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PAK1 is a novel cardiac protective signaling molecule

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 399-403 doi: 10.1007/s11684-014-0380-9

摘要：

We review here the novel cardiac protective effects of the multifunctional enzyme, p21-activated kinase 1 (PAK1), a member of a serine/threonine protein kinase family. Despite the large body of evidence from studies in noncardiac tissue indicating that PAK1 activity is key in the regulation of a number of cellular functions, the role of PAK1 in the heart has only been revealed over the past few years. In this review, we assemble an overview of the recent findings on PAK1 signaling in the heart, particularly its cardiac protective effects. We present a model for PAK1 signaling that provides a mechanism for specifically affecting cardiac cellular processes in which regulation of protein phosphorylation states by protein phosphatase 2A (PP2A) predominates. We discuss the anti-adrenergic and antihypertrophic cardiac protective effects of PAK1, as well as its role in maintaining ventricular Ca2+ homeostasis and electrophysiological stability under physiological, β-adrenergic and hypertrophic stress conditions.

关键词： p21-activated kinase 1 (PAK1)     heart    

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Involvement of p38 mitogen-activated protein kinase in the regulation of platelet-derived growth factor

GONG Xiaowei, WEI Jie, LI Yusheng, CHENG Weiwei, DENG Peng, JIANG Yong

《医学前沿（英文）》 2007年 第1卷 第3期   页码 248-252 doi: 10.1007/s11684-007-0047-x

摘要： The aim of this study was to investigate the role of p38 mitogen-activated protein kinase (MAPK) in cell migration induced by platelet-derived growth factor (PDGF). Western blot was performed to detect the phosphorylation of p38 in NIH3T3 cells treated with PDGF. A Transwell cell migration system was used to determine the effects of PDGF treatment on the migration of NIH3T3 cells and the influence of deficiency on this process in a gene knockout (p38) mouse embryonic fibroblast cell line. On the stimulation of PDGF, the migration of NIH3T3 cells was significantly increased (〈0.001) compared to the control and p38 MAP kinase was simultaneously phosphorylated. Furthermore, the PDGF-induced cell migration was significantly blocked in gene knockout (p38) mouse embryonic fibroblasts (MEFs) (〈0.001) as compared with the wild type cells (p38). p38 MAPK plays an important role in the regulation of cell migration induced by PDGF.

关键词： control     stimulation     mitogen-activated     growth factor     process    

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Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence

Huanping Wang, Haitao Meng, Jinghan Wang, Yinjun Lou, Yile Zhou, Peipei Lin, Fenglin Li, Lin Liu, Huan Xu, Min Yang, Jie Jin

《医学前沿（英文）》 2020年 第14卷 第3期   页码 327-334 doi: 10.1007/s11684-019-0712-x

摘要： This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells ( = 0.025), higher 2-microglobulin levels ( = 0.036), and higher lactate dehydrogenase levels ( = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, = 0.002; median OS 16.8 vs. 45.9 months, <0.001) were strongly associated with short progression-free survival (PFS) ( = 0.002) and overall survival (OS) ( <0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS ( = 0.006) and OS ( = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.

关键词： 1p32.3 deletion     1q21 gain     prognosis     multiple myeloma     FISH     bortezomib     thalidomide    

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Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

《化学科学与工程前沿（英文）》 2023年 第17卷 第2期   页码 123-138 doi: 10.1007/s11705-022-2194-7

摘要： The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many tissues. NAD(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most cancers. Therefore, it could be a target for cancer therapy. Because it is a quinone reductase, many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose tumours. Its expression is higher in tumours than in normal tissues, and using target drugs such as β-lapachone to reduce side effects in normal tissues can help. However, the physicochemical properties of β-lapachone limit its application. The problem can be solved by using nanosystems to deliver β-lapachone. This mini-review summarizes quinone-based fluorescent, near-infrared and two-photon fluorescent probes, as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drug β-lapachone. This review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

关键词： NAD(P)H:quinone oxidoreductase 1     cancer therapy     target     probe     nanosystem    

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Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1     stereociliary bundles     kinocilium     planar cell polarity     hearing     mice    

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noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis

《医学前沿（英文）》   页码 924-938 doi: 10.1007/s11684-023-1004-z

摘要： Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.

关键词： ovarian cancer     lncRNA LOC646029     metastasis     microRNA 627-3p     SPRED1    

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Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 462-476 doi: 10.1007/s11684-013-0270-6

摘要：

Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell (CSC) populations. In this study, we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. However, the CSC-like cells exhibited resistance to gemcitabine-induced apoptosis. Collectively, the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.

