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91.
Yuhai Bi Weifeng Shi Jianjun Chen Quanjiao Chen Zhenghai Ma Gary Wong Wenxia Tian Renfu Yin Guanghua Fu Yongchun Yang William J. Liu Chuansong Quan Qianli Wang Shenghu He Xiangdong Li Qianfeng Xia Lixin Wang Zhaohui Pan Laixing Li Hong Li Wen Xu Ying Luo Hui Zeng Lianpan Dai Haixia Xiao Kirill Sharshov Alexander Shestopalov Yi Shi Jinghua Yan Xuebing Li Yingxia Liu Fumin Lei Wenjun Liu George F. Gao 《中国科学:生命科学英文版》2017,60(12):1386-1391
正Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005). 相似文献
92.
Cao R Yi W Wu Q Guan X Feng M Ma C Chen Z Song H Peng W 《Bioorganic & medicinal chemistry letters》2008,18(24):6558-6561
A series of new beta-carboline derivatives, bearing a benzylidine substituent at position-1, has been prepared and evaluated in vitro against a panel of human cell lines. The N(2)-benzylated beta-carbolinium bromates represented the most interesting cytotoxic activities. In particular, compounds 19 were found to be the most potent compounds with IC(50) values lower than 5 microM against 10 strains human tumor cell lines. These results confirmed that the N(2)-benzyl substituent on the beta-carboline ring played an important role in the modulation of the cytotoxic activities and suggested that further development of such compounds may be interest. 相似文献
93.
Investigation of rifampicin-induced hepatotoxicity in rat hepatocytes maintained in gel entrapment culture 总被引:1,自引:0,他引:1
Rifampicin-induced hepatotoxicity has been well recognized in animals and patients. However, it is undetectable in cultured
hepatocyte monolayers in vitro at the equivalent toxic concentration in vivo. This study investigated the rifampicin-induced
toxicity on rat hepatocytes in gel entrapment vs. in monolayer culture. Thiazolyl tetrazolium reduction and albumin secretion
were routinely detected to identify the toxic responses of rat hepatocytes to rifampicin, while reactive oxygen species (ROS)
accumulation and intracellular glutathione (GSH) content were assayed as biomarkers of oxidative stress. In addition, Nile
red staining and malondialdehyde (MDA) generation were, respectively, used as endpoints for lipid accumulation and peroxidation.
After treatment of hepatocytes for 96 h at a serum rifampicin concentration (12 μM), gel-entrapped rat hepatocytes showed
significant cellular damage indicated by alternations of all parameters indicated above, while hepatocyte monolayers did not
show severe responses. In contrast to a lack of protections by cytochrome P 450 inhibitors, the ROS scavenger (glycyrrhizic
acid) and thiol compounds (N-acetylcysteine and GSH) significantly reduced rifampicin toxicity in gel-entrapped hepatocytes. It appears that gel-entrapped
rat hepatocytes reflected significant hepatotoxicity of rifampicin in vivo, and this toxicity was most possibly associated
with oxidative stress and lipid accumulation. 相似文献
94.
The Src homology phosphotyrosyl phosphatase 2 (SHP2) plays a positive role
in HER2-induced signaling and transformation, but its mechanism of action is
poorly understood. Given the significance of HER2 in breast cancer, defining a
mechanism for SHP2 in the HER2 signaling pathway is of paramount importance.
In the current report we show that SHP2 positively modulates the
Ras-extracellular signal-regulated kinase 1 and 2 and the
phospoinositide-3-kinase-Akt pathways downstream of HER2 by increasing the
half-life the activated form of Ras. This is accomplished by dephosphorylating
an autophosphorylation site on HER2 that serves as a docking platform for the
SH2 domains of the Ras GTPase-activating protein (RasGAP). The net effect is
an increase in the intensity and duration of GTP-Ras levels with the overall
impact of enhanced HER2 signaling and cell transformation. In conformity to
these findings, the HER2 mutant that lacks the SHP2 target site exhibits an
enhanced signaling and cell transformation potential. Therefore, SHP2 promotes
HER2-induced signaling and transformation at least in part by
dephosphorylating a negative regulatory autophosphorylation site. These
results suggest that SHP2 might serve as a therapeutic target against breast
cancer and other cancers characterized by HER2 overexpression.The Src homology phosphotyrosyl phosphatase 2
(SHP2)2 functions as a
positive effector of cell growth and survival
(1–4),
migration and invasion
(5–8),
and morphogenesis and transformation
(9–11).
In receptor-tyrosine kinase signaling
(12–14),
SHP2 positively transduces the Ras-extracellular signal-regulated kinase 1 and
2 (ERK1/2) and the phosphoinositide-3-kinase-Akt (or protein kinase B)
signaling pathways. SHP2 also promotes cell transformation induced by the
constitutively active form of fibroblast growth factor receptor 3 and v-Src
(9,
11). The discovery of
germline-activating SHP2 mutations in Noonan and LEOPARD syndrome patients
(15–18)
and the subsequent experimental demonstration of these phenotypes in knockin
and transgenic mice expressing these mutants
(19,
20) has led to the conclusion
that disregulation of SHP2 is responsible for these disease states.
