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| 1 | Oxidative stress and diabetes:antioxidative strategies显示文摘Diabetes mellitus is one of the major public health problems worldwide.Considerable recent evidence suggests that the cellular reduction-oxidation(redox)imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in p-cell dysfunction and insulin resistance.Reactive oxide species(ROS)can also directly oxidize certain proteins(defined as redox modification)involved in the diabetes process.There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility,storage instability and nonselectivity of antioxidants.Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS.We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus.Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes. | Pengju Zhang Tao Li Xingyun Wu Edouard C.Nice Canhua Huang Yuanyuan Zhang | 2020 | Frontiers of Medicine2020，14，5： | 29 |
| 2 | The discovery and validation of colorectal cancer biomarkers显示文摘 | Ching‐SengAng JasonPhung Edouard C.Nice | 2010 | Biomed Chromatogr (鈥?)2010，，1： | 2 |
| 3 | Repurposing econazole as a pharmacological autophagy inhibitor to treat pancreatic ductal adenocarcinoma显示文摘Pancreatic ductal adenocarcinoma(PDAC)is characterized by the highest mortality among carcinomas.The pathogenesis of PDAC requires elevated autophagy,inhibition of which using hydroxychloroquine has shown promise.However,current realization is impeded by its suboptimal use and unpredictable toxicity.Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach.Here,using a patient-derived organoid model,we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents,through which econazole(ECON),an antifungal compound,emerged as the top candidate.Further testing in cell-line and xenograft models of PDAC validated this activity,which occurred as a direct consequence of dysfunctional autophagy.More specifically,ECON boosted autophagy initiation but blocked lysosome biogenesis.RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3(ATF3).Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1(ID-1)led to inactivation of the AKT/mammalian target of rapamycin(m TOR)pathway,thus giving rise to autophagosome accumulation in PDAC cells.The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis.Furthermore,ECON,as an autophagy inhibitor,exhibited synergistic effects with trametinib on PDAC.This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth. | Ningna Weng Siyuan Qin Jiayang Liu Xing Huang Jingwen Jiang Li Zhou Zhe Zhang Na Xie Kui Wang Ping Jin Maochao Luo Liyuan Peng Edouard C.Nice Ajay Goel Suxia Han Canhua Huang Qing Zhu | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 2 |
| 4 | Oral squamous cell carcinomas:state of the field and emerging directions显示文摘Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% oforal malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases werereported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ),and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oralmucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involvesgenetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeuticinterventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCCand OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors,thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC.Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitatecomprehension and provide several prospective outlooks for the fields. | Yunhan Tan Zhihan Wang Mengtong Xu Bowen Li Zhao Huang Siyuan Qin Edouard C.Nice Jing Tang Canhua Huang | 2023 | International Journal of Oral Science2023，15，4： | 0 |
| 5 | Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant显示文摘The single-nucleotide polymorphism(SNP)of p53,in particular the codon 72 variants,has recently been implicated as a critical regulator in tumor progression.However,the underlying mechanism remains elusive.Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation.Proteome-wide mapping of p53-interacting proteins uncovered a specific interaction of the codon 72 proline variant(but not p5372R)with phosphoserine aminotransferase 1(PSAT1).Interestingly,p53^(72P)-PSAT1 interaction resulted in dissociation of peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)that otherwise bound to p53^(72P),leading to subsequent nuclear translocation of PGC-1αand activation of oxidative phosphorylation(OXPHOS)and tricarboxylic acid(TCA)cycle.Depletion of PSAT1 restored p53^(72P)-PGC-1αinteraction and impeded the OXPHOS and TCA function,resulting in mitochondrial dysfunction and metastasis suppression.Notably,pharmacological targeting the PSAT1-p53^(72P)interaction by aminooxyacetic acid(AOA)crippled the growth of liver cancer cells carrying the p53^(72P)variant in both in vitro and patient-derived xenograft models.Moreover,AOA plus regorafenib,an FDA-proved drug for hepatocellular carcinoma and colorectal cancer,achieved a better anti-tumor effect on tumors carrying the p53^(72P)variant.Therefore,our findings identified a gain of function of the p53^(72P)variant on mitochondrial function and provided a promising precision strategy to treat tumors vulnerable to p53^(72P)-PSAT1 perturbation. | Jingwen Jiang Hai-Ning Chen Ping Jin Li Zhou Liyuan Peng Zhao Huang Siyuan Qin Bowen Li Hui Ming Maochao Luo Na Xie Wei Gao Edouard C.Nice Qiang Yu Canhua Huang | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 0 |
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