关键词： drug resistance     cancer stem cell     checkpoint kinase 1 (CHK1)     PF-00477736     lung cancer     tumorigenicity    

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Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase

Irina A SHURYGINA, Michael G SHURYGIN, Nataliya I AYUSHINOVA, Galina B GRANINA, Nikolay V ZELENIN

《化学科学与工程前沿（英文）》 2012年 第6卷 第2期   页码 232-237 doi: 10.1007/s11705-012-1286-1

摘要： Ninety male Wistar rats were selected under the “Guide for the Care and Use of Laboratory Animals” for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK (mitogen activated protein kinase) SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation (30 d) as the SB 203580 was applied (% volume of collagen 43.60 (41.05 – 60.15) 73.54 (66.87 – 78.01) in control, = 0.002). Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased (78.14 (72.77 – 81.14), = 0.022 control). SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.

关键词： connective tissue     mitogen activated protein kinase (MAPK)     p38     JNK    

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breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinasecancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase 1

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 186-195 doi: 10.1007/s11705-015-1540-4

摘要： Increased expression levels of the RNA splicing regulator Transformer2 (abbreviated Tra2 ) have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2 and the highly similar Tra2 protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2 reduces splicing inclusion of a poison exon in the mRNA encoding Tra2 , thereby up-regulating Tra2 protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2 alone. Discovery of this cross-regulation pathway, and its by-pass by joint depletion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 (CHK1) gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing     gene expression     breast cancer     DNA damage     CHK1    

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AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 248-262 doi: 10.1007/s11684-012-0206-6

摘要：

The AML1-ETO fusion transcription factor is generated by the t(8;21) translocation, which is present in approximately 4%–12% of adult and 12%–30% of pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary events. In this review, we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies for t(8;21) positive AML that involve targeting the fusion protein itself, the proteins that bind to it, or the genes that it regulates. Recently published studies suggest that a targeted therapy for t(8;21) positive AML is feasible and may be coming sometime soon.

关键词： AML1-ETO     mouse model     leukemia     t(8     21)     pathway hits     mutation     hematopoiesis     Kasumi-1     CD34+    

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Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 309-315 doi: 10.1007/s11684-009-0043-4

摘要： Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 0.008±0.002 of controls, =0.009; in liver: 0.165±0.006 0.017±0.006 of controls, =0.004; in small intestine: 0.215±0.009 0.016±0.002 of controls, =0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 0.003±0.001 of controls, =0.008; in small intestine: 0.006±0.001 0.003±0.001 of controls, =0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

关键词： graft vs host disease     proteinase-activated receptor     murine model     hematopoietic stem cell transplantation    

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Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 46-53 doi: 10.1007/s11684-010-0010-0

摘要： Mitogen-activated protein kinase (MAPK) signaling pathway, one of the most important signaling pathways in eukaryotic organism, is involved in multiple cellular events such as cell growth, differentiation, and apoptosis. MAPK is of great importance to the normal function of organisms, while its dysfunction results in various diseases. So far, inhibitors specifically against each subfamilies of MAP kinase have been developed, while more endeavors are needed to discover the compounds selectively targeting a particular subfamily member. Most of the kinase inhibitors exert their functions in an ATP-competitive way or a non-ATP-competitive way. Further studies on the effective mechanism of the MAPK inhibitors and their therapeutic roles in the treatment of diseases are helpful for the illumination of MAP kinase function, the development of novel inhibitors, and the therapy of diseases caused by the dysfunction of the MAPK pathway.

关键词： mitogen-activated protein kinase     drug target     inhibitor     signal transduction     disease    

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用高光谱发光法研究Cu(Inx,Ga1–x)Se2 (CIGS)模块中由P1引起的功率损耗的成因 Article

César Omar Ramírez Quiroz, Laura-Isabelle Dion-Bertrand, Christoph J. Brabec, Joachim Müller, Kay Orgassa

《工程（英文）》 2020年 第6卷 第12期   页码 1395-1402 doi: 10.1016/j.eng.2019.12.019

摘要： <p style="text-align: justify;">在本文中，我们利用了高光谱高分辨率光致发光映射技术，这是一个强大的工具，可用于选择和优化在Cu(Inx,Ga1-x)Se2（CIGS）模块上对子电池进行图案化互连的激光烧蚀工艺。具体而言，通过分析在CIGS沉积之前烧蚀的标准P1图案线，我们发现了沿着下部的钼槽边缘的异常发射猝灭效应。通过扫描电子显微镜（SEM）比较了P1边缘的横截面的形貌，我们进一步合理化产生这种效应的起因，但无法用厚度变化解释光发射的减少。我们还研究了激光诱导对CIGS沉积后的P1图案线带来的损伤。我们的发现能更好地理解P1引起的功率损耗，并为改进与行业相关的模块互连方案提供了新的见解。p>

关键词： Cu(Inx     Ga1–x)Se2     电池到模块的效率差距     由P1引起的功率损耗     高光谱光致发光     激光烧蚀短程热效应    

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Synthesis of zeolite Na-P1 from coal fly ash produced by gasification and its application as adsorbent

