians
by Kangil Kim
Religions 2023, 14(6), 784; https://doi.org/10.3390/rel14060784 - 13 Jun 2023
Viewed by 2028
Abstract
Paul’s expression “in the heavenlies” provides an intriguing showcase of the power dynamics of the divine–human relationship (e.g., 1:3, 20; 2:6; 3:10; 6:12). While scholars have identified the theme of union with Christ as an interpretive key for understanding believers’ position in the [...] Read more.
Paul’s expression “in the heavenlies” provides an intriguing showcase of the power dynamics of the divine–human relationship (e.g., 1:3, 20; 2:6; 3:10; 6:12). While scholars have identified the theme of union with Christ as an interpretive key for understanding believers’ position in the heavenlies, few have provided adequate attention to “in the heavenlies” according to the significance of theosis. I argue that a patristic idea of theosis offers an interpretive lens in understanding believers’ lives in the heavenlies. Thus, this study aims to situate the discussion on the heavenlies vis-à-vis the conversation around theosis in the New Testament. Full article
(This article belongs to the Section Religions and Theologies)
14 pages, 540 KiB  
Article
Kinship and Leadership in 1 Timothy: A Study of Filial Framework and Model for Christian Communities in Asia Minor
by Daniel K. Darko
Religions 2023, 14(2), 169; https://doi.org/10.3390/rel14020169 - 29 Jan 2023
Viewed by 2425
Abstract
This essay examines the kinship framework and lexemes in the directives for leadership in 1 Timothy, aiming to curb the influence of false teachers and to bolster internal cohesion in the communities. It explores the author’s appeal to household conduct, natural and fictive [...] Read more.
This essay examines the kinship framework and lexemes in the directives for leadership in 1 Timothy, aiming to curb the influence of false teachers and to bolster internal cohesion in the communities. It explores the author’s appeal to household conduct, natural and fictive kinship, and group dynamics couched in filial parlance vis-à-vis the undisputed Pauline letters. The study sheds light on the authorial framework, and suggests that the notion of a departure from ‘love-patriarchalism’ or egalitarian Paul developing later into hierarchical kinship framework in 1 Timothy may be misleading. It becomes apparent that the letter’s kinship lexemes are consistent with what we find in the undisputed letters. Thus, the pseudonymous author, an associate of Paul, does not appeal to or use kinship lexemes any differently from the undisputed letters or elsewhere in Greco-Roman discourse. This does not establish Pauline authorship, but suggest that the notion that the kinship lexemes reflect an elevated hierarchical institutional development in a post-Pauline era, that is uncharacteristic of Paul in the authorship debate, may need to be reconsidered if not revised. Full article
(This article belongs to the Special Issue Biblical Texts and Traditions: Paul’s Letters)
15 pages, 1793 KiB  
Article
Light Microscopy and Proteomic Patterns of Ovulation in Cervical Mucus
by Yolanda Fernandez-Hermida, Federica Vincenzoni, Domenico Milardi, Anna Laura Astorri, Andrea Urbani, Giuseppe Grande and Rafael Azagra
Life 2022, 12(11), 1815; https://doi.org/10.3390/life12111815 - 7 Nov 2022
Cited by 3 | Viewed by 4033
Abstract
There is an increasing number of couples interested in identifying the fertile window for the purpose of conceiving. From what has been published so far, it can be concluded that there are no reliable methods to predict ovulation, and, therefore, to predict the [...] Read more.
There is an increasing number of couples interested in identifying the fertile window for the purpose of conceiving. From what has been published so far, it can be concluded that there are no reliable methods to predict ovulation, and, therefore, to predict the fertile window. Proteins of the cervical mucus (CM) could behave as biomarkers to allow the early and precise identification of ovulation. CM samples were collected from the lumen of the cervical canal from women of reproductive age, on three different days of the same menstrual cycle. Samples were first analyzed and classified by light microscopy. High-resolution mass spectrometry and bioinformatic analysis were performed afterwards to determine the in vivo changes of CM protein composition. CM underwent cyclical changes in its biophysical composition, which were evidenced by changes in the crystallographic patterns observed under the light microscope. The proteomic analysis revealed changes in the protein composition of CM along the cycle. Twenty-five out of the forty-eight total proteins identified could become potential biomarkers of ovulation. The coordinated changes in the composition of the CM around the time of ovulation could be happening to specifically grant access to a foreign body, such as the sperm might be. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology)
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15 pages, 1520 KiB  
Article
Short-Chain Fatty Acids Modulate Sperm Migration through Olfactory Receptor 51E2 Activity
by Emanuela Teveroni, Fiorella Di Nicuolo, Edoardo Vergani, Carmine Bruno, Giuseppe Maulucci, Giada Bianchetti, Anna Laura Astorri, Giuseppe Grande, Jacopo Gervasoni, Lavinia Santucci, Marco De Spirito, Andrea Urbani, Alfredo Pontecorvi, Francesca Mancini and Domenico Milardi
Int. J. Mol. Sci. 2022, 23(21), 12726; https://doi.org/10.3390/ijms232112726 - 22 Oct 2022
Cited by 13 | Viewed by 2487
Abstract
The non-orthotopic expression of olfactory receptors (ORs) includes the male reproductive system, and in particular spermatozoa; their active ligands could be essential to sperm chemotaxis and chemical sperm–oocyte communication. OR51E2 expression has been previously reported on sperm cells’ surface. It has been demonstrated [...] Read more.
