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https://www.readbyqxmd.com/read/27933748/exploring-glucocorticoid-receptor-agonists-mechanism-of-action-through-mass-cytometry-and-radial-visualizations
#1
Yann Abraham, Bertran Gerrits, Marie-Gabrielle Ludwig, Michael Rebhan, Caroline Gubser Keller
Recent advances in combining flow cytometry and mass spectrometry have led to the development of mass cytometry, allowing for the interrogation of complex cell populations on an unprecedented scale. The volumes and high dimensionality of mass cytometry data pose significant challenges in terms of analysis and visualization. We implement a method called Radviz (1-3), where multidimensional single cell data can be visualized as a projection that maintains the original dimensions and data complexity whilst facilitating analysis and visualization...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933736/structural-insight-into-the-anti-prion-compound-inhibition-mechanism-of-native-prion-folding-over-misfolding
#2
Jiwon Choi, Rajiv Gandhi Govindaraj, Jae Wook Hyeon, Kyungro Lee, SongLing Ma, Su Yeon Kim, Jeongmin Lee, Kyoung Tai No
Transition of a physiological folded prion (PrP(C) ) into a pathogenic misfolded prion (PrP(S)(c) ) causes lethal neurodegenerative disorders and prion diseases. Anti-prion compounds have been developed to prevent this conversion; however, their mechanism of action remains unclear. Recently, we reported two anti-prion compounds, BMD29 and 35, identified by in silico and in vitro screening. In this study, we used extensive explicit-solvent molecular dynamics simulations to investigate ligand binding inhibition by anti-prion compounds in prion folding over misfolding behavior at acidic pH...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933734/improved-quality-of-life-in-asthma-patients-under-long-term-therapy-assessed-by-ahq-japan
#3
Yuji Tohda, Takashi Iwanaga, Hiroyuki Sano, Hiroaki Kume, Kazuto Hirata, Noriyuki Ohkura, Isao Tachibana, Yoshihiro Nishimura, Hisako Matsumoto, Yoshiaki Minakata, Masanori Yoshikawa, Masaki Fujimura
BACKGROUND AND OBJECTIVES: Assessment of the effects of long-term management on patient quality of life (QOL) would be extremely useful for determining asthma treatment strategies. However, no studies have evaluated QOL over an extended period of time. This study evaluated the changes in QOL, drug management and disease severity in the same asthma patients at an interval of approximately 9 years. METHODS: We re-surveyed asthma patients enrolled in a survey conducted in 2004 to evaluate the effects of approximately a decade of treatment on disease severity and QOL assessed by the Japanese Asthma Health Questionnaire (AHQ-JAPAN)...
December 9, 2016: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/27933733/mannich-bases-of-1-2-4-triazole-3-thione-containing-adamantane-moiety-synthesis-preliminary-anticancer-evaluation-and-molecular-modeling-studies
#4
Milorad Z Milošev, Katarina Jakovljević, Milan D Joksović, Tatjana Stanojković, Ivana Z Matić, Milka Perović, Vesna Tešić, Selma Kanazir, Milan Mladenović, Marko V Rodić, Vukadin M Leovac, Snežana Trifunović, Violeta Marković
A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e and 5j on the cell cycle were investigated by flow cytometric analysis...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933730/reactivity-of-9-aminoacridine-drug-quinacrine-with-glutathione-limits-its-anti-prion-activity
#5
Martin Šafařík, Tibor Moško, Zbigniew Zawada, Eva Šafaříková, Martin Dračínský, Karel Holada, Jaroslav Šebestík
Quinacrine - the drug based on 9-aminoacridine - failed in clinical trials for prion diseases, whereas it was active in in-vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abundant glutathione. Here, we described the semi-large-scale synthesis of the acridinylated glutathione and the consequences of its formation on biological and biophysical activities. The acridinylated glutathione is one order of magnitude weaker prion protein binder than the parent quinacrine...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933716/risks-and-treatment-strategies-for-de-novo-hepatitis-b-virus-infection-from-anti-hbc-positive-donors-in-pediatric-living-donor-liver-transplantation
#6
Chong Dong, Wei Gao, Nan Ma, Chao Sun, Wei-Ping Zheng, Kai Wang, Zhong-Yang Shen
The aim of this study was to analyze the incidence and risk factors of de novo HBV infection in pediatric patients receiving living donor liver transplants (LDLT) from HBcAb-positive donors, and to explore its treatment strategies. The data of 101 pediatric recipients receiving LDLT in Tianjin First Central Hospital between September 2006 and December 2012 were retrospectively analyzed. The HBV markers were regularly tested before and after the surgery, including HBsAb, HBsAg, HBeAg, HBeAb, and HBcAb. The median follow-up period was 25...
