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https://www.readbyqxmd.com/read/28734271/development-and-validation-of-sensitive-lc-ms-ms-method-for-the-quantification-of-suvn-502-and-its-metabolite-and-its-application-for-first-in-human-pharmacokinetic-study
#1
Ramakrishna Nirogi, Devender Reddy Ajjala, Raghupathi Aleti, Lakshmiprasanna Rayapati, Hanumanth Rao Pantangi, Rajesh Kumar Boggavarapu, Naga Surya Prakash Padala
A sensitive and rapid LC-MS/MS method was developed and validated for the quantification of SUVN-502 and M1 of SUVN-502, a 5-HT6 receptor antagonist for the treatment of dementia associated with Alzheimer's disease. Following solid-phase extraction, SUVN-502 and M1 of SUVN-502 and IS were eluted with 10mM ammonium acetate (pH 4.0) and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the respective transitions of m/z 478.2→377.7 for SUVN-502 and m/z 464...
April 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28734243/caveolin-1-related-autophagy-initiated-by-aldosterone-induced-oxidation-promotes-liver-sinusoidal-endothelial-cells-defenestration
#2
Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28734165/rhodamine-spirolactam-sensors-operated-by-sulfur-cooperated-metal-complexation
#3
Gisuk Heo, Dahye Lee, Chi Gwan Kim, Jung Yun Do
New rhodamine Schiff base sensors were developed to improve selective sensing by introducing sulfide, ester, and dithiocarbonate groups, as well as using ketones coupled to rhodamine-hydrazine. Metal sensing proceeded through the 1:1 complexation of the metal ion for most sensors in the presence of Cu(2+) and Hg(2+). A sensor carrying a dithiocarbonate group responded selectively to Hg(2+) showing a strong colorimetric change and intense fluorescence. The association constants of the sensors were determined from a linear plot performed at micro-molar concentrations to afford values in the range of 10(4)...
July 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28732433/the-effect-of-salt-space-on-clinical-findings-and-peak-expiratory-flow-in-children-with-mild-to-moderate-asthma-a-randomized-crossover-trial
#4
Saeideh Mazloomzadeh, Niousha Bakhshi, Akefeh Ahmadiafshar, Mehdi Gholami
The asthma treatment and control might be associated with significant burden on family and community' thus exploring other therapeutic plans could be desirable. The aim of this study was to investigate the effect of salt space on clinical findings and peak expiratory flow rate among children with asthma. In this randomized crossover trial, 34 patients aged 6-14 years old with mild to moderate asthma were selected and randomly divided into two groups. The first group went through a period of salt therapy by staying in the salt room for one hour, three times a week for 3 consecutive weeks and then was under observation for three weeks...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28732389/loss-of-sun2-promotes-the-progression-of-prostate-cancer-by-regulating-fatty-acid-oxidation
#5
Cheng Yajun, Ye Chen, Li Xiaosa, Wang Xiao, Chen Jia, Wang Zhong, Xu Bin
The role of Sun2 has been described by previous studies in various types of cancers, including breast cancer and lung cancer. However, its role and potential molecular mechanism in the progression of prostate cancer have not been fully elucidated. In the present study, we found that Sun2 expression was reduced in prostate cancer tissues compared with paired normal tissues, and that low expression of Sun2 was significantly correlated with Higher Gleason scores, postoperative T stage (pT), Lymph nodal invasion and Clinical pathological stages...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732382/novel-strategies-to-prevent-the-development-of-multidrug-resistance-mdr-in-cancer
#6
REVIEW
Jinglu Wang, Nicole Seebacher, Huirong Shi, Quancheng Kan, Zhenfeng Duan
The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732374/the-protective-effect-of-pft%C3%AE-on-alcohol-induced-osteonecrosis-of-the-femoral-head
#7
Yi-Xuan Chen, Dao-Yu Zhu, Jun-Hui Yin, Wen-Jing Yin, Yue-Lei Zhang, Hao Ding, Xiao-Wei Yu, Jiong Mei, You-Shui Gao, Chang-Qing Zhang
Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/β-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited osteogenesis by impairing the accumulation of β-catenin in both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3β (GSK-3β)...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732358/lenalidomide-restores-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-from-multiple-myeloma-patients-via-deactivating-notch-signaling-pathway
#8
Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li, Chunkang Chang
Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732288/lncrna-hotair-alleviates-rheumatoid-arthritis-by-targeting-mir-138-and-inactivating-nf-%C3%AE%C2%BAb-pathway
#9
Hong-Ju Zhang, Qiao-Feng Wei, Shu-Jun Wang, Hong-Jie Zhang, Xiu-Ying Zhang, Qin Geng, Yan-Hui Cui, Xiu-Hua Wang
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited...
