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https://www.readbyqxmd.com/read/29339778/a-novel-human-muscle-cell-model-of-duchenne-muscular-dystrophy-created-by-crispr-cas9-and-evaluation-of-antisense-mediated-exon-skipping
#1
Takenori Shimo, Kana Hosoki, Yusuke Nakatsuji, Toshifumi Yokota, Satoshi Obika
Oligonucleotide-mediated splicing modulation is a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Recently, eteplirsen, a phosphorodiamidate morpholino oligomer-based splice-switching oligonucleotide (SSO) targeting DMD exon 51, was approved by the U.S. Food and Drug Administration as the first antisense-based drug for DMD patients. For further exploring SSOs targeting other exons in the DMD gene, the efficacy of exon skipping and protein rescue with each SSO sequence needs evaluations in vitro...
January 16, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29335203/inhibitor-of-the-human-telomerase-reverse-trancriptase-htert-gene-promoter-induces-cell-apoptosis-via-a-mitochondrial-dependent-pathway
#2
Yuyin Li, Guojun Pan, Yue Chen, Qian Yang, Tiantian Hao, Lianbo Zhao, Long Zhao, Yusheng Cong, Aipo Diao, Peng Yu
Telomerase is aberrantly expressed in many cancers and plays an important role in the development of cellular immortality and oncogenesis, which makes it a potential cancer therapeutic target for drug discovery. Here, we constructed a firefly luciferase reporter driven by the human telomerase reverse trancriptase (hTERT) gene promoter to screen for inhibitory compounds. Compound 5c was discovered and shown to significantly inhibit the promoter activity of hTERT gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b was shown to be a more potent inhibitor of hTERT gene promoter activity and subsequent expression of hTERT mRNA and protein...
December 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29323267/scaffold-free-generation-of-uniform-adipose-spheroids-for-metabolism-research-and-drug-discovery
#3
Aloysius J Klingelhutz, Francoise A Gourronc, Anna Chaly, David A Wadkins, Anthony J Burand, Kathleen R Markan, Sharon O Idiga, Meng Wu, Matthew J Potthoff, James A Ankrum
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29300349/enhanced-and-selective-antiproliferative-activity-of-methotrexate-functionalized-nanocapsules-to-human-breast-cancer-cells-mcf-7
#4
Catiúscia P de Oliveira, Sabrina L Büttenbender, Willian A Prado, Aline Beckenkamp, Ana C Asbahr, Andréia Buffon, Silvia S Guterres, Adriana R Pohlmann
Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl ester derivative, using two mechanisms of drug incorporation (encapsulation and surface functionalization) in the in vitro cellular uptake and antiproliferative activity in non-tumoral immortalized human keratinocytes (HaCaT) and in human breast carcinoma cells (MCF-7)...
January 4, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29283676/the-effect-of-solithromycin-a-cationic-amphiphilic-drug-on-the-proliferation-and-differentiation-of-human-meibomian-gland-epithelial-cells
#5
Yang Liu, Wendy R Kam, Prabhavathi Fernandes, David A Sullivan
PURPOSE: We previously discovered that azithromycin (AZM) acts directly on immortalized human meibomian gland epithelial cells (IHMGECs) to stimulate their lipid and lysosome accumulation and overall differentiation. We hypothesize that this phospholipidosis-like effect is due to AZM's cationic amphiphilic drug (CAD) nature. If our hypothesis is correct, then other CADs (e.g., solithromycin [SOL]) should be able to duplicate AZM's action on IHMGECs. Our purpose was to test this hypothesis...
December 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29278707/metformin-ameliorates-activation-of-hepatic-stellate-cells-and-hepatic-fibrosis-by-succinate-and-gpr91-inhibition
#6
Giang Nguyen, So Young Park, Cong Thuc Le, Won Sun Park, Dae Hee Choi, Eun-Hee Cho
BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA)...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29276788/a-role-for-soluble-il-6-receptor-in-osteoarthritis
#7
Graham Akeson, Charles J Malemud
Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines present at elevated levels in the synovial fluid of individuals with confirmed clinical diagnosis of rheumatoid arthritis (RA) and osteoarthritis (OA). The mechanism of action of IL-6 was shown to involve its capacity to interact with a membrane-bound IL-6 receptor (mIL-6Rα), also known as the "classical" IL-6 pathway, or through its interaction with a soluble IL-6 receptor (sIL-6R) termed the "trans-signaling" pathway. Activation of downstream signaling is transduced via these IL-6 receptors and principally involves the Janus Kinase/Signal Transduction and Activators of Transcription (JAK/STAT) signaling pathway that is further regulated by glycoprotein-130 (gp130) interacting with the IL-6/mIL-6R complex...
