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Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Marthe Lefevre, Yann Klinger, Mahmoud Al-Qaryouti, Maryline Le Béon, Khaled Moumani
Temporal distribution of earthquakes is key to seismic hazard assessment. However, for most fault systems shortness of large earthquake catalogues makes this assessment difficult. Its unique long earthquake record makes the Dead Sea fault (DSF) exceptional to test earthquake behaviour models. A paleoseismological trench along the southern section of the DSF, revealed twelve surface-rupturing earthquakes during the last 8000 years, of which many correlate with past earthquakes reported in historical chronicles...
March 14, 2018: Scientific Reports
Sean M McClure, Patrick L Ahl, Jeffrey T Blue
PURPOSE: The purpose was to evaluate DSF for high throughput screening of protein thermal stability (unfolding/ aggregation) across a wide range of formulations. Particular focus was exploring PROTEOSTAT® - a commercially available fluorescent rotor dye - for detection of aggregation in surfactant containing formulations. Commonly used hydrophobic dyes (e.g. SYPRO™ Orange) interact with surfactants, complicating DSF measurements. METHODS: CRM197 formulations were prepared and analyzed in standard 96-well plate rT-PCR system, using SYPRO™ Orange and PROTEOSTAT® dyes...
March 5, 2018: Pharmaceutical Research
Linlin Miao, Jia Su, Xuezhi Zhuo, Lifeng Luo, Yihan Kong, Jingxin Gou, Tian Yin, Yu Zhang, Haibing He, Xing Tang
The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethyleneglycol)-b-poly(lactide-co-glycolide)/poly(ε-caprolactone) (mPEG5k-b-PLGA2k/PCL3.4k) micelles were developed for encapsulation of DSF -by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed...
March 5, 2018: Molecular Pharmaceutics
Xi Tang, Yongzhao Guo, Bo Jiang, Sitong Liu
Increasing attention has been paid to the anammox community for its significant function in high-efficiency wastewater treatment. However, bacterial interaction in terms of bacterial communication is still elusive. This study firstly explored the intra- and interspecific communication of bacteria in the anammox community using metagenomic sequence data obtained during bioreactor operation. We verified the existence of multiple bacterial communication gene (BCG) subtypes by alignment with the constructed BCG database containing 11 identified gene subtypes...
February 28, 2018: Water Research
Li Liu, Tao Li, Xing-Jun Cheng, Cui-Ting Peng, Chang-Cheng Li, Li-Hui He, Si-Min Ju, Ning-Yu Wang, Ting-Hong Ye, Mao Lian, Qing-Jie Xiao, Ying-Jie Song, Yi-Bo Zhu, Luo-Ting Yu, Zhen-Ling Wang, Rui Bao
DspI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, was proposed to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule in the pathogen Pseudomonas aeruginosa (P. aeruginosa). The present study provided a structural basis for the dehydration reaction mechanism of DspI during CDA synthesis. Structural analysis reveals that Glu126, Glu146, Cys127, Cys131 and Cys154 are important for its enzymatic function. Moreover, we show that the deletion of dspI results in a remarkable decreased in the pyoverdine production, flagella-dependent swarming motility, and biofilm dispersion as well as attenuated virulence in P...
March 2, 2018: Scientific Reports
Imran Shair Mohammad, Wei He, Lifang Yin
PURPOSE: A multidrug resistance (MDR) modulator, disulfiram (DSF), was incorporated into pure paclitaxel (PTX) nanoparticles to construct a smart paclitaxel-disulfiram nanococrystals (PTX-DSF Ns) stabilized by β-lactoglobulin (β-LG), with the aim to reverse MDR and therefore enhnce cytotoxicity towards Taxol-resistant A549 cells (A549/TAX). METHOD: PTX-DSF Ns was prepared by antisolvent precipitation method. Flow cytometry was used to determine the cell uptake, drug efflux inhibition, cell cycle phase arrest and apoptosis...
