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Petra D Cravens, Rehana Z Hussain, William A Miller-Little, Li-Hong Ben, Benjamin M Segal, Emily Herndon, Olaf Stüve
BACKGROUND: Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS...
2016: PloS One
Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
John S Thompson, Debra L Hardin, Judy F Glass, Joshua Dziba, Jeffrey Campion, Stephen A Brown
We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31...
2016: SOJ Immunology
Hyun-Je Kim, Nari Byun, Ohsang Kwon, Chung-Gyu Park
The number of patients in need of organ transplantation is continuously on the rise. However, because of organ donor shortage, xenotransplantation has been highlighted as an alternative. Among the various porcine organs and tissues, porcine islets are considered to be the best-matching implantable candidates for clinical application based on recent progress in nonhuman primate pre-clinical studies. Nevertheless, before initiation of clinical trials, it should be confirmed whether the requisite xeno-antigen sensitization would have a deleterious effect on subsequent allo-transplantation or vice versa...
October 20, 2016: Biochemical and Biophysical Research Communications
Yandong Zhang, Xinchun Yu, Shuhui Sun, Qian Li, Yunli Xie, Qiang Li, Yifan Zhao, Jianfeng Pei, Wenmin Zhang, Peng Xue, Zhijun Zhou, Yubin Zhang
The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells...
October 19, 2016: Toxicology and Applied Pharmacology
Virginia Moreno, Eulogio J Llorent-Martínez, Mohammed Zougagh, Angel Ríos
A supercritical carbon dioxide medium was used for the decoration of functionalized multi-walled carbon nanotubes (MWCNTs) with metallic nanoparticles. This procedure allowed the rapid and simple decoration of carbon nanotubes with the selected metallic nanoparticles. The prepared nanomaterials were used to modify screen-printed electrodes, improving their electrochemical properties and allowing to obtain a wide range of working electrodes based on carbon nanotubes. These electrodes were applied to the amperometric determination of vitamin B6 in food and pharmaceutical samples as an example of the analytical potentiality of the electrodes thus prepared...
December 1, 2016: Talanta
Zhangguo Chen, Katherine Gowan, Sonia M Leach, Sawanee S Viboolsittiseri, Ameet K Mishra, Tanya Kadoishi, Katrina Diener, Bifeng Gao, Kenneth Jones, Jing H Wang
BACKGROUND: Whole genome next generation sequencing (NGS) is increasingly employed to detect genomic rearrangements in cancer genomes, especially in lymphoid malignancies. We recently established a unique mouse model by specifically deleting a key non-homologous end-joining DNA repair gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in germinal center B cells. This mouse model spontaneously develops mature B cell lymphomas (termed G1XP lymphomas). RESULTS: Here, we attempt to employ whole genome NGS to identify novel structural rearrangements, in particular inter-chromosomal translocations (CTXs), in these G1XP lymphomas...
October 21, 2016: BMC Genomics
Jeffrey Cummings, Philip Scheltens, Ian McKeith, Rafael Blesa, John E Harrison, Paulo H F Bertolucci, Kenneth Rockwood, David Wilkinson, Wouter Wijker, David A Bennett, Raj C Shah
BACKGROUND: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes. OBJECTIVE: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm. METHODS: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Taeyeon Kim, Sukhyeong Cho, Sun-Mi Lee, Han Min Woo, Jinwon Lee, Youngsoon Um, Jin-Ho Seo
Biological production of 2,3-butandiol (2,3-BD) has received great attention as an alternative to the petroleum-based 2,3-BD production. In this study, a high production of 2,3-BD in fed-batch fermentation was investigated with a newly isolated bacterium designated as Raoultella ornithinolytica B6. The isolate produced 2,3-BD as the main product using hexoses (glucose, galactose, and fructose), pentose (xylose) and disaccharide (sucrose). The effects of temperature, pH-control schemes, and agitation speeds on 2,3-BD production were explored to optimize the fermentation conditions...
2016: PloS One
Carl B Gillombardo, Rebecca Darrah, Thomas E Dick, Michael Moore, Nathan Kong, Michael J Decker, Fang Han, Motoo Yamauchi, Mathias Dutschmann, Sausan Azzam, Kingman P Strohl
RATIONALE: Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES: To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS: Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo...
October 15, 2016: Respiratory Physiology & Neurobiology
Chih-Hung Lee, Jau-Shiuh Chen, Hsien-Ching Chiu, Chien-Hui Hong, Ching-Yi Liu, Yng-Cun Ta, Li-Fang Wang
BACKGROUND: Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. OBJECTIVE: We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice...
October 3, 2016: Journal of Dermatological Science
Modar Kassan, Ajit Vikram, Qiuxia Li, Young-Rae Kim, Santosh Kumar, Julia Jacob, Irani Kaikobad
OBJECTIVE: Endoplasmic reticulum (ER) stress leads to vascular endothelial dysfunction in hypertension. The role of microRNAs in vascular ER stress is not fully understood. Here we examined the role of vascular microRNA-204 (miR-204) in inducing endothelial ER stress and dysfunction by governing the expression of the SIRTUIN1 (SIRT1) lysine deacetylase. DESIGN AND METHOD: Human Umbilical Vein cells (HUVECs) were treated with tunicamycin or transfected with miR-204 Mimic or siRNA SIRT1...