Furthermore, somatic activating SHP2 mutations were discovered in juvenile
myelomonocytic leukemia, acute myelogenous leukemia, and chronic
myelomonocytic (18,
21) and are suggested to play
a causative role.SHP2 possesses two Src homology 2 (SH2) domains in the N-terminal region
that allow the protein to localize to substrate microdomains after tyrosyl
phosphorylation of interacting proteins. The phosphotyrosyl phosphatase (PTP)
domain in the C-terminal region is responsible for dephosphorylation of target
substrates (13,
22). Mutation of the critical
Cys residue in the active site of SHP2 abolishes its phosphatase activity,
leading to the production of a dominant-negative protein
(23). The activity of SHP2 is
regulated by an intramolecular conformational switch. SHP2 assumes a
“closed conformation” when inactive and an “open
conformation” when active. In the closed conformation the N-SH2 domain
interacts with the PTP domain, physically impeding the activity of the enzyme.
Upon engagement of the SH2 domains with phosphotyrosine, the PTP domain is
relieved of autoinhibition and dephosphorylates target substrates
(23–26).
Interaction between specific residues on the N-SH2 and the PTP domains
mediates the closed conformation. Mutation of these residues leads to a
constitutively active SHP2, and the occurrence of such mutations in humans
causes the development of Noonan syndrome and associated leukemia
(16–18).Recently, we have shown that inhibition of SHP2 in the HER2-positive breast
cancer cell lines abolishes mitogenic and cell survival signaling and reverses
transformation, leading to differentiation of malignant cells into a normal
breast epithelial phenotype
(27). Given the significance
of HER2 in breast cancer, the finding that SHP2 plays a positive role was very
interesting. We, thus, sought to investigate the molecular mechanism that
underlies the positive role of SHP2 in HER2-induced signaling and
transformation. To do so, it was first necessary to decipher the identity of
SHP2 substrates whose dephosphorylation promotes the oncogenic functions of
HER2. Using the recently developed substrate-trapping mutant of SHP2 as a
reagent (28), we have
identified HER2 itself as an SHP2 substrate. We have further shown that SHP2
dephosphorylates an autophosphorylation site on HER2 that serves as a docking
site for the SH2 domains of the Ras GTPase-activating protein (Ras-GAP), the
down-regulator of Ras. This effect of SHP2 increases the intensity and
duration of GTP-Ras levels with the overall impact of enhanced HER2 signaling
and cell transformation. 相似文献
95.
Plasmacytoid dendritic cells (pDC) are essential innate immune system cells that are lost from the circulation in human immunodeficiency virus (HIV)–infected individuals associated with CD4+ T cell decline and disease progression. pDC depletion is thought to be caused by migration to tissues or cell death, although few studies have addressed this directly. We used precise methods of enumeration and in vivo labeling with 5-bromo-2′-deoxyuridine to track recently divided pDC in blood and tissue compartments of monkeys with acute pathogenic simian immunodeficiency virus (SIV) infection. We show that pDC are lost from blood and peripheral lymph nodes within 14 days of infection, despite a normal frequency of pDC in bone marrow. Paradoxically, pDC loss masked a highly dynamic response characterized by rapid pDC mobilization into blood and a 10- to 20-fold increase in recruitment to lymph nodes relative to uninfected animals. Within lymph nodes, pDC had increased levels of apoptosis and necrosis, were uniformly activated, and were infected at frequencies similar to CD4+ T cells. Nevertheless, remaining pDC had essentially normal functional responses to stimulation through Toll-like receptor 7, with half of lymph node pDC producing both TNF-α and IFN-α. These findings reveal that cell migration and death both contribute to pDC depletion in acute SIV infection. We propose that the rapid recruitment of pDC to inflamed lymph nodes in lentivirus infection has a pathologic consequence, bringing cells into close contact with virus, virus-infected cells, and pro-apoptotic factors leading to pDC death. 相似文献
96.
Bi X Lopez C Bacchi CJ Rattendi D Woster PM 《Bioorganic & medicinal chemistry letters》2006,16(12):3229-3232
A series of polyaminoguanidines and polyaminobiguanides were synthesized and evaluated as potential antitrypanosomal agents. These analogues inhibit trypanothione reductase (TR) with IC50 values as low as 0.95 microM, but do not inhibit the closely related human enzyme glutathione reductase (GR). The most effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50 values of 0.18, 0.09 and 0.18 microM, respectively. These agents represent a promising new class of potential antitrypanosomal agents. 相似文献
97.
