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https://www.readbyqxmd.com/read/28821555/p53-non-genotoxic-activation-and-mtorc1-inhibition-lead-to-effective-combination-for-neuroblastoma-therapy
#1
Myrthala Moreno-Smith, Anna Lakoma, Zaowen Chen, Ling Tao, Kathleen A Scorsone, Linda Schild, Kevin Aviles-Padilla, Rana Nikzad, Yankai Zhang, Rikhia Chakraborty, Jan J Molenaar, Sanjeev Vasudevan, Vivien Sheehan, Eugene S Kim, Silke Paust, Jason M Shohet, Eveline Barbieri
mTORC1 inhibitors are promising agents for neuroblastoma therapy, however they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. <br /><br />Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the anti-tumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first and second generation MDM2 inhibitors to reactivate p53...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#2
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28817740/influence-of-microtextured-implant-surfaces-on-peri-implantitis-and-its-treatment-a-preclinical-trial
#3
Juan C Rodriguez, Tapan Koticha, Diana L Eubanks, Ivan Rudek, Fred J Molz, Ludovica Chiavaccini, Andrew Claude, Steven Elder, Hom-Lay Wang
PURPOSE: The prevalence of peri-implantitis has increased significantly, forcing clinicians to search for ways to prevent it. Laser-microtextured surfaces promote soft tissue attachment and provide a tight seal around implants. Hence, the aim of this study was to examine the clinical, radiographic, and histologic features of ligature-induced peri-implantitis, as well as the effect of surgical treatment of these induced peri-implantitis lesions on laser-microtextured implants in a controlled animal model...
August 17, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28814742/the-candida-albicans-hir-histone-chaperone-regulates-the-yeast-to-hyphae-transition-by-controlling-the-sensitivity-to-morphogenesis-signals
#4
Sabrina Jenull, Michael Tscherner, Megha Gulati, Clarissa J Nobile, Neeraj Chauhan, Karl Kuchler
Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812266/oxytocin-and-social-relationships-from-attachment-to-bond-disruption
#5
Oliver J Bosch, Larry J Young
Social relationships throughout life are vital for well-being and physical and mental health. A significant amount of research in animal models as well as in humans suggests that oxytocin (OT) plays an important role in the development of the capacity to form social bonds, the mediation of the positive aspects of early-life nurturing on adult bonding capacity, and the maintenance of social bonding. Here, we focus on the extensive research on a socially monogamous rodent model organism, the prairie vole (Microtus ochrogaster)...
August 16, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#6
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810912/inhibition-of-trpm7-suppresses-cell-proliferation-of-colon-adenocarcinoma-in-vitro-and-induces-hypomagnesemia-in-vivo-without-affecting-azoxymethane-induced-early-colon-cancer-in-mice
#7
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, F Kelly Galbraith Kawabata, David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
BACKGROUND: Magnesium (Mg(2+)) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg(2+) homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process. METHODS: To establish a possible link between systemic magnesium (Mg(2+)) status, the Mg(2+) conducting channel TRPM7 in colon epithelial cells, and colon carcinogenesis, in vitro whole-cell patch clamp electrophysiology, qPCR, and pharmacological tools were used probing human colorectal adenocarcinoma HT-29 as well as normal primary mouse colon epithelial cells...
August 15, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28806382/orbital-cellulitis-following-orbital-blow-out-fracture
#8
Je Yeon Byeon, Hwan Jun Choi
Orbital cellulitis and abscess have been described in the literature as complication that usually occur secondary to infection in the maxillary, ethmoidal, and frontal sinuses. If left untreated, it can lead to blindness, cavernous sinus thrombosis, meningitis, or cerebral abscess. Orbital fractures are a common sequela of blunt orbital trauma, but are only rarely associated with orbital cellulitis. So, the authors present rare orbital cellulitis after orbital blow-out fracture. A 55-year-old Asian complains of severe orbital swelling and pain on the left side...
August 10, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28805828/mutations-in-keops-complex-genes-cause-nephrotic-syndrome-with-primary-microcephaly
#9
Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt
Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805142/intravenous-immunoglobulins-modify-relapsing-membranous-glomerulonephritis-after-kidney-transplantation-a-case-report
#10
Sanne Steyaert, Jo Van Dorpe, Anne Hoorens, Wim Van Biesen, Steven Van Laecke
OBJECTIVES: Recurrence of membranous glomerulonephritis after transplant is common and is an important cause of loss of renal graft. This case supports the effect of immunoglobulins in the treatment of this disease after transplantation. It is the first report in the literature with a follow-up of more than 10 years and because of the sustained effect of the immunoglobulins, it strengthens the idea that this can alter long-term outcome. METHODS: Single case study and search of the literature...
August 14, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28803601/ultrasound-guided-transversus-abdominis-plane-block-improves-postoperative-analgesia-and-early-recovery-in-patients-undergoing-retroperitoneoscopic-urologic-surgeries-a-randomized-controlled-double-blinded-trial
#11
Ge Qu, Xu-Lei Cui, Hong-Ju Liu, Zhi-Gang Ji, Yu-Guang Huang
Objective To evaluate the effects of ultrasound-guided transversus abdominis plane (TAP) block on postoperative analgesia and early recovery in patients undergoing retroperitoneoscopic urologic surgeries. Methods This was a randomized, controlled, double-blinded trial. Eligible patients scheduled for retroperitoneoscopic urologic surgeries were randomly assigned to two groups. Group TAP received ultrasound-guided TAP block with 0.5% ropivacaine 20 ml at 30 minutes before surgery, and Group C received TAP sham block with normal saline...
