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https://www.readbyqxmd.com/read/29352668/the-effect-of-single-and-repeated-prefrontal-intermittent-theta-burst-stimulation-on-cortical-reactivity-and-working-memory
#1
Sung Wook Chung, Nigel C Rogasch, Kate E Hoy, Paul B Fitzgerald
BACKGROUND: With an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex. OBJECTIVE/HYPOTHESIS: This study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS...
January 8, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29352232/the-silent-healer-mir-205-5p-up-regulation-inhibits-epithelial-to-mesenchymal-transition-in-colon-cancer-cells-by-indirectly-up-regulating-e-cadherin-expression
#2
Diana Gulei, Lorand Magdo, Ancuta Jurj, Lajos Raduly, Roxana Cojocneanu-Petric, Alin Moldovan, Cristian Moldovan, Adrian Florea, Sergiu Pasca, Laura-Ancuta Pop, Vlad Moisoiu, Liviuta Budisan, Cecilia Pop-Bica, Cristina Ciocan, Rares Buiga, Mihai-Stefan Muresan, Rares Stiufiuc, Calin Ionescu, Ioana Berindan-Neagoe
EMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352118/pi3k-mtor-inhibition-promotes-the-regression-of-experimental-vascular-malformations-driven-by-pik3ca-activating-mutations
#3
Laura di Blasio, Alberto Puliafito, Paolo Armando Gagliardi, Valentina Comunanza, Desiana Somale, Giulia Chiaverina, Federico Bussolino, Luca Primo
Somatic activating mutations within the PIK3CA gene have been recently detected in sporadic lymphatic and venous malformations, and in vascular malformations (VM) associated to overgrowth syndromes, such as CLOVES and Klippel-Trenaunay syndrome. Although VM are often limited to specific tissue areas and can be well treated, in extended or recurrent lesions novel therapeutic approaches are needed. We generated a mouse model of VM by local expression of PIK3CA-activating mutation in endothelial cells. PIK3CA-driven lesions are characterized by large areas of hemorrhage, hyperplastic vessels, infiltrates of inflammatory cells, and elevated endothelial cell density...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352030/the-daunting-polygenicity-of-mental-illness-making-a-new-map
#4
REVIEW
Steven E Hyman
An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric disorders has emerged from advances in genomic technology, new computational tools and the growth of international consortia committed to data sharing. The resulting large-scale, unbiased genetic studies have begun to yield new biological insights and with them the hope that a half century of stasis in psychiatric therapeutics will come to an end. Yet a sobering picture is coming into view; it reveals daunting genetic and phenotypic complexity portending enormous challenges for neurobiology...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29352004/therapeutic-application-of-an-extract-of-helicobacter-pylori-ameliorates-the-development-of-allergic-airway-disease
#5
Yolanda van Wijck, Stan de Kleijn, Gerrit John-Schuster, Tinne C J Mertens, Pieter S Hiemstra, Anne Müller, Hermelijn H Smits, Christian Taube
Epidemiological and experimental studies have shown that exposure to the gastric bacterium Helicobacter pylori, especially in early life, prevents the development of asthma. Recent mouse studies have shown that this protective effect does not require live bacteria and that treatment with an extract of H. pylori in neonates prevents the development of airway inflammation and goblet cell metaplasia. In the current study, the effect of administration of an extract of H. pylori was assessed in a therapeutic study design with application of the extract just prior to allergen challenge...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29352001/keap1-editing-using-crispr-cas9-for-therapeutic-nrf2-activation-in-primary-human-t-lymphocytes
#6
Sanjeev Noel, Sul A Lee, Mohanraj Sadasivam, Abdel R A Hamad, Hamid Rabb
Oxidant stress modifies T lymphocyte activation and function. Previous work demonstrated that murine T cell-specific kelch like-ECH-associated protein 1 (Keap1) deletion enhances antioxidant capacity and protects from experimental acute kidney injury. In this study, we used CRISPR technology to develop clinically translatable human T cell-specific KEAP1 deletion. Delivery of KEAP1 exon 2 specific Cas9:guide RNA in Jurkat T cells led to significant (∼70%) editing and upregulation of NRF2-regulated antioxidant genes NADPH dehydrogenase quinone 1 (NQO1) (up to 11-fold), heme oxygenase 1 (HO1) (up to 11-fold), and GCLM (up to 2-fold)...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351998/detection-of-experimental-and-clinical-immune-complexes-by-measuring-ship-1-recruitment-to-the-inhibitory-fc%C3%AE-riib
#7