December 9, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27933715/efficacy-of-self-monitoring-of-blood-glucose-versus-retrospective-continuous-glucose-monitoring-in-improving-glycaemic-control-in-diabetic-kidney-disease-patients
#7
Ester Chai Kheng Yeoh, Boon Khim Lim, Sharon Fun, Julia Tong, Lee Ying Yeoh, Chee Fang Sum, Tavintharan Subramaniam, Su Chi Lim
AIMS: Patients with diabetic kidney disease (DKD) on anti-diabetic agents, are at greater risk of glycemic variations, both hypoglycemia and hyperglycemia. We aimed to compare glycemic control (using HbA1c) and hypoglycemia incidence in patients with Stage 3 DKD (eGFR 30-60 ml/min/1.73 m(2) ), receiving retrospective CGM-guided anti-diabetic therapy versus self-monitoring of blood glucose (SMBG) over 3 months. METHODS: Thirty patients with HbA1c > 8% were randomized to 6-day retrospective CGM or SMBG...
December 9, 2016: Nephrology
https://www.readbyqxmd.com/read/27933695/multiconfigurational-effects-in-theoretical-resonance-raman-spectra
#8
Yingjin Ma, Stefan Knecht, Markus Reiher
We analyze resonance Raman spectra of the nucleobase uracil in the short-time approximation calculated with multiconfigurational methods. We discuss the importance of static electron correlation by means of density-matrix renormalization group self-consistent field (DMRG-SCF) calculations. Our DMRG-SCF results reveal that a minimal active orbital space that leads to a qualitatively correct description of the resonance Raman spectrum of uracil should encompass parts of the $\sigma/\sigma^{\ast}$ bonding/anti-bonding orbitals of the pyrimidine ring...
December 8, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/27933686/risk-of-incident-mycobacterium-tuberculosis-infection-in-patients-with-inflammatory-bowel-disease-a-nationwide-population-based-study-in-south-korea
#9
S N Hong, H J Kim, K H Kim, S-J Han, I M Ahn, H S Ahn
BACKGROUND: The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. AIM: To evaluate the risk of incident TB among IBD patients. METHODS: Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications...
January 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27933584/matrine-treatment-blocks-nogoa-induced-neural-inhibitory-signaling-pathway-in-ongoing-experimental-autoimmune-encephalomyelitis
#10
Quan-Cheng Kan, Hui-Jun Zhang, Yuan Zhang, Xing Li, Yu-Ming Xu, Rodolfo Thome, Ming-Liang Zhang, Nan Liu, Yao-Juan Chu, Guang-Xian Zhang, Li Zhu
Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood...
December 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27933567/impact-of-endoscopic-ultrasound-guided-fine-needle-aspiration-in-prospective-liver-transplant-recipients-with-hepatocellular-carcinoma-and-lymphadenopathy
#11
Narendra S Choudhary, Rajesh Puri, Sanjiv Saigal, Prashant Bhangui, Neeraj Saraf, Vinit Shah, Mukesh Nasa, Haimanti Sarin, Mridula Guleria, Randhir Sud, Arvinder S Soin
BACKGROUND: Diagnosis of metastatic disease is important in patients with cirrhosis and hepatocellular carcinoma (HCC) to prevent futile liver transplantation. Some of these patients have metastatic lymphadenopathy; however, it is difficult to perform percutaneous fine-needle aspiration due to presence of collateral and anatomic location. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of lymph nodes offers several advantages like real-time vision, proximity to target, and avoidance of collaterals...
December 8, 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/27933551/pentoxifylline-alleviates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-in-rats-possibly-via-inhibiting-tlr-4-nf-%C3%AE%C2%BAb-signaling-pathway
#12
Da-Yong Xia, Hua-Sheng Zhang, Ling-Yun Wu, Xiang-Sheng Zhang, Meng-Liang Zhou, Chun-Hua Hang
Early brain injury (EBI) after subarachnoid hemorrhage (SAH) generally causes significant and lasting damage. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, has shown anti-inflammatory and neuroprotective properties in several brain injury models, but the role of PTX with respect to EBI following SAH remains uncertain. The purpose of this study was to investigate the effects of PTX on EBI after SAH in rats. Adult male Sprauge-Dawley rats were randomly assigned to the sham and SAH groups. PTX (30 or 60 mg/kg) or an equal volume of the administration vehicle (normal saline) was administrated at 30 min intervals following SAH...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933547/anti-neuroinflammatory-effects-of-fucoxanthin-via-inhibition-of-akt-nf-%C3%AE%C2%BAb-and-mapks-ap-1-pathways-and-activation-of-pka-creb-pathway-in-lipopolysaccharide-activated-bv-2-microglial-cells
#13
Dong Zhao, Seung-Hwan Kwon, Yoon Sun Chun, Ming-Yao Gu, Hyun Ok Yang
Microglia play a critical role in controlling the homeostasis of the brain, but over-activated microglia secrete pro-inflammatory mediators and cytokines, which induce neuronal cell death. Fucoxanthin (Fx), a marine carotenoid, has demonstrated a variety of beneficial health effects. Despite accumulating evidence supporting the immune-modulating effects of Fx in vitro, the underlying signaling pathways remain unknown. In the present study, Fx dose-dependently inhibited the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), prostaglandin (PG) E2, and nitric oxide (NO) productions, and also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933510/anti-fibrotic-effects-of-salvia-miltiorrhiza-and-ligustrazine-injection-on-lx-2-cells-involved-with-increased-n-myc-downstream-regulated-gene-2-expression
#14
Jin Zheng, Li-Tian Ma, Qin-You Ren, Yue Hu, Yang Bai, Huan Bian, Yi Zhang, Yong-Chun Zhou, Ming-Hui Yang
OBJECTIVE: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstream-regulated gene 2 (NDRG2, a tumor suppressor gene). METHODS: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay...