2017: Journal of Functional Morphology and Kinesiology
https://www.readbyqxmd.com/read/29273728/allopurinol-and-risk-of-benign-prostatic-hyperplasia-in-a-finnish-population-based-cohort
#8
Ville Kukko, Antti Kaipia, Kirsi Talala, Kimmo Taari, Teuvo L J Tammela, Anssi Auvinen, Teemu J Murtola
BACKGROUND: Metabolic syndrome and obesity are linked with hyperuricemia, and it has also been proposed that oxidative stress associated with hyperuricemia may promote benign prostatic hyperplasia (BPH). However, it is currently unknown whether use of antihyperuricemic medication is associated with risk of developing BPH. We studied the association between BPH and use of antihyperuricemic allopurinol in a Finnish population-based cohort. METHODS: The study cohort consisted of 74,754 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC)...
December 22, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29273061/diagnosis-and-treatment-of-alt-tumors-is-trabectedin-a-new-therapeutic-option
#9
REVIEW
Luca Pompili, Carlo Leonetti, Annamaria Biroccio, Erica Salvati
Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required for achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively referred to as Alternative Lengthening of Telomeres (ALT). ALT mechanisms involve different types of homology-directed telomere recombination and synthesis...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29222786/nerve-growth-factor-induced-angiogenesis-1-endothelial-cell-tube-formation-assay
#10
Philip Lazarovici, Adi Lahiani, Galit Gincberg, Dikla Haham, Arnon Fluksman, Ofra Benny, Cezary Marcinkiewicz, Peter I Lelkes
Nerve growth factor (NGF) is a neurotrophin promoting survival, proliferation, differentiation, and neuroprotection in the embryonal and adult nervous system. NGF also induces angiogenic effects in the cardiovascular system, which may be beneficial in engineering new blood vessels and for developing novel anti-angiogenesis therapies for cancer. Angiogenesis is a cellular process characterized by a number of events, including endothelial cell migration, invasion, and assembly into capillaries. In vitro endothelial tube formation assays are performed using primary human umbilical vein endothelial cells, human aortic endothelial cells, and other human or rodent primary endothelial cells isolated from the vasculature of both tumors and normal tissues...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29206210/immortalization-of-porcine-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-transgenic-liver-cells-using-sv40-large-t-antigen
#11
Hee Young Kang, Young-Kwon Choi, Yeon Ik Jeong, Kyung-Chul Choi, Sang-Hwan Hyun, Woo-Suk Hwang, Eui-Bae Jeung
Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11βhydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts...
December 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29192179/cmscaller-an-r-package-for-consensus-molecular-subtyping-of-colorectal-cancer-pre-clinical-models
#12
Peter W Eide, Jarle Bruun, Ragnhild A Lothe, Anita Sveen
Colorectal cancers (CRCs) can be divided into four gene expression-based biologically distinct consensus molecular subtypes (CMS). This classification provides a potential framework for stratified treatment, but to identify novel CMS-drug associations, translation of the subtypes to pre-clinical models is essential. The currently available classifier is dependent on gene expression signals from the immune and stromal compartments of tumors and fails to identify the poor-prognostic CMS4-mesenchymal group in immortalized cell lines, patient-derived organoids and xenografts...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29187162/isolation-and-characterization-of-a-new-naturally-immortalized-human-breast-carcinoma-cell-line-kaimrc1
#13
Rizwan Ali, Nosaibah Samman, Hajar Al Zahrani, Atef Nehdi, Sabhi Rahman, Abdul Latif Khan, Mohamed Al Balwi, Lolwah Abdullah Alriyees, Manal Alzaid, Ahmed Al Askar, Mohamed Boudjelal
BACKGROUND: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds...
November 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29183847/breath-figures-in-tissue-engineering-and-drug-delivery-state-of-the-art-and-future-perspectives
#14
REVIEW
Maria Teresa Calejo, Tanja Ilmarinen, Heli Skottman, Minna Kellomäki
The breath figure (BF) method is an easy, low-cost method to prepare films with a highly organized honeycomb-like porous surface. The particular surface topography and porous nature of these materials makes them valuable substrates for studying the complex effects of topography on cell fate, and to produce biomimetic materials with high performance in tissue engineering. Numerous researchers over the last two decades have studied the effects of the honeycomb topography on a variety of primary and immortalized cell lines, and drew important conclusions that can be translated to the construction of optimal biomaterials for cell culture...
