A5100672613- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Chromatin Remodeling and Cancer
- Cancer Cells and Metastasis
- Protein Degradation and Inhibitors
- Oral and Maxillofacial Pathology
- Circular RNAs in diseases
- Multiple Myeloma Research and Treatments
- Estrogen and related hormone effects
- Receptor Mechanisms and Signaling
- Genetic and rare skin diseases.
- Peptidase Inhibition and Analysis
- Ion Transport and Channel Regulation
- Genomic variations and chromosomal abnormalities
- Biomarkers in Disease Mechanisms
- Cancer Treatment and Pharmacology
- Cardiac and Coronary Surgery Techniques
- Angiogenesis and VEGF in Cancer
- Cytomegalovirus and herpesvirus research
- Biochemical and Molecular Research
- Oral and gingival health research
- Genomics and Chromatin Dynamics
- Anesthesia and Neurotoxicity Research
- Calcium signaling and nucleotide metabolism
Second Hospital of Yichang
2025
Fudan University
1999-2023
Zhongshan Hospital
2021
China Medical University
2020
Shanghai Institute of Planned Parenthood Research
2016-2017
Henan University Huaihe Hospital and Huaihe Clinical Institute
2014
Abstract The Smoothened receptor (SMO) belongs to the Class Frizzled of G protein-coupled (GPCR) superfamily, constituting a key component Hedgehog signalling pathway. Here we report crystal structure multi-domain human SMO, bound and stabilized by designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. reveals precise arrangement three distinct domains: seven-transmembrane helices domain (TMD), hinge (HD) intact extracellular cysteine-rich (CRD). This architecture...
Abstract Background Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic processes in COPD. Methods We first quantified and localized circFOXO3 mouse lung epithelial cell line MLE12 by quantitative reverse-transcription PCR situ hybridization. Next, was suppressed therapeutic...
Oxymatrine is an alkaloid obtained primarily from Sophora roots and has been shown to show anticancer effects in various cancers. However, the cellular molecular of this agent on cervical cancer have poorly characterized. Here, we investigated antitumor effect oxymatrine a human cell line (HeLa). Our results showed that application significantly inhibited growth tumorigenesis dose-dependent manner induced apoptosis through caspase-dependent pathways as determined using flow cytometry TUNEL...
Small-molecule inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) face clinical limitations due to adverse effects. This study aimed evaluate the novel compound SB218078 as a dual-targeting agent against both tumor angiogenesis and epithelial-mesenchymal transition (EMT) in breast cancer, while exploring its mechanisms action. The anti-angiogenic effects were investigated using vitro models cell migration, invasion, tube formation, alongside vivo zebrafish developmental...
Berberine (BBR), a natural alkaloid compound, is used as non-prescription drug in China for treating diarrhea and gastroenteritis. Many studies have revealed that BBR possesses anticancer effect. However, the molecular mechanisms underlying its action far from being fully elucidated. This study aimed to determine effect of on hedgehog (Hh) activity growth cancers addiction Hh activity. The was determined by dual luciferase assays quantitative RT-PCR analyses. inhibition medulloblastoma which...
A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton natural product artemisinin or first breaking into structurally simpler and stable intermediates then reconstructing diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as most potent, an IC50 value 9.53 nM against Hh signaling pathway. Complementary mechanism studies confirmed that...
Rationale: Primary and acquired resistance to Smoothened (Smo) inhibitors largely hampered their clinical efficacy.Given the important functions of hedgehog (Hh) pathway in bone formation development, permanent defects growth caused by Smo further restrict use for pediatric tumor patients.Anti-apoptotic Bcl-2 proteins regulate Hh activity engaging a homology (BH) domain sequence found suppressor fused (Sufu).In this study, we tested effect SIAIS361034, Proteolysis Targeting Chimera (PROTAC)...
A systemic medicinal chemistry campaign was conducted based on a literature hit compound 5 bearing the 4,5-dihydro-2H-benzo[b][1,5]oxazocin-6(3H)-one core through cyclization of two side substituents bicyclic skeleton combined with N-atom walking or ring and central expansion extraction approaches, leading to several series structurally unique tricyclic compounds. Among these, 29a identified as most potent against Hedgehog (Hh) signaling pathway showing an IC50 value 23 nM. Mechanism studies...
The major obstacle limiting the efficacy of current Smoothened (Smo) inhibitors is primary and acquired resistance mainly caused by Smo mutations Gli amplification. In this context, developing Hh targeting Gli, final effector signaling pathway, may combat resistance. study we found that solasonine, a natural glycoalkaloid compound, significantly inhibited hedgehog (Hh) pathway activity. Meanwhile, solasonine obviously inhibit alkaline phosphatase (ALP) activity in C3H10T1/2 cells,...
Abstract Tamoxifen is administered for estrogen receptor positive (ER + ) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER than five such treatment. was also approved by the FDA as a chemopreventive agent those deemed at high risk development cancer. The side effects are substantial concern because these extended methods administration. In this...
The aberrant activation of hedgehog (Hh) signaling pathway is closely related to human diseases. upstream protein, N-terminal product sonic (ShhN) overexpressed in many cancers and considered as a promising antitumor target. Inhibitors that bind ShhN break its interaction with the 12-transmembrane glycoprotein patched (Ptch) protein are highly wanted tune down abnormal Hh activation. However, research inhibitors remains lacking. In this paper, we computationally screened potential against...
Abstract Both bench and bedside investigations have challenged the supportive role of Hedgehog (Hh) activity in progression colorectal cancers, thus raising a critical need to further deeply determine contribution Hh growth cancer. Combining multiple complementary means, including vitro vivo inflammatory cancer models, pathological analysis clinical patients samples. We report that cells hijack prostaglandin E2 (PGE2) non-canonically promote transcriptional factor Gli Gli-dependent...