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https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#1
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445853/cannabidiol-%C3%AE-9-tetrahydrocannabinol-interactions-on-acute-pain-and-locomotor-activity
#2
Stevie C Britch, Jenny L Wiley, Zhihao Yu, Brian H Clowers, Rebecca M Craft
BACKGROUND: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ(9)-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. METHODS: In Experiment 1, CBD (0, 10 or 30mg/kg) was administered 15min before THC (0, 1.8, 3.2, 5.6 or 10mg/kg), and rats were tested for antinociception and locomotion 15-360min post-THC injection. In Experiments 2 and 3, CBD (30mg/kg) was administered 13h or 15min before THC (1...
April 15, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28445838/addition-of-insulin-like-growth-factor-i-to-the-maturation-medium-of-bovine-oocytes-subjected-to-heat-shock-effects-on-the-production-of-reactive-oxygen-species-mitochondrial-activity-and-oocyte-competence
#3
I J Ascari, N G Alves, J Jasmin, R R Lima, C C R Quintão, G Oberlender, E A Moraes, L S A Camargo
This study was performed to investigate the effects of insulin-like growth factor-I (IGF-I) addition to in vitro maturation (IVM) medium on apoptosis, mitochondrial membrane potential, ROS production, and developmental competence of bovine oocytes subjected to heat shock. Two temperatures (conventional: 24 h at 38.5°C, or heat shock: 12 h at 41°C followed by 12 h at 38.5°C) and 3 IGF-I concentrations (0, 25, and 100 ng/mL) were tested during IVM. The oocytes were then fertilized in vitro, and the presumptive zygotes were cultured until reaching the blastocyst stage...
March 25, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#4
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445713/deregulation-of-%C3%AE-synuclein-in-parkinson-s-disease-insight-from-epigenetic-structure-and-transcriptional-regulation-of-snca
#5
REVIEW
Subhrangshu Guhathakurta, Eugene Bok, Baggio A Evangelista, Yoon-Seong Kim
Understanding regulation of α-synuclein has long been a central focus for Parkinson's disease (PD) researchers. Accumulation of this protein in the Lewy body or neurites, mutations in the coding region of the gene and strong association of α-synuclein encoding gene multiplication (duplication/triplication) with familial form of PD have indicated the importance of this molecule in pathogenesis of the disease. Several years of research identified many potential faulty pathways associated with accumulation of α-synuclein inside dopaminergic neurons and its transmission to neighboring ones...
April 23, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28445029/nhs-esters-as-versatile-reactivity-based-probes-for-mapping-proteome-wide-ligandable-hotspots
#6
Carl C Ward, Jordan I Kleinman, Daniel K Nomura
Most of the proteome is considered undruggable oftentimes hindering translational efforts for drug discovery. Identifying previously unknown druggable hotspots in proteins would enable strategies for pharmacologically interrogating these sites with small-molecules. Activity-based protein profiling (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity-based chemical probes to map reactive, functional, and ligandable hotspots in complex proteomes, which has enabled inhibitor discovery against various therapeutic protein targets...
April 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28444960/in-vivo-absorption-and-metabolism-of-leptosperin-and-methyl-syringate-abundantly-present-in-manuka-honey
#7
Akari Ishisaka, Shinichi Ikushiro, Mie Takeuchi, Yukako Araki, Maki Juri, Yui Yoshiki, Yoshichika Kawai, Toshio Niwa, Noritoshi Kitamoto, Toshiyuki Sakaki, Hirohito Ishikawa, Yoji Kato
SCOPE: Manuka honey, which shows strong non-peroxide-dependent antibacterial activity, contains unique components, such as methyl syringate 4-O-β-D-gentiobioside (leptosperin) and its aglycone, methyl syringate (MSYR). To determine the potential for biological activity evoked by the ingestion of leptosperin and MSYR, we investigated the absorption and metabolism of these components in manuka honey. METHODS AND RESULTS: The incubation of MSYR with liver microsomes or S9 fractions in vitro resulted in the formation of MSYR-glucuronide (MSYR-GA), MSYR-sulfate (MSYR-S), and syringic acid as metabolites...
