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| 1 | Luteolin prevents uric acid-induced pancreatic β-cell dysfunction显示文摘Elevated uric acid causes direct injury to pancreaticβ-cells.In this study,we examined the effects of luteolin,an important antioxidant,on uric acid-inducedβ-cell dysfunction.We first evaluated the effect of luteolin on nitric oxide(NO)formation in uric acid-stimulated Min6 cells using the Griess method.Next,we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor(NF)-κB.Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase(iNOS)in uric acid-treated cells.Finally,we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion(GSIS)in Min6 cells and freshly isolated mouse pancreatic islets.We found that luteolin significantly inhibited uric acid-induced NO production,which was well correlated with reduced expression of iNOS mRNA and protein.Furthermore,decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid.Besides,luteolin significantly increased MafA expression in Min6cells exposed to uric acid,which was reversed by overexpression of iNOS.Moreover,luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets.In conclusion,luteolin protects pancreaticβ-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreaticβ-cells in hyperuricemiaassociated diabetes. | Ying Ding Xuhui Shi Xuanyu Shuai Yuemei Xu Yun Liu Xiubin Liang Dong Wei Dongming Su | 2014 | The Journal of Biomedical Research2014，28，4： | 3 |
| 2 | Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kαinhibitors显示文摘Phosphatidylinositol 3-kinase alpha(PI3Kα)inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma(ESCC).It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3Kαinhibitors in an aim to improve the clinical responsive rate in ESCC.Here,ESCC PDXs with CCND1 amplification were found to be more sensitive to CYH33,a novel PI3Kα-selective inhibitor currently in clinical trials for the treatment of advanced solid tumors including ESCC.Elevated level of cyclin D1,p21 and Rb was found in CYH33-sensitive ESCC cells compared to those in resistant cells.CYH33 significantly arrested sensitive cells but not resistant cells at G1 phase,which was associated with accumulation of p21 and suppression of Rb phosphorylation by CDK4/6 and CDK2.Hypo-phosphorylation of Rb attenuated the transcriptional activation of SKP2 by E2F1,which in turn hindered SKP2-mediated degradation of p21 and reinforced accumulation of p21.Moreover,CDK4/6 inhibitors sensitized resistant ESCC cells and PDXs to CYH33.These findings provided mechanistic rationale to evaluate PI3Kαinhibitors in ESCC patients harboring amplified CCND1 and the combined regimen with CDK4/6 inhibitors in ESCC with proficient Rb. | Xu Zhang Yuxiang Wang Xi Zhang Yanyan Shen Kang Yang Qingyang Ma Yuemei Qiao Jiajie Shi Yi Wang Lan Xu Biyu Yang Gaoxiang Ge Landian Hu Xiangyin Kong Chunhao Yang Yi Chen Jian Ding Linghua Meng | 2023 | Signal Transduction and Targeted Therapy2023，8，5： | 0 |
| 3 | Nanomedicine-Leveraged Intratumoral Coordination and Redox Reactions of Dopamine for Tumor-Specific Chemotherapy显示文摘Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous ions.In contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral redox reactions of DA for producing cytotoxic species in situ.For this purpose,we have constructed a Mn-engineered,DA-loaded nanomedicine.Based on the unique size effect of the nanocarrier,this nanomedicine will not enter the central nervous system but can effectively accumulate in the tumor region,after which the nanocarrier can degrade to release Mn^(2+)and DA in response to the mild acidic intracelluar microenvironment of cancer cells.DA can chelate Mn^(2+)to form a binary coordination complex,where the strong metal-ligand interaction significantly promotes electron delocalization and elevates the reducibility of Mn center,favoring two sequential one-electron oxygen reduction reactions forming H_(2)O_(2),which can be further converted into highly oxidizing ·OH under the cocatalysis by Mn^(2+)and intracellular Fe^(2+).Additionally,as a twoelectron oxidation product of DA ligand,DA-oquinone is potent in exhausting cellular sulfhydryl and depleting reduced glutathione,inhibiting the intrinsic antioxidative mechanism of cancer cells,finally triggering severe oxidative damages in a synergistic manner.It is expected that such a strategy of nanotechnology-mediated metal-ligand coordination and subsequent nontoxicity-to-toxicity transition of DA in tumor may provide a promising prospect for future chemotherapy design. | Bowen Yang Yuedong Guo Yuemei Wang Jiacai Yang Heliang Yao Jianlin Shi | 2022 | CCS Chemistry2022，4，5： | 0 |
| 4 | RADIATION EFFECT ON Bi(Pb)-Sr-Ca-Cu-O BY 35MeV PROTON IRRADIATION显示文摘Specimens of Bi(Pb)-Sr-Ca-Cu-O are irradiated by 35Me V proton at 70K,the critical zero-resistance temperature increases with the proton fluence within the range(2.21×10^(13)-3.54×10^(14)p/cm^(2)).This increase is about 5K at 3.54 ×10^(14)p/cm^(2) for specimen-1 and is about 10K at 4.42×10^(13)p/cm^(2) for specimen-2.The critical current at 107K for specimen-l increases by a factor of five.An endothermic reaction appears in the annealing process. | YU Jinnan WANG Yuzhu GAO Zhongcai CHEN Yiren SHI Yuemei | 1990 | Chinese Physics Letters1990，7，12： | 0 |
| 5 | Radiation Effect on YBa_(2)Cu_(3)O_(7-δ) by 35 MeV Proton Irradiation显示文摘The specimens of YBa_(2)Cu_(3)O_(7-δ)are irradiated by 35 MeV proton at 70K,the sero-resistance temperature TC0 is increased with the proton fluence within the range(2.21 × 10^(13)-1.77 × 10^(14)p/cm^(2)).Tc0 is increased from 91 to 97K at the fluence 1.77 × 10^(14)p/cm^(2) and critical current is also enhanced. | YU Jinnan GAO Zhongcai WANG Yuzhu CHEN Yiren SHI Yuemei | 1991 | Chinese Physics Letters1991，8，7： | 0 |
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