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https://www.readbyqxmd.com/read/28324845/pharmacological-effects-of-%C3%AE-d-mannuronic-acid-m2000-on-mir-146a-irak1-traf6-and-nf-%C3%AE%C2%BAb-gene-expression-as-target-molecules-in-inflammatory-reactions
#1
Seyed Shahabeddin Mortazavi Jahromi, Mehdi Malek Jamshidi, Ali Farazmand, Zahra Aghazadeh, Mehdi Yousefi, Abbas Mirshafiey
BACKGROUND: Impaired expression and function of microRNAs (miRNAs) are involved in the pathogenesis of many autoimmune and inflammatory diseases. Moreover, there is a close relationship between TLRs and miRNAs and impairment in regulating their expression which can play a vital role in the immunopathogenesis of many inflammatory reactions. This research aimed to study the pharmaceutical effects of M2000 (β-d-mannuronic acid) on the expression of miR-146a and its two target molecules (IRAK1 and TRAF6), and the transcription factor NF-κB in the HEK-Blue hTLR2 cell line...
January 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28302436/pharmacological-characterization-of-dopamine-receptors-in-the-rice-striped-stem-borer-chilo-suppressalis
#2
Gang Xu, Shun-Fan Wu, Gui-Xiang Gu, Zi-Wen Teng, Gong-Yin Ye, Jia Huang
Dopamine is an important neurotransmitter and neuromodulator in both vertebrates and invertebrates and is the most abundant monoamine present in the central nervous system of insects. A complement of functionally distinct dopamine receptors mediate the signal transduction of dopamine by modifying intracellular Ca(2+) and cAMP levels. In the present study, we pharmacologically characterized three types of dopamine receptors, CsDOP1, CsDOP2 and CsDOP3, from the rice striped stem borer, Chilo suppressalis. All three receptors show considerable sequence identity with orthologous dopamine receptors...
March 13, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28296171/calcium-dependent-nedd4-2-upregulation-mediates-degradation-of-the-cardiac-sodium-channel-nav1-5-implications-for-heart-failure
#3
Ling Luo, Feifei Ning, Yuan Du, Bingxue Song, Dandan Yang, Samantha C Salvage, Ya Wang, James A Fraser, Shetuan Zhang, Aiqun Ma, Tingzhong Wang
AIM: Reductions of voltage-gated sodium channel (Nav1.5) function/expression provide a slowed-conduction substrate for cardiac arrhythmias. Nedd4-2, which is activated by calcium, post-translationally modulates Nav1.5. We aim to investigate whether elevated intracellular calcium ([Ca(2+) ]i ) reduces Nav1.5 through Nedd4-2 and its role in heart failure (HF). METHODS: Using a combination of biochemical, electrophysiological, cellular and in vivo methods, we tested the effect and mechanism of calcium on Nedd4-2 and in turn Nav1...
March 10, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28294531/tyrphostin-ag556-increases-the-activity-of-large-conductance-ca-2-activated-k-channels-by-inhibiting-epidermal-growth-factor-receptor-tyrosine-kinase
#4
Yan Wang, Hai-Ying Sun, Ying-Guang Liu, Zheng Song, Gang She, Guo-Sheng Xiao, Yan Wang, Gui-Rong Li, Xiu-Ling Deng
The present study was designed to investigate whether large conductance Ca(2+) -activated K(+) (BK) channels were regulated by epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase. BK current and channel tyrosine phosphorylation level were measured in BK-HEK 293 cells expressing both functional α-subunits and the auxiliary β1-subunits using electrophysiology, immunoprecipitation and Western blotting approaches, respectively, and the function of rat cerebral basilar arteries was determined with a wire myography system...
March 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28291693/synthesis-and-evaluation-of-a-ligand-targeting-the-%C3%AE-and-%C3%AE-opioid-receptors-for-drug-delivery-to-lung-cancer
#5
Guo Li, Philip S Low
A well-established approach to developing new imaging agents and treatments for cancer begins with the recognition of receptors that are overexpressed in cancer cells. Ideally, these same receptors would also be absent, or minimally expressed, in healthy tissue. The mu (μ) and delta (δ) opioid receptors (MOR and DOR respectively) match these criteria, with expression in cancer cells that is higher than primary lung epithelial cells. Naltrexone is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence or prevention of relapse from opioid addiction...