December 8, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27933483/covalent-immobilization-of-human-placental-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-onto-glutaraldehyde-activated-silica-coupled-with-lc-tof-ms-for-anti-cancer-drug-screening-applications
#15
Yin Bai, Wen-Di Zhou, Xian-Min Mu, Qian Zhang, Chen Yu, Bin Di, Meng-Xiang Su
Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), a potential target in breast cancer prevention and therapy, was extracted from human placenta and immobilized on nonporous silica (∼5 μm) with a covalent method for the first time. The optimum initial enzyme concentration and immobilization time during the immobilization process were 0.42 mg mL(-1) and 12 h, repectively. The binding was confirmed by scanning electron microscope (SEM) and infrared spectroscopy (FT-IR). It could improve the pH, thermal and storage stability compared to free enzyme...
December 8, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27933472/tumor-necrosis-factor-alpha-inhibitors-did-not-influence-postoperative-morbidity-after-elective-surgical-resections-in-crohn-s-disease
#16
Paulo Gustavo Kotze, Mansur Paulo Saab, Bárbara Saab, Lorete Maria da Silva Kotze, Marcia Olandoski, Lilian Vital Pinheiro, Carlos Augusto Real Martinez, Maria de Lourdes Setsuko Ayrizono, Daniela de Oliveira Magro, Claudio Saddy Rodrigues Coy
BACKGROUND: The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined. AIMS: To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy. METHODS: This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded)...
December 8, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27933449/clearing-the-fog-a-review-of-the-effects-of-dietary-omega-3-fatty-acids-and-added-sugars-on-chemotherapy-induced-cognitive-deficits
#17
REVIEW
Tonya S Orchard, Monica M Gaudier-Diaz, Kellie R Weinhold, A Courtney DeVries
Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis...
December 8, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27933426/characterization-of-the-first-fully-human-anti-tem1-scfv-in-models-of-solid-tumor-imaging-and-immunotoxin-based-therapy
#18
Xiaopeng Yuan, Mingjuan Yang, Xiang Chen, Xuhua Zhang, Shrey Sukhadia, Najia Musolino, Huijing Bao, Tingtao Chen, Chen Xu, Qirui Wang, Stephen Santoro, Daniel Ricklin, Jia Hu, Ruihe Lin, Wei Yang, Zhijun Li, Weijun Qin, Aizhi Zhao
Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope...
December 8, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27933391/-tapering-and-termination-of-immunosuppressive-treatment-in-spondyloarthritides-including-psoriatic-arthritis
#19
REVIEW
G Scholz, B Möller
BACKGROUND: Immunomodulatory long-term treatment has also become the standard treatment for spondyloarthritides (SpA), including psoriatic arthritis (PsA); however, uncertainty exists about dose reduction or termination of treatment after remission or low disease activity. OBJECTIVE: When is it possible to reduce medication or terminate treatment for SpA? MATERIAL AND METHODS: An extensive non-systematic literature search was performed focusing on practice guidelines, systematic meta-analyses and clinical trials on medicinal long-term treatment and voluntary medication reduction in axial and peripheral SpA, including PsA...
December 8, 2016: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/27933340/enhancement-of-pharmacological-effects-of-uricosuric-agents-by-concomitant-treatment-with-pyrazinamide-in-rats
#20
Tetsuya Taniguchi, Naoki Ashizawa, Koji Matsumoto, Takashi Iwanaga
Our goal was to establish a model for the evaluation of the effects of uricosuric agents and to clarify the underlying mechanism(s). The effects of a uricosuric agent co-treated with pyrazinamide, an anti-tubercular agent, on urate handling were examined in rats. Furthermore, the effects of uricosuric agents on urate uptake were evaluated using the vesicles of rat renal brush-border membrane. Treatment with probenecid, at a dose of 100 mg/kg, significantly increased the urinary urate to creatinine ratio (UUA/UCRE) in pyrazinamide-treated rats although the same treatment did not produce any uricosuric effects in intact rats...
December 8, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
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