September 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28802926/nonmotor-symptoms-and-natural-history-of-parkinson-s-disease-evidence-from-cognitive-dysfunction-and-role-of-noninvasive-interventions
#12
Roberta Biundo, Eleonora Fiorenzato, Angelo Antonini
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802598/effect-of-parecoxib-sodium-pretreatment-combined-with-dexmedetomidine-on-early-postoperative-cognitive-dysfunction-in-elderly-patients-after-shoulder-arthroscopy-a-randomized-double-blinded-controlled-trial
#13
Jian Lu, Gang Chen, Hongmei Zhou, Qinghe Zhou, Zhipeng Zhu, Cheng Wu
STUDY OBJECTIVE: To evaluate effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy. DESIGN: Randomized, double-blind study. SETTING: University-affiliated teaching hospital. PATIENTS: One hundred and fifty-two elderly patients scheduled for shoulder arthroscopy. INTERVENTIONS: At 15min before the induction of anesthesia, 152 patients received intravenously parecoxib sodium 40mg and dexmedetomidine at a dose of 0...
September 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28801532/activation-of-nkx2-5-calr-p53-signaling-pathway-by-hyperglycemia-induces-cardiac-remodeling-and-dysfunction-in-adult-zebrafish
#14
Sun Yanyi, Wang Qiuyun, Fang Yuehua, Wu Chunfang, Lu Guoping, Chen Zhenyue
Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia...
August 11, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28801243/peroxiredoxin-2-plays-a-pivotal-role-as-multimodal-cytoprotector-in-the-early-phase-of-pulmonary-hypertension
#15
Enrica Federti, Alessandro Matte', Alessandra Ghigo, Immacolata Andolfo, Cimino James, Angela Siciliano, Christophe Leboeuf, Anne Janin, Francesco Manna, Soo Young Choi, Achille Iolascon, Elisabetta Beneduce, Davide Melisi, Dae Won Kim, Sonia Levi, Lucia De Franceschi
Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homestasis is yet to be fully defined. Here, we showed that Prx2(-/-) mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH...
August 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28798972/diagnostic-precision-of-triage-algorithms-for-mass-casualty-incidents-english-version
#16
A R Heller, N Salvador, M Frank, J Schiffner, R Kipke, C Kleber
BACKGROUND: Regarding survival and quality of life recent mass casualty incidents again emphasize the importance of early identification of the correct degree of injury/illness to enable prioritization of treatment amongst patients and their transportation to an appropriate hospital. The present study investigated existing triage algorithms in terms of sensitivity (SE) and specificity (SP) as well as its process duration in a relevant emergency patient cohort. METHODS: In this study 500 consecutive air rescue missions were evaluated by means of standardized patient records...
August 10, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28795680/-severe-disease-of-immune-imbalance-in-icu-persistent-inflammation-immunosuppression-catabolism-syndrome
#17
Heyi Su, Zexun Mo, Zhen Chen, Zhenhui Guo
Terminology of persistent inflammation immunosuppression and catabolism syndrome (PICS) is developed based on the concept of multiple organ failure (MOF), which reflect that the preponderance is gradually reversed from pro-inflammation to anti-inflammation, and eventually the state of simultaneously persistent inflammation and severe immunosuppression appeared. Although the improvement of rescue technology and management increase the early survival rates of patient with critical illnesses, the long-term outcomes of most patients are not optimistic...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28794020/adenovirus-core-protein-vii-down-regulates-the-dna-damage-response-on-the-host-genome
#18
Daphne C Avgousti, Ashley N Della Fera, Clayton J Otter, Christin Herrmann, Neha J Pancholi, Matthew D Weitzman
Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier for successful infection. The adenovirus genome is packaged with protein VII, a viral-encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790240/-successful-treatment-of-acute-empyema-due-to-rupture-of-pyogenic-liver-abscess
#19
Isamu Watanabe, Naoki Kanauchi, Hikaru Watanabe, Akira Hamada
Cases of rescue after rupture of pyogenic liver abscess into the thorax are rare. Here, we report 2 cases of rescue in patients with acute empyema due to rupture of a suppurative abscess into the thorax. Case 1:A 61-year-old male had high fever of 39 °C and right abdominal pain. Thoracic computed tomography(CT) showed encapsulated pleural effusion in the right thorax and ring-like enhancement in the right liver. The diagnosis was acute empyema caused by rupture of liver abscess. The pathogenic bacteria were Streptococcus group...
August 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28779958/efficacy-of-indocyanine-green-mediated-sonodynamic-therapy-on-rheumatoid-arthritis-fibroblast-like-synoviocytes
#20
Qin Tang, Shufang Chang, Zhonghua Tian, Jiangchuan Sun, Lan Hao, Zhigang Wang, Shenyin Zhu
Sonodynamic therapy (SDT) has become a new therapeutic method because of its activation of certain sensitizers by ultrasound. Some studies have reported that indocyanine green (ICG) has the characteristics of a sonosensitizer and favorable fluorescence imaging in synovitis of early inflammatory arthritis. In this study, we aimed to investigate the cytotoxic effect of ICG-mediated SDT on MH7A cells in vitro and the potential mechanisms involved. ICG was found to be taken up mainly in cytoplasm, with maximal uptake in 4 h...
August 2, 2017: Ultrasound in Medicine & Biology
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