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https://www.readbyqxmd.com/read/28734947/platelet-derived-growth-factor-receptor-alpha-contributes-to-human-hepatic-stellate-cell-proliferation-and-migration
#1
Alexander Kikuchi, Tirthadipa Pradhan-Sundd, Sucha Singh, Shanmugam Nagarajan, Nick Loizos, Satdarshan Monga
Platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor, is up-regulated in hepatic stellate cells (HSCs) during chronic liver injury. HSCs mediate hepatic fibrosis through their activation from a quiescent state partially in response to pro-fibrotic growth factors. HSC activation entails enhanced expression of pro-fibrotic genes, increase in proliferation, and increase in motility, which facilitates migration within the hepatic lobule. We show co-localization of PDGFRα in murine carbon tetrachloride, bile duct ligation (BDL), and 0...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734155/activation-of-mtor-is-involved-in-anti-%C3%AE-2gpi-%C3%AE-2gpi-induced-expression-of-tissue-factor-and-il-8-in-monocytes
#2
Longfei Xia, Hong Zhou, Ting Wang, Yachao Xie, Ting Wang, Xiaoyan Wang, Jinchuan Yan
Previous study has demonstrated that activation of the mammalian target of rapamycin (mTOR) pathway in endothelial cells (ECs) results in the formation of chronic vascular lesions associated with antiphospholipid syndrome (APS). In addition, it has been shown that stimulation of monocytes and ECs by antiphospholipid antibodies (aPL) leads to a prothrombotic and proinflammatory state and up-regulated expression of tissue factor (TF) and inflammatory cytokines. However, the role of mTOR in pathogenic mechanisms of APS remains largely unexplored...
June 1, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28733877/expanding-the-spectrum-of-colonic-manifestations-in-tuberous-sclerosis-l-cell-neuroendocrine-tumor-arising-in-the-background-of-rectal-pecoma
#3
David L Kolin, Kai Duan, Bo Ngan, J Ted Gerstle, Monika K Krzyzanowska, Gino R Somers, Ozgur Mete
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition that predisposes to numerous proliferative lesions, including perivascular epithelioid cell tumors (PEComas), such as lymphangioleiomyomatosis (LAM) and angiomyolipomas, and rare neuroendocrine neoplasms. We describe herein a TSC2-harboring tuberous sclerosis patient manifesting with a synchronous well-differentiated L-cell rectal neuroendocrine tumor and leiomyomatosis-like LAM of the rectum. The background large bowel wall was thickened by confluent nodular areas comprising vessels and spindle-to-epithelioid cells, which are immunoreactive for myoid (smooth muscle actin, muscle specific actin, and desmin) and melanocytic markers (HMB45, Melan-A, microphthalmia transcription factor, and CD117)...
July 21, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28731988/roles-of-mitogen-activating-protein-kinase-kinase-kinase-kinase-3-map4k3-in-preterm-skeletal-muscle-satellite-cell-myogenesis-and-mammalian-target-of-rapamycin-complex-1-mtorc1-activation-regulation
#4
Chu-Yi Guo, Mu-Xue Yu, Jie-Min Dai, Si-Nian Pan, Zhen-Tong Lu, Xiao-Shan Qiu, Si-Qi Zhuang
BACKGROUND Preterm skeletal muscle genesis is a paradigm for myogenesis. The role of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cells myogenesis or its relationship to mammalian target of rapamycin complex 1 (mTORC1) activity have not been previously elaborated. MATERIAL AND METHODS Small interfering RNA (siRNA) interference technology was used to inhibit MAP4K3 expression. Leucine stimulation experiments were performed following MAP4K3-siRNA interference...
