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https://www.readbyqxmd.com/read/29150953/new-algorithm-for-simulation-of-proteoglycan-loss-and-collagen-degeneration-in-the-knee-joint-data-from-the-osteoarthritis-initiative
#1
Mika E Mononen, Petri Tanska, Hanna Isaksson, Rami K Korhonen
Osteoarthritis is a harmful joint disease but prediction of disease progression is problematic. Currently, there is only one modeling framework which can be applied to predict the progression of knee osteoarthritis but it only considers degenerative changes in the collagen fibril network. Here, we have developed the framework further by considering all of the major tissue changes (proteoglycan content, fluid flow and collagen fibril network) occurring in osteoarthritis. While excessive levels of tissue stresses controlled degeneration of the collagen fibril network, excessive levels of tissue strains controlled the decrease in proteoglycan content and the increase in permeability...
November 18, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29150643/%C3%AE-eudesmol-an-oxygenized-sesquiterpene-stimulates-appetite-via-trpa1-and-the-autonomic-nervous-system
#2
Kazuaki Ohara, Takafumi Fukuda, Yuko Ishida, Chika Takahashi, Rena Ohya, Mikio Katayama, Kunitoshi Uchida, Makoto Tominaga, Katsuya Nagai
Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150642/rescue-of-pfos-induced-human-sertoli-cell-injury-by-overexpressing-a-p-fak-y407e-phosphomimetic-mutant
#3
Haiqi Chen, Ying Gao, Dolores D Mruk, Xiang Xiao, Constance M John, Paul J Turek, Wing-Yee Lui, Will M Lee, Bruno Silvestrini, C Yan Cheng
PFOS induces Sertoli cell injury using testicular cells isolated from rodent testes, but it remains unknown if PFOS has similar effects in humans. Herein, we maintained human Sertoli cells in a mitotically active state in vitro, thus enabling transfection experiments that altered gene expression to explore the molecular mechanism(s) underlying toxicant-induced cell injury. Human Sertoli cells obtained from men at ages 15, 23, 36 and 40 were cultured in vitro. These differentiated Sertoli cells remained mitotically active when cultured in the presence of 10% FBS (fetal bovine serum), with a replication time of ~1-3 weeks...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150544/estimation-of-circulating-drug-metabolite-exposure-in-human-using-in-vitro-data-and-physiologically-based-pharmacokinetic-modelling-example-of-a-high-metabolite-parent-drug-ratio
#4
R Scott Obach, Jian Lin, Emi Kimoto, Sridhar Duvvuri, Timothy Nicholas, Eugene P Kadar, Larry M Tremaine, Aarti Sawant Basak
TBPT ((R)-4-((4-(((4-((tetrahydrofuran-3-yl)oxy)benzo[d]isoxazol-3-yl)oxy)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-ol), a serotonin-4 receptor partial agonist, is metabolized to two metabolites: an N-dealkylation product (M1) and a cyclized oxazolidine structure (M2). After administration to humans, the exposure to M1 was low and the exposure to M2 was high, relative to the parent drug, despite this being the opposite in vitro. In this study, projection of the plasma metabolite/parent ratios for M1 and M2 was attempted, using in vitro metabolism, binding, and permeability data in static and dynamic PBPK models...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#5
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149941/pathophysiology-of-septic-shock
#6
REVIEW
James A Russell, Barret Rush, John Boyd
Fundamental features of septic shock are vasodilation, increased permeability, hypovolemia, and ventricular dysfunction. Vasodilation owing to increased nitric oxide and prostaglandins is treated with vasopressors (norepinephrine first). Increased permeability relates to several pathways (Slit/Robo4, vascular endothelial growth factor, angiopoietin 1 and 2/Tie2 pathway, sphingosine-1-phosphate, and heparin-binding protein), some of which are targets for therapies. Hypovolemia is common and crystalloid is recommended for fluid resuscitation...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149574/transscleral-passive-and-iontophoretic-transport-theory-and-analysis
#7
S Kevin Li, Jinsong Hao
INTRODUCTION: The sclera is considered the "static barrier," a main barrier for transscleral drug delivery. The characterization of passive and iontophoretic transport across the sclera in vitro is the first step towards our ability to predict transscleral drug delivery. Although previous studies have investigated this topic, the quantitative structure permeation relationships (QSPR) for passive and iontophoretic transscleral transport are not available. AREAS COVERED: This review evaluated previous passive permeation and iontophoresis results of transscleral transport in vitro and examined QSPR for transscleral permeation of small permeants and macromolecules...
