Uric acid promotes aortic valve calcification via mediating valve interstitial cell osteogenic differentiation and endothelial dysfunction DOI Open Access
Jialiang Zhang, Wenhua Lei, Jing Zhou

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 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

Language: Английский

Gastric Cancer Models Developed via GelMA 3D Bioprinting Accurately Mimic Cancer Hallmarks, Tumor Microenvironment Features, and Drug Responses DOI Open Access
Mingguang Ju, Zining Jin, Xue Yu

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

1
The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility DOI Creative Commons
Md. Ataur Rahman, Maroua Jalouli,

Sujay Kumar Bhajan

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 437 - 437

Published: March 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

Language: Английский

Citations

0
Uric acid promotes aortic valve calcification via mediating valve interstitial cell osteogenic differentiation and endothelial dysfunction DOI Open Access
Jialiang Zhang, Wenhua Lei, Jing Zhou

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 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

Language: Английский

Citations

0