Elucidating the Neuroprotective Mechanisms of G‐3702 in Ischemic Stroke via Integrated Metabolomics and Computational Approaches DOI Creative Commons
Cong Wang,

Fang Zhang,

Qi Zheng

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(4)

Published: April 1, 2025

ABSTRACT Aims Ischemic stroke (IS) remains a leading cause of disability worldwide, necessitating the development more effective treatments. While DL‐3‐n‐butylphthalide (NBP) has shown promise in treating IS, its clinical application is limited by hepatotoxicity. G‐3702, structural analog NBP, emerged as potential alternative with reduced hepatotoxicity and proposed pro‐angiogenic effects. However, precise mechanisms underlying G‐3702's therapeutic effects IS remain unclear, hindering optimization identification novel targets. This gap understanding particularly significant given treatments to address ischemia‐induced vascular damage improve long‐term recovery. Methods Here, we employed an integrated approach combining metabolomics, transcriptomics, machine learning elucidate action photothrombotic mouse model. Untargeted metabolomics pathway analysis explored metabolic impacts, while network pharmacology algorithms refined key target identification. We validated computational insights through immunofluorescence qPCR experiments. Results Our results demonstrated that G‐3702 significantly improved neurological outcomes cerebral cortex necrosis mice. Metabolomics implicated Avb3 integrin effects, analyses highlighted PI3K‐Akt HIF‐1α pathways central this action. Machine prioritized biomarkers targets, including BDNF, FGF2, ITGAV, ITGB3, SRC, RHOA. Immunofluorescence confirmed enhanced angiogenesis, increased expression these angiogenesis‐related genes following treatment. Conclusion These findings suggest promotes angiogenesis ischemic brain area primarily via pathway, offering mechanistic explanation for IS. By elucidating mode action, study not only enhances but also contributes broader field treatment identifying mechanism elucidation advances may serve model future drug efforts other complex disorders. Ultimately, work translation therapy opens new avenues optimizing post‐stroke

Language: Английский

Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma DOI Open Access
Md. Ataur Rahman,

Meser M. Ali

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 2975 - 2975

Published: Aug. 27, 2024

Malignant gliomas present great difficulties in treatment, with little change over the past 30 years median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing formation new vasculature (antiangiogenic treatments) or destroying formed tumor (vascular disrupting agents) show promise. This study summarizes existing knowledge regarding processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses activation redundant proangiogenic pathways, heightened cell invasion metastasis, induced hypoxia, creation vascular mimicry channels, regulation immune microenvironment. Subsequently, we explore potential strategies overcome this resistance, such as combining other methods, personalizing treatments for each patient, focusing on therapeutic targets, incorporating immunotherapy, utilizing drug delivery systems based nanoparticles. Additionally, would like discuss limitations methods future directions enhance beneficial effects patients GBM. Therefore, review aims research outcome GBM provide a more promising opportunity thoroughly exploring mechanisms investigating novel strategies.

Language: Английский

Citations

11
Recent Advances and Future Directions on Small Molecule VEGFR Inhibitors in Oncological Conditions DOI

Amandeep Thakur,

Mandeep Rana,

Anshul Mishra

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 272, P. 116472 - 116472

Published: May 6, 2024

Language: Английский

Citations

10
The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy DOI Creative Commons
Deqian Xie,

Guandu Li,

Zhonghua Zheng

et al.

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335

Published: Jan. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Language: Английский

Citations

2
Physiological and tumor-associated angiogenesis: Key factors and therapy targeting VEGF/VEGFR pathway DOI Open Access

Patryk Lorenc,

Agata Sikorska, Sara Molenda

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117585 - 117585

Published: Oct. 22, 2024

Language: Английский

Citations

8
Tumor microenvironment and cancer metastasis: molecular mechanisms and therapeutic implications DOI Creative Commons
Çıgır Biray Avci, Bakiye Göker Bağca, Masoud Nikanfar