February 27, 2018: Pharmaceutical Research
Yodpong Chantarasorn, Settapong Techalertsuwan, Pongsavit Siripanthong, Anurak Tamerug
PURPOSE: The purpose of this study is to describe a new technique for small-incision scleral fixation of intraocular lens (IOL) using double 10-0 polypropylene sutures, and to report the outcomes of IOL position compared with intrascleral IOL fixation at 12-month follow-up. STUDY DESIGN: A retrospective comparative study. METHOD: This new technique, called double sutured scleral fixated-IOL (DSF-IOL), was created to help with long-term knots strengthening by applying double sutures to each IOL haptic using an augmented Clove-hitch knot instead of the conventional knots tied by single suture...
February 20, 2018: Japanese Journal of Ophthalmology
Ning Meng, Hua Tang, Hao Zhang, Chengshi Jiang, Li Su, Xiao Min, Wannian Zhang, Hua Zhang, Zhenyuan Miao, Wen Zhang, Chunlin Zhuang
Small-molecule inhibitors that block the Keap1-Nrf2 protein-protein interactions are being intensely pursued as a new therapeutic strategy for oxidative stress-related diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, inflammation and myocarditis. However, there are not enough studies on antioxidant treatments using small molecules in myocarditis. We herein provided a series of novel hydronaphthoquinones as the Keap1-Nrf2 interaction inhibitors targeting LPS-induced myocarditis both in vitro and in vivo...
February 8, 2018: Free Radical Biology & Medicine
Hanumantha Rao Madala, Surendra R Punganuru, Francis Ali-Osman, Ruiwen Zhang, Kalkunte S Srivenugopal
There is great interest in repurposing disulfiram (DSF), a rapidly metabolizing nontoxic drug, for brain cancers and other cancers. To overcome the instability and low therapeutic efficacy, we engineered passively-targeted DSF-nanoparticles (DSFNPs) using biodegradable monomethoxy (polyethylene glycol) d,l-lactic-co-glycolic acid (mPEG-PLGA) matrix. The physicochemical properties, cellular uptake and the blood brain-barrier permeability of DSFNPs were investigated. The DSFNPs were highly stable with a size of ∼70 nm with a >90% entrapment...
January 9, 2018: Oncotarget
Samuel Askin, Thomas E H Bond, Alanna E Sorenson, Morgane J J Moreau, Helma Antony, Rohan A Davis, Patrick M Schaeffer
High-throughput differential scanning fluorimetry of GFP-tagged proteins (HT-DSF-GTP) was applied for the identification of novel enzyme inhibitors acting by a mechanism termed: selective protein unfolding (SPU). Four different protein targets were interrogated with the same library to identify target-selective hits. Several hits selectively destabilized bacterial biotin protein ligase. Structure-activity relationship data confirmed a structure-dependent mechanism of protein unfolding. Simvastatin and altenusin were confirmed to irreversibly inactivate biotin protein ligase...
January 29, 2018: Chemical Communications: Chem Comm
Iftekhar Hassan, Azmat Ali Khan, Shazia Aman, Wajhul Qamar, Hossam Ebaid, Jameel Al-Tamimi, Ibrahim M Alhazza, Ahmed M Rady
The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions...
January 26, 2018: Scientific Reports
Ponraj K Sundaram, Pawan Kumar Jain
Elevation of a depressed skull fracture (DSF) overlying a venous sinus is generally avoided due to risk of sinus injury. Rarely, the sinus may be compressed by the fractured segment, causing intracranial hypertension (IH) or encephalopathy and can only be diagnosed with cerebral angiography or MR imaging techniques. The posterior third of the superior sagittal sinus (SSS) was found involved in all the reported cases. There is no consensus on its management, but most patients did not have any sinus thrombosis and improved after elevation of the compressing DSF alone...
