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https://www.readbyqxmd.com/read/28903496/editor-s-highlight-development-of-novel-neural-embryonic-stem-celltests-for-high-throughput-screening-of-embryotoxic-chemicals
#1
Kumiko Kobayashi, Noriyuki Suzuki, Kiyoshi Higashi, Akane Muroi, Florian Le Coz, Hirohisa Nagahori, Koichi Saito
There is a great demand for appropriate alternative methods to rapidly evaluate the developmental and reproductive toxicity of a wide variety of chemicals. We used the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes as a basis for establishing a rapid and highly reproducible invitro embryotoxicity test known as the Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST). In this study, we developed novel neural-Luc ESTs using two marker genes for neural development, tubulin beta-3 (Tubb3) and Reelin (Reln), and evaluated the capacity of these tests to predict developmental toxicity...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903487/from-the-cover-arsenic-induces-hippocampal-neuronal-apoptosis-and-cognitive-impairments-via-an-up-regulated-bmp2-smad-dependent-reduced-bdnf-trkb-signaling-in-rats
#2
Rukmani Pandey, Vipin Rai, Juhi Mishra, Kapil Mandrah, Somendu Kumar Roy, Sanghamitra Bandyopadhyay
Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated cognitive deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling of rat hippocampal neurons, marked by NeuN. Investigating apoptotic mechanism through invivo and invitro studies revealed that arsenic promoted bone morphogenetic protein-2 (BMP2) expression, supported by increased BMP-receptor2 (BMPR2) and p-Smad1/5 in hippocampal neurons...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903485/editor-s-highlight-mechanistic-toxicity-tests-based-on-an-adverse-outcome-pathway-network-for-hepatic-steatosis
#3
Michelle M Angrish, Charlene A McQueen, Elaine Cohen-Hubal, Maribel Bruno, Yue Ge, Brian N Chorley
Risk assessors use liver endpoints in rodent toxicology studies to assess the safety of chemical exposures. Yet, rodent endpoints may not accurately reflect human responses. For this reason and others, human-based invitro models are being developed and anchored to adverse outcome pathways to better predict adverse human health outcomes. Here, a networked adverse outcome pathway-guided selection of biology-based assays for lipid uptake, lipid efflux, fatty acid oxidation, and lipid accumulation were developed...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903484/novel-role-of-fbxw7-circular-rna-in-repressing-glioma-tumorigenesis
#4
Yibing Yang, Xinya Gao, Maolei Zhang, Sheng Yan, Chengjun Sun, Feizhe Xiao, Nunu Huang, Xuesong Yang, Kun Zhao, Huangkai Zhou, Suyun Huang, Bo Xie, Nu Zhang
Background: Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods: CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues...
March 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28866193/injectable-natural-polymer-compound-for-tissue-engineering-of-intervertebral-disc-in-vitro-study
#5
Masoud Ghorbani, Jafar Ai, Mohammad Reza Nourani, Mahmoud Azami, Batool Hashemi Beni, Shiva Asadpour, Sima Bordbar
Intervertebral disc degeneration is recognized to be the leading cause for chronic low-back pain. Injectable hydrogel is one of the great interests for tissue engineering and cell encapsulation specially for intervertebral (IVD) affecting rate of regeneration success, in this study we assessed viscoelastic properties of a Chitosan-β glycerophosphate-hyaluronic acid, Chondroitin-6-sulfate, type 2 of Collagen, gelatin, fibroin silk (Ch-β-GP-HA-CS-Col-Ge-FS) hydrogel which was named as NP hydrogel that is natural extracellular matrix of IVD...
November 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28865294/thiazolo-4-5-d-pyridazine-analogues-as-a-new-class-of-dihydrofolate-reductase-dhfr-inhibitors-synthesis-biological-evaluation-and-molecular-modeling-study
#6
Menna A Ewida, Dalal A Abou El Ella, Deena S Lasheen, Heba A Ewida, Yomna I El-Gazzar, Hussein I El-Subbagh
A new series of 1,3-thiazoles and thiazolo[4,5-d]pyridazine both bearing the 2-thioureido function were designed, synthesized and evaluated for their invitro DHFR inhibition and antitumor activities. Compound 26 proved to be the most active DHFR inhibitor (IC50 of 0.06μM). Compound 4, 20 and 21 showed in vitro antitumor activity against a collection of cancer cell lines. Compound 26 proved lethal to HS 578T breast cancer cell line with IC50 value of 0.8μM, inducing cell cycle arrest and apoptosis. Molecular modeling studies concluded that recognition with key amino acids Phe 31 and Arg 22 is essential for DHFR binding...
August 24, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28843244/in-vitro-leukoagglutination-a-rare-hematological-cause-of-spurious-leukopenia
#7
Sadia Sultan, Syed Muhammad Irfan
Leukopenia secondary to leukocytic agglutination is caused by an ethylene diamine tetra acetic acid (EDTA) which may appear in both benign and malignant states. Ethylene diamine tetra acetic acid induced platelets clumping in peripheral blood has been well established, but invitro leukocytic aggregation is very rarest hematological finding. Pseudo-leukopenia resulting from leukoagglutinins has been reported in the cirrhotic state, infections, autoimmune disorders, uremia, in immunosuppressed state or in various malignancies...