The non-orthotopic expression of olfactory receptors (ORs) includes the male reproductive system, and in particular spermatozoa; their active ligands could be essential to sperm chemotaxis and chemical sperm–oocyte communication. OR51E2 expression has been previously reported on sperm cells’ surface. It has been demonstrated in different cellular models that olfactory receptor 51E2 (OR51E2) binds volatile short-chain fatty acids (SCFAs) as specific ligands. In the present research, we make use of Western blot, confocal microscopy colocalization analysis, and the calcium-release assay to demonstrate the activation of sperm cells through OR51E2 upon SCFAs stimulus. Moreover, we perform a novel modified swim-up assay to study the involvement of OR51E2/SCFAs in sperm migration. Taking advantage of computer-assisted sperm analysis (CASA system), we determine the kinematics parameters of sperm cells migrating towards SCFAs-enriched medium, revealing that these ligands are able to promote a more linear sperm-cell orientation. Finally, we obtain SCFAs by mass spectrometry in cervico-vaginal mucus and show for the first time that a direct incubation between cervical mucus and sperm cells could promote their activation. This study can shed light on the possible function of chemosensory receptors in successful reproduction activity, laying the foundation for the development of new strategies for the treatment of infertile individuals. Full article
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18 pages, 2060 KiB  
Article
PTTG1/ZEB1 Axis Regulates E-Cadherin Expression in Human Seminoma
by Emanuela Teveroni, Fiorella Di Nicuolo, Edoardo Vergani, Giada Bianchetti, Carmine Bruno, Giuseppe Maulucci, Marco De Spirito, Tonia Cenci, Francesco Pierconti, Gaetano Gulino, Pierfrancesco Bassi, Alfredo Pontecorvi, Domenico Milardi and Francesca Mancini
Cancers 2022, 14(19), 4876; https://doi.org/10.3390/cancers14194876 - 5 Oct 2022
Cited by 6 | Viewed by 2542
Abstract
(1) Background: PTTG1 sustains the EMT process and the invasiveness of several neoplasms. We previously showed the role of nuclear PTTG1 in promoting invasiveness, through its transcriptional target MMP2, in seminoma in vitro models. Here, we investigated the key players involved in PTTG1-mediated [...] Read more.
(1) Background: PTTG1 sustains the EMT process and the invasiveness of several neoplasms. We previously showed the role of nuclear PTTG1 in promoting invasiveness, through its transcriptional target MMP2, in seminoma in vitro models. Here, we investigated the key players involved in PTTG1-mediated EMT in human seminoma. (2) Methods: Two seminoma cell lines and four human seminoma tumor specimens were used. E-Cadherin gene regulation was investigated using Western blot, real-time PCR, and luciferase assay. Immunoprecipitation, ChIP, RE-ChIP, and confocal microscopy analysis were performed to evaluate the interplay between PTTG1 and ZEB1. Matrigel invasion and spheroid formation assays were applied to functionally investigate PTTG1 involvement in the EMT of seminoma cell lines. RNA depletion and overexpression experiments were performed to verify the role of PTTG1/ZEB1 in E-Cadherin repression and seminoma invasiveness. E-Cadherin and ZEB1 levels were analyzed in human testicular tumors from the Atlas database. (3) Results: PTTG1 transcriptionally represses E-Cadherin in seminoma cell lines through ZEB1. The cooperation of PTTG1 with ZEB1 has a significant impact on cell growth/invasion properties involving the EMT process. Analysis of the Atlas database of testicular tumors showed significantly lower E-Cadherin levels in seminoma, where PTTG1 showed nuclear staining. Finally, PTTG1 and ZEB1 strongly localize together in the periphery of the tumors. (4) Conclusions: These results strengthen the evidence for a role of PTTG1 in the EMT process in human seminomas through its cooperation with the transcriptional repressor ZEB1 on the E-Cadherin gene. Our data enrich the molecular characterization of seminoma, suggesting that PTTG1 is a prognostic factor in seminoma clinical management. Full article
(This article belongs to the Section Molecular Cancer Biology)
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