November 17, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#8
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148852/sildenafil-citrate-improves-the-delivery-and-anticancer-activity-of-doxorubicin-formulations-in-a-mouse-model-of-breast-cancer
#9
Khaled Greish, Maryam Fateel, Sara Abdelghany, Nanitha Rachel, Houman Alimoradi, Moiz Bakhiet, Ahmed Alsaie
Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of Sildenafil on tumor vasculatures could result in an improvement of anticancer drug concentration in tumor tissues, and hence improve its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro...
November 17, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29148850/atad2-in-cancer-a-pharmacologically-challenging-but-tractable-target
#10
Muzammal Hussain, Yang Zhou, Yu Song, H M Adnan Hameed, Hao Jiang, Yaoquan Tu, Jiancun Zhang
ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a "difficult to drug" or "least druggable" target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148846/preparation-and-evaluation-of-curcumin-loaded-self-assembled-micelles
#11
Lu-Lu Wang, Dan-Dan He, Shu-Xia Wang, Yun-Hao Dai, Jian-Ming Ju, Cheng-Lei Zhao
Objective Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. Methods Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method...
November 17, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29148277/care-ful-definition-of-consent
#12
Emese Ilyes
This proposal is an attempt to intervene in psychology's violent past and troubling present by calling for notions of "care-ful" practice, compelling us to recognize and celebrate the permeable, porous, and flexible boundaries between bodies and selves. With this heuristic of care, this article hopes to trouble the separation between rigor and relational responsibility, to trouble objectivism, to oust the illusion of cool rationality, and to offer an affective understanding of consent that refuses to deny sexuality in bodies oppressed with the label of intellectually disabled...
November 1, 2017: Journal of Health Psychology
https://www.readbyqxmd.com/read/29148103/extracytoplasmic-function-sigma-factor-%C3%AF-d-confers-resistance-to-environmental-stress-by-enhancing-mycolate-synthesis-and-modifying-peptidoglycan-structures-in-corynebacterium-glutamicum
#13
Koichi Toyoda, Inui Masayuki
Mycolates are α-branched, β-hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here we report that the extracytoplasmic function sigma factor σ(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder...
November 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29148026/the-influence-of-hemodialysis-membrane-permeability-on-serum-procalcitonin-values-in-patients-on-maintenance-hemodialysis
#14
Taoufiq Aatif, Yassir Zajjari, Anas Jeaidi
BACKGROUND: Procalcitonin (PCT) has emerged as a marker of infection and it could be useful for detection of systemic bacterial infections in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The aim of this study was to assess the influence of HD membrane permeability to PCT serum levels in noninfected HD patients on maintenance HD. METHODS: In a prospective comparative study, we measured PCT serum levels and C reactive protein (CRP) before and after HD in 36 sessions (18 sessions of HD with low-flux = Group L; and 18 sessions with high flux membranes = Group H), in 18 chronic HD patients without history of infection...