July 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#10
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732278/advances-of-small-molecule-targeting-of-kinases
#11
REVIEW
Norbert Berndt, Rezaul M Karim, Ernst Schönbrunn
Reversible protein phosphorylation regulates virtually all aspects of life in the cell. As a result, dysregulation of protein kinases, the enzymes responsible for transferring phosphate groups from ATP to proteins, are often the cause or consequence of many human diseases including cancer. Almost three dozen protein kinase inhibitors (PKIs) have been approved for clinical applications since 1995, the vast majority of them for the treatment of cancer. According to the NCI, there are more than 100 types of cancer...
July 18, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28732250/structural-biology-of-telomerase-and-its-interaction-at-telomeres
#12
REVIEW
Yaqiang Wang, Juli Feigon
Telomerase is an RNP that synthesizes the 3' ends of linear chromosomes and is an important regulator of telomere length. It contains a single long non-coding telomerase RNA (TER), telomerase reverse transcriptase (TERT), and other proteins that vary among organisms. Recent progress in structural biology of telomerase includes reports of the first cryo-electron microscopy structure of telomerase, from Tetrahymena, new crystal structures of TERT domains, telomerase RNA structures and models, and identification in Tetrahymena telomerase holoenzyme of human homologues of telomere-associated proteins that have provided a more unified view of telomerase interaction at telomeres as well as insights into the role of telomerase RNA in activity and assembly...
July 18, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28732164/electrochemical-intercalation-of-mg-2-into-anhydrous-and-hydrated-crystalline-tungsten-oxides
#13
Ruocun Wang, Ching-Chang Chung, Yang Liu, Jacob L Jones, Veronica Augustyn
The reversible intercalation of multivalent cations, especially Mg(2+), into a solid-state electrode is an attractive mechanism for next-generation energy storage devices. These reactions typically exhibit poor kinetics due to a high activation energy for interfacial charge-transfer and slow solid-state diffusion. Interlayer water in V2O5 and MnO2 has been shown to improve Mg(2+) intercalation kinetics in non-aqueous electrolytes. Here, the effect of structural water on Mg(2+) intercalation in non-aqueous electrolytes is examined in crystalline WO3 and the related hydrated and layered WO3·nH2O (n = 1, 2)...
July 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28732068/effects-of-liver-stage-clearance-by-primaquine-on-gametocyte-carriage-of-plasmodium-vivax-and-p-falciparum
#14
Rahel Wampfler, Natalie E Hofmann, Stephan Karl, Inoni Betuela, Benson Kinboro, Lina Lorry, Mariabeth Silkey, Leanne J Robinson, Ivo Mueller, Ingrid Felger
BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses. METHODS: Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo...
