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Ziqian Wang, Wenjie Xu, Ting Song, Zongwei Guo, Lu Liu, Yudan Fan, Anhui Wang, Zhichao Zhang
Based on a known selective Mcl-1 inhibitor, 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylic acid, we applied a fragment-based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl-1 over the Bcl-2 protein. After we deconstructed the 1H-indole-2-carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1-position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X-ray crystallography...
December 2, 2016: Archiv der Pharmazie
Jose Diaz-Romero, Sibylle Kürsener, Sandro Kohl, Dobrila Nesic
During monolayer expansion, a necessary step in autologous chondrocyte implantation, human articular chondrocytes (HAC) dedifferentiate and lose their capacity to produce stable hyaline cartilage. Determining HAC potency and learning how to trigger their redifferentiation would improve cell-based cartilage regeneration therapies. We previously identified S100B and S100A1 proteins as markers of HAC redifferentiation potential. Here, we aimed to: (i) demonstrate a correlation between S100B + A1-positive HAC in monolayer culture and their neochondrogenesis capacity in pellet culture; (ii) develop an S100B + A1 cell-based ELISA, and (iii) prove that S100B + A1 induction in HAC increases their chondrogenic capacity...
November 11, 2016: Journal of Cellular Physiology
C Kruse, P Eiken, P Vestergaard
: Clustering analysis can identify subgroups of patients based on similarities of traits. From data on 10,775 subjects, we document nine patient clusters of different fracture risks. Differences emerged after age 60 and treatment compliance differed by hip and lumbar spine bone mineral density profiles. INTRODUCTION: The purposes of this study were to establish and quantify patient clusters of high, average and low fracture risk using an unsupervised machine learning algorithm...
November 16, 2016: Osteoporosis International
Aijuan Zhou, Jiaguang Zhang, Kaili Wen, Zhihong Liu, Guoying Wang, Wenzong Liu, Aijie Wang, Xiuping Yue
BACKGROUND: Volatile fatty acids (VFAs) production from waste activated sludge (WAS) digestion is constrained by unbalanced nutrient composition (low carbon-to-nitrogen ratio). Characteristics conditioning by extra carbon sources, normally in the mixture of raw solid, has been reported to be an efficient approach to enhance WAS acidification. However, little attention has been paid to the contributions of other adjustment forms. Moreover, the corresponding ecological estimation has not been investigated yet...
2016: Biotechnology for Biofuels
Rui C Pereira, Daniela Martinelli, Ranieri Cancedda, Chiara Gentili, Alessandro Poggi
Autologous chondrocyte implantation is the current gold standard cell therapy for cartilage lesions. However, in some instances, the heavily compromised health of the patient can either impair or limit the recovery of the autologous chondrocytes and a satisfactory outcome of the implant. Allogeneic human articular chondrocytes (hAC) could be a good alternative, but the possible immunological incompatibility between recipient and hAC donor should be considered. Herein, we report that allogeneic hAC inhibited T lymphocyte response to antigen-dependent and -independent proliferative stimuli...
2016: Frontiers in Immunology
L Macfarlane, T Parkin, I Ramsey
The adrenocorticotrophic hormone (ACTH) stimulation test has been widely used and recommended as a monitoring method for dogs receiving trilostane; however, it has never been validated for this purpose. As trilostane is relatively short acting, there could be variation in the results depending on the time since the last dose of trilostane and results may not reflect clinical control. Additionally, tetracosactide (synthetic ACTH) can be expensive in some countries and has had limited availability throughout much of Europe...
November 1, 2016: Veterinary Record
Gang Wang, Congdi Shang, Li Wang, Haonan Peng, Shiwei Yin, Yu Fang
A pyrenyl unit (Py) was chemically connected to a perylene bisimide moiety (PBI) via a long and flexible linker, 4,7,10-trioxa-1,13-tridecanediamine (TOA), resulting in a fluorescent dyad, PBI-TOA-Py. UV-Vis absorption and fluorescence studies revealed that the two fluorescent units of PBI-TOA-Py behave independently. However, efficient Förster Resonance Energy Transfer (FRET) from the Py unit to the PBI moiety in solution state was also observed. Temperature and solvent effect studies demonstrated that the energy transfer efficiency is highly dependent upon solution temperature and solvent nature...