June 28, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28289711/the-volume-regulated-anion-channel-lrrc8-in-nodose-neurons-is-sensitive-to-acidic-ph
#6
Runping Wang, Yongjun Lu, Susheel Gunasekar, Yanhui Zhang, Christopher J Benson, Mark W Chapleau, Rajan Sah, François M Abboud
The leucine rich repeat containing protein 8A (LRRC8A), or SWELL1, is an essential component of the volume-regulated anion channel (VRAC) that is activated by cell swelling and ionic strength. We report here for the first time to our knowledge its expression in a primary cell culture of nodose ganglia neurons and its localization in the soma, neurites, and neuronal membrane. We show that this neuronal VRAC/SWELL1 senses low external pH (pHo) in addition to hypoosmolarity. A robust sustained chloride current is seen in 77% of isolated nodose neurons following brief exposures to extracellular acid pH...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288113/germline-mutations-in-abl1-cause-an-autosomal-dominant-syndrome-characterized-by-congenital-heart-defects-and-skeletal-malformations
#7
Xia Wang, Wu-Lin Charng, Chun-An Chen, Jill A Rosenfeld, Aisha Al Shamsi, Lihadh Al-Gazali, Marianne McGuire, Nicholas Ah Mew, Georgianne L Arnold, Chunjing Qu, Yan Ding, Donna M Muzny, Richard A Gibbs, Christine M Eng, Magdalena Walkiewicz, Fan Xia, Sharon E Plon, James R Lupski, Christian P Schaaf, Yaping Yang
ABL1 is a proto-oncogene well known as part of the fusion gene BCR-ABL1 in the Philadelphia chromosome of leukemia cancer cells. Inherited germline ABL1 changes have not been associated with genetic disorders. Here we report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found to occur de novo or cosegregate with disease in five individuals (families 1-3)...
March 13, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28287601/targeted-plasma-membrane-delivery-of-a-hydrophobic-cargo-encapsulated-in-a-liquid-crystal-nanoparticle-carrier
#8
Okhil K Nag, Jawad Naciri, Eunkeu Oh, Christopher M Spillmann, James B Delehanty
The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer...
February 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286863/increase-in-dye-dendrimer-ratio-decreases-cellular-uptake-of-neutral-dendrimers-in-raw-cells
#9
Sriram Vaidyanathan, Milan Kaushik, Casey Dougherty, Rahul Rattan, Sascha N Goonewardena, Mark M Banaszak Holl, Janet Monano, Stassi DiMaggio
Neutral generation 3 poly(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OGn) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1-2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer (n = 4+), and a stochastic mixture (n = 4avg). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n)...
September 12, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28280061/purinergic-receptor-transactivation-by-the-%C3%AE-2-adrenergic-receptor-increases-intracellular-ca-2-in-non-excitable-cells
#10
Wayne Stallaert, Emma T van der Westhuizen, Anne-Marie Schonegge, Bianca Plouffe, Mireille Hogue, Viktoria Lukashova, Asuka Inoue, Satoru Ishida, Junken Aoki, Christian Le Gouill, Michel Bouvier
The β2 adrenergic receptor (β2AR) increases intracellular Ca(2+) in a variety of cell types. By combining pharmacological and genetic manipulations, we reveal a novel mechanism through which the β2AR promotes Ca(2+) mobilization (pEC50 = 7.32 ± 0.10) in non-excitable human embryonic kidney (HEK)-293S cells. Down-regulation of Gs with sustained cholera toxin pre-treatment and the use Gs-null HEK293 (ΔGs-HEK293) cells generated using the CRISPR/Cas9 system, combined with pharmacological modulation of cAMP formation revealed a Gs-dependent but cAMP-independent increase in intracellular Ca(2+) following β2AR stimulation...
