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Valsamma Abraham, Andrew Parambath, Debria S Joe, Horace M DeLisser
Platelet endothelial cell adhesion molecule (PECAM-1) has been implicated in angiogenesis through processes that involve stimulation of endothelial cell motility. Previous studies suggest that PECAM-1 tyrosine phosphorylation mediates the recruitment and then activation of the tyrosine phosphatase SHP-2, which in turn promotes the turnover of focal adhesions and the extension of filopodia, processes critical to cell motility. While these studies have implicated PECAM-1-dependent signaling in PECAM-1-mediated cell motility, the involvement of PECAM-1 ligand binding in cell migration is undefined...
November 2016: Physiological Reports
Yukari Ohta, Ryoichi Hasegawa, Kanako Kurosawa, Toshio Koizumi, Allyn H Maeda, Hiroshi Nishimura, Hitomi Okada, Chen Qu, Kaori Saito, Takashi Watanabe, Yuji Hatada
Enzymatic catalysis is an eco-friendly strategy for the production of high-value low-molecular-weight aromatic compounds from lignin. Although well-definable aromatic monomers have been obtained from synthetic lignin-model dimers, enzymatic-selective production of platform monomers from natural lignin has not been accomplished. In this study, we successfully achieved highly specific production of aromatic monomers with a phenylpropane structure directly from natural lignin using a cascade reaction of ß-O-4 cleaving bacterial enzymes in one pot...
November 22, 2016: ChemSusChem
Sung-Hsin Kuo, Li-Tzong Chen, Chung-Wu Lin, Kun-Huei Yeh, Chia-Tung Shun, Yi-Shin Tzeng, Jyh-Ming Liou, Ming-Shiang Wu, Ping-Ning Hsu, Ann-Lii Cheng
We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with (DLBCL[MALT]) and without ('pure' DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of CagA and CagA-signaling molecules (p-SHP2 and p-ERK) is associated with the HP-dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored...
November 18, 2016: Blood
Yelin Wu, Yanchun Quan, Yuanqi Liu, Keiwei Liu, Hongquan Li, Ziwei Jiang, Tian Zhang, Hu Lei, Katherine A Radek, Dongqing Li, Zhenhua Wang, Jilong Lu, Wang Wang, Shizhao Ji, Zhaofan Xia, Yuping Lai
Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes...
November 10, 2016: Nature Communications
Luciana Gneo, Pierdomenico Ruggeri, Lucia Cappabianca, Antonietta Rosella Farina, Natalia Di Ianni, Andrew Reay Mackay
TrkAIII expression in neuroblastoma (NB) associates with advanced stage disease, worse prognosis, post therapeutic relapse, and in NB models TrkAIII exhibits oncogenic activity and promotes chemotherapeutic-resistance. Here, we report a potential therapeutic "Achilles heel" for the TrkAIII oncoprotein in a SH-SY5Y NB model that is characterised by one-way TRAIL-induced, pro-apoptotic crosstalk between the TRAIL receptor signaling pathway and TrkAIII that results in the delayed induction of apoptosis. In TrkAIII SH-SY5Y cells, blocked in the intrinsic apoptosis pathway by elevated constitutive Bcl-2, Bcl-xL and Mcl-1 expression, TRAIL induced delayed caspase-dependent apoptosis via the extrinsic pathway and completely abrogated tumourigenic capacity in vitro...
November 4, 2016: Oncotarget
Anthony C Bishop
Recent data sets that catalog the missense mutations in thousands of human genomes have revealed a vast and largely unexplored world of non-canonical protein sequences that are expressed in humans. The functional consequences of most human missense mutations, however, are unknown, and the accuracy with which their effects can be predicted by computational algorithms remains unclear. Among humans of European descent, the most common missense mutation in the catalytic domain of SH2-containing protein tyrosine phosphatase 1 (SHP-1) converts the enzyme's canonical valine 451 to methionine (V451M)...