Richard J Stopforth, Robert J Oldham, Alison L Tutt, Patrick Duriez, H T Claude Chan, Brock F Binkowski, Chad Zimprich, Dun Li, Philip G Hargreaves, Mei Cong, Venkat Reddy, Maria J Leandro, Geraldine Cambridge, Anja Lux, Falk Nimmerjahn, Mark S Cragg
Fc γ receptors (FcγR) are involved in multiple aspects of immune cell regulation, are central to the success of mAb therapeutics, and underpin the pathology of several autoimmune diseases. However, reliable assays capable of accurately measuring FcγR interactions with their physiological ligands, IgG immune complexes (IC), are limited. A method to study and detect IC interactions with FcγRs was therefore developed. This method, designed to model the signaling pathway of the inhibitory FcγRIIB (CD32B), used NanoLuc Binary Interaction Technology to measure recruitment of the Src homology 2 domain-containing inositol phosphatase 1 to the ITIM of this receptor...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351801/high-expression-of-tmem40-is-associated-with-the-malignant-behavior-and-tumorigenesis-in-bladder-cancer
#8
Zhen-Fei Zhang, Han-Rong Zhang, Qing-Yan Zhang, Shu-Yu Lai, Yu-Zhen Feng, Yi Zhou, Si-Rong Zheng, Rong Shi, Jue-Yu Zhou
BACKGROUND: Bladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood. METHODS: Real-time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell lines...
January 19, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#9
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29350825/ang-ii-facilitated-cd11-ly6chi-cells-reprogramming-into-m1-like-macrophage-through-erk1-2-or-p38-stat3-pathway-and-involved-in-eam
#10
Hongxiang Lu, Yan Wu, Xiaoyi Shao, Shanshan Zhou, Yuanyuan Jiang, Rong Chen, Gangjun Zong, Huaxi Xu, Zhaoliang Su
Macrophage, a highly plastic population, is widely distributed. Macrophage functions are settled and acquired polarization programs in response to microenvironmental signals and involved in many inflammatory disorders, such as experimental autoimmune myocarditis (EAM). Phenotypic and functional changes in macrophage are considered as an important determinant of disease progression and/or regression. Angiotensin II (ANG II), as a powerful proinflammatory factor, plays critical roles in inflammatory diseases and macrophage recruitment...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350421/involvement-of-xanthine-oxidase-inhibition-with-the-antioxidant-property-of-nanoencapsulated-melaleuca-alternifolia-essential-oil-in-fish-experimentally-infected-with-pseudomonas-aeruginosa
#11
M D Baldissera, C F Souza, P H Doleski, R C V Santos, R P Raffin, B Baldisserotto
Nanoencapsulated Melaleuca alternifolia essential oil (tea tree oil, TTO) is a natural alternative treatment, with 100% therapeutic efficacy in fish experimentally infected with Pseudomonas aeruginosa, and has also potent protective effects linked with antioxidant properties. However, the pathways responsible for the antioxidant capacity remain unknown. Thus, this study evaluated whether the inhibition of seric xanthine oxidase (XO) activity can be considered a pathway involved in the antioxidant capacity of nanoencapsulated TTO in fish experimentally infected with P...
January 19, 2018: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29350067/soluble-neuregulin1-is-strongly-up-regulated-in-the-rat-model-of-charcot-marie-tooth-1a-disease
#12
Benedetta Elena Fornasari, Giulia Ronchi, Davide Pascal, Davide Visigalli, Giovanna Capodivento, Lucilla Nobbio, Isabelle Perroteau, Angelo Schenone, Stefano Geuna, Giovanna Gambarotta
Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve development through the activation of the transmembrane co-receptors ErbB2-ErbB3. Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and transiently up-regulated after acute peripheral nerve injury, thus suggesting that they play a crucial role also in the response to nerve damage. Here we show that in the rat experimental model of the peripheral demyelinating neuropathy Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms (soluble, type α and β, type a and b) is strongly up-regulated, as well as the expression of NRG1 co-receptors ErbB2-ErbB3, thus showing that CMT1A nerves have a gene expression pattern highly reminiscent of injured nerves...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29349896/treatment-with-low-doses-of-aspirin-during-chronic-phase-of-experimental-chagas-disease-increases-oesophageal-nitrergic-neuronal-subpopulation-in-mice
#13
Cristina Lorena Massocatto, Neide Martins Moreira, Eliane Muniz, Silvana Marques de Araújo, Phileno Pinge-Filho, Robson Marcelo Rossi, Eduardo José de Almeida Araújo, Débora de Mello Gonçales Sant'ana
Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function...