September 2016: Journal of Hypertension
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Hui Bai, Bing Bai, Lin Zhang, Wei Huang, Yue-Wen Mu, Hua-Jin Zhai, Si-Dian Li
The recent discovery of borospherene B40 marks the onset of a new kind of boron-based nanostructures akin to the C60 buckyball, offering opportunities to explore materials applications of nanoboron. Here we report on the feasibility of Li-decorated B40 for hydrogen storage using the DFT calculations. The B40 cluster has an overall shape of cube-like cage with six hexagonal and heptagonal holes and eight close-packing B6 triangles. Our computational data show that Lim&B40(1-3) complexes bound up to three H2 molecules per Li site with an adsorption energy (AE) of 0...
October 18, 2016: Scientific Reports
Hung-Yen Chin, Li-Hsuan Chiu, Kuan-Cheng Lin, Chi-Hsin Chiang, Chin-Jung Wang
OBJECTIVE: To examine the alteration in the cellular dynamics of the urethral tissue after a simulated birth trauma in a mouse model. MATERIALS AND METHODS: A total of 36 B6 mice received vaginal distention treatment, and four untreated mice were used as controls. Specimens were collected every 24 hours after the injury for 9 consecutive days and examined using immunofluorescent staining for cell markers including c-kit, smooth muscle actin (SMA), and vimentin...
October 2016: Taiwanese Journal of Obstetrics & Gynecology
Simmi Kharb, D Aggarwal, J Bala, S Nanda
BACKGROUND: Folate, vitamin B12 and vitamin B6 are required for homocysteine metabolism and their deficiency can result in increased homocysteine concentration. Homocysteine concentrations have been found to be increased in late pregnancy toward nonpregnant values. OBJECTIVE: To study folate, vitamin B12 and homocysteine levels in cord blood and maternal blood in preeclampsia. MATERIALS AND METHODS: One hundred fifty pregnant women attending Out Patient Department of Department of Obstetrics and Gynaecology were recruited for the study...
October 10, 2016: Current Hypertension Reviews
Imranul Alam, Amie K McQueen, Dena Acton, Austin M Reilly, Rita L Gerard-O'Riley, Dana K Oakes, Charishma Kasipathi, Abigail Huffer, Weston B Wright, Michael J Econs
Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic bone disorder due to dysfunctional osteoclast activity. ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures. ADO2 can result in osteomyelitis, visual loss and bone marrow failure. Currently, there is no cure for ADO2, and until recently no appropriate animal model of ADO2 existed to understand better the pathogenesis of this disease and to test new therapies...
October 14, 2016: Bone
Valentina A Andreeva, Valérie Deschamps, Benoît Salanave, Katia Castetbon, Charlotte Verdot, Emmanuelle Kesse-Guyot, Serge Hercberg
Despite some advantages over traditional methods, Web-based studies elicit concerns about generalizability. To address this issue, we compared dietary intakes between an electronic (e-) cohort study and a nationally representative survey. We studied 49,443 French volunteers aged 18-74 years recruited during 2009-2010 in the NutriNet-Santé Study, a general population-based e-cohort study. The Etude Nationale Nutrition Santé (ENNS; 2006-2007), a cross-sectional study with a nationally representative sample of 2,754 French adults aged 18-74 years, served as the reference data set...
October 15, 2016: American Journal of Epidemiology
Shweta Sharma, Ashwni Kumar Verma, Jyotsana Singh, B Venkatesh Teja, Naresh Mittapelly, Gitu Pandey, Sandeep Urandur, Ravi Shukla, Rituraj Konwar, Prabhat Ranjan Mishra
This study reports the development of Vitamin B6 (VitB6) modified pH sensitive charge reversal nanoparticles for efficient intracellular delivery of Doxorubicin (DOX). Herein, VitB6 was conjugated to stearic acid and the nanoparticles of the lipid were formulated by solvent injection method (DOX-B6-SA-NP). Due to the pKa (5.6) of VitB6, DOX-B6-SA-NP showed positive charge and enhanced release of DOX at pH 5. Confocal microscopy illustrated that DOX-B6-SA-NP treatment keep higher DOX accumulation inside the cells that conventional pH insensitive lipid nanoparticles (DOX-SA-NP)...
October 14, 2016: ACS Applied Materials & Interfaces
Henrika Wickström, Johan O Nyman, Mathias Indola, Heidi Sundelin, Leif Kronberg, Maren Preis, Jukka Rantanen, Niklas Sandler
Printing technologies were recently introduced to the pharmaceutical field for manufacturing of drug delivery systems. Printing allows on demand manufacturing of flexible pharmaceutical doses in a personalized manner, which is critical for a successful and safe treatment of patient populations with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care...
October 13, 2016: AAPS PharmSciTech
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