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https://www.readbyqxmd.com/read/28728108/new-tacrine-dimers-with-antioxidant-linkers-as-dual-drugs-anti-alzheimer-s-and-antiproliferative-agents
#1
Jesús M Roldán-Peña, Daniel Alejandre-Ramos, Óscar López, Inés Maya, Irene Lagunes, José M Padrón, Luis Emiliano Peña-Altamira, Manuela Bartolini, Barbara Monti, Maria L Bolognesi, José G Fernández-Bolaños
We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28728086/nanostructured-lipid-systems-modified-with-waste-material-of-propolis-for-wound-healing-design-in-vitro-and-in-vivo-evaluation
#2
Hélen Cássia Rosseto, Lucas de Alcântara Sica de Toledo, Lizziane Maria Belloto de Francisco, Elisabetta Esposito, Yunsook Lim, Giuseppe Valacchi, Rita Cortesi, Marcos Luciano Bruschi
Propolis, a natural compound that can accelerate the wound healing process, is mainly used as ethanolic extract. The extractive solution may also be obtained from the propolis by-product (BP), transforming this waste material into a pharmaceutical active ingredient. Even if propolis does not show toxicity, when used as an extract over harmed skin or mucosa, the present ethanol content may be harmful to the tissue recovering, besides hindering the drug release. This study describes the development of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) as topical propolis delivery systems and the investigation of their in vitro and in vivo activities...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28691691/development-of-a-clay-based-bioink-for-3d-cell-printing-for-skeletal-application
#3
Tilman Ahlfeld, Gianluca Cidonio, David Kilian, Sarah Duin, Ashwini Rahul Akkineni, Jon I Dawson, Shoufeng Yang, Anja Lode, Richard Oreffo, Michael Gelinsky
Three-dimensional printing of cell-laden hydrogels has evolved as a promising approach on the route to patient-specific or complex tissue engineered constructs. However, it is still challenging to print structures with both, high shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay, called Laponite, to build up scaffolds utilizing the extrusion-based method 3D plotting. By blending with alginate and methylcellulose, a bioink was developed which allowed easy extrusion, achieving scaffolds with high printing fidelity...
July 10, 2017: Biofabrication
https://www.readbyqxmd.com/read/28686713/transcriptome-wide-comparison-of-the-impact-of-atoh1-and-mir-183-family-on-pluripotent-stem-cells-and-multipotent-otic-progenitor-cells
#4
Michael Ebeid, Prashanth Sripal, Jason Pecka, Kirk W Beisel, Kelvin Kwan, Garrett A Soukup
Over 5% of the global population suffers from disabling hearing loss caused by multiple factors including aging, noise exposure, genetic predisposition, or use of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after HC loss is the limited ability of mammalian auditory HCs to spontaneously regenerate. Understanding the molecular mechanisms orchestrating HC development is expected to facilitate cell replacement therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28674248/a-nanoparticle-based-ophthalmic-formulation-of-dexamethasone-enhances-corneal-permeability-of-the-drug-and-prolongs-its-corneal-residence-time
#5
Noriaki Nagai, Yosuke Nakazawa, Yoshimasa Ito, Kazutaka Kanai, Norio Okamoto, Yoshikazu Shimomura
We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEXnano dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.026% methyl p-hydroxybenzoate (MP), 0.014% propyl p-hydroxybenzoate (PP), and 0.5% methylcellulose were used, and the DEXnano dispersion was prepared by the bead mill method. The mean particle size of DEXnano dispersion was 78 nm. Antimicrobial activity of the DEXnano dispersion were measured by using Escherichia coli, and the corneal epithelium-debrided rat model and HCE-T cells (immortalized human corneal epithelial cell line) were used to estimate the corneal toxicity...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28660853/fluorescence-lifetime-based-bioassays
#6
Franz-Josef Meyer-Almes
Fluorescence lifetime (FLT) is a robust intrinsic property and material constant of fluorescent matter. Measuring this important physical indicator has evolved from a laboratory curiosity to a powerful and established technique for a variety of applications in drug discovery, medical diagnostics and basic biological research. This distinct trend was mainly driven by improved and meanwhile affordable laser and detection instrumentation on the one hand and the development of suitable FLT probes and biological assays on the other...
June 29, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28654058/in-vitro-assays-to-assess-blood-brain-barrier-mesh-like-vessel-formation-and-disruption
#7
Riya Thomas, Kazandra Diaz, Kevin P Koster, Leon M Tai
Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by astrocytes, pericytes and brain endothelial cells (BECs). Here, we detail methods to assess BBB coverage using single cultures of immortalized human BECs, single cultures of primary mouse BECs, and a humanized triple culture model (BECs, astrocytes and pericytes) of the BBB. To highlight the applicability of the assays to disease states, we describe the effect of oligomeric amyloid-β (oAβ), which is an important contributor to Alzheimer's disease (AD) progression, on BBB coverage...