June 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28830009/humanization-of-jaa-f11-a-highly-specific-anti-thomsen-friedenreich-pancarcinoma-antibody-and-invitro-efficacy-analysis
#8
Swetha Tati, John C Fisk, Julia Abdullah, Loukia Karacosta, Taylor Chrisikos, Padraic Philbin, Susan Morey, Diala Ghazal, Fatma Zazala, Joseph Jessee, Sally Quataert, Stephen Koury, David Moreno, Jing Ying Eng, Vladislav V Glinsky, Olga V Glinskii, Muctarr Sesay, Anthony W Gebhard, Karamveer Birthare, James R Olson, Kate Rittenhouse-Olson
JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11)...
August 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28822333/virtual-screening-and-repositioning-of-inconclusive-molecules-of-beta-lactamase-bioassays-a-data-mining-approach
#9
Akshata Gad, Andrew Titus Manuel, Jinuraj K R, Lijo John, Sajeev R, Shanmuga Priya V G, Abdul Jaleel U C
This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28750029/ubiquinol-cytochrome-c-reductase-core-protein-1-may-be-involved-in-delayed-cardioprotection-from-preconditioning-induced-by-diazoxide
#10
Zonghong Long, Guangyou Duan, Hong Li, Tingting Yi, Xiaoxiao Wu, Feng Chen, Zhuoxi Wu, Yuqi Gao
This study aimed to use long-term diazoxide treatment to establish a loss-of-cardioprotection model and then perform proteomics analysis to explore which proteins of mitochondrial inner membrane (MIM) are potentially involved in delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20 mg•kg-1•d-1) to establish a loss-of-cardioprotection model in different groups. Detection of serum cTnI levels and cell apoptosis assays in heart tissue were performed. Then, rats MIM after 0, 4 and 6 weeks of diazoxide treatment was isolated and proteomics analysis was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28679777/efficacy-of-onalespib-a-long-acting-second-generation-hsp90-inhibitor-as-a-single-agent-and-in-combination-with-temozolomide-against-malignant-gliomas
#11
Alessandro Canella, Alessandra M Welker, Ji Young Yoo, Jihong Xu, Fazly S Abbas, Divya Kesanakurti, Prabhakaran Nagarajan, Christine E Beattie, Erik P Sulman, Joseph L Liu, Joy Gumin, Frederick F Lang, Metin Gurcan, Balveen Kaur, Deepa Sampath, Vinay K Puduvalli
HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities or are unable to cross the blood brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas invitro and invivo<br /><br />Experimental Design: The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28675355/induction-of-interferon-and-interferon-induced-antiviral-effector-genes-following-a-primary-bovine-herpesvirus-1-bhv-1-respiratory-infection
#12
Rahwa Osman, Patricia Gonzalez-Cano, Robert Brownlie, Philip J Griebel
Invitro investigations have identified a variety of mechanisms by which herpesviruses evade interferon-stimulated antiviral effector mechanisms. However, these immune evasion mechanisms have not been evaluated during a bovine herpesvirus-1 (BHV-1) infection. This study investigated the transcription and secretion of type I and II interferons (IFNs) and the transcription of IFN-stimulated genes (ISGs) during a primary BHV-1 infection of the upper respiratory tract (URT) in naïve calves. IFN-α, -β and -γ transcription in nasal turbinates and protein levels in nasal secretions increased following infection...
July 5, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28671624/effect-of-polymers-on-the-physicochemical-properties-and-biological-performance-of-fenoprofen-calcium-dihydrate-triacetyl-%C3%AE-cyclodextrin-complex
#13
Hussein O Ammar, Tarek S Makram, Shaimaa Mosallam
BACKGROUND: Fenoprofen calcium dehydrate (FCD) is counted as a non-steroidal, anti-inflammatory, anti-arthritic drug. FCD is slightly water soluble. It is indicated for mild pain relief, where the suggested dosage is 200 mg orally every 4 to 6 h. AIM: Reduce dissolution efficiency, reach an extended therapeutic effect and reduce the frequency of the drug side effects. METHOD: Combination of the co-evaporated drug:triacetyl-β-cyclodextrin complex prepared in a ratio of 1:3 and either of two polymers-hydroxylpropylmethyl cellulose (HPMC) or ethyl cellulose (EC)-in the same formulation...
