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Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

《医学前沿（英文）》 2008年第2卷第4期页码 323-331 doi: 10.1007/s11684-008-0062-6

摘要： Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration, hypertrophy and growth. Crk-associated substrate (CAS), the first discovered member of the adapter protein CAS family, has been shown to be a critical cellular component that regulates various smooth muscle functions. In this review, the molecular structure and protein interactions of the CAS family members are summarized. Evidence for the role of CAS in the regulation of vascular smooth muscle contractility is presented. Contraction stimulation induces CAS phosphorylation on Tyr-410 in arterial smooth muscle, creating the binding site for the Src homology (SH) 2/SH3 protein CrkII, which activates neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin assembly and force development. The functions of CAS in cell migration, hypertrophy and growth are also summarized. Abelson tyrosine kinase (Abl), c-Src, focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), protein tyrosine phosphatase-proline, glutamate, serine and threonine sequence protein (PTP-PEST) and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS. The downstream signaling partners of CAS in the context of cell motility, hypertrophy, survival and growth are also discussed. These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions. Furthermore, the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

关键词： Contraction stimulation phosphatase-proline molecular structure discovered hypertension

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Protein phosphatase 2A, a key player in Alzheimer’s disease

Rong LIU, Qing TIAN

《医学前沿（英文）》 2009年第3卷第1期页码 8-12 doi: 10.1007/s11684-009-0017-6

摘要： Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer’s disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neurofibrillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation underlie PP2A inactivation in AD. β-amyloid (Aβ) over-production, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer’s disease.

关键词： protein phosphatase 2A Alzheimer’s disease holoenzyme composition protein phosphatase 2A inhibitors Leu309 demethylation Tyr307 phosphorylation

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Proline-2′-deoxymugineic acid, a phytosiderophore analog, drives beneficial rhizobacterial community

《农业科学与工程前沿（英文）》 doi: 10.15302/J-FASE-2023531

摘要：

● Proline-2′-deoxymugineic (PDMA) significantly altered the bacterial community in the peanut rhizosphere.

关键词： Beneficial rhizobacteria recruitment peanut plant-soil micronutrition enhancement proline-2′-deoxymugineic acid stable microbial network

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Measurement of bone alkaline phosphatase and relative study with osteosarcoma

YANG Zhiping, LI Jianmin, LI Xin, HUO Yanqing, SUN Guangzhi

《医学前沿（英文）》 2007年第1卷第1期页码 54-57 doi: 10.1007/s11684-007-0011-9

摘要： The objective of this paper is to explore the value of bone alkaline phosphatase (BALP) for diagnosing osteosarcoma, evaluating the effect of the chemotherapy, judging the prognosis and supervising the relapse and metastasis. The immunoassay was used to check the BALP of the blood serum that was from 42 primary osteosarcoma patients. Alkaline phosphatase (ALP) in blood serum was checked with auto biochemistry equipment. The biopsy tissue and the lesion resected in operation were treated with pathology and histological response was counted. The patients were followed up from five months to 49 months with an average of 24.3 months. Eighteen cases relapsed and transferred, among which, 16 of them were dead, and others were survival to the end of the follow-up. BALP was more sensitive than ALP in diagnosing osteosarcoma ( = 0.015). Fifteen cases decreased to normal value in ALP after preoperative chemotherapy, and 34 cases decreased in BALP. Both ALP and BALP in all cases decreased to normal value in postoperative. There was significant difference in positive correlation between the decrease of BALP and the increase of histological response ( = 0.001, = 0.642). In the followup, there was significant difference in BALP between the group of relapse and transfer and the group of free disease survival ( = 0.000). As a check marker in blood serum, BALP, reflecting the process of ossification, has a higher sensitivity than ALP. It has applied value in the diagnosis of osteosarcoma, reflection of the effect of chemotherapy and forecast the prognosis.