March 9, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28279738/modifying-plasmid-loaded-hsa-nanoparticles-with-cell-penetrating-peptides-cellular-uptake-and-enhanced-gene-delivery
#11
J Mesken, A Iltzsche, D Mulac, K Langer
Gene therapy bears great potential for the cure of a multitude of human diseases. Research efforts focussed on the use of viral delivery vectors in the past decades, neglecting non-viral gene therapies of physical or chemical origin due to low transfection efficiency. However, side effects such as activation of oncogenes and inflammatory reactions upon immune cell activation are major obstacles impeding the clinical applicability of viral gene therapy vectors. The aim of this study was the development of a non-viral gene delivery system based on plasmid-loaded human serum albumin nanoparticles, which are biocompatible, biodegradable, and non-toxic in relevant concentrations...
March 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28274193/a-peptide-based-biological-coating-for-enhanced-corrosion-resistance-of-titanium-alloy-biomaterials-in-chloride-containing-fluids
#12
Noah Muruve, Yuanchao Feng, Jaye Platnich, Daniel Hassett, Randall Irvin, Daniel Muruve, Frank Cheng
Titanium alloys are common materials in the manufacturing of dental and orthopedic implants. Although these materials exhibit excellent biocompatibility, corrosion in response to biological fluids can impact prosthesis performance and longevity. In this work, a PEGylated metal binding peptide (D-K122-4-PEG), derived from bacteria Pseudomonas aeruginosa, was applied on a titanium (Ti) alloy, and the corrosion resistance of the coated alloy specimen was investigated in simulated chloride-containing physiological fluids by electrochemical impedance spectroscopy and micro-electrochemical measurements, surface characterization, and biocompatibility testing...
March 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28273180/synthesis-in-vitro-and-in-vivo-evaluation-of-3%C3%AE-18f-fluorocholic-acid-for-the-detection-of-drug-induced-cholestasis-in-mice
#13
Stef De Lombaerde, Sara Neyt, Ken Kersemans, Jeroen Verhoeven, Lindsey Devisscher, Hans Van Vlierberghe, Christian Vanhove, Filip De Vos
INTRODUCTION: Drug-induced cholestasis is a liver disorder that might be caused by interference of drugs with the hepatobiliary bile acid transporters. It is important to identify this interference early on in drug development. In this work, Positron Emission Tomography (PET)-imaging with a 18F labeled bile acid analogue was introduced to detect disturbed hepatobiliary transport of bile acids. METHODS: 3β-[18F]fluorocholic acid ([18F]FCA) was prepared by nucleophilic substitution of a mesylated precursor with [18F]fluoride, followed by deprotection with sodium hydroxide...
2017: PloS One
https://www.readbyqxmd.com/read/28265686/inhibition-of-cloned-herg-potassium-channels-by-risperidone-and-paliperidone
#14
Hong Joon Lee, Jin-Sung Choi, Bok Hee Choi, Sang June Hahn
Risperidone and one of its active metabolites, paliperidone, are widely used for the treatment of schizophrenia. We used a patch-clamp study to investigate the effects of paliperidone on hERG potassium channels expressed in HEK cells. Western blot analyses were used to study the effects of risperidone and paliperidone on hERG and hERG 3.1 isoform channel trafficking. Risperidone and paliperidone inhibited the hERG tail currents in a concentration-dependent manner with IC50 values of 0.16 and 0.57 μM, respectively...
March 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28265616/cryptolepine-and-quindoline-understanding-their-photophysics
#15
Inês F A Mariz, Sandra Pinto, João Lavrado, Alexandra Paulo, José M G Martinho, Ermelinda M S Maçôas
Quindoline (QUIND, indolo[3,2-b]quinoline) and cryptolepine (CRYPT, 5-methyl-10H-indolo[3,2-b]quinoline) together with their corresponding derivatives have been studied for decades due to their important biological activity against diseases like malaria. The biological activity of drugs is routinely investigated using fluorescence based methods. However, recent reports show that the photophysics of CRYPT and its analogues is not yet understood. Herein, the photophysics of CRYPT and QUIND is studied in aqueous solutions at different pH values and in both protic and aprotic solvents of different polarities...