April 26, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28444832/real-time-activation-of-central-cholinergic-circuits-during-recognition-memory
#8
Sonia Bonnì, Viviana Ponzo, Francesco Di Lorenzo, Carlo Caltagirone, Giacomo Koch
Short Latency Afferent Inhibition (SAI) is a paired-pulse Transcranial Magnetic Stimulation (TMS) protocol that consists in the inhibition of the Motor Evoked Potentials (MEPs) by afferent sensory impulses. SAI is thought to be mediated by cholinergic projections over M1 and can be considered a putative marker of central cholinergic activity. It's known that memory processes are regulated by acetylcholine. Nonetheless the influence of memory tasks on SAI has not been investigated. Here we tested changes in SAI circuits in healthy subjects performing a computerized non-verbal recognition memory task (RMT) requiring to recognize previously encoded faces...
April 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28444784/earlier-defibrotide-initiation-post-diagnosis-of-veno-occlusive-disease-sinusoidal-obstruction-syndrome-improves-day-100-survival-following-haematopoietic-stem-cell-transplantation
#9
Paul G Richardson, Angela R Smith, Brandon M Triplett, Nancy A Kernan, Stephan A Grupp, Joseph H Antin, Leslie Lehmann, Maja Miloslavsky, Robin Hume, Alison L Hannah, Bijan Nejadnik, Robert J Soiffer
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States...
April 26, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28444763/manganese-concentration-mapping-in-the-rat-brain-with-mri-pet-and-autoradiography
#10
Geoffrey J Topping, Andrew Yung, Paul Schaffer, Cornelia Hoehr, Rick Kornelsen, Piotr Kozlowski, Vesna Sossi
PURPOSE: Mn(2+) is used a contrast agent and marker for neuronal activity with magnetic resonance imaging (MRI) in rats and mice, but its accumulation is generally not assessed quantitatively. In this work, non-radioactive Mn and (52) Mn are injected simultaneously in rats, and imaged with MRI, positron emission tomography (PET) and autoradiography (AR). Mn distributions are compared between modalities, to assess the potential and limitations on quantification of Mn with MRI, and to investigate the potential of multimodal measurement of Mn accumulation...
April 26, 2017: Medical Physics
https://www.readbyqxmd.com/read/28444628/moving-beyond-age-an-exploratory-qualitative-study-on-the-context-of-young-african-american-men-and-women-s-sexual-debut
#11
Yzette Lanier, Jennifer M Stewart, Jean J Schensul, Barbara J Guthrie
African American youth continue to be disproportionately affected by HIV. Early sexual debut has been identified as a major determinant of HIV risk. However, emerging research suggests that the overarching context in which first sex occurs may have greater implications for sexual health than simply age alone. The purpose of this exploratory, qualitative study was to better understand the broader context of African Americans' sexual debut. In-depth, semi-structured interviews were conducted with 10 African American men and women aged 18-24 years...
April 25, 2017: Journal of Racial and Ethnic Health Disparities
https://www.readbyqxmd.com/read/28443046/craving-behavior-intervention-in-ameliorating-college-students-internet-game-disorder-a-longitudinal-study
#12
Lin-Yuan Deng, Lu Liu, Cui-Cui Xia, Jing Lan, Jin-Tao Zhang, Xiao-Yi Fang
Craving, as a central feature of addiction and a precursor of relapse, is targeted recently in addiction intervention. While Internet gaming disorder (IGD), conceptualized as a behavioral addiction, is lack of effective treatment practice and exploration of its mechanism. This research aims to test the effectiveness and detect the active ingredients of craving behavior intervention (CBI) in mitigation of IGD among young adults. A total of 63 male college students with IGD were assigned into the intervention group (six-session CBI intervention) or the waiting-list control group...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#13
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28442797/pre-and-post-sexual-exposure-prophylaxis-of-hiv-an-update
#14
REVIEW
Yogesh S Marfatia, Sheethal K Jose, Reema R Baxi, Ruchi J Shah
Pitfalls in current HIV prevention strategies include late HIV testing, vulnerability among youth and females; lack of emphasis on treatment, low acceptance of circumcision, and nonavailability of protective vaccines. Continuing high-risk sexual behavior, forceful sex, coercive and nonconsensual sex, rape, and unprotected sexual activities make women the most vulnerable to acquisition of sexually transmitted infection/HIV and necessitates a more radical approach of prevention in high-risk individuals who do not have HIV...