July 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28731193/promotion-of-glycolysis-by-hotair-through-glut1-upregulation-via-mtor-signaling
#5
Shibo Wei, Qing Fan, Liang Yang, Xiaodong Zhang, Yingbo Ma, Zhihong Zong, Xiangdong Hua, Dongming Su, Hongzhi Sun, Hangyu Li, Zhen Liu
The long non-coding RNA HOX transcript antisense RNA (HOTAIR) plays a key role in the progression of various carcinomas. However, whether or not HOTAIR influences glucose metabolism and the specific underlying mechanism in hepatocellular carcinoma (HCC) cells remain unclear. In the present study, we found markedly increased HOTAIR expression in 84 HCC tissues and demonstrated that HOTAIR overexpression promoted cell proliferation using Cell Counting Kit-8. The effect on glucose metabolism regulated by HOTAIR in HCC cells was determined by detecting lactate and glucose levels: HOTAIR promoted glycolysis by upregulating glucose transporter isoform 1 (GLUT1) and activating mammalian target of rapamycin (mTOR) signaling, whereas knockdown of HOTAIR suppressed this effect...
July 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731147/beclin-1-overexpression-inhibits-chondrocyte-apoptosis-and-downregulates-extracellular-matrix-metabolism-in-osteoarthritis
#6
Bin Song, Hong Song, Weiguo Wang, Hongru Wang, Hanyuan Peng, Jing Cui, Rong Wang, Hua Huang, Wei Wang, Lili Wang
In the present study, the expression of Beclin 1 in osteoarthritis (OA) cartilage tissue was investigated, and also its role in proliferation, apoptosis and expression of matrix metalloproteinases (MMPs) in chondrocytes obtained from patients with OA. Beclin 1 expression in cartilage tissue from OA patients, and in the age- and sex-matched controls, was detected by immunohistochemistry, semi-quantitative polymerase chain reaction and western blotting. Chondrocytes were divided into control and Beclin 1-overexpressed groups...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730764/mtor-deregulation-in-oral-cavity-squamous-cell-carcinoma
#7
Nicholas S Mastronikolis, Evangelos Tsiambas, Theodoros A Papadas, Panagiotis P Fotiades, Athanasios T Papadas, Stylianos N Mastronikolis, Ioannis Kastanioudakis, Vasileios Ragos
Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF)...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730721/ephb4-mutation-implicated-in-capillary-malformation-arteriovenous-malformation-syndrome-a-case-report
#8
JiaDe Yu, Jenna L Streicher, Livija Medne, Ian D Krantz, Albert C Yan
Capillary malformation-arteriovenous malformation (CM-AVM) syndrome, due to inactivating mutations in RASA1 in 68% of cases, is characterized by the development of cutaneous capillary malformations and arteriovenous malformations or fistulas; no known genetic etiology has been identified in patients with CM-AVM syndrome without RASA1 mutations. We present the case of a child with RASA1-negative CM-AVM syndrome with a de novo missense mutation in EPHB4, a transmembrane tyrosine kinase receptor essential for vasculogenesis...
July 21, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#9
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730470/dissecting-kinase-effector-signaling-using-the-raprtap-methodology
#10
Anne-Marie Ray, Jennifer E Klomp, Kerrie B Collins, Andrei V Karginov
Kinases are involved in a broad spectrum of cell behaviors. A single kinase can interact with different ligands each eliciting a specific cellular response. Dissecting downstream signaling pathways of kinases is a key step to understanding physiological and pathological cell process. However, directing kinase activity to specific substrates remains challenging. Here, we present a new tool to selectively activate a kinase in a specific protein complex in living cells. This technology uses a rapamycin-inducible kinase activation coupled to interaction with FKBP12-binding domain (FRB) tagged protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730238/altered-expression-of-mtor-and-autophagy-in-term-normal-human-placentas
#11
Qiu Xia Zhang, Quan Na, Weiwei Song
Mammalian target of rapamycin (mTOR) and autophagy have been implied in trophoblast cells proliferation and invasion. This study investigated whether mTOR and autophagy were involved in placental development and fetal programming. A total of 90 term normal placentas (37-42 gestational weeks) were collected from women who underwent elective cesarean section, with large for gestational age (LGA), fetal growth restriction (FGR), and appropriate for gestational age (AGA) infants (n=30, respectively). Capillary volume density within peripheral villi significantly decreased in the FGR placentas compared with the AGA group (p<0...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#12
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729395/relationship-between-exercise-volume-and-muscle-protein-synthesis-in-a-rat-model-of-resistance-exercise
#13
Riki Ogasawara, Yuki Arihara, Junya Takegaki, Koichi Nakazato, Naokata Ishii
Resistance exercise (RE) volume is recognized as an important factor that stimulates muscle protein synthesis (MPS) and is considered, at least in part, to be involved in the mammalian target of rapamycin complex 1 (mTORC1)-associated signaling. However, the effects of relatively high doses of muscle contractions on mTORC1 and MPS remain unclear. In the present study, we used an animal model of RE to investigate the relationship between RE volume and MPS. Male Sprague-Dawley rats were subjected to RE, and muscle samples were obtained 6 h after performing 1, 3, 5, 10, or 20 sets of RE...
