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Ying-Hua Li,Yin-Yin Wang,Shan Zhong,Zhi-Li Rong,Yong-Ming Ren,Zhi-Yong Li,Shu-Ping Zhang,Zhi-Jie Chang,Li Liu 한국분자세포생물학회 2009 Molecules and cells Vol.27 No.1
Ligand-dependent or independent oligomerization of receptor protein tyrosine kinase (RPTK) is often an essential step for receptor activation and intracellular signaling. The novel oncogene with kinase-domain (NOK) is a unique RPTK that almost completely lacks an ectodomain, expresses intracellularly and activates constitutively. However, it is unknown whether NOK can form oligomer or what function oligomerization would have. In this study, two NOK deletion mutants were generated by either removing the ectodomain (NOKECD) or including the endodomain (NOK-ICD). Co-immunoprecipitation demonstrated that the transmembrane (TM) domain of NOK was essential for its intermolecular interaction. The results further showed that NOK aggregated more closely as lower order oligomers (the dimer- and trimer-sized) than either deletion mutant did since NOK could be cross-linked by both Sulfo-EGS and formaldehyde, whereas either deletion mutant was only sensitive to Sulfo-EGS. Removing the NOK TM domain (NOK-ICD) not only markedly promoted higher order oligomerization, but also altered the subcellular localization of NOK and dramatically elevated the NOK-mediated constitutive activation of extracellular signal-regulated kinase (ERK). Moreover, NOK-ICD but not NOK or NOKECD was co-localized with the upstream signaling molecule RAS on cell membrane. Thus, TM-mediated intermolecular contacting may be mainly responsible for the constitutive activation of NOK and contribute to the autoinhibitory effect on RAS/MAPK signaling.
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Zhang Yun-Ying,Guo Jin-Meng,Wei Zhi-Qiang,Zhang Xiao-Tong,Liu Si-Ruo,Guo Hui-Fang,Dong Shuanglin 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.2
To better understand the olfactory mechanism of Mythimna loreyi, a worldwide migratory pest, we for the first time conducted a large scale identification of olfactory-related genes and investigation of their sex expression profiles by transcriptomic analysis. A total of 42,832 unigenes were obtained by transcriptome sequencing, as sembly and annotation, with an average length of 1,229 bp and N50 of 2,086 bp. In particular, 138 olfactoryrelated genes were identified by homologous blasting, including 33 odorant binding proteins (OBPs), 16 che mosensory proteins (CSPs), 63 odorant receptors (ORs), 24 ionotropic receptors (IRs) and two sensory neuron membrane proteins (SNMPs). Further, by using differential gene expression (DGE) and fragments per kilobase per million fragments (FPKM) values to compare the transcript levels between female and male antennae, we found that 22 olfactory-related genes (9 OBPs, one CSP and 12 ORs) were sex biased, with 10 genes being male biased and 12 genes female biased. In addition, sex and tissue expression profiles determined by qPCR of 15 selected genes confirmed the reliability of sex expression profiles obtained by the transcriptomic analysis, and demonstrated that most olfactory-related genes were specifically or primarily expressed in antennae, suggesting their roles in olfaction, while a few genes were highly expressed in other tissues, implying their non-olfaction functions. This study provides an important basis for further functional study of olfactory genes in M. loreyi.
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Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1
Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.
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Zhang Yun-Ying,Guo Jin-Meng,Wei Zhi-Qiang,Zhang Xiao-Tong,Liu Si-Ruo,Guo Hui-Fang,Dong Shuanglin 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.3
To better understand the olfactory mechanism of Mythimna loreyi, a worldwide migratory pest, we for the first time conducted a large scale identification of olfactory-related genes and investigation of their sex expression profiles by transcriptomic analysis. A total of 42,832 unigenes were obtained by transcriptome sequencing, as sembly and annotation, with an average length of 1,229 bp and N50 of 2,086 bp. In particular, 138 olfactoryrelated genes were identified by homologous blasting, including 33 odorant binding proteins (OBPs), 16 che mosensory proteins (CSPs), 63 odorant receptors (ORs), 24 ionotropic receptors (IRs) and two sensory neuron membrane proteins (SNMPs). Further, by using differential gene expression (DGE) and fragments per kilobase per million fragments (FPKM) values to compare the transcript levels between female and male antennae, we found that 22 olfactory-related genes (9 OBPs, one CSP and 12 ORs) were sex biased, with 10 genes being male biased and 12 genes female biased. In addition, sex and tissue expression profiles determined by qPCR of 15 selected genes confirmed the reliability of sex expression profiles obtained by the transcriptomic analysis, and demonstrated that most olfactory-related genes were specifically or primarily expressed in antennae, suggesting their roles in olfaction, while a few genes were highly expressed in other tissues, implying their non-olfaction functions. This study provides an important basis for further functional study of olfactory genes in M. loreyi.