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 12, 2024

The tumor microenvironment (TME) plays a crucial role in cancer development and metastasis. This review summarizes the current research on how TME promotes metastasis through molecular pathways, focusing key components, such as cancer-associated fibroblasts, immune cells, endothelial cytokines, extracellular matrix. Significant findings have highlighted that alterations cellular communication within enable cells to evade surveillance, survive, invade other tissues. highlights roles of TGF-β VEGF signaling promoting angiogenesis matrix remodeling, which facilitate Additionally, we explored metabolic reprogramming stromal influenced by nutrient availability TME, drives progression. study also evaluated therapeutic strategies targeting these interactions disrupt By providing multidisciplinary perspective, this suggests understanding basis can lead more effective therapies identify potential avenues for future research. Future should prioritize unraveling complex environment, could novel personalized treatments. Moreover, advancements technologies single-cell analysis, spatial transcriptomics, epigenetic profiling offer promising identifying new targets improving efficacy immunotherapies, particularly context

Language: Английский

Citations

7
Glyoxalase I Inhibitors Targeting Breast Cancer-Associated Endothelial Cells: An Integrated Network Pharmacology and Experimental Investigation DOI
Honglin Jiang, Lu Yang,

Qiuyue Sun

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141868 - 141868

Published: Feb. 1, 2025

Language: Английский

Citations

1
Discovery of 1-phenyl-1,2,3-triazole ureas as dual VEGFR-2/JNK-1 type II kinase inhibitors targeting pancreatic cancer DOI
Wagdy M. Eldehna, Eslam Roshdy,

Maha-Hamadien Abdulla

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142372 - 142372

Published: March 1, 2025

Language: Английский

Citations

1
Diabetic retinopathy: a comprehensive review of pathophysiology and emerging treatments DOI

Mukul Shyam,

Sidharth Sen,

Aleen Veronica

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: April 9, 2025

Language: Английский

Citations

1
Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance DOI Creative Commons
Fahad Hassan Shah,

Yoon Seok Nam,

Jun Young Bang

et al.

Archives of Pharmacal Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Abstract Angiogenesis, the process of new blood vessel formation, is a fundamental physiological implicated in several pathological disorders. The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are crucial for angiogenesis vasculogenesis. Among them, tyrosine kinase receptor VEGFR-2 primarily expressed cells (ECs). These regulate various responses, including differentiation, cell proliferation, migration, survival, by binding to VEGF mitogens. Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) key regulator this process, making it prime target therapeutic intervention. Several drugs targeting have been approved currently utilized halt axis VEGF-VEGFR. This review will focus on recent developments molecular structure function VEGFR-2, mechanism activation, its downstream signaling pathway. It also discuss therapies experimental inhibit resistance mechanism.

Language: Английский

Citations

1
Increase in Vascular Endothelial Growth Factor (VEGF) Expression and the Pathogenesis of iMCD-TAFRO DOI Creative Commons
Gordan Srkalović,

Sally Nijim,

Maya Blanka Srkalovic

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1328 - 1328

Published: June 14, 2024

TAFRO (thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (F/R), renal failure (R), and organomegaly (O)) is a heterogeneous clinical subtype of idiopathic multicentric Castleman disease (iMCD) associated with significantly poorer prognosis than other subtypes iMCD. symptomatology can also be seen in pathological contexts outside iMCD, but it unclear if those cases should considered representative different entity or simply severe presentation infectious, malignant, rheumatological diseases. While interleukin-6 (IL-6) an established driver iMCD-TAFRO pathogenesis subset patients, the etiology unknown. Recent case reports literature reviews on patients suggest that vascular endothelial growth factor (VEGF), interplay VEGF IL-6 concert, rather as single cytokine, may drivers for pathophysiology, especially injury. In this review, we discuss possible role pathophysiology manifestations iMCD-TAFRO. particular, involved pathology through its ability to activate RAS/RAF/MEK/ERK PI3K/AKT/mTOR signaling pathways. Further elucidating VEGF-IL-6 axis additional shed light therapeutic options treatment who do not respond to, otherwise relapse following, targeting drugs. This review investigates potential related pathways future.

Language: Английский

Citations

4