March 7, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28263860/subcellular-distribution-of-the-18kda-translocator-protein-and-transcript-variant-pbr-s-in-human-cells
#16
Guo-Jun Liu, Ryan J Middleton, Richard B Banati
Despite continued interest in the 18kDa translocator protein (PBR/TSPO) as a biomarker and a therapeutic target for a range of diseases, its functional role, such as in the steroid synthesis pathway and energy metabolism has either become contentious or remains to be described more precisely. The PBR/TSPO gene consists of four exons, while a shorter isoform termed PBR-S lacks exon 2. The PBR-S 102-codon open reading frame differs to that of PBR/TSPO, resulting in a protein that is completely unrelated to PBR/TSPO...
March 2, 2017: Gene
https://www.readbyqxmd.com/read/28256197/hsv-1-icp27-induces-apoptosis-by-promoting-bax-translocation-to-mitochondria-through-interacting-with-14-3-3%C3%AE
#17
Ji Ae Kim, Jin Chul Kim, Jung Sun Min, Inho Kang, Jeongho Oh, Jeong Keun Ahn
The subcellular localization of Bax plays crucial role for during apoptosis. In response to apoptotic stimuli, Bax translocates from the cytoplasm to the mitochondria where it promotes the release of cytochrome c to the cytoplasm. In cells infected with HSV-1, apoptosis is triggered or blocked by diverse mechanisms. Here, we show that HSV-1 ICP27 induces apoptosis and modulates mitochondrial membrane potential in HEK 293T cells. We found that ICP27 interacts with 14-3-3θ which sequesters Bax to the cytoplasm...
March 3, 2017: BMB Reports
https://www.readbyqxmd.com/read/28254693/tlr4-md2-specific-peptides-stalled-in%C3%A2-vivo-lps-induced-immune-exacerbation
#18
Seolhee Park, Hyeon-Jun Shin, Masaud Shah, Hey-Young Cho, Muhammad Ayaz Anwar, Asma Achek, Hyuk-Kwon Kwon, Byugsung Lee, Tae Hyeon Yoo, Sangdun Choi
Negative regulation of Toll-like receptor-4 (TLR4) is anticipated to control the pathogen-induced exaggerated immune response. However, effective TLR4 antagonists with scarce off-target effects are yet to be developed. To fill this void, we sought to design small peptide-inhibitors of the TLR4/MD2-LPS interaction. Here we report novel TLR4-antagonistic peptides (TAP), identified through phage display, endowed with the LPS-induced proinflammation inhibition, and confirmed in mice. TAPs-attributed TLR4-antagonism were initially evaluated through NF-κB inhibition in HEK-blue hTLR4 and RAW264...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28254629/the-effect-of-nanoparticle-size-and-nls-density-on-nuclear-targeting-in-cancer-and-normal-cells-impaired-nuclear-import-and-aberrant-nanoparticle-intracellular-trafficking-in-glioma
#19
Salma N Tammam, Hassan M E Azzazy, Alf Lamprecht
The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer...
February 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28254579/resveratrol-induced-autophagy-is-dependent-on-ip3rs-and-on-cytosolic-ca-2
#20
Tomas Luyten, Kirsten Welkenhuyzen, Gemma Roest, Elzbieta Kania, Liwei Wang, Mart Bittremieux, David I Yule, Jan B Parys, Geert Bultynck
Previous work revealed that intracellular Ca(2+) signals and the inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are essential to increase autophagic flux in response to mTOR inhibition, induced by either nutrient starvation or rapamycin treatment. Here, we investigated whether autophagy induced by resveratrol, a polyphenolic phytochemical reported to trigger autophagy in a non-canonical way, also requires IP3Rs and Ca(2+) signaling. Resveratrol augmented autophagic flux in a time-dependent manner in HeLa cells...
February 28, 2017: Biochimica et Biophysica Acta
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