Read by QxMD icon Read

Chemical screen beta cell

Weixi Liu, Hang Ma, Nicholas A DaSilva, Kenneth N Rose, Shelby L Johnson, Lu Zhang, Chunpeng Wan, Joel A Dain, Navindra P Seeram
Medicinal plants are promising candidates for Alzheimer's disease (AD) research but there is lack of systematic algorithms and procedures to guide their selection and evaluation. Herein, we developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Aβ) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation...
September 29, 2016: Neurochemistry International
Coraline Simon, Matthias Onghena, Adrian Covaci, Els Van Hoeck, Joris Van Loco, Tara Vandermarken, Kersten Van Langenhove, Heidi Demaegdt, Birgit Mertens, Karin Vandermeiren, Marie-Louise Scippo, Marc Elskens
Endocrine activity of 65 compounds migrating from polycarbonate replacement plastic baby bottles was assessed using in vitro cell based assays (reporter gene assays) involving 7 nuclear receptors, i.e. human steroid hormones receptors (oestrogen, androgen, progesterone and glucocorticoid receptors), human thyroid beta and peroxisome proliferator-activated gamma receptors, and the mouse aryl hydrocarbon receptor. The chemicals were tested at 4 concentrations ranging from 0.001mM to 1mM. Only twelve chemicals did not show any activity towards any of the nuclear receptors, while fifty three compounds showed a possible endocrine activity...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Diana A Stavreva, Lyuba Varticovski, Ludmila Levkova, Anuja A George, Luke Davis, Gianluca Pegoraro, Vicki Blazer, Luke Iwanowicz, Gordon L Hager
Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP)-tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TRβ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TRβ, this GFP-GR-TRβ chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3',5'-triiodothyronine, or rT3) was inactive...
August 10, 2016: Toxicology
Hui Zeng, Min Guo, Ting Zhou, Lei Tan, Chi Nok Chong, Tuo Zhang, Xue Dong, Jenny Zhaoying Xiang, Albert S Yu, Lixia Yue, Qibin Qi, Todd Evans, Johannes Graumann, Shuibing Chen
Genome-wide association studies (GWASs) have increased our knowledge of loci associated with a range of human diseases. However, applying such findings to elucidate pathophysiology and promote drug discovery remains challenging. Here, we created isogenic human ESCs (hESCs) with mutations in GWAS-identified susceptibility genes for type 2 diabetes. In pancreatic beta-like cells differentiated from these lines, we found that mutations in CDKAL1, KCNQ1, and KCNJ11 led to impaired glucose secretion in vitro and in vivo, coinciding with defective glucose homeostasis...
September 1, 2016: Cell Stem Cell
Chia-Wen Amy Hsu, Jinghua Zhao, Menghang Xia
The farnesoid X receptor (FXR) is a nuclear receptor responsible for homeostasis of bile acids, lipids, and glucose. Compounds that alter endogenous FXR signaling can be used as therapeutic candidates or identified as potentially hazardous compounds depending on exposure doses and health states. Therefore, there is an increasing need for high-throughput screening assays of FXR activity to profile large numbers of environmental chemicals and drugs. This chapter describes a workflow of FXR modulator identification and characterization...
2016: Methods in Molecular Biology
LaQueta K Hudson, Meghan E Dancho, Jianhua Li, Johanna B Bruchfeld, Ahmed A Ragab, Mingzhu M He, Meaghan Bragg, Delaney Lenaghan, Michael D Quinn, Jason R Fritz, Matthew V Tanzi, Harold A Silverman, William M Hanes, Yaakov A Levine, Valentin A Pavlov, Peder S Olofsson, Jesse Roth, Yousef Al-Abed, Ulf Andersson, Kevin J Tracey, Sangeeta S Chavan
Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by beta cell destruction, insulin deficiency and hyperglycemia. Activated macrophages and autoimmune T cells play a crucial role in the pathogenesis of hyperglycemia in NOD murine diabetes models, but the molecular mechanisms of macrophage activation are unknown. We recently identified pigment epithelium-derived factor (PEDF) as an adipocyte-derived factor that activates macrophages and mediates insulin resistance. Reasoning that PEDF might participate as a proinflammatory mediator in murine diabetes, we measured PEDF levels in NOD mice...
