检索结果-南通市图书馆

Nano Research 2019年第8期12卷 1959-1966页

作者： Bo Dai Xingyu Wu Christopher J. Butch Jianquan Wang Ziyang Wang Yisheng Wang Shuming Nie Qian Lu Yiqing Wang Yitao Ding Drum Tower Clinical Medical College Nanjing Medical UniversityNanjing 210008China Department of Biomedical Engineering College of Engineering and Applied SciencesNanjing UniversityNanjing 210008China Department of Biomedical Engineering University of Illinois at Urbana-ChampaignIllinois 61801USA

The clinical translation of nanomedicine is hindered by the low delivery efficiency, and consequently drug concentration in tumor sites falls short of the therapeutic effective range which leads to poor clinical outcomes. One important lesson learned from the development of antibody-drug-conjugates (ADCs) is that to achieve significant clinical benefits, extremely potent cytotoxic agents and cleavable linkers should be used. By encapsulating maytansinoid, AP3, which is 100-1,000 times more potent than most conventional small molecule anticancer drugs, in pH-sensitive acetalated dextran-polyethylene glycol (PEG)(ADP) nanocarriers, even with only 1% drug loading, we were able to eradicate tumors in 50% of tested animals with negligible side effects, while free AP3 only showed marginal efficacy and severe liver damages. This study suggests that besides improving the low efficiency of nano-delivery systems, the potency of drug to be delivered is also critical to the clinical outcomes of nanomedicine. Our results also showed that ADP nanoparticles (NPs) were able to expand the narrow therapeutic window of maytansinoids in a similar manner to the ADCs.

关键词： nanomedicine drug delivery maytansinoid extremely potent drug pH-sensitive nanocarrier

A new generation M^(pro)inhibitor with potent activity against SARS-CoV-2 Omicron variants

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2023年第4期8卷 1970-1982页

作者： Chong Huang Huiping Shuai Jingxin Qiao Yuxin Hou Rui Zeng Anjie Xia Lingwan Xie Zhen Fang Yueyue Li Chaemin Yoon Qiao Huang Bingjie Hu Jing You Baoxue Quan Xiu Zhao Nihong Guo Shiyu Zhang Ronggang Ma Jiahao Zhang Yifei Wang Ruicheng Yang Shanshan Zhang Jinshan Nan Haixing Xu Falu Wang Jian Lei Hin Chu Shengyong Yang State Key Laboratory of Biotherapy and Cancer Center and National Clinical Research Center for Geriatrics West China HospitalSichuan UniversityChengduSichuan 610041China State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Department of Microbiology Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengduSichuan 610041China

Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public *** molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals eithershow limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of thesedrugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a newgeneration antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). Thiscompound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, butalso other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced ***, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstandingsafety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigationprovides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.

关键词： treatment predominant potent

DYNORPHIN:INTRATHECAL INJECTION PRODUCES potent ANALGESIC EFFECT

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Science Bulletin 1983年第9期28卷 1289-1290页

作者：韩济生谢翠微 Department of Physiology Beijing Medical College Department of Physiology

Goldstein et al. found in the porcine pituitary a potent opioid peptide dynorphin composed of 17 amino acids with leu-enkephalin as its N terminal sequence. In guinea pig ileum assay system, it is about 700 times more

关键词： potent porcine guinea opioid Goldstein pituitary naloxone anesthesia reversal subsequent

Effects of highly potent atrial natriuretic peptide on circulating reninangiotensin-aldosterone system and cardiac function in dogs with ischemic heart failure

在线全文

学校读者我要写书评

暂无评论

Journal of Medical Colleges of PLA(China) 1997年第2期12卷 136-139页

作者：吴宏超钱学贤冯常森王佳勇张勇施傅涛

The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.

关键词： highly potent atrial natriuretic peptide renin-angiotensin-aldosterone system myocardial ischemia heart failure

Grifolin,a potent antitumor natural product,upregulates death-associated protein kinase 1(DAPK1)via p53 in nasopharyngeal carcinoma cells

在线全文

学校读者我要写书评

暂无评论

中国病理生理杂志 2010年第A10期26卷 2006-2006页

作者： LUO Xiang-jian1,LI Li-li1,DENG Qi-pan1,YU Xin-fang1,LUO Fei-jun1,YANG Li-fang1,XIAO Lan-bo1,CHEN Xiao-yan1,YE Mao1,LIU Ji-kai2,CAO Ya1(1Cancer Research Institute,Xiangya School of Medicine,Central South University,Changsha 410078,China 2Department of Phytochemistry,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650204,China)