January 2017: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/28442416/molecular-characterization-and-expression-of-interleukin-10-and-interleukin-22-in-golden-pompano-trachinotus-ovatus-in-response-to-streptococcus-agalactiae-stimulus
#15
Yinhui Peng, Xiaohui Cai, Guoyin Zhang, Junlin Wang, Yuan Li, Zhiwen Wang, Bei Wang, Xiangying Xiong, Zaohe Wu, Jichang Jian
In the present study, members of the interleukin (IL)-10 family of cytokines, including IL-10 (TOIL-10) and IL-22 (TOIL-22) of golden pompano (Trachinotus ovatus), were cloned for the first time, and their expression patterns and 3D structures analyzed. The full-length cDNA sequences of TOIL-10 and TOIL-22 contained open reading frames of 564 and 567 bp, respectively. TOIL-10 and TOIL-22 shared higher homology (78%-89%) with the corresponding genes from various fish relative to other species (25%-34%) and contained the IL-10 family signature and four cysteine residues that are well conserved in other vertebrate IL-10 members...
April 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28442391/an-exploratory-high-density-eeg-investigation-of-the-misinformation-effect-attentional-and-recollective-differences-between-true-and-false-perceptual-memories
#16
John E Kiat, Robert F Belli
The misinformation effect, a phenomenon in which eyewitness memories are altered via exposure to post-event misinformation, is one of the most important paradigms used to investigate the reconstructive nature of human memory. The aim of this study was to use the misinformation effect paradigm to investigate differences in attentional and recollective processing between true and false event memories. Nineteen participants completed a variant of the misinformation paradigm in which recognition responses to true and misinformation based event details embedded within a narrative context, were investigated using high-density (256-channel) EEG with a 1-day delay between event exposure and test...
April 22, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28442378/antihyperlipidemic-and-antiapoptotic-potential-of-zingerone-on-alcohol-induced-hepatotoxicity-in-experimental-rats
#17
Vijay Mani, Sivaranjani Arivalagan, Aktarul Islam Siddique, Nalini Namasivayam
The ultimate aim of this present study was to investigate the antihyperlipidemic and antiapoptotic potential of zingerone (ZO) on alcohol induced hepatotoxicity in experimental rats. Male albino wistar rats were divided in four groups. Groups 1 and 2 rats received isocaloric glucose and dimethyl sulphoxide (2% DMSO), liver toxicity was induced in groups 3 and 4 by supplementing 30% ethanol post orally for 60 days. In addition, groups 2 and 4 received zingerone (20 mg/kg body weight in 2% DMSO) daily during the final 30 days of the experimental period...
April 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28441895/ketamine-s-dose-related-effects-on-anxiety-symptoms-in-patients-with-treatment-refractory-anxiety-disorders
#18
Paul Glue, Natalie J Medlicott, Sarah Harland, Shona Neehoff, Bridie Anderson-Fahey, Martin Le Nedelec, Andrew Gray, Neil McNaughton
The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0...
April 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28440500/indirect-effects-of-x-irradiation-on-proliferation-and-osteogenic-potential-of-bone-marrow-mesenchymal-stem-cells-in-a-local-irradiated-rat-model
#19
Ruilian Sun, Guoying Zhu, Jianping Wang, Ling Tong, Jianglong Zhai
Cancer survivors after radiotherapy may suffer a variety of bone‑related adverse side effects, including radioactive osteoporosis and fractures. Localized irradiation is a common treatment modality for malignancies. Recently, a series of reactions and injuries called indirect effects (remote changes in bone when other parts of the body are irradiated) have been reported on the indirect irradiated area of bone tissue after radiotherapy. To address this issue, we developed a rat localized irradiation model...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439226/the-phosphodiesterase-10a-inhibitor-pf-2545920-enhances-hippocampal-excitability-and-seizure-activity-involving-the-upregulation-of-glua1-and-nr2a-in-post-synaptic-densities
#20
Yanke Zhang, Baobing Gao, Fangshuo Zheng, Shanshan Lu, Yun Li, Yan Xiong, Qin Yang, Yong Yang, Pengfei Fu, Fei Xiao, Xuefeng Wang
Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted attention as a potential therapy for neurological and psychiatric disorders. We hypothesized that PF-2545920 plays an important role in status epilepticus (SE) and investigated the underlying mechanisms...
2017: Frontiers in Molecular Neuroscience
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