June 10, 2016: Molecular Medicine
Corina Danciu, Florina Bojin, Rita Ambrus, Delia Muntean, Codruta Soica, Virgil Paunescu, Mirabela Cristea, Iulia Pinzaru, Cristina Dehelean
Incorporation of fisetin, quercetin and kaempferol in beta cyclodextrins was proved by scanning electron microscopy (SEM), differencial scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Pure compounds and their complexes where tested for antiproliferative and pro-apoptotic activity on the B164A5 murine melanoma cell line and for the antimicrobial properties on the selected strains. The phytocompounds present in a different manner in vitro chemopreventive and weak antimicrobial activity. Incorporation in beta cyclodextrins had a mixt effect on the biological activity conducing to decrease, increase or consistent effect compared to pure phytocompound depending on the screened process and on the chosen combination...
June 20, 2016: Anti-cancer Agents in Medicinal Chemistry
Nivedita Lahiri, Rupal R Shah, Emilie Layre, David Young, Chris Ford, Megan B Murray, Sarah M Fortune, D Branch Moody
Global control of tuberculosis has become increasingly complicated with the emergence of multidrug-resistant strains of Mycobacterium tuberculosis First-line treatments are anchored by two antibiotics, rifampin and isoniazid. Most rifampin resistance occurs through the acquisition of missense mutations in the rifampin resistance-determining region, an 81-base pair region encoding the rifampin binding site on the β subunit of RNA polymerase (rpoB). Although these mutations confer a survival advantage in the presence of rifampin, they may alter the normal process of transcription, thereby imposing significant fitness costs...
July 1, 2016: Journal of Biological Chemistry
Lingling Feng, Brandoch Cook, Su-Yi Tsai, Ting Zhou, Brooke LaFlamme, Todd Evans, Shuibing Chen
Sorely missing from the "toolkit" for directed differentiation of stem/progenitor cells are agonists of the BMP-signaling pathway. Using a high-throughput chemical screen, we discovered that PD407824, a checkpoint kinase 1 (CHK1) inhibitor, increases the sensitivity of cells to sub-threshold amounts of BMP4. We show utility of the compound in the directed differentiation of human embryonic stem cells toward mesoderm or cytotrophoblast stem cells. Blocking CHK1 activity using pharmacological compounds or CHK1 knockout using single guide RNA (sgRNA) confirmed that CHK1 inhibition increases the sensitivity to BMP4 treatment...
May 31, 2016: Cell Reports
Carina Lotz-Jenne, Urs Lüthi, Sabine Ackerknecht, François Lehembre, Tobias Fink, Manuel Stritt, Matthias Wirth, Simona Pavan, Ruben Bill, Urs Regenass, Gerhard Christofori, Nathalie Meyer-Schaller
An epithelial to mesenchymal transition (EMT) enables epithelial tumor cells to break out of the primary tumor mass and to metastasize. Understanding the molecular mechanisms driving EMT in more detail will provide important tools to interfere with the metastatic process. To identify pharmacological modulators and druggable targets of EMT, we have established a novel multi-parameter, high-content, microscopy-based assay and screened chemical compounds with activities against known targets. Out of 3423 compounds, we have identified 19 drugs that block transforming growth factor beta (TGFβ)-induced EMT in normal murine mammary gland epithelial cells (NMuMG)...
May 3, 2016: Oncotarget
Scott Auerbach, Dayne Filer, David Reif, Vickie Walker, Alison C Holloway, Jennifer Schlezinger, Supriya Srinivasan, Daniel Svoboda, Richard Judson, John R Bucher, Kristina A Thayer
BACKGROUND: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U...
