Gastric Cancer Models Developed via GelMA 3D Bioprinting Accurately Mimic Cancer Hallmarks, Tumor Microenvironment Features, and Drug Responses

Small, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Current in vitro models for gastric cancer research, such as 2D cell cultures and organoid systems, often fail to replicate the complex extracellular matrix (ECM) found vivo. For first time, this study utilizes a gelatin methacryloyl (GelMA) hydrogel, biomimetic ECM-like material, 3D bioprinting construct physiologically relevant model. GelMA's tunable mechanical properties allow precise manipulation of cellular behavior within physiological ranges. Genetic phenotypic analyses indicate that bioprinted GelMA (3Db) model accurately mimics clinical tumor characteristics reproduces key hallmarks, proliferation, invasion, migration, angiogenesis, Warburg effect. Comparisons gene expression drug responses between 3Db patient-derived xenograft models, both constructed from primary cells, validate model's relevance. The ability closely simulate vivo conditions highlights its crucial role identifying treatment targets predicting patient-specific responses, showcasing potential high-throughput screening applications. This is report pivotal GelMA-based advancing research regenerative medicine.

Язык: Английский

---

The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility

Cells, Год журнала: 2025, Номер 14(6), С. 437 - 437

Опубликована: Март 14, 2025

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α stabilized activates transcription genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, therapeutic resistance. Angiogenesis glycolytic reprogramming mediated by HIF-1 proliferation, survival, metastasis. Its dysfunction concurrently impairs homeostasis, undermining follicular growth, hormone synthesis, vascular network, consequently contributing to Moreover, induces persistent inflammation oxidative stress, an environment damaging reproductive health. Due dual function cancer growth infertility, a potential target. Strategies including small molecule inhibitors nanoparticle-mediated delivery drugs possess reduce activity, hence reducing while protecting fertility. This review seeks clarify molecular basis effects on providing insights into novel treatment approaches target both controlling disease preserving

Язык: Английский

---

Uric acid promotes aortic valve calcification via mediating valve interstitial cell osteogenic differentiation and endothelial dysfunction

The FASEB Journal, Год журнала: 2025, Номер 39(6)

Опубликована: Март 18, 2025

Abstract Aortic valve calcification is a lethal valvular heart disease lacking effective drug therapy. However, whether uric acid involved in the development of aortic unclear. Two‐sample Mendelian randomization (MR) analyses confirmed causal relationship between and disease. Uric levels were assessed tissue from patients with/without calcification. To investigate impact hyperuricemia on calcification, apolipoprotein E knockout (ApoE −/− ) mice fed high‐fat diet (HFD) also given an adenine diet, with some receiving allopurinol their drinking water. RNA sequencing was performed interstitial cells (VICs) endothelial (VECs) acid. MR analysis has revealed effect Furthermore, our clinical data indicate positive correlation elevated serum calcium score. Specifically, upregulated calcified valves. In ApoE mice, adenine‐diet‐induced accelerated demonstrated that acid‐promoted osteogenic differentiation, primarily through activation hypoxia‐inducible factor‐1alpha (HIF‐α). Additionally, impaired barrier function by activating HIF‐α, resulting increased macrophage infiltration mice. Inhibiting HIF‐1α suppressed differentiation reduced injury both vitro vivo presence This study reveals new role suggesting acid‐lowering drugs or inhibition as potential treatments for associated

Язык: Английский

---

Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Май 18, 2025

Abstract Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development vascular lymphatic systems, tissue repair, maintenance homeostasis. VEGF ligands their receptors orchestrate cell proliferation, migration, survival, playing pivotal role in dynamic remodeling. Dysregulated drives diverse pathological conditions, including tumor cardiovascular diseases, ocular disorders. Excessive activity promotes growth, invasion, metastasis, while insufficient contributes to impaired wound healing ischemic diseases. VEGF-targeted therapies, such as monoclonal antibodies tyrosine kinase inhibitors, have revolutionized treatment diseases involving offering significant clinical benefits oncology ophthalmology. These therapies inhibit angiogenesis slow disease progression, but they often face challenges therapeutic resistance, suboptimal efficacy, adverse effects. To further explore these issues, this review provides comprehensive overview receptors, elucidating molecular mechanisms regulatory networks. It evaluates latest progress examines strategies address current challenges, resistance mechanisms. Moreover, discussion includes emerging innovative drug delivery systems combination highlighting continuous efforts improve effectiveness safety treatments. This highlights translational potential recent discoveries biology improving patient outcomes.

Язык: Английский

---

Endometriosis: An Immunologist’s Perspective

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5193 - 5193

Опубликована: Май 28, 2025

Endometriosis, a complex inflammatory disease, affects significant proportion of women reproductive age, approximately 10–15%. The disease involves the growth endometrial glands and stroma outside uterine cavity, leading to tissue remodeling fibrosis. Hormonal imbalances, accompanied by local general inflammation pain, are key features endometriosis. Endometriotic lesions associated with overproduction cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, extracellular vesicles. Genetic predisposition cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast Th1 in early phase, Th2 late T regulatory cells play crucial role Reduced NK cell function impaired immune vigilance contribute growth. strong condition endometrium poses barrier proper implantation zygote, contributing infertility these patients. Cytokines from various types vary severity disease. microbiota endometriosis is still under study. Endometriosis autoimmunity ovarian cancer. treatments surgery commonly used; however, recent interest focuses on anti-inflammatory immunomodulatory therapies, including anti-cytokine antibodies. Modulating response has proven critical; more research needed optimize treatment for

Язык: Английский

---

Enhancement of endometrial receptivity by Bushen Zhuyun Decoction via cryptotanshinone-mediated TRIM28 induction and HIF-1α suppression

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119943 - 119943

Опубликована: Май 1, 2025

Язык: Английский

---