Dou Z Chen RY Wang Z Ji G Peng G Qiao X Fu J Meng X Bulterys M Ma Y Zhao Y Wang N Zhang F 《PloS one》2010,5(10):e13737
Background
The HIV epidemic among former plasma donors (FPDs) in rural Central China in the early-mid 1990s is likely the largest known HIV-infected cohort in the world related to commercial plasma donation but has never been fully described. The objectives of this study are to estimate the timing and geographic spread of HIV infection in this cohort and to demonstrate the impact of antiretroviral therapy on survival outcomes.Methodology/Principal Findings
HIV-infected FPDs were identified using the national HIV epidemiology and treatment databases. Locations of subjects were mapped. Dates of infection and survival were estimated using the midpoint date between initial-final plasma donation dates from 1985–2008 among those with plasma donation windows ≤2 years. Among 37084 FPDs in the two databases, 36110 were included. 95% were located in focal areas of Henan Province and adjacent areas of surrounding provinces. Midpoint year between initial-final plasma donation dates was 1994 among FPDs with known donation dates. Median survival from infection to AIDS was 11.8 years and, among those not treated, 1.6 years from AIDS to death. Among those on treatment, 71% were still alive after five years. Using Cox proportional hazard modeling, untreated AIDS patients were 4.9 times (95% confidence interval 4.6–5.2) more likely to die than those on treatment.Conclusions/Significance
The epidemic of HIV-infected FPD in China was not widespread throughout China but rather was centered in Henan Province and the adjacent areas of surrounding provinces. Even in these areas, infections were concentrated in focal locations. Overall, HIV infections in this cohort peaked in 1994, with median survival of 13.4 years from infection to death among those not treated. Among AIDS patients on treatment, 71% were still alive after five years. 相似文献98.
YingWu Shi Chun Li HongMei Yang Tao Zhang Yan Gao Min Chu Jun Zeng Qing Lin OuTiKuEr YuGuo Li Xiangdong Huo Kai Lou 《Journal of microbiology (Seoul, Korea)》2017,55(4):267-272
This study details the introduction of a gfp marker into an endophytic bacterial strain (Achromobacter marplatensis strain 17, isolated from sugar beet) to monitor its colonization of sugar beet (Beta. vulgaris L.). Stability of the plasmid encoding the gfp was confirmed in vitro for at least 72 h of bacterial growth and after the colonization of tissues, under nonselective conditions. The colonization was observed using fluorescence microscopy and enumeration of culturable endophytes in inoculated sugar beet plants that grew for 10 or 20 days. gfp-Expressing strains were re-isolated from the inner tissues of surface-sterilized roots and stems of inoculated plants, and the survival of the Achromobacter marplatensis 17:gfp strain in plants 20 days after inoculation, even in the absence of selective pressure, suggests that it is good colonizer. These results also suggest that this strain could be a useful tool for the delivery of enzymes or other proteins into plants. In addition, the study highlights that sugar beet plants can be used effectively for detailed in vitro studies on the interactions between A. marplatensis strain 17 and its host, particularly if a gfp-tagged strain of the pathogen is used. 相似文献
99.
完达山东部林区野猪种群数量和栖息地特征的初步分析 总被引:3,自引:0,他引:3
2008 年11 月18 日至2009 年3 月20 日,为了调查黑龙江省完达山东部林区野猪种群数量和栖息地特征,我们采用随机布设样线的方法在东方红林业局境内13 个林场共布设大样方40 个,样线200 条。调查结果表明,东方红林业局境内野猪分布平均密度为0.175 头/ km2 , 种群数量为546 ~ 680 头;野猪主要分布在河口、奇源、青山、五林洞、独木河、海音山和东林7 个林场,位于海拔300 ~ 800 m 的范围内。1989 年调查的野猪平均密度为0.372 头/ km2 ,种群数量为1302 ; 2002 年调查的野猪平均密度为0. 342 头/ km2 , 种群数量为1 198 头。近年来野猪种群密度降低,种群数量呈加速下降趋势。对野猪栖息地特征分析表明,野猪喜欢选择中坡位、阳坡、坡度小于5°、地表植被盖度大于30% 、隐蔽度和郁闭度在25% ~ 50% 之间的生境。阔叶林、灌丛是野猪的主要栖息地。非法捕猎、森林采伐、坚果采摘和东北虎的捕食是造成野猪种群数量减少、栖息地质量下降的主要因素。 相似文献
100.
Bing Tan Jinxiang Tan Hongfei Du Zhen Quan Xiangdong Xu Xiaoliang Jiang Chunli Luo Xiaohou Wu 《Molecular and cellular biochemistry》2014,385(1-2):95-102
p62/sequestosome-1 is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis, and plays an important role at the crossroad between autophagy and cancer. But, the connection between autophagy and cancer is complex and in some cases contradictory. Human colorectal cancer tissues from patients were analyzed for expression of p62 and Microtubule-associated protein light chain 3 (LC3, an autophagosome marker) using immunostaining, western blotting, real-time PCR, and confocal microscopy. To study the effects of p62 on autophagy and cell growth, shRNA for p62 was applied and cell growth curve was monitored in human colorectal cancer cell. In vivo experiments were done using the mouse xenograft model. We showed that up-regulated expression of p62 and LC3 in colorectal cancer tissues. We also demonstrated that specifically knockdown the expression of p62 showed significantly inhibitory effects not only on autophagy activation, but also on tumor growth both in vitro and xenograft tumors model. The ectopic overexpression of p62 and autophagy activation contributes to colorectal tumorigenesis. p62 and autophagy will be therapy targets for the treatment of colorectal cancer. 相似文献