January 24, 2018: British Journal of Neurosurgery
Yu V Arkhipov, A Askaruly, A E Davletov, D Yu Dubovtsev, Z Donkó, P Hartmann, I Korolov, L Conde, I M Tkachenko
Dynamic characteristics of strongly coupled classical one-component Coulomb and Yukawa plasmas are obtained within the nonperturbative model-free moment approach without any data input from simulations so that the dynamic structure factor (DSF) satisfies the first three nonvanishing sum rules automatically. The DSF, dispersion, decay, sound speed, and other characteristics of the collective modes are determined using exclusively the static structure factor calculated from various theoretical approaches including the hypernetted chain approximation...
July 28, 2017: Physical Review Letters
Mirella Bucci
No abstract text is available yet for this article.
January 16, 2018: Nature Chemical Biology
Hristo Svilenov, Uroš Markoja, Gerhard Winter
Various stability indicating techniques find application in the early stage development of novel therapeutic protein candidates. Some of these techniques are used to select formulation conditions that provide high protein physical stability. Such approach is highly dependent on the reliability of the stability indicating technique used. In this work, we present a formulation case study where we evaluate the ability of differential scanning fluorimetry (DSF) and isothermal chemical denaturation (ICD) to predict the physical stability of a model monoclonal antibody during accelerated stability studies...
January 9, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Sofie Depluverez, Simon Daled, Stijn De Waele, Sören Planckaert, Jolien Schoovaerts, Dieter Deforce, Bart Devreese
Burkholderia cenocepacia is an opportunistic pathogen that is commonly isolated from patients with cystic fibrosis (CF). Several virulence factors have been identified, including extracellular enzymes that are secreted by type II and type VI secretion systems. The activity of these secretion systems is modulated by quorum sensing. Apart from the classical acylhomoserine lactone quorum sensing, B. cenocepacia also uses the diffusible signal factor system (DSF) i.e. 2-undecenoic acid derivatives that are recognized by specific receptors resulting in changes in biofilm formation, motility and virulence...
January 11, 2018: Rapid Communications in Mass Spectrometry: RCM
Rupal Jivan, Jade Peres, Leonard Howard Damelin, Reubina Wadee, Robin Bruce Veale, Sharon Prince, Demetra Mavri-Damelin
Oesophageal squamous cell carcinoma (OSCC) is highly prevalent in developing countries but there has been little recent progress into efficacious yet affordable treatment strategies. Drug repurposing is one attractive approach for cancer therapy. Disulfiram (DSF), used to treat alcoholism, inhibits cancer growth and we previously found that DSF perturbs protein degradation/turnover pathways in vitro. This was enhanced by combining DSF with the anti-diabetic drug metformin (Met). Here, we investigated DSF with/without Met, against OSCC in vivo...
March 28, 2018: Cancer Letters
Sang Yun Kim, So Hyun Nam, Jae Seok Min, Min Chan Kim
Purpose: Duodenal stump fistula (DSF) is a serious complication after gastrectomy for gastric cancer. Although risk evaluation and management of DSF were presented by some investigators, there was no technical attempt has been made to prevent DSF during laparoscopic gastrectomy until now. Methods: Consecutive 99 patients were enrolled from April 2014 to February 2016 in 2 institutes. All patients were performed laparoscopic gastrectomy for gastric cancer. After cutting of duodenal stump, laparoscopic reinforcement suture (LARS) commenced with continuous invagination method or interrupted method by barbed suture...
December 2017: Annals of Surgical Treatment and Research
Moe Wehbe, Armaan K Malhotra, Malathi Anantha, Cody Lo, Wieslawa H Dragowska, Nancy Dos Santos, Marcel B Bally
Clioquinol (CQ) is an FDA-approved topical antifungal agent known to kill cancer cells. This facilitated the initiation of clinical trials in patients with refractory hematologic malignancies. These repurposing efforts were not successful; this was likely due to low intracellular levels of the drug owing to poor absorption and rapid metabolism upon oral administration. CQ forms a sparingly soluble copper complex (Cu(CQ)2) that exhibits enhanced anticancer activity in some cell lines. We have utilized a novel method to synthesize Cu(CQ)2 inside liposomes, an approach that maintains the complex suspended in solution and in a format suitable for intravenous administration...
December 16, 2017: Drug Delivery and Translational Research
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