Senescence-associated secretory phenotype (SASP) and uterine fibroids: Association with PD-L1 activation and collagen deposition

Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102314 - 102314

Опубликована: Апрель 24, 2024

Язык: Английский

---

Bromodomain-Containing Protein 9 Regulates Signaling Pathways and Reprograms the Epigenome in Immortalized Human Uterine Fibroid Cells

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 905 - 905

Опубликована: Янв. 11, 2024

Bromodomain-containing proteins (BRDs) are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD dysfunction has been linked to diseases, including tumorigenesis. However, the role BRDs pathogenesis uterine fibroids (UFs) is entirely unknown. The present study aimed determine expression pattern BRD9 UFs matched myometrium further assess impact a inhibitor on UF phenotype epigenetic/epitranscriptomic changes. Our studies demonstrated that levels were significantly upregulated compared myometrium, suggesting aberrant may contribute UFs. We then evaluated potential roles using its specific inhibitor, I-BRD9. Targeted inhibition suppressed tumorigenesis with increased apoptosis cell cycle arrest, decreased proliferation, extracellular matrix deposition cells. latter key hallmark Unbiased transcriptomic profiling coupled downstream bioinformatics analysis extensively targeted impacted cycle- ECM-related pathways reprogrammed epigenome epitranscriptome Taken together, our support critical cells strong interconnection between other controlling progression. might provide non-hormonal treatment option for this common benign tumor women reproductive age.

Язык: Английский

---

Surface-Conjugated Galactose on Electrospun Polycaprolactone Nanofibers: An Innovative Scaffold for Uterine Tissue Engineering

ACS Omega, Год журнала: 2024, Номер 9(32), С. 34314 - 34328

Опубликована: Авг. 1, 2024

The uterus, a vital organ in the female reproductive system, nurtures and supports developing embryos until maturity. This study focuses on addressing uterine related problems by creating nanofibrous scaffold to regenerate myometrial tissue, closely resembling native extracellular matrix (ECM) for enhanced efficacy. To achieve this, we utilized polycaprolactone (PCL) as biomaterial employed an electrospinning technique generate PCL nanofibers both random aligned orientations. Due inherent hydrophobic nature of nanofibers, two-step wet chemistry surface modification is used, involving conjugation galactose onto them. Galactose, lectin-binding sugar, was chosen enhance scaffold's hydrophilicity, thereby improving cell adhesion fostering l-selectin-based interactions between cells. These interactions, turn, activated fibroblasts, leading ECM remodeling. optimized process successfully generated nanofibers. Subsequent carried out, modified subjected various physicochemical characterization, such ninhydrin assay, enzyme-linked lectin assay techniques that revealed successful conjugation, mechanical characterization assess any changes material bulk properties resulting from modification. tensile strength galactose-modified fibers reached 0.041 ± 0.01 MPa, outperforming unmodified (0.026 MPa), (0.011 0.001 (0.016 0.002 MPa). Cytocompatibility studies with human fibroblast cells showed viability proliferation scaffolds. Initial pilot were attempted current subcutaneous implantation dorsal area Wistar rats biocompatibility tissue response before proceeding intrauterine indicated did not induce adverse inflammation vivo. In conclusion, our introduces surface-modified engineering, offering promise damage advancing health well-being.

Язык: Английский

---

Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study

Frontiers in Medicine, Год журнала: 2022, Номер 9

Опубликована: Ноя. 7, 2022

To study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding among five sociodemographic index regions, 21 204 countries for decision-making, which would enable policymakers to distribute limited resources devise policies more rationally.Data uterine fibroids (UNs) from 1990 2019, including DALYs, were obtained 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated assess morbidity, DALY trends.The incident cases UFs increased 5,769,658 (95%UI, 7,634,3995-4,274,824) incidences 9,643,336 7,178,053-12,714,741) 2017, age-standardized incidence rate steady at 225.67/100,000 persons 167.33-298.87) 241.18/100,000 179,45-318.02) 2019. The ratio high (SDI) region showed a unimodal distribution, with peaks 2005. Between 2009 death declined globally, especially low-SDI low-middle SDI regions. In contrast 860,619 DALYs 473,067-1,505,289) 1990, number 1,378,497 710,915-2,475,244) had significantly, whereas decreased expressively an EAPC -1.93 (95%CI, -2.16 -1.71).The global burden between prominently worldwide, while deaths no evident growth. Lower regions carried incremental UFs, disease reduction observed higher It is time we paid attention underprivileged regional quality health protection.