Yixin Zhang, Lu Zhou, Liqing Chen, Yang Guo, Fanhui Guo, Jianjun Wu, Baiqian Dai

《化学科学与工程前沿（英文）》 2021年 第15卷 第3期   页码 518-527 doi: 10.1007/s11705-020-1926-9

摘要： The coal fly ash produced by gasification is estimated to be over 80 million ton per year in China by 2021. It has mainly been disposed as solid waste by landfill. There is lack of study focused on its utilization. In this paper, the coal fly ash produced by gasification was at first analyzed and then applied to synthesize zeolite as an adsorbent. The effects of synthesis conditions on the cation exchange capacity (CEC) of zeolite were investigated. The results from X-ray diffraction and scanning electron microscope indicated that the crystallinity of the synthesized zeolite is the most important factor to affect the CEC. When the synthesized zeolite with the highest CEC (275.5 meq/100 g) was used for the adsorption of Cr(VI) from aqueous solution, the maximum adsorption capacity for Cr(VI) was found to be 17.924 mg/g. The effects of pH, contact time and initial concentration on the adsorption of Cr(VI) were also investigated. The adsorption kinetics and isotherms can be well described by the pseudo-second-order model and Langmuir isotherm model, respectively.

关键词： coal fly ash     gasification     zeolite     Na-P1     chromium(VI)    

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Adsorption of 1,3-propanediol from synthetic mixture using polymeric resin as adsorbents

TANTAYAKOM, P. PRASITCHOKE, C. MUANGNAPOH

《化学科学与工程前沿（英文）》 2009年 第3卷 第1期   页码 52-57 doi: 10.1007/s11705-009-0087-7

摘要： The aim of this work was to separate 1,3-PDO from a synthetic mixture using polymeric resins, Amberlite XAD-7 and XAD-16 resins. The equilibrium adsorption of 1,3-PDO onto two polymeric resins were investigated in binary and tertiary systems. Experimental results of binary component adsorption equilibrium indicated that the adsorption capacity ( ) of 1,3-PDO at 160 g/L onto XAD-7 and XAD-16 was 835.96 and 584.61 mg 1,3-PDO/g dry resin, respectively. The adsorption isotherms were closely predicted by the Langmuir-Freundlich model among the two isotherm model tested. The value of n of 1,3-PDO adsorbed on XAD-7 are much higher than those on XAD-16. This result suggested that XAD-7 resin has a higher affinity for the 1,3-PDO adsorption than XAD-16 resin. Moreover, the value of adsorption capacity of 1,3-PDO in the binary and tertiary component were compared at the same conditions. In the tertiary system, although the selectivity of 1,3-PDO from XAD-7 was approximately six times higher than XAD-16, the adsorption capacity of 1,3-PDO at 160 g/L onto XAD-16 was higher than XAD-7. Interestingly, the reusability of XAD-7 and XAD-16 resins in the three cycle times shows a slight loss of adsorption capacity. Furthermore, the investigation about desorption by an ethanol/water mixture at 50% ( / ) indicated that the desorption yield of 1,3-PDO from XAD-7 was lower than XAD-16 resin for both the binary and tertiary component. This was due to the more favorable adsorption characteristics of XAD-7 resin than XAD-16 resin.

关键词： adsorption     1     3-propanediol     glycerol     polymeric resin     adsorption isotherm    

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标题 作者 时间 类型 操作

PAK1 is a novel cardiac protective signaling molecule

null

期刊论文

Involvement of p38 mitogen-activated protein kinase in the regulation of platelet-derived growth factor

GONG Xiaowei, WEI Jie, LI Yusheng, CHENG Weiwei, DENG Peng, JIANG Yong

期刊论文

Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence

Huanping Wang, Haitao Meng, Jinghan Wang, Yinjun Lou, Yile Zhou, Peipei Lin, Fenglin Li, Lin Liu, Huan Xu, Min Yang, Jie Jin

期刊论文

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

期刊论文

Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

期刊论文

noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis

期刊论文

Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like

null

期刊论文

Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase

Irina A SHURYGINA, Michael G SHURYGIN, Nataliya I AYUSHINOVA, Galina B GRANINA, Nikolay V ZELENIN

期刊论文

breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinasecancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase 1

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

期刊论文

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

期刊论文

Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

期刊论文

Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

期刊论文

用高光谱发光法研究Cu(Inx,Ga1–x)Se2 (CIGS)模块中由P1引起的功率损耗的成因

César Omar Ramírez Quiroz, Laura-Isabelle Dion-Bertrand, Christoph J. Brabec, Joachim Müller, Kay Orgassa

期刊论文

Synthesis of zeolite Na-P1 from coal fly ash produced by gasification and its application as adsorbent

Yixin Zhang, Lu Zhou, Liqing Chen, Yang Guo, Fanhui Guo, Jianjun Wu, Baiqian Dai

期刊论文

Adsorption of 1,3-propanediol from synthetic mixture using polymeric resin as adsorbents

TANTAYAKOM, P. PRASITCHOKE, C. MUANGNAPOH

期刊论文