Grifolin,a secondary metabolite isolated from the fresh fruiting bodies of mushroom Albatrellus confluens,inhibits the growth of some cancer cell lines in vitro by induction of apoptosis in the previous studies of our ***,the mechanisms are not completely *** expression profiling analysis of apoptosis-related gene provided a clue that death-associated protein kinase 1(dapk1)gene was upregulated at least twofold in response to grifolin treatment in

关键词： nasopharyngeal potent understood antitumor metabolite profiling mushroom induction targeting fresh

Combination of suicide gene and interleukin 2 gene transfer elicited potent antitumor effects on murine melanoma

在线全文

学校读者我要写书评

暂无评论

中国实验血液学杂志 1997年第3期5卷 299-299页

作者： Dianwen Ju, Baomei Wang, Qun Tao, Yizhi Yu, Xuetao CaoDepartment of Immunology, The Secoiul Military MedicalUniversity, Shanghai 200433

Antitumor effects of combined transfer of suicidegene and cytokine gene were investigated in this *** harboring ***. cytosine deaminase (CD)gene (Ad-CD) and murine interleukin 2 (IL-2) gene(Ad-IL-2) were used for gene transfer in vitro and invivo. C57BL/6 mice were inoculated subcutaneously withB16F10 melanoma cells and three days later treated withadenovirus injection at the site of tumor *** inhibition of tumor growth was achieved

关键词： melanoma interleukin antitumor potent murine deaminase cytokine Adenovirus inoculated cytosine

Hippocampal stem cells:so they are multipotent!

在线全文

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2011年第5期3卷 270-272页

作者： Verdon Taylor Centre for Stem Cell Biology Department of Biomedical ScienceUniversity of SheffieldWestern BankSheffield S102TNUK Department of Molecular Embryology Max Planck Institute of Immunobiology and EpigeneticsStubeweg 51Freiburg D-79108Germany

Although neurogenesis continues throughout life in the mammalian brain,the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains *** a recent landmark paper by Bonaguidi et al.(2011)published in Cell,the authors provide clonal evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.

关键词： al. potent stem

The Emission Reduction potential of Non-CO_2 Greenhouse Gases in China and Its Policy Implications

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Agricultural Research 2013年第4期5卷 87-92页

作者： Delin HUANG Songfeng CAI Zhen WANG Institute of Agricultural Economics and Development the Chinese Academy of Agriculture Science

Using the improved Energy-Environmental Version of the GTAP Model (GTAP-E) and the sixth version of emission database of non-CO2 greenhouse gases, we simulate the emission reduction potential of non-CO2 greenhouse gases in China and its policy implications. The results show that at present, China is a country with the greatest emission of non-CO2 greenhouse gases in the world, and the emission will account for about 20% of the world's total emission in 2020. The proportion of emission of non-CO2 greenhouse gases from the agricultural sector reaches 73%. In the next 10 years, the emission of non-CO2 gases from cattle and sheep, industry and service industry will experience the highest growth rate; the growth rate of emission from service industry will be higher than that of emission from industry, and the emission from service industry will exceed that from industry after 2010. China can implement emission reduction policy of non-CO2 greenhouse gases to ease the international pressure of CO2 emission reduction. Although the high carbon tax collected can reduce considerable non-CO2 emission, there is little difference in policy efficiency between high carbon tax and low carbon tax. So, in the implementation of emission reduction carbon tax policy of non-CO2 gases, it is necessary to control the carbon tax at a low level.

关键词： Non-CO2 greenhouse gases Emission reduction potent

THE ANALGESIC EFFECT OF DYNORPHIN A IN SPINAL CORD OF THE RAT potentIATED BY DYNORPHIN B

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Science Bulletin 1985年第12期30卷 1688-1692页

作者：谢国玺韩济生 Department of Physiology Beijing Medical College

The analgesic effect of dynorphin (dyn) at the spinal level was first reported in 1982 by Piercey et al. in mice and by Han et al. in rats. These findings have been verified by some investigators using intrathecal injection of dyn, but not with kappa receptor agonist USO, 488. In 1982, a new [Leu] enkephalin C terminal extended peptide dyn B (rimorphin) was found and the original 17-residue peptide dyn was re-

关键词： analgesic analgesia verified agonist residue opioid morphine weighing titer potent

CALCULATION OF THE FIELD GRADIENT FROM COMPLEX potentIAL FUNCTION

在线全文

学校读者我要写书评

暂无评论

Chinese Science Bulletin 1983年第1期28卷 136-137页

作者：徐建民 Beijing Institute of Mining and Metallurgy Ministry of Metallurgical Industry

Take the static electric field as an example. Suppose there is a two-dimensional harmonic field on complex plane Z, whose complex potential function W=U(x,y)+iV(x,y). Then the magnitude of electric field gradient

关键词： magnitude harmonic 逻里加成双比 potent