|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress显示文摘Parkinson's disease(PD) is a neurodegenerative disease characterized by a persistent decline of dopaminergic(DA) neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum(ER)stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent antioxidative stress properties and protects against DA neuronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine(6-OHDA)-induced cytotoxicity by attenuating ER stress. Furthermore, treatment of a DA neuronal cell line(SN4741) and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results suggest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD. | Kai Tao Bao Wang Dayun Feng Wei Zhang Fangfang Lu Juan Lai Lu Huang Tiejian Nie Qian Yang | 2016 | Neuroscience Bulletin2016，32，1： | 5 |
| 2 | Trends of Mortality in End-Stage Liver Disease—China,2008–2020显示文摘Introduction:Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases(ESLDs).Notably,in China,deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders.Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization,which could in turn help reduce the overall global burden of these diseases.Methods:Data were obtained from China’s Disease Surveillance Points system.The presentation includes both crude and age-standardized mortality rates,stratified by sex,residential location,and region.Using Joinpoint Regression,trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change(AAPC).Results:In 2020,the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals.A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts,respectively.Noticeably,the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China,respectively.A positive correlation was noticed between age-specific ESLD mortality rates and advancing age.Interestingly,an annual decrease in the ESLD mortality rate was observed from 2008 to 2020.In urban contexts,the AAPC of cirrhosis was noted to be higher than that of liver cancer.Conclusions:The mortality rate associated with ESLDs in China decreased between 2008 and 2020.Nevertheless,the death burden attributable to ESLD continues to be alarmingly high.Future initiatives should prioritize the reduction of ESLD mortality in particular populations:males,elderly individuals,and those residing in rural regions of South and Southwest China.The emphasis of future interventions should beplaced on antiviral therapy for adults diagnosed with viral hepatitis,and on the prevention of hepatitis B virus(HBV)infection across all demographics. | Xiaoxiao Wang Huixin Liu Jinlei Qi Fangfang Zeng Lijun Wang Peng Yin Feng Liu Hongbo Li Yunning Liu Jiangmei Liu Lai Wei Xiaofeng Liang Yu Wang Huiying Rao Maigeng Zhou | 2023 | China CDC weekly2023，5，30： | 1 |
| 3 | YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer显示文摘PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients,and their indications are expanding incessantly.Currently,most PD-1/PD-L1 agents are administered intravenously,which may be uncomfortable for some cancer patients.Herein,we develop a novel oral-delivered small molecular,YPD-29B,which specifically targets human PD-L1.Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1,but did not inhibit any other immune checkpoints.Mechanistically,YPD-29B induced human PD-L1 dimerization and internalization,which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro.YDP-29B was modified as the YPD-30 prodrug to improve druggability.Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells,we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo.Taken together,our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy. | Fangfang Lai Ming Ji Lei Huang Yunchen Wang Nina Xue Tingting Du Kai Dong Xiaoqing Yao Jing Jin Zhiqiang Feng Xiaoguang Chen | 2022 | Acta Pharmaceutica Sinica B2022，12，6： | 1 |
| 4 | An Old Story Retold: Loss of G1 Control Defines A Distinct Genomic Subtype of Esophageal Squamous Cell Carcinoma显示文摘Esophageal squamous cell carcinoma(ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration(CNA) and loss of heterozygosity(LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations(NSSMs) in102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology(GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B(30.9%), amplification of 11q13.3 covering CCND1(30.9%), and TP53 point mutation(50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC.Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes.These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting. | Qiyan Wang Jian Bai Amir Abliz Ying Liu Kenan Gong Jingjing Li Wenjie Shi Yaqi Pan Fangfang Liu Shujuan Lai Haijun Yang Changdong Lu Lixin Zhang Wei Chen Ruiping Xu Hong Cai Yang Ke Changqing Zeng | 2015 | Genomics, Proteomics & Bioinformatics2015，13，4： | 1 |
| 5 | Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiaes by cell-free nuclear extracts 显示文摘 | YUAN Fenghua LAI Fangfang GU Liya | 2009 | Method2009，48，： | 1 |
| 6 | S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung显示文摘Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy. | Mengyao Hao Rong Fu Jun Tai Zhenhuan Tian Xia Yuan Yang Chen Mingjin Wang Huimin Jiang Ming Ji Fangfang Lai Nina Xue Liping Bai Yizhun Zhu Xiaoxi Lv Xiaoguang Chen Jing Jin | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 1 |
| 7 | Review of Black Start on New Power System Based on Energy Storage Technology显示文摘With the continuous development of new energy generation technology and the increasingly complex power grid environment,the traditional black start scheme cannot meet the requirements of today’s power grid in order to ensure the stable operation of the power system can be restored quickly in the face of large power outages,so a more complete black start scheme needs to be developed to cope with the new power system.With the development of energy storage technology,the limitations of the traditional black-start scheme can be solved by new energy farms with energy storage configuration.Therefore,this paper investigates the problems faced by black-start,the key technologies of energy storage assisted new energy black-start,and introduces the research related to new energy black-start technology to provide reference for future research and application of new energy black-start. | Jin Fan Litao Niu Cuiping Li Gang Zhang He Li Yiming Wang Junhui Li Qinglong Song Jiacheng Sun Jianglong Pan Fangfang Lai | 2023 | Energy Engineering2023，120，12： | 0 |
| 8 | Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection显示文摘The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections.Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AzD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity.The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase(GyrB,IC_(50)=49 nmol/L)and a modest inhibitory effect on TopoⅣ(ParE,IC_(50)=1.513μmol/L)of Staphylococcus aureus.It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration(MIC)of less than 0.03μg/mL,which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S.aureus.Compound 28 had better protective effects than the positive control drugs such as DS-2969(5)and AZD5099(6)in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus(MRSA)infection.It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models.Moreover,compound 28 has much lower mitochondrial toxicity than AZD5099(6)as well as excellent therapeutic indexes and pharmacokinetic properties.At present,compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection.On the other hand,compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli(MIC=1μg/mL),which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently.In addition,the structure-activity relationships of the compounds were also studied. | Xintong Zhao Jing Feng Jie Zhang Zunsheng Han Yuhua Hu Hui-Hui Shao Tianlei Li Jie Xia Kangfan Lei Weiping Wang Fangfang Lai Yuan Lin Bo Liu Kun Zhang Chi Zhang Qingyun Yang Xinyu Luo Hanyilan Zhang Chuang Li Wenxuan Zhang Song Wu | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员