November 9, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/29147695/synthesis-of-an-ethyleneimine-tetrahedral-dna-nanostructure-complex-and-its-potential-application-as-a-multi-functional-delivery-vehicle
#15
Taoran Tian, Tao Zhang, Tengfei Zhou, Shiyu Lin, Sirong Shi, Yunfeng Lin
Nowadays, DNA nanostructures are extensively researched for their biocompatibility, editable functionality, and structural stability. Tetrahedral DNA nanostructures (TDNs), widely known for their membrane permeability, are regarded as potential candidates for drug delivery. However, the stability and membrane permeability of TDNs call for further enhancement if in vivo usage is ascribed. To overcome the drawbacks of TDNs, ethylene imine (PEI, 25 kDa, branched)-a classic cationic polymer in the field of gene delivery-was applied...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29147575/cell-death-and-cell-lysis-are-separable-events-during-pyroptosis
#16
Lucian DiPeso, Daisy X Ji, Russell E Vance, Jordan V Price
Although much insight has been gained into the mechanisms by which activation of the inflammasome can trigger pyroptosis in mammalian cells, the precise kinetics of the end stages of pyroptosis have not been well characterized. Using time-lapse fluorescent imaging to analyze the kinetics of pyroptosis in individual murine macrophages, we observed distinct stages of cell death and cell lysis. Our data demonstrate that cell membrane permeability resulting from gasdermin D pore formation is coincident with the cessation of cell movement, loss of mitochondrial activity, and cell swelling, events that can be uncoupled from cell lysis...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29147545/protein-labeling-for-live-cell-fluorescence-microscopy-with-a-highly-photostable-renewable-signal
#17
Nina G Bozhanova, Mikhail S Baranov, Natalia V Klementieva, Karen S Sarkisyan, Alexey S Gavrikov, Ilia V Yampolsky, Elena V Zagaynova, Sergey A Lukyanov, Konstantin A Lukyanov, Alexander S Mishin
We present protein-PAINT - the implementation of the general principles of PAINT (Point Accumulation for Imaging in Nanoscale Topography) for live-cell protein labeling. Our method employs the specific binding of cell-permeable fluorogenic dyes to genetically encoded protein tags. We engineered three mutants of the bacterial lipocalin Blc that possess different affinities to a fluorogenic dye and exhibit a strong increase in fluorescence intensity upon binding. This allows for rapid labeling and washout of intracellular targets on a time scale from seconds to a few minutes...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147515/stereochemistry-and-biological-activity-of-chlorinated-lipids-a-study-of-danicalipin-a-and-selected-diastereomers
#18
J Boshkow, S Fischer, A M Bailey, S Wolfrum, E M Carreira
The syntheses of (+)-16-epi- and (+)-11,15-di-epi-danicalipin A (2 and 3) are reported. The conformations of the parent diols 5 and 6 as well as the corresponding disulfates 2 and 3 were determined on the basis of J-based configuration analysis and supported by calculations. The impact of configuration on membrane permeability in Gram-negative bacteria and mammalian cell lines was assessed as well as cytotoxicity. Although diastereomer 2 showed similar behavior to natural (+)-danicalipin A (1), strikingly, the more flexible C11,C15-epimer 3 had no effect on permeability and proved equally or more toxic towards multiple cell lines...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147482/combined-postconditioning-with-ischemia-and-cyclosporine-a-restore-oxidative-stress-and-histopathological-changes-in-reperfusion-injury-of-diabetic-myocardium
#19
Reza Badalzadeh, Seyed Mahmoud Tabatabaei, Mustafa Mohammadi, Arash Khaki, Dariush Mohammadnezhad
Objectives: Chronic diabetes impedes cardioprotection in reperfusion injury and hence protecting the diabetic heart would have important outcomes. In this study, we evaluated whether combined postconditioning with ischemia and cyclosporine-A can restore oxidative stress and histopathological changes in reperfusion injury of the diabetic myocardium. Materials and Methods: Streptozocin-induced diabetic hearts and nondiabetic controls in eight subgroups (with or without receiving ischemic-postconditioning (IPostC), cyclosporine-A, an inhibitor of mitochondrial permeability transition, or both of them) suffered from 30 min regional ischemia followed by 45 min reperfusion on an isolated-heart Langendorff system...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29147086/edible-packaging-film-derived-from-mechanically-deboned-chicken-meat-proteins-effect-of-transglutaminase-on-physicochemical-properties
#20
Damla Yayli, Sadettin Turhan, Furkan Turker Saricaoglu
In this study, effect of transglutaminase (TGase) addition on physical, water barrier, optical and mechanical properties of mechanically deboned chicken meat protein (MDCM-P) films was investigated. When TGase was added to the films, the thickness increased, but the solubility decreased. Films treated with TGase exhibited higher water vapor permeability than control film (p<0.05). When TGase concentration increased, the L* values of films decreased, but a* and b* values increased. All films showed very good barrier properties against UV light...
2017: Korean Journal for Food Science of Animal Resources
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