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Ying-ying Xu,Hai-ru Yu,Jia-yi Sun,Zhao Zhao,Shuang Li,Xin-feng Zhang,Zhi-xuan Liao,Ming-ke Cui,Juan Li,Chan Li,Qiang Zhang 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2
Purpose Although the interferon (IFN) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. Materials and Methods PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. Results PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFN signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFN-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFN-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. Conclusion These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.
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Li Zhi-yu,Liu Ying,Han Zhuo-na,Li Xiang,Wang Yue-ying,Cui Xun,Zhang Ying 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.6
WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC–TAK1–ATF2–TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT–ANP signaling is implicated in cardiac physiology and pathophysiology.
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Hong Zhi Zhang,Meng Qing Wang,Ying Qiang Xie,Mei Xiang,Ping Li,Yu Yan Li,Li Sheng Zhang 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.3
Aphidius gifuensis is an important biological control agent of aphid. It stores sugar as energy reserves before the onset of diapause, a form of dormancy that occurs when environmental conditions become unfavorable for development. In this study, cDNA of three relevant enzymes, trehalose-6-phosphate synthase (TPS), glycogen synthase (GYS) and glycogen phosphorylase (GP) were cloned, and their expression profiles in the preparation and maintenance of diapause, and post-diapause development were analyzed. The results showed that AgTPS, AgGYS and AgGP encoded proteins consisting of 807, 690 and 844 amino acids respectively. The expression profiles of three genes were significantly affected by diapause-inducing condition. The increase of transcription of AgGYS and AgGP were followed by the up-regulate of AgTPS expression in the preparation of diapause, expression of all three genes were inhibited while diapause is maintained, and expression of AgGYS was upregulated when diapause was terminated. These results suggested that trehalose is accumulated before initiation of diapause and glycogen may play an important role in post-diapause development.
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Liu Ying,Zhang Xin,Zhang Li,Oliver Brian G,Wang Hong Guang,Liu Zhi Peng,Chen Zhi Hong,Wood Lisa,Hsu Alan Chen-Yu,Xie Min,McDonald Vanessa,Wan Hua Jing,Luo Feng Ming,Liu Dan,Li Wei Min,Wang Gang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.4
Purpose: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. Methods: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. Results: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. Conclusions: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.
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Jun Zhang,De-Song Tang,Shu-Ying Gong,Ying-Bin Zhang,Ping Chen,Zhi-Lei Gu 한국차학회 2015 한국차학회지 Vol.- No.S
The relationships among the concentrations of chemical compositions, scores of sensory quality and price were studied based on 112 jasmine tea samples. Linear correlation analysis showed that 5 quality attributes (appearance, liquor color, aroma, taste and infused leaves) were positively correlated with each other and to the sum. 5 quality attributes and total quality score were logarithm relevant to price with the coefficients of determination R2 were 0.855, 0.667, 0.836, 0.900, 0.906 and 0.914. The six taste attributes could be grossly divided into two groups. Tenderness, sweetness, freshness and mellowness were grouped showing positive correlation with taste score, total quality score and price, while heaviness and thickness were grouped for opposite correlation. There were positive correlation within the same group and negative correlation between two different groups. The concentrations of polyphenols, amino acid, water extract, gallocatechin (GC), epigallocatechin (EGC), catechin (C), epicatechin (EC), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG) and epicatechin gallate (ECG) in tea infusions were negatively correlated with tenderness, sweetness, freshness, mellowness, taste score, total quality score and price but positively correlated with heaviness and thickness (except some individual components), while gallic acid (GA) was the opposite. Multiple linear regression equations of taste score and total quality score were established. The back substitution was of high correlation between predicted and actual value and acceptance rate was over 90%. The relationships among the concentrations of chemical compositions, scores of sensory quality and price were studied based on 112 jasmine tea samples. Linear correlation analysis showed that 5 quality attributes (appearance, liquor color, aroma, taste and infused leaves) were positively correlated with each other and to the sum. 5 quality attributes and total quality score were logarithm relevant to price with the coefficients of determination R2 were 0.855, 0.667, 0.836, 0.900, 0.906 and 0.914. The six taste attributes could be grossly divided into two groups. Tenderness, sweetness, freshness and mellowness were grouped showing positive correlation with taste score, total quality score and price, while heaviness and thickness were grouped for opposite correlation. There were positive correlation within the same group and negative correlation between two different groups. The concentrations of polyphenols, amino acid, water extract, gallocatechin (GC), epigallocatechin (EGC), catechin (C), epicatechin (EC), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG) and epicatechin gallate (ECG) in tea infusions were negatively correlated with tenderness, sweetness, freshness, mellowness, taste score, total quality score and price but positively correlated with heaviness and thickness (except some individual components), while gallic acid (GA) was the opposite. Multiple linear regression equations of taste score and total quality score were established. The back substitution was of high correlation between predicted and actual value and acceptance rate was over 90%.
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