July 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28732056/inferring-microbial-interactions-in-thermophilic-and-mesophilic-anaerobic-digestion-of-hog-waste
#15
Grace Tzun-Wen Shaw, An-Chi Liu, Chieh-Yin Weng, Chu-Yang Chou, Daryi Wang
Anaerobic digestion (AnD) is a microbiological process that converts organic waste materials into biogas. Because of its high methane content, biogas is a combustible energy source and serves as an important environmental technology commonly used in the management of animal waste generated on large animal farms. Much work has been done on hardware design and process engineering for the generation of biogas. However, little is known about the complexity of the microbiology in this process. In particular, how microbes interact in the digester and eventually breakdown and convert organic matter into biogas is still regarded as a "black box...
2017: PloS One
https://www.readbyqxmd.com/read/28732031/breast-tissue-ablation-with-irreversible-electroporation-in-rabbits-a-safety-and-feasibility-study
#16
Wenlong Zhang, Wanning Wang, Wei Chai, Xiaomei Luo, Jiannan Li, Jian Shi, Liqi Bi, Lizhi Niu
BACKGROUND AND AIM: Irreversible electroporation (IRE) was confirmed to control several solid tumors effectively in vivo. Our preclinical study aimed to assess the feasibility and safety of IRE in the breast of rabbit. METHODS: Thirty New Zealand white rabbits were randomly divided into 3 groups of 10 rabbits (control group, IRE group A, and B). Two mono-electrode needles were inserted into the breast tissue by percutaneous puncture. Electrocardiogram and vital signs were monitored before, during, and after ablation...
2017: PloS One
https://www.readbyqxmd.com/read/28732007/a-data-driven-modeling-approach-to-identify-disease-specific-multi-organ-networks-driving-physiological-dysregulation
#17
Warren D Anderson, Danielle DeCicco, James S Schwaber, Rajanikanth Vadigepalli
Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28731736/enhancing-entropy-and-enthalpy-fluctuations-to-drive-crystallization-in-atomistic-simulations
#18
Pablo M Piaggi, Omar Valsson, Michele Parrinello
Crystallization is a process of great practical relevance in which rare but crucial fluctuations lead to the formation of a solid phase starting from the liquid. As in all first order first transitions, there is an interplay between enthalpy and entropy. Based on this idea, in order to drive crystallization in molecular simulations, we introduce two collective variables, one enthalpic and the other entropic. Defined in this way, these collective variables do not prejudge the structure into which the system is going to crystallize...
July 7, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28731733/experimental-realization-of-type-ii-dirac-fermions-in-a-pdte_-2-superconductor
#19
Han-Jin Noh, Jinwon Jeong, En-Jin Cho, Kyoo Kim, B I Min, Byeong-Gyu Park
A Dirac fermion in a topological Dirac semimetal is a quadruple-degenerate quasiparticle state with a relativistic linear dispersion. Breaking either time-reversal or inversion symmetry turns this system into a Weyl semimetal that hosts double-degenerate Weyl fermion states with opposite chiralities. These two kinds of quasiparticles, although described by a relativistic Dirac equation, do not necessarily obey Lorentz invariance, allowing the existence of so-called type-II fermions. The recent theoretical discovery of type-II Weyl fermions evokes the prediction of type-II Dirac fermions in PtSe_{2}-type transition metal dichalcogenides, expecting experimental confirmation...
July 7, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28731705/reversible-self-assembly-of-degradable-polymersomes-with-upper-critical-solution-temperature-in-water
#20
Thomas Wolf, Timo Rheinberger, Johanna Simon, Frederik R Wurm
Temperature-induced self-assembly of block copolymers allows the formation of smart nanodimensional structures. Mostly, non-degradable LCST segments are applied to prepare such dynamic aggregates. However, degradable UCST block copolymers that would allow the swelling or disassembly at elevated temperatures with eventual backbone hydrolysis have not been reported to date. We present the first well-defined degradable poly(phosphonate)s with adjustable UCST. The organocatalytic anionic ring-opening copolymerization of 2-alkyl-2-oxo-1,3,2-dioxaphospholanes provided functional polymers with excellent control over molecular weight and copolymer composition...
July 21, 2017: Journal of the American Chemical Society
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