November 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29169185/co-culture-of-human-alveolar-epithelial-haelvi-and-macrophage-thp-1-cell-lines
#15
Stephanie Kletting, Sarah Barthold, Urska Repnik, Gareth Griffiths, Brigitta Loretz, Nicole Schneider-Daum, Cristiane de Souza Carvalho-Wodarz, Claus-Michael Lehr
The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an immunological barrier, in particular for larger molecules and nanoparticles. This paper describes a new co-culture of human cell lines representing both cell types. Acquiring, culturing and maintaining primary alveolar epithelial cells presents significant logistical and technical difficulties. The recently established human alveolar epithelial lentivirus immortalized cell line, hAELVi, when grown on permeable filters, form monolayers with high functional and morphological resemblance to alveolar type I cells...
November 23, 2017: ALTEX
https://www.readbyqxmd.com/read/29167929/prediction-of-metabolism-induced-hepatotoxicity-on-three-dimensional-hepatic-cell-culture-and-enzyme-microarrays
#16
Kyeong-Nam Yu, Sashi Nadanaciva, Payal Rana, Dong Woo Lee, Bosung Ku, Alexander D Roth, Jonathan S Dordick, Yvonne Will, Moo-Yeal Lee
Human liver contains various oxidative and conjugative enzymes that can convert nontoxic parent compounds to toxic metabolites or, conversely, toxic parent compounds to nontoxic metabolites. Unlike primary hepatocytes, which contain myriad drug-metabolizing enzymes (DMEs), but are difficult to culture and maintain physiological levels of DMEs, immortalized hepatic cell lines used in predictive toxicity assays are easy to culture, but lack the ability to metabolize compounds. To address this limitation and predict metabolism-induced hepatotoxicity in high-throughput, we developed an advanced miniaturized three-dimensional (3D) cell culture array (DataChip 2...
November 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29161777/structure-based-design-and-evaluation-of-synthetic-porphyrin-derivatives-as-g-quadruplex-stabilizing-anticancer-agents
#17
R N Bhadane, D B Meshram, R M Gilhotra
G-quadruplex structures formed in telomeres and proto-oncogene represent a potentially useful target for anticancer drugs. Stabilization of this arrangement may inhibit the further action of different enzymes involved in cancer cell immortalization. In present work structure based drug design and synthesis was carried out on series of meso-substituted porphyrin analogues. The interaction of porphyrin derivatives with G-quadruplex DNA has been explored by virtual screening procedure. Some of the potential binding agents were then synthesized and evaluated in-vitro by MTT and PCR stop assay...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29156121/the-toxmatrix-chemo-genomic-profiling-identifies-interactions-that-reveal-mechanisms-of-toxicity
#18
Zhi-Bin Tong, Ruili Huang, Yuhong Wang, Carleen Klumpp-Thomas, John Braisted, Zina Itkin, Paul Shinn, Menghang Xia, Anton Simeonov, David Gerhold
A chemical genomics 'Toxmatrix' method was developed to elucidate mechanisms of cytotoxicity using neuronal models. Quantitative high-throughput screening (qHTS) was applied to systematically screen each toxicant against a panel of 70 modulators, drugs or chemicals that act on a known target, to identify interactions that either protect or sensitize cells to each toxicant. Thirty-two toxicants were tested at 10 concentrations for cytotoxicity to SH-SY5Y human neuroblastoma cells, with results fitted to the Hill equation to determine an IC50 for each toxicant...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29132924/impact-of-capsaicin-an-active-component-of-chili-pepper-on-pathogenic-chlamydial-growth-chlamydia-trachomatis-and-chlamydia-pneumoniae-in-immortal-human-epithelial-hela-cells
#19
Kazuya Yamakawa, Junji Matsuo, Torahiko Okubo, Shinji Nakamura, Hiroyuki Yamaguchi
Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells...
November 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29129222/both-cytopathic-and-non-cytopathic-bovine-viral-diarrhea-virus-bvdv-induced-autophagy-at-a-similar-rate
#20
Mrigendra K S Rajput, Karim Abdelsalam, Mahmoud F Darweesh, Lyle J Braun, Jason Kerkvliet, Adam D Hoppe, Christopher C L Chase
Autophagy is a cellular process that maintains cellular homeostasis by the proteolytic recycling of cytoplasm. Autophagy occurs at basal levels in almost all cells. It is upregulated in cellular stress including starvation, oxidative stress or during infection. Several viruses including flavivirus have developed strategies to subvert or use autophagy for their efficient replication. Bovine viral diarrhea virus (BVDV) is a member of the Flaviviridae family and the pestivirus virus group. BVDV is responsible for significant economic loss in cattle industry worldwide...
December 2017: Veterinary Immunology and Immunopathology
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