June 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28651607/the-long-non-coding-rna-bc200-bcyrn1-is-critical-for-cancer-cell-survival-and-proliferation
#8
Evan P Booy, Ewan Ks McRae, Amit Koul, Francis Lin, Sean A McKenna
BACKGROUND: BC200 is a long non-coding RNA expressed at high levels in the brain and elevated in a variety of tumour types. BC200 has a hypothesized role in translational regulation; however, to date the functional role of BC200 in both normal and diseased states remains poorly characterized. METHODS: Detailed BC200 expression analyses were performed in tumor cell lines, primary and non-tumorigenic cultured breast and lung cells, and a panel of normal human tissues by quantitative real-time PCR and confirmed by northern blot...
June 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28640863/induced-pluripotent-stem-cell-derived-limbal-epithelial-cells-lipsc-as-a-cellular-alternative-for-in-vitro-ocular-toxicity-testing
#9
Edith Aberdam, Isabelle Petit, Linda Sangari, Daniel Aberdam
Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28628795/knockout-of-the-nogo-b-gene-attenuates-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#10
Bo Zhu, Shaobo Chen, Xiaoding Hu, Xiaofeng Jin, Yichen Le, Lihuan Cao, Zhonghua Yuan, Zhen Lin, Songmin Jiang, Lichun Sun, Long Yu
Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells...
July 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28615694/selective-serotonin-reuptake-inhibitor-fluoxetine-impairs-e-cadherin-mediated-cell-adhesion-and-alters-calcium-homeostasis-in-pancreatic-beta-cells
#11
Huang-Yu Chang, Shu-Ling Chen, Meng-Ru Shen, Mei-Lang Kung, Lee-Ming Chuang, Yun-Wen Chen
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca(2+)]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca(2+)]i...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607007/synergistic-activity-with-notch-inhibition-and-androgen-ablation-in-erg-positive-prostate-cancer-cells
#12
Ahmed A Mohamed, Shyh-Han Tan, Charles P Xavier, Shilpa Katta, Wei Huang, Lakshmi Ravindranath, Muhammad Jamal, Hua Li, Meera Srivastava, Eri S Srivatsan, Taduru L Sreenath, David G McLeod, Alagarsamy Srinivasan, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava
The oncogenic activation of the ETS related gene (ERG) due to gene fusions is present in over half of prostate cancer (CaP) in Western countries. Due to its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for CaP. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified; confirming that NOTCH factors are direct transcriptional targets of ERG...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28586195/ex-vivo-cell-based-screening-platform-for-modulators-of-hepatosteatosis
#13
Shan Yu, Emily Chen, Lance Sherwood, Mitchell Hull, Ashley K Woods, Matthew S Tremblay
Nonalcoholic fatty liver disease (NAFLD) is the result of the ectopic accumulation of lipids in hepatic cells and is the early stage of liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. While some mechanisms of aberrant lipid storage are understood, unbiased phenotypic drug screening holds the potential to identify new therapeutic small molecule mechanisms that reverse lipid accumulation in hepatic cells and prevent disease progression. Immortalized hepatocyte cell lines are often used as in vitro models of hepatocyte function, including in the study of lipid accumulation...
June 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28584711/quercetin-reduces-hydroxyurea-induced-cytotoxicity-in-immortalized-mouse-aortic-endothelial-cells
#14
Zachary M Kiser, Monica D M McGee, Racquel J Wright, Alexander Quarshie, Gale W Newman, Karen R Randall, Jonathan K Stiles, Adel Driss, Jacqueline M Hibbert
BACKGROUND: Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage...
2017: PeerJ
https://www.readbyqxmd.com/read/28582447/action-of-ym155-on-clear-cell-renal-cell-carcinoma-does-not-depend-on-survivin-expression-levels
#15
Mei Yi Sim, Hung Huynh, Mei Lin Go, John Shyi Peng Yuen
The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155...
2017: PloS One
https://www.readbyqxmd.com/read/28566574/quantitative-targeted-absolute-proteomics-qtap-based-pharmacoproteomics-the-importance-of-international-collaboration
#16
Tetsuya Terasaki
 Proteins such as membrane transporters, enzymes, receptors and channels play key roles in drug absorption, distribution, metabolism, and elimination, and also influence efficacy and the likelihood of adverse reactions. Therefore, if we can quantify the activities of these molecules, it may be possible to predict the behavior of candidate drugs in humans in disease states; such methodology would be extremely helpful for efficient drug development. We have developed an in silico method to select appropriate peptides within amino acid sequences in order to quantify targeted proteins by LC-MS/MS in selected reaction monitoring (SRM) mode...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#17
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates p-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28541801/enemies-or-weapons-in-hands-investigational-anti-diabetic-drug-glibenclamide-and-cancer-risk
#18
REVIEW
Rui Gao, Tao Yang, Wei Xu
Epidemiological evidence suggests that diabetes is associated with elevated cancer risk through the actions of hyperglycemia, hyperinsulinemia and chronic inflammation. Metformin, a first-line medication for type 2 diabetes mellitus, arouses growing concerns on its anti-cancer effect. However, data regarding the effect of glibenclamide on tumor growth and cancer risk are less consistent, which may be a potential anti-cancer drug. Areas covered: In this review, we clarified probable underlying mechanisms in preclinical studies and reviewed epidemiological evidence on glibenclamide's cancer risk in clinical studies...
July 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#19
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, Zhijian J Chen
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#20
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
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