December 2, 2016: Biochemical and Biophysical Research Communications
Mirko Pesce, Sara Franceschelli, Alessio Ferrone, Antonia Patruno, Alfredo Grilli, Maria Anna De Lutiis, Francesca R Pluchinotta, Sonia Bergante, Guido Tettamanti, Graziano Riccioni, Mario Felaco, Lorenza Speranza
It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
Yaron Carmi, Tyler R Prestwood, Matthew H Spitzer, Ian L Linde, Jonathan Chabon, Nathan E Reticker-Flynn, Nupur Bhattacharya, Hong Zhang, Xiangyue Zhang, Pamela A Basto, Bryan M Burt, Michael N Alonso, Edgar G Engleman
BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells...
November 3, 2016: JCI Insight
Hossein Arabi, Habib Zaidi
PURPOSE: The authors evaluate the performance of shape-based averaging (SBA) technique for whole-body bone segmentation from MRI in the context of MRI-guided attenuation correction (MRAC) in hybrid PET/MRI. To enhance the performance of the SBA scheme, the authors propose to combine it with statistical atlas fusion techniques. Moreover, a fast and efficient shape comparison-based atlas selection scheme was developed and incorporated into the SBA method. METHODS: Clinical studies consisting of PET/CT and MR images of 21 patients were used to assess the performance of the SBA method...
November 2016: Medical Physics
Aditi Sharma, Pankaj Sharma, Achchhe Lal Vishwakarma, Mrigank Srivastava
Filarial parasites cause functional impairment of host Dendritic cells (DCs). However, effects of early infection on individual DC subsets are not known. In this study, we infected BALB/c mice with infective larvae stage-3 of lymphatic filarial parasite Brugia malayi (Bm-L3) and studied its effect on FACS-sorted DC subsets. While Myeloid DCs (mDCs) accumulated within day 3 post-infection (p.i.), Lymphoid DCs (LDCs) and CD8(+) Plasmacytoid DCs (pDCs) peaked at day 7 p.i. in the spleens and mesenteric lymph nodes (mLNs) of infected mice...
October 31, 2016: Infection and Immunity
Melanie Tran, Zhihong Yang, Suthat Liangpunsakul, Li Wang
BACKGROUND: Chronic ethanol (EtOH) consumption causes alcoholic liver disease (ALD), and disruption of the circadian system facilitates the development of ALD. Small heterodimer partner (SHP) is a nuclear receptor and critical regulator of hepatic lipid metabolism. This study aimed at depicting circadian metabolomes altered by chronic EtOH-plus-binge and Shp deficiency using high-throughput metabolomics. METHODS: Wild-type (WT) C57BL/6 and Shp(-/-) mice were fed the control diet (CD) or Lieber-DeCarli EtOH liquid diet (ED) for 10 days followed by a single bout of maltose (CD + M) or EtOH (ED + E) binge on the 11th day...
December 2016: Alcoholism, Clinical and Experimental Research
Insup Choi, Ji-Won Byun, Sang Myun Park, Ilo Jou, Eun-Hye Joe
Mutation of leucine-rich repeat kinase 2 (LRRK2) causes an autosomal dominant and late-onset familial Parkinson's disease (PD). Recently, we reported that LRRK2 directly binds to and phosphorylates the threonine 474 (T474)-containing Thr-X-Arg(Lys) (TXR) motif of focal adhesion kinase (FAK), thereby inhibiting the phosphorylation of FAK at tyrosine (Y) 397 residue (pY397-FAK), which is a marker of its activation. Mechanistically, however, it remained unclear how T474-FAK phosphorylation suppressed FAK activation...