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Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

《医学前沿（英文）》 2008年第2卷第3期页码 235-238 doi: 10.1007/s11684-008-0044-8

摘要： The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation, protein phosphatase 2A (PP2A) activity, and on tau phosphorylation. Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein, and the phosphorylation levels of PP2A Y307 and tau at different sites, as well as PP2A activity were detected at different time points after siRNA transfection. Twelve hours after siRNA transfection, the protein level of Src was dramatically decreased, with decreased PP2A Y307 phosphorylation. However, the total PP2A protein level was also decreased, together with a decreased PP2A activity. Tau was hyperphosphorylated at the Ser198/199/202 sites. Multiple factors may be involved in the cellular regulation of PP2A activity. Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.

关键词： hyperphosphorylation PP2A activity cellular regulation siRNA siRNA transfection

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Expression and clinical implication of PRL-1 and PRL-3 in transitional cell carcinoma of bladder

Bin HAO, Changwei LIU, Huixiang LI

《医学前沿（英文）》 2009年第3卷第2期页码 197-203 doi: 10.1007/s11684-009-0036-3

摘要： The mRNA and protein expression of phosphatase of regenerating liver 1 (PRL-1) and phosphatase of regenerating liver 3 (PRL-3) in transitional cell carcinoma of bladder (BTCC) and normal epithelia of bladder was investigated, and the relationship between the BTCC and pathological changes was clarified. The expression of PRL-1 and PRL-3 mRNA was detected by using reverse transcription polymerase chain reaction (RT-PCR) in 30 cases of BTCC and 10 cases of normal bladder, and the expression of PRL-1 and PRL-3 protein was checked by using immunohistochemistry in 30 cases of BTCC and 15 cases of normal bladder. The expression levels of PRL-1 and PRL-3 mRNA and protein were higher in BTCC than those in normal bladder epithelia ( <0.05). The increased expression of PRL-1 and PRL-3 mRNA and protein was detectable in deep invasion and metastasis of BTCC ( <0.05). There was no correlation between the expression of PRL-1 and PRL-3 and gender, age or recurrence of BTCC (all >0.05). A significantly positive correlation was found between PRL-1 and PRL-3 in BTCC ( <0.05). PRL-1 and PRL-3 are expressed consistently and may contribute to the growth, differentiation, invasion and metastasis of BTCC.

关键词： transitional cell carcinoma of bladder phosphatase of regenerating liver 1 phosphatase of regenerating liver 3 reverse transcription polymerase chain reaction immunohistochemistry

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Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

null

《医学前沿（英文）》 2016年第10卷第1期页码 52-60 doi: 10.1007/s11684-016-0433-3

摘要：

Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P= 0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC-specific overall survival (HR, 2.799; 95% CI, 1.346–5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

关键词： PPM1D hepatocellular carcinoma prognosis target therapy

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Enzyme-instructed self-assembly of peptides containing phosphoserine to form supramolecular hydrogels as potential soft biomaterials

Jie Zhou, Xuewen Du, Jiaqing Wang, Natsuko Yamagata, Bing Xu

《化学科学与工程前沿（英文）》 2017年第11卷第4期页码 509-515 doi: 10.1007/s11705-017-1613-7

摘要： Enzyme-instructed self-assembly (EISA) offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phosphotyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phosphoserine and phosphotyrosine. Conjugating a phosphoserine to the -terminal of a well-established self-assembling peptide backbone, (naphthalene-2-ly)-acetyl-diphenylalanine (NapFF), affords a novel hydrogelation precursor for EISA. The incorporation of phosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors’ propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.

关键词： enzyme-instructed self-assembly phosphoserine phosphatase supramolecular hydrogel

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Keratin 5-Cre-driven deletion of

Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang

《医学前沿（英文）》 2020年第14卷第3期页码 305-317 doi: 10.1007/s11684-019-0722-8

摘要： Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in -secretase component genes. We and other researchers showed that ( ) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF- , IL-23A, IL-1 and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.

关键词： acne inversa mouse model interleukin 1 family member 6 small proline rich protein 2D key inflammatory cytokine