October 31, 2016: Journal of Physical Chemistry. B
Dandan Wang, Guoguang Chen, Lili Ren
Amiodarone hydrochloride (AMD) is used in the treatment of a wide range of cardiac tachyarrhythmias, including both ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). The objectives of this study were to improve the solubility and bioavailability in fasted state and to reduce the food effect of AMD by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD). The complex was prepared through a saturated water solution combined with the freeze-drying method and then characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry...
October 18, 2016: AAPS PharmSciTech
Longbin Zheng, Ying Li, Xuesong Li, Jiayuan Kou, Zhaoyu Zhong, Yueqing Jiang, Zhongni Liu, Ye Tian, Liming Yang
BACKGROUND/AIMS: Sonodynamic therapy (SDT) is considered a new approach for the treatment of atherosclerosis. We previously confirmed that hydroxyl acetylated curcumin (HAC) was a sonosensitizer. In this study, we investigated the mechanism of THP-1 macrophage apoptosis and autophagy induced by HAC mediated SDT (HAC-SDT). METHODS: Cell viability was measured using a CCK-8 assay. Laser scanning confocal microscopy was used to measure the levels of intracellular reactive oxygen species (ROS), sub-cellular HAC localization, BAX and cytochrome C translocation, LC3 expression, monodansylcadaverine staining and Dil-labeled oxidized low density lipoprotein (Dil-ox-LDL) uptake...
October 17, 2016: Cellular Physiology and Biochemistry
Zhiyong Xie, Juncui Xu, Fazhi Xie, Shiquan Xiong
A reduced graphene oxide (rGO)/Fe3O4 composites modified screen-printed carbon electrode (SPCE) was used to determinate As(III) in a HAc-NaAc buffer solution. The rGO/Fe3O4 composites were prepared by a simple and one-pot synthesis method, and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (SEM), FT-IR and Raman spectra. The electrochemical behaviors of the composite electrode were characterized by cycle voltammetry and electrochemical impedance spectroscopy. The experimental parameters, such as supporting electrolyte, solution pH, deposition potential, deposition time were optimized, respectively...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Kate Grossman, Mary Beth Beasley, Sidney S Braman
RATIONALE: Hepatoid adenocarcinoma (HAC) is a rare malignant lung tumor that histologically resembles typical hepatocellular carcinoma (HCC) when it is metastatic to the lung. To date, this clinical entity has not been highlighted in the pulmonary literature. OBJECTIVE: We present a review of all known cases of HAC, including the relevant clinical and histopathological features important for pulmonologists. MEASUREMENTS AND MAIN RESULTS: The purpose of this report is to present a new case of HAC, with typical clinical and histologic features of this malignancy, and to summarize findings of previously reported cases...
October 2016: Respiratory Medicine
Jae Hac Ko, Zeyu Ma, Xiao Jin, Qiyong Xu
Research has been conducted to investigate the effects of daily aeration frequency on leachate quality and waste settlement in simulated hybrid landfill bioreactors. Four laboratory-scale reactors were constructed and operated for about 10 months to simulate different bioreactor operations, including one anaerobic bioreactor and three hybrid bioreactors with different aeration frequencies (1, 2, and 4 times per day). Chemical oxygen demand (COD) and biochemical oxygen demand (BOD5) reduced more than 96% of the initial concentrations in all aerated bioreactors...
September 15, 2016: Journal of the Air & Waste Management Association
Roberta Pascolutti, Xianqiang Sun, Joseph Kao, Roy L Maute, Aaron M Ring, Gregory R Bowman, Andrew C Kruse
The immune checkpoint receptor PD-1 and its ligand, PD-L1, have emerged as key regulators of anti-tumor immunity in humans. Recently, we reported an ultra-high-affinity PD-1 mutant, termed high-affinity consensus (HAC) PD-1, which shows superior therapeutic efficacy in mice compared with antibodies. However, the molecular details underlying the action of this agent remain incompletely understood, and a molecular view of PD-1/PD-L1 interactions in general is only beginning to emerge. Here, we report the structure of HAC PD-1 in complex with PD-L1, showing that it binds PD-L1 using a unique set of polar interactions...