October 2016: Experimental Neurobiology
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evan, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is increasingly being exploited for human drug metabolism studies. However, its model stability, inter-communication between human hepatocytes and mouse non-parenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expression has not been investigated. We examined these issues in FRGN [Fah(-/-), Rag2(-/-), and IL-2rg(-/-) on NOD background] and chimeric mice: mFRGN, and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
October 27, 2016: Journal of Pharmacology and Experimental Therapeutics
Moreshwar Desai, Bhoomika Mathur, Zeena Eblimit, Hernan Vasquez, Heinrich Taegtmeyer, Saul Karpen, Daniel J Penny, David D Moore, Sayeepriyadarshini Anakk
: Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term Cholecardia. Fxr; Shp double knockout (DKO) mice, a model for bile acid overload, display cardiac hypertrophy, bradycardia, and exercise intolerance. In addition, DKO mice exhibit an impaired cardiac response to catecholamine challenge...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
: Bile acids (BAs) play critical physiological functions in cholesterol homeostasis and deregulation of BA metabolism causes cholestatic liver injury. Maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor, however its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Dongkyu Kim, Sook Hee Ku, Hyosuk Kim, Ji Hoon Jeong, Minhyung Lee, Ick Chan Kwon, Donghoon Choi, Sun Hwa Kim
Gene therapy is aimed at selectively knocking up or knocking down the target genes involved in the development of diseases. In many human diseases, dysregulation of disease-associated genes is occurred concurrently: some genes are abnormally turned up and some are turned down. In the field of non-viral gene therapy, plasmid DNA (pDNA) and small interfering RNA (siRNA) are suggested as representative regulation tools for activating and silencing the expression of genes of interest, representatively. Herein, we simultaneously loaded both siRNA (Src homology region 2 domain-containing tyrosine phosphatase-1 siRNA, siSHP-1) for anti-apoptosis and pDNA (hypoxia-inducible vascular endothelial growth factor expression vector, pHI-VEGF) for angiogenesis in a single polymeric nanocarrier and used to synergistically attenuate ischemia-reperfusion (IR)-induced myocardial infarction, which is mainly caused by dysregulating of cardiac apoptosis and angiogenesis...
October 18, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Fenfang Wu, Liyong Chen, Yong Ren, Xiaojing Yang, Tongzhou Yu, Bo Feng, Shangwu Chen, Anlong Xu
Lamprey, the primitive jawless vertebrate, uses variable lymphocyte receptor (VLR) as alternative adaptive immune system instead of immunoglobulin (Ig)-based receptors used in jawed vertebrates. In the present study, we characterized a potential inhibitory receptor of VLRB from leucocytes in lamprey. It is a novel ITIM-containing IgSF protein and was therefore named as NICIP. NICIP has two Ig-like domains in extracellular region, a transmembrane domain and two classical ITIM motifs in cytoplasmic domain. It is mainly expressed on the surface of granulocytes and monocytes and can interact with VLRB...
October 20, 2016: Scientific Reports
Lei Xu, Meng-Ke Zhai, Fei Wang, Lin Sun, Hong-Bin Du
We herein report a series of microporous metal-porphyrinic frameworks (MPFs), denoted as NUPF-2M, based on rare earth (RE) clusters. NUPF-2M represent the first examples of RE cluster-based MPFs, possessing a rarely seen shp-a topology and exhibiting high thermal and thermal stabilities. After a post-metallization process with FeCl3, NUPF-2M is catalytically active as an efficient heterogeneous catalyst for intermolecular N-H carbene insertion.
October 20, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Xiaojiaoyang Li, Zihang Yuan, Runping Liu, Hozeifa M Hassan, Hang Yang, Rong Sun, Luyong Zhang, Zhenzhou Jiang
Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model...
October 12, 2016: Toxicology and Applied Pharmacology
Helena Soler, Jonatan Dorca-Arévalo, Marta González, Sara Esmeralda Rubio, Jesús Ávila, Eduardo Soriano, Marta Pascual
Alzheimer's disease (AD), the most common cause of dementia nowadays, has been linked to alterations in the septohippocampal pathway (SHP), among other circuits in the brain. In fact, the GABAergic component of the SHP, which controls hippocampal rhythmic activity crucial for learning and memory, is altered in the J20 mouse model of AD-a model that mimics the amyloid pathology of this disease. However, AD is characterized by another pathophysiological hallmark: the hyperphosphorylation and aggregation of the microtubule-associated protein Tau...
September 15, 2016: Neurobiology of Aging
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