Язык: Английский

---

Targeting fibrotic signaling pathways by EGCG as a therapeutic strategy for uterine fibroids

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Май 25, 2023

Abstract Fibrosis is characterized by excessive accumulation of extracellular matrix, which a key feature uterine fibroids. Our prior research supports the tenet that inhibition fibrotic processes may restrict fibroid growth. Epigallocatechin gallate (EGCG), green tea compound with powerful antioxidant properties, an investigational drug for An early phase clinical trial showed EGCG was effective in reducing size and its associated symptoms; however, mechanism action(s) has not been completely elucidated. Here, we probed effects on signaling pathways involved cell fibrosis. Viability myometrial cells greatly affected treatment (1–200 µM). Cyclin D1, protein cycle progression, increased significantly reduced EGCG. mRNA or levels proteins, including fibronectin ( FN1 ), collagen COL1A1 plasminogen activator inhibitor-1 PAI-1 connective tissue growth factor CTGF actin alpha 2, smooth muscle ACTA2 ) cells, suggesting antifibrotic effects. altered activation YAP, β-catenin, JNK AKT, but Smad 2/3 mediating process. Finally, conducted comparative study to evaluate ability regulate fibrosis synthetic inhibitors. We observed displayed greater efficacy than ICG-001 (β-catenin), SP600125 (JNK) MK-2206 (AKT) inhibitors, were equivalent verteporfin (YAP) SB525334 (Smad) regulating expression mediators. These data indicate exhibits anti-fibrotic cells. results provide insight into mechanisms behind against

Язык: Английский

---

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions

MedComm, Год журнала: 2023, Номер 4(6)

Опубликована: Дек. 1, 2023

Abstract The endometrium is a unique human tissue with an extraordinary ability to undergo hormone‐regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. cyclical repair of manifest as changes in endometrial epithelialization, glandular regeneration, vascularization. mechanisms encompass inflammation, coagulation, fibrinolytic system balance. However, specific conditions such endometriosis or TCRA treatment can disrupt process regeneration. There uncertainty about traditional clinical treatments' efficacy side effects, finding new therapeutic interventions essential. Researchers have made substantial progress perspective regenerative medicine toward maintaining recent years. Such encompasses integration biomaterials, tissue‐engineered scaffolds, stem cell therapies, 3D printing. This review analyzes mechanisms, diseases, associated discusses advantages disadvantages currently employed practice. Additionally, it highlights significant this domain. Finally, we cells biologics among available medicine, providing insights into future strategies.

Язык: Английский

---

A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5752 - 5752

Опубликована: Март 17, 2023

Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points UL initiation development. The main reason for this pronounced inter- intratumoral heterogeneity resulting from diverse complicated mechanisms underlying pathobiology. In review, we comprehensively analyse risk protective factors development, cellular composition, hormonal paracrine signalling, epigenetic regulation genetic abnormalities. We conclude need to carefully update concept genesis in light current data. Staying within framework existing hypotheses, introduce possible timeline development key events—from potential prerequisites beginning formation onset driver passenger changes.

Язык: Английский

---

Pathogenesis of uterine fibroids: current understanding and future directions

Fertility and Sterility, Год журнала: 2024, Номер 122(1), С. 6 - 11

Опубликована: Март 5, 2024

Язык: Английский

---

Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy

Cells, Год журнала: 2024, Номер 13(13), С. 1106 - 1106

Опубликована: Июнь 26, 2024

Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates recurrence and metastasis. The five-year survival for uLMS patients between 25 76%, approaching 10-15% metastatic disease at initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in pathogenesis. Notably, drugs block abnormal functions these remarkably improve patients. However, due to chemotherapy resistance, there remains need novel can target effectively. In this review article, we provide an overview recent progress ascertaining regulatory mechanisms from perspective aberrant pathways, including DNA repair, immune checkpoint blockade, protein kinase intracellular signaling hedgehog pathway. We emerging role epigenetics epitranscriptome pathogenesis uLMS. addition, discuss serum markers, artificial intelligence (AI) combined machine learning, shear wave elastography, current management medical treatment options, ongoing clinical trials Comprehensive, integrated, deeper insights into pathobiology underlying molecular will help develop strategies treat aggressive tumor.

Язык: Английский

---

Comparative efficacy of uterine artery embolization versus laparoscopic myomectomy in treating uterine fibroids: a propensity score matched analysis

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 7, 2025

The aim of this study was to comparatively analyze the therapeutic effects uterine artery embolization (UAE) and laparoscopic myomectomy (LM) on fibroids determine which treatment method is more beneficial for patients. A retrospective conducted 396 patients who underwent UAE (n = 153) or LM 243) from April 2010 September 2019. After 1:1 propensity score matching (PSM), a comparative analysis surgical trauma magnitude, postoperative recovery time, improvement in associated symptoms quality life, adverse events, recurrence rates, further interventions. In PSM, 66 pairs (132 patients) were successfully matched. Both treatments significantly alleviated enhanced life. Compared group, group had less intraoperative bleeding (P < 0.001), lower rate hemoglobin decrease shorter operation, postoperative, overall hospital stays 0.05), all statistically significant. Moreover, showed notable advantages activities 0.05). However, faced higher hospitalization costs 0.001). Adverse event rates (7.6% vs. 9.1%) reintervention 7.6%) relatively low not different between groups > can improve patient enhance their both methods have events reinterventions. LM, presents such as trauma, faster recovery, rate, but has costs.

Язык: Английский

---