October 4, 2016: Structure
Nathalie Mayer, Silvia Lopa, Giuseppe Talò, Arianna B Lovati, Marielle Pasdeloup, Stefania A Riboldi, Matteo Moretti, Frédéric Mallein-Gerin
Articular cartilage has poor healing ability and cartilage injuries often evolve to osteoarthritis. Cell-based strategies aiming to engineer cartilaginous tissue through the combination of biocompatible scaffolds and articular chondrocytes represent an alternative to standard surgical techniques. In this context, perfusion bioreactors have been introduced to enhance cellular access to oxygen and nutrients, hence overcoming the limitations of static culture and improving matrix deposition. Here, we combined an optimized cocktail of soluble factors, the BIT (BMP-2, Insulin, Thyroxin), and clinical-grade collagen sponges with a bidirectional perfusion bioreactor, namely the oscillating perfusion bioreactor (OPB), to engineer in vitro articular cartilage by human articular chondrocytes (HACs) obtained from osteoarthritic patients...
2016: PloS One
Ltk Do, M Wittayarat, T Terazono, Y Sato, M Taniguchi, F Tanihara, T Takemoto, Y Kazuki, K Kazuki, M Oshimura, T Otoi
The current applications for cat cloning include production of models for the study of human and animal diseases. This study was conducted to investigate the optimal fusion protocol on in vitro development of transgenic cloned cat embryos by comparing duration of electric pulse. Cat fibroblast cells containing a human artificial chromosome (HAC) vector were used as genetically modified nuclear donor cells. Couplets were fused and activated simultaneously with a single DC pulse of 3.0 kV/cm for either 30 or 60 μs...
December 2016: Reproduction in Domestic Animals, Zuchthygiene
Ang Ren, Rui Liu, Zhi-Gang Miao, Xue Zhang, Peng-Fei Cao, Tian-Xi Chen, Chen-Yang Li, Liang Shi, Ai-Liang Jiang, Ming-Wen Zhao
Ganoderma lucidum is one of the most important medicinal fungi, but the lack of basic study on the fungus has hindered the further development of its value. To investigate the roles of the redox system in G. lucidum, acetic acid (HAc) was applied as a reactive oxygen species (ROS) stress inducer, and hydrogen-rich water (HRW) was used to relieve the ROS stress in this study. Our results demonstrate that the treatment of 5% HRW significantly decreased the ROS content, maintained biomass and polar growth morphology of mycelium, and decreased secondary metabolism under HAc-induced oxidative stress...
August 23, 2016: Environmental Microbiology
Kaczorowska-Hac Barbara, Luszczyk Marcin, Antosiewicz Jedrzej, Ziolkowski Wieslaw, Adamkiewicz-Drozynska Elzbieta, Mysliwiec Malgorzata, Milosz Ewa, Kaczor Jan Jacek
The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin...
December 2016: Annals of Hematology
Jessica S Chen, Ron A Adelman
BACKGROUND AND OBJECTIVE: Timely treatment of age-related macular degeneration (AMD) is integral in improving outcomes. To catch choroidal neovascularization as soon as possible, patients should monitor vision at home. The objective of this study is to explore the Hyperacuity App (HAC) as a screen for progression of disease in AMD. PATIENTS AND METHODS: A cross-sectional, single-center study was performed with 33 subjects. Consent was obtained and patient information was protected in accordance with the protocol approved by the Yale Human Research Protection Program...
August 1, 2016: Ophthalmic Surgery, Lasers & Imaging Retina
Kayvan Mohkam, Florian Fanget, Benjamin Darnis, Brahim Harbaoui, Agnès Rode, Bruno Charpiat, Christian Ducerf, Jean-Yves Mabrut
BACKGROUND: Doppler ultrasound (DUS) arterial abnormalities (DAA) after orthotopic liver transplantation (OLT) often represent a sign of hepatic artery (HA) complication (HAC). The standard management of DAA involves computed tomographic angiography (CTA) followed by invasive vascular intervention (IVI) or observation. We evaluated the contribution of systemic vasodilators (SVD) to the management of DAA after OLT. METHODS: Between 2005 and 2015, 91 of 514 OLT recipients developed DAA (defined by HA resistive index [HARI] <0...
December 2016: Transplantation
Yong Wang, Liyuan Chai, Zhihui Yang, Mubarak Hussani, Ruiyang Xiao, Chongjian Tang
Ficus tikoua (F. tikoua) was a promising species for Antimony (Sb) phyto-remediation due to widely growing in mining area. However, little was known on its tolerance mechanisms towards Sb. The determination of the distribution and chemical speciation of Sb in F. tikoua is essential for understanding the mechanisms involved in Sb accumulation, transportation, and detoxification. The present study investigated the subcellular distribution and chemical forms of Sb in F. tikoua. The plant was exposed to different Sb concentrations (0, 30, 90 and 180 μmol/L) for 30 days...
August 19, 2016: International Journal of Phytoremediation
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