July 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28729346/distinct-pka-regulatory-subunits-mediate-pge2-inhibition-of-tgf%C3%AE-1-stimulated-collagen-i-translation-and-myofibroblast-differentiation
#14
Scott H Wettlaufer, L Raghu Penke, Katsuhide Okunishi, Marc Peters-Golden
Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Here we examined the role of specific PKAR subunit isoforms in these inhibitory actions in transforming growth factorβ-1 (TGFβ-1)-stimulated human lung fibroblasts (HLFs)...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#15
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28728363/effect-of-different-levels-of-protein-concentrates-supplementation-on-the-growth-performance-plasma-amino-acids-profile-and-mtor-cascade-genes-expression-in-early-weaned-yak-calves
#16
Quhani Peng, Nazir Ahmad Khan, B Xue, T H Yan, Z S Ahmad Wang
Objective: Yak is anone of the most important livestock species in the alpine-meadow grasslands of Qinghai-Tibetan plateau. WeThis study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to the changes occurring in the plasma- amino acids, and -insulin profile, and to the signaling activity of mammalian target of rapamycin (mTOR) cascade, in order to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks...
June 27, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28727712/intervertebral-foramen-injection-of-ozone-relieves-mechanical-allodynia-and-enhances-analgesic-effect-of-gabapentin-in-animal-model-of-neuropathic-pain
#17
Wen-Jun Luo, Fan Yang, Fei Yang, Wei Sun, Wei Zheng, Xiao-Liang Wang, Fang-Fang Wu, Jiang-Lin Wang, Jia-Shuang Wang, Su-Min Guan, Jun Chen
BACKGROUND: In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. OBJECTIVE: This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#18
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28724580/il-7-restores-t-lymphocyte-immunometabolic-failure-in-septic-shock-patients-through-mtor-activation
#19
Fabienne Venet, Julie Demaret, Benjamin J Blaise, Christelle Rouget, Thibaut Girardot, Estellie Idealisoa, Thomas Rimmelé, François Mallet, Alain Lepape, Julien Textoris, Guillaume Monneret
T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28724574/the-microvascular-niche-instructs-t-cells-in-large-vessel-vasculitis-via-the-vegf-jagged1-notch-pathway
#20
Zhenke Wen, Yi Shen, Gerald Berry, Farhad Shahram, Yinyin Li, Ryu Watanabe, Yaping Joyce Liao, Jörg J Goronzy, Cornelia M Weyand
Microvascular networks in the adventitia of large arteries control access of inflammatory cells to the inner wall layers (media and intima) and thus protect the immune privilege of the aorta and its major branches. In autoimmune vasculitis giant cell arteritis (GCA), CD4 T helper 1 (TH1) and TH17 cells invade into the wall of the aorta and large elastic arteries to form tissue-destructive granulomas. Whether the disease microenvironment provides instructive cues for vasculitogenic T cells is unknown. We report that adventitial microvascular endothelial cells (mvECs) perform immunoregulatory functions by up-regulating the expression of the Notch ligand Jagged1...
July 19, 2017: Science Translational Medicine
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