August 2016: Environmental Health Perspectives
Ajit Singh Rathore, Neha Keshri, Devi Charan Shetty, Saurabh Juneja
BACKGROUND: Increased iron overload is frequent problem in thalassemia patients, and this is monitored by serum ferritin levels or chemical assessment of the iron levels in liver tissue. However, repeated monitoring of serum ferritin levels to assess the iron overload is an invasive procedure associated with practical problems. AIMS: To use Perl's Prussian blue reaction to evaluate the iron overload in beta-thalassemia patients by staining the oral cytosmears. MATERIALS AND METHODS: The study comprised 35 patients diagnosed with beta-thalassemia...
January 2016: International Journal of Applied and Basic Medical Research
Michael S Boosalis, Jose I Sangerman, Gary L White, Roman F Wolf, Ling Shen, Yan Dai, Emily White, Levi H Makala, Biaoru Li, Betty S Pace, Mehdi Nouraie, Douglas V Faller, Susan P Perrine
High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions...
2015: PloS One
Xiling Lei, Jing Yu, Qi Niu, Jianhua Liu, Patrick C Fraering, Fang Wu
Known γ-secretase inhibitors or modulators display an undesirable pharmacokinetic profile and toxicity and have therefore not been successful in clinical trials for Alzheimer's disease (AD). So far, no compounds from natural products have been identified as direct inhibitors of γ-secretase. To search for bioactive molecules that can reduce the amount of amyloid-beta peptides (Aβ) and that have better pharmacokinetics and an improved safety profile, we completed a screen of ~400 natural products by using cell-based and cell-free γ-secretase activity assays...
2015: Scientific Reports
Marlene Thai Kim, Ruili Huang, Alexander Sedykh, Wenyi Wang, Menghang Xia, Hao Zhu
BACKGROUND: Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program...
May 2016: Environmental Health Perspectives
Mathias W Hackl, Markus Lakemeyer, Maria Dahmen, Manuel Glaser, Axel Pahl, Katrin Lorenz-Baath, Thomas Menzel, Sonja Sievers, Thomas Böttcher, Iris Antes, Herbert Waldmann, Stephan A Sieber
Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts and through the use of beta-lactones, which remain the only specific inhibitors of ClpP discovered to date. Beta-lactones have served as chemical tools to manipulate ClpP in several organisms; however, their potency, selectivity and stability is limited. Despite detailed structural insights into the composition and conformational flexibility of the ClpP active site, no rational efforts to design specific non-beta-lactone inhibitors have been reported to date...
July 8, 2015: Journal of the American Chemical Society
Megan R Schwarzman, Janet M Ackerman, Shanaz H Dairkee, Suzanne E Fenton, Dale Johnson, Kathleen M Navarro, Gwendolyn Osborne, Ruthann A Rudel, Gina M Solomon, Lauren Zeise, Sarah Janssen
BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk...
December 2015: Environmental Health Perspectives
Charles H Jones, Akhila Gollakota, Mingfu Chen, Tai-Chun Chung, Anitha Ravikrishnan, Guojian Zhang, Blaine A Pfeifer
Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters)...
July 2015: Biomaterials
Afsaneh Porzoor, Benjamin Alford, Helmut M Hügel, Danilla Grando, Joanne Caine, Ian Macreadie
A family of 21 polyphenolic compounds consisting of those found naturally in danshen and their analogues were synthesized and subsequently screened for their anti-amyloidogenic activity against the amyloid beta peptide (Aβ42) of Alzheimer's disease. After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001). TEM and immunoblotting analysis also showed that selected compounds were capable of hindering fibril formation even after prolonged incubations...
2015: Biomolecules
Lianhong Yin, Lingli Zheng, Lina Xu, Deshi Dong, Xu Han, Yan Qi, Yanyan Zhao, Youwei Xu, Jinyong Peng
BACKGROUND: Inverse docking technology has been a trend of drug discovery, and bioinformatics approaches have been used to predict target proteins, biological activities, signal pathways and molecular regulating networks affected by drugs for further pharmacodynamic and mechanism studies. METHODS: In the present paper, inverse docking technology was applied to screen potential targets from potential drug target database (PDTD). Then, the corresponding gene information of the obtained drug-targets was applied to predict the related biological activities, signal pathways and processes networks of the compound by using MetaCore platform...
2015: BMC Complementary and Alternative Medicine
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"