July 3, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28608141/triterpenoids-principle-of-wedelia-calendulacea-attenuated-diethynitrosamine-induced-hepatocellular-carcinoma-via-down-regulating-oxidative-stress-inflammation-and-pathology-via-nf-kb-pathway
#14
Amita Verma, Deepika Singh, Firoz Anwar, Prakash Chandra Bhatt, Fahad Al-Abbasi, Vikas Kumar
The aerial part of Wedelia calendulacea have been used in Ayurveda, Unani, Tibetan, Siddha and other folk medicine systems to protect the liver and renal tissue. Liver is considered as primary metabolizing site of body, which is prone to damage by endogenous and exogenous toxicants. A reason for liver toxicity, and major causes of the hepatocellular carcinoma (HCC). 19-α-Hydroxyurs-12(13)-ene-28 oic acid-3-O-β-D-glucopyranoside (HEG), a triterpenoids found in the higher plants, has been known to possess protective effect against various toxicants...
June 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28584149/different-resistance-mechanisms-for-cadazolid-and-linezolid-in-clostridium-difficile-found-by-whole-genome-sequencing-analysis
#15
Patrick Caspers, Hans H Locher, Philippe Pfaff, Sarah Diggelmann, Georg Rueedi, Daniel Bur, Daniel Ritz
Cadazolid (CDZ) is a new antibiotic currently in clinical development for the treatment of Clostridium difficile infections. CDZ interferes with the bacterial protein synthesis machinery. The aim of the present study was to identify resistance mechanisms for CDZ and compare the results to those obtained for linezolid (LZD) in C. difficile by whole-genome sequencing (WGS) of strains generated by in vitro passages and to those obtained for LZD-resistant clinical isolates. Clones of C. difficile 630 selected with CDZ during 46 passages had a maximally 4-fold increase in CDZ MIC, while the LZD MIC for clones selected with LZD increased up to 16-fold...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28575494/golgi-phosphoprotein-3-promotes-glioma-progression-via-inhibiting-rab5-mediated-endocytosis-and-degradation-of-epidermal-growth-factor-receptor
#16
Xiuping Zhou, Shao Xie, Shishuang Wu, Yanhua Qi, Zhaohao Wang, Hao Zhang, Dong Lu, Xu Wang, Yu Dong, Guanzheng Liu, Dongxu Yang, Qiong Shi, Wenbin Bian, Rutong Yu
Background.: Golgi phosphoprotein 3 (GOLPH3) is associated with worse prognosis of gliomas, but its role and mechanism in glioma progression remain largely unknown. This study aimed to explore the role and mechanism of GOLPH3 in glioma progression. Methods.: The expression of GOLPH3 in glioma tissues was detected by quantitative PCR, immunoblotting, and immunohistochemistry. GOLPH3's effect on glioma progression was examined using cell growth assays and intracranial glioma model...
June 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#17
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3(+)CD4(+)IL-9(+) and CD3(+)CD8(+)IL-9(+) cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28532060/design-and-characterization-of-biodegradable-macroporous-hybrid-inorganic-organic-polymer-for-orthopedic-applications
#18
Sunita PremVictor, Jibin Kunnumpurathu, M G Gayathri Devi, K Remya, Vineeth M Vijayan, Jayabalan Muthu
We have engineered hybrid polymer products based on a hybrid inorganic-organic comacromer consisting of hydroxyapatite (HA), carboxyl terminated polypropylene fumarate (CTPPF), PEG300 and ascorbic acid (AA) as a bone graft material. The integration and the spatial distribution of HA in the polymer backbone were facilitated by silanisation and 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling technique. These comacromers and crosslinked polymer products were characterized by Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) and Raman mapping techniques...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28529065/brown-adipose-tissue-and-lipid-metabolism-imaging
#19
REVIEW
Andreas Paulus, Wouter van Marken Lichtenbelt, Felix M Mottaghy, Matthias Bauwens
PURPOSE: Brown adipose tissue (BAT) research has evolved from an underestimated to a fast developing field. Its assumed curing properties for the world wide epidemic obesity, and its related diseases, makes this tissue an interesting target for a broad amount of non-invasive molecular BAT tracers. Apart from (18)F-FDG PET/CT there are several methods to detect BAT and measure its metabolism in a more appropriate way. Especially interesting is the measure of lipid turnover, because fatty acids comprise the main fuel for active BAT...
May 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28507941/in-vitro-cytotoxicity-effects-of-197-au-pamamg4-and-198-au-pamamg4-nanocomposites-against-mcf7-and-4t1-breast-cancer-cell-lines
#20
Simin Janitabar-Darzi, Reza Rezaei, Kamal Yavari
Purpose: Study on gold based therapeutic agents for cancer cells deracination has become under scrutiny in recent years owing to effective treatments are not available for rapidly progressive cancers. The aim of present study was to examine efficiency of radioactive (198)Au/PAMAMG4 and non-radioactive (197)Au/PAMAMG4 nancomposites against 4T1 and MCF7 breast cancer cell lines. Methods: The PAMAMG4 dendrimer was treated with the gold anions and then, the mixture was chemically reduced by NaBH4. Prepared (197)Au/PAMAMG4 was bombarded by thermal neutrons in the Tehran Research Reactor to (198)Au/PAMAMG4 be produced...
April 2017: Advanced Pharmaceutical Bulletin
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