Novel 3,4-Dihydroisocoumarins Inhibit Human P-gp and BCRP in Multidrug Resistant Tumors and Demonstrate Substrate Inhibition of Yeast Pdr5

In this study, the three natural compounds 6-methoxymellein (3), angelicoin B (4) and ellagic acid as well as nine novel 3,4-dihydroisocoumarins (Figure 1) were analyzed regarding their cytotoxicity in cancer cells and inhibition of the endogenously expressed human ABC transporters P-gp, BCRP, and MRP1 and of the yeast transporter Pdr5. For further insights into the mechanism of action, Pdr5 ATPase and substrate transport assays were performed. These results were complemented with molecular docking studies that indicate that differences in the inhibitory power of the investigated 3,4-dihydroisocoumarins with respect to P-gp-mediated transport result from differences in the compounds’ binding affinities to P-gp. FIGURE 1 Figure 1. Structures of natural and synthetic 3,4-dihydroisocoumarins. Materials and Methods Chemicals and Reagents A549 and HCT-15 cells were purchased from the German Collection of Microorganisms and Cell Cultures (Braunschweig, Germany) and H69AR cells from the American Type Culture Collection (Manassas, VA, United States). Dr. Erasmus Schneider (Wadsworth Center, New York State Department of Health, Albany, NY, United States) kindly provided the MCF-7/MX cells. Cell culture media and supplements were purchased from Thermo Fisher Scientific (Waltham, MA, United States). Yeast extract, peptone, and D-glucose were purchased from Carl Roth (Karlsruhe, Germany). Hoechst 33342, rhodamine 6G (R6G) and adenosine 5′-triphosphate (ATP)...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Publication date: December 2020Source: Social Science &Medicine, Volume 266Author(s): Trang Thu Do, Andrea Whittaker
Source: Social Science and Medicine - Category: Psychiatry & Psychology Source Type: research
You could consider this a follow-up to one of last week’s posts: Are You Most Loyal to Purpose or People? I want to share another way of framing the mindset of being loyal to purpose ahead of people, especially for those who’d prefer to shift into greater loyalty to purpose. Putting purpose first isn’t dehumanizing if you frame it a certain way – if your purpose actually involves serving people. If, however, your purpose is mainly self-centered, like if it’s based on individual achievements that will be of little or no benefit to others, then I think you’re more likely to run in...
Source: Steve Pavlina's Personal Development Blog - Category: Psychiatry & Psychology Authors: Tags: Abundance Values Source Type: blogs
Publication date: November 2020Source: Human Pathology: Case Reports, Volume 22Author(s): Susha Varghese, Timothy Helliwell, Chandrasekar Coonoor
Source: Human Pathology: Case Reports - Category: Pathology Source Type: research
Publication date: November 2020Source: Human Pathology: Case Reports, Volume 22Author(s): Shohei Matsuo, Yoshitane Tsukamoto, Eiichiro Mabuchi, Shunichi Negoro, Seiichi Hirota
Source: Human Pathology: Case Reports - Category: Pathology Source Type: research
Publication date: Available online 22 September 2020Source: Pathology - Research and PracticeAuthor(s): Yasamin Pahlavan, Mina Mohammadi Nasr, Elaheh Dalir Abdolahinia, Zahra Pirdel, Saiedeh Razi Soofiyani, Samaneh Siahpoush, Kazem Nejati
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Publication date: Available online 21 September 2020Source: Pathology - Research and PracticeAuthor(s): He Zhang, Yi Wang, Yanfeng Wang, Daoyuan Wu, Enguang Lin, Qingxin Xia
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Publication date: Available online 21 September 2020Source: Pathology - Research and PracticeAuthor(s): Yuichi Koyama, Teppei Morikawa, Yu Miyama, Jimpei Miyakawa, Taketo Kawai, Haruki Kume, Motoji Sawabe, Tetsuo Ushiku
Source: Pathology Research and Practice - Category: Pathology Source Type: research
This study aimed to evaluate the influence of loading frequency on the fatigue mechanical behavior of adhesively cemented polymer-infiltrated ceramic-network (PICN) and lithium disilicate (LD) simplified monolithic restorations. Thirty (30) disc-shaped specimens (Ø = 10 mm; thickness = 1.0 mm) of each ceramic material (PICN - Enamic, Vita Zahnfabrik or LD - IPS e.max CAD, Ivoclar Vivadent) were produced and adhesively cemented onto dentin analogue discs made of fiber and epoxy resin material (Ø = 10 mm; thickness = 2.0 mm). PICN and LD cemented assemblies were randomly ...
Source: Journal of the Mechanical Behavior of Biomedical Materials - Category: Materials Science Authors: Tags: J Mech Behav Biomed Mater Source Type: research
CONCLUSION: Within the limitations of the present study, attachments with PEEK and PEKK inserts combined with titanium patrices are favorable for long-term use, both for orthogonal and tilted implants. All three attachment systems showed a high variability of the retentive forces at baseline and for subsequent cycles. This should be taken into consideration for clinical use. PMID: 32957206 [PubMed - in process]
Source: Journal of the Mechanical Behavior of Biomedical Materials - Category: Materials Science Authors: Tags: J Mech Behav Biomed Mater Source Type: research
Abstract The present study evaluated the effect of the zirconia nanoparticles on the physical and mechanical properties of ZrO2-bearing Lithium Silicate (ZLS) glass-ceramics fabricated by SPS method. Flexural strength of the rectangular bar shapes, fracture toughness by indentation method, Vickers microhardness with a diamond pyramid indenter and, the relative density of the samples were measured. Statistical analysis was performed and Weibull failure probabilities were obtained. The results of flexural strength were analyzed with Weibull distribution analysis (95% confidence interval). According to Weibull analys...
Source: Journal of the Mechanical Behavior of Biomedical Materials - Category: Materials Science Authors: Tags: J Mech Behav Biomed Mater Source Type: research
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