January 19, 2018: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#14
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29349520/experimental-study-of-5-fluorouracil-encapsulated-ethosomes-combined-with-co2-fractional-laser-to-treat-hypertrophic-scar
#15
Zhen Zhang, Jun Chen, Jun Huang, Yan Wo, Yixin Zhang, Xiangdong Chen
OBJECTIVE: This study is designed to explore permeability of ethosomes encapsulated with 5-florouracil (5-FU) mediated by CO2 fractional laser on hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO2 fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear hypertrophic scar model will be evaluated. METHODS: The permeated amount of 5-FU and retention contents of 5-FU were both determined by high-performance liquid chromatography (HPLC)...
January 18, 2018: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29349293/experimenter-gender-and-replicability-in-science
#16
REVIEW
Colin D Chapman, Christian Benedict, Helgi B Schiöth
There is a replication crisis spreading through the annals of scientific inquiry. Although some work has been carried out to uncover the roots of this issue, much remains unanswered. With this in mind, this paper investigates how the gender of the experimenter may affect experimental findings. Clinical trials are regularly carried out without any report of the experimenter's gender and with dubious knowledge of its influence. Consequently, significant biases caused by the experimenter's gender may lead researchers to conclude that therapeutics or other interventions are either overtreating or undertreating a variety of conditions...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29348812/design-and-synthesis-of-isoquinolidinobenzodiazepine-dimers-a-novel-class-of-antibody-drug-conjugate-payload
#17
Sean W Smith, Vasu Jammalamadaka, Dmitry Borkin, Jianyu Zhu, Sylvia J Degrado, Jennifer Lu, Jianqing Huang, Ying-Ping Jiang, Nareshkumar Jain, Jagath R Junutula
Antibody-drug conjugates (ADCs) represent an important class of emerging cancer therapeutics. Recent ADC development efforts highlighted the use of pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers. We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class of PBD dimer family of DNA damaging payloads. We have successfully synthesized all three IQB stereoisomers, experimentally showed that the purified (S,S)-D211 isomer is functionally more active than (R,R)-D221 and (S,R)-D231 isomers by >50,000-fold and ∼200-fold, respectively...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348441/sdf1-gradient-associates-with-the-distribution-of-c-kit-cardiac-cells-in-the-heart
#18
Outi Renko, Anna-Maria Tolonen, Jaana Rysä, Johanna Magga, Erja Mustonen, Heikki Ruskoaho, Raisa Serpi
Identification of the adult cardiac stem cells (CSCs) has offered new therapeutic possibilities for treating ischemic myocardium. CSCs positive for the cell surface antigen c-Kit are known as the primary source for cardiac regeneration. Accumulating evidence shows that chemokines play important roles in stem cell homing. Here we investigated molecular targets to be utilized in modulating the mobility of endogenous CSCs. In a four week follow-up after experimental acute myocardial infarction (AMI) with ligation of the left anterior descending (LAD) coronary artery of Sprague-Dawley rats c-Kit+ CSCs redistributed in the heart...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347891/changing-character-a-narrative-review-of-personality-change-in-psychotherapies-for-personality-disorder
#19
John R Keefe, Robert J DeRubeis
OBJECTIVE: Personality disorder (PD) is a negative prognostic indicator for treatment, and absolute improvements in functioning among these patients are often modest. This may be because personality features that give rise to dysfunction in PD are not targeted optimally during most treatments. METHOD: Attachment, mentalization, core beliefs, and personality organization/defense use were identified as personality constructs that have been pursued in treatment studies and that are proposed to underlie PD...
January 19, 2018: Psychotherapy Research: Journal of the Society for Psychotherapy Research
https://www.readbyqxmd.com/read/29346932/gap-junction-coupling-and-atp-sensitive-potassium-channels-in-human-%C3%AE-cell-clusters-effects-on-emergent-dynamics
#20
A Loppini, M G Pedersen, M Braun, S Filippi
The importance of gap-junction coupling between β cells in pancreatic islets is well established in mouse. Such ultrastructural connections synchronize cellular activity, confine biological heterogeneity, and enhance insulin pulsatility. Dysfunction of coupling has been associated with diabetes and altered β-cell function. However, the role of gap junctions between human β cells is still largely unexplored. By using patch-clamp recordings of β cells from human donors, we previously estimated electrical properties of these channels by mathematical modeling of pairs of human β cells...
September 2017: Physical Review. E
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