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https://www.readbyqxmd.com/read/29792670/biomarker-based-metabolic-labeling-for-redirected-and-enhanced-immune-response
#1
Shanshan Li, Bingchen Yu, Jiajia Wang, Yueqin Zheng, Huajie Zhang, Margaret J Walker, Zhengnan Yuan, He Zhu, Jun Zhang, Peng George Wang, Binghe Wang
Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Such an approach can be an alternative strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases. Herein we describe the development of a new strategy to selectively label targets with an antibody-recruiting moiety through its covalent and stable installation, complementing existing methods of employing reversible binding...
May 24, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29791802/the-power-of-shielding-low-toxicity-and-high-transfection-performance-of-cationic-graft-copolymers-containing-poly-2-oxazoline-side-chains
#2
Anne-Kristin Trützschler, Tanja Bus, Martin Sahn, Anja Traeger, Christine Weber, Ulrich S Schubert
In this study we show the potential of oligo(2-ethyl-2-oxazoline) (OEtOx) shielded graft copolymers of (2 aminoethyl)-methacrylate (AEMA) and N methyl (2-aminoethyl) methacrylate (MAEMA) for pDNA delivery in HEK cells. Copolymers were synthesized via the macromonomer method using a combination of cationic ring opening polymerization (CROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization to vary the degree of grafting (DG = 10% and 30%) as well as the side chain degree of polymerization (DP = 5 and 20)...
May 23, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29790812/-express-nav1-7-is-phosphorylated-by-fyn-tyrosine-kinase-which-modulates-channel-expression-and-gating-in-a-cell-type-dependent-manner
#3
Yangyang Li, Tengteng Zhu, Huan Yang, Sulayman Dib-Hajj, Stephen Waxman, Ye Yu, Tian-Le Xu, Xiaoyang Cheng
Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, a Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29790738/design-and-development-of-polysaccharide-doxorubicin-peptide-bioconjugates-for-dual-synergistic-effects-of-integrin-targeted-and-cell-penetrating-peptides-for-cancer-chemotherapy
#4
Alexandra A P Mansur, Sandhra Maria Carvalho, Zelia Ines Portela Lobato, Maria de Fátima Leite, Armando da Silva Cunha, Herman S Mansur
Polymer-drug conjugation is an attractive approach for target delivering insoluble and highly toxic drugs to tumor sites to overcome the side-effects caused by cancer chemotherapy. In this study we designed and synthesized novel polymer-drug-peptide conjugates for improved specificity on targeting cancer cells. Chemically modified polysaccharide, carboxymethylcellulose (CMC), was conjugated with doxorubicin (DOX) anticancer drug by amide bonds and dually biofunctionalized with integrin-target receptor tripeptide (RGD) and L-arginine (R) as cell-penetrating amino acid for synergistic targeting and enhancing internalization by cancer cells...
May 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29790340/%C3%AE-diimines-as-versatile-derivatizable-ligands-in-ruthenium-ii-p-cymene-anticancer-complexes
#5
Lorenzo Biancalana, Lucinda K Batchelor, Tiziana Funaioli, Stefano Zacchini, Marco Bortoluzzi, Guido Pampaloni, Paul J Dyson, Fabio Marchetti
α-Diimines are among the most robust and versatile ligands available in synthetic coordination chemistry, possessing finely tunable steric and electronic properties. A series of novel cationic ruthenium(II) p-cymene complexes bearing simple α-diimine ligands, [(η6 - p-cymene)RuCl{κ2 N-(HCNR)2 }]NO3 (R = Cy, [1]NO3 ; R = 4-C6 H10 OH, [2]NO3 ; R = 4-C6 H4 OH, [3]NO3 ), were prepared in near-quantitative yields as their nitrate salts. [2]NO3 displays high water solubility. The potential of the α-diimine ligand in [3]NO3 as a carrier of bioactive molecules was investigated via esterification reactions with the hydroxyl groups...
May 23, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29780379/point-mutation-of-a-non-elastase-binding-site-in-human-%C3%AE-1-antitrypsin-alters-its-anti-inflammatory-properties
#6
Yotam Lior, Mariana Zaretsky, David E Ochayon, Diana Lotysh, Boris M Baranovski, Ronen Schuster, Ofer Guttman, Amir Aharoni, Eli C Lewis
Introduction: Human α1-antitrypsin (hAAT) is a 394-amino acid long anti-inflammatory, neutrophil elastase inhibitor, which binds elastase via a sequence-specific molecular protrusion (reactive center loop, RCL; positions 357-366). hAAT formulations that lack protease inhibition were shown to maintain their anti-inflammatory activities, suggesting that some attributes of the molecule may reside in extra-RCL segments. Here, we compare the protease-inhibitory and anti-inflammatory profiles of an extra-RCL mutation (cys232pro) and two intra-RCL mutations (pro357cys, pro357ala), to naïve [wild-type (WT)] recombinant hAAT, in vitro , and in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29775503/artificial-rod-and-cone-photoreceptors-with-human-like-spectral-sensitivities
#7
Byeongho Park, Heehong Yang, Tai Hwan Ha, Hyun Seo Park, Seung Ja Oh, Yong-Sang Ryu, Youngho Cho, Hyo-Suk Kim, Juyeong Oh, Dong Kyu Lee, Chulki Kim, Taikjin Lee, Minah Seo, Jaebin Choi, Young Min Jhon, Deok Ha Woo, Seok Lee, Seok Hwan Kim, Hyuk-Jae Lee, Seong Chan Jun, Hyun Seok Song, Tai Hyun Park, Jae Hun Kim
Photosensitive materials contain biologically engineered elements and are constructed using delicate techniques, with special attention devoted to efficiency, stability, and biocompatibility. However, to date, no photosensitive material has been developed to replace damaged visual-systems to detect light and transmit the signal to a neuron in the human body. In the current study, artificial nanovesicle-based photosensitive materials are observed to possess the characteristics of photoreceptors similar to the human eye...
May 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29775047/probing-cancer-cells-through-intracellular-aggregation-induced-emission-kinetic-rate-of-copper-nanoclusters
#8
Anushree Dutta, Upashi Goswami, Arun Chattopadhyay
pH responsive luminescent copper nanoclusters (Cu NCs) with aggregation induced emission (AIE) characteristics have been synthesized. Upon internalization into living cells, the NCs displayed cellular pH environment dependent luminescence change with orange-red emission at pHi 4.5 while bright green emission was observed over time at pHi 7.4, through their AIE attributes. Further, the intracellular AIE kinetics of the NC probe was measured in MCF-7 cells and compared with HEK-293 cells. Intriguingly, intracellular rate constant value derived for AIE kinetics in MCF-7 cells was found 3-fold higher than that in HEK-293 cell lines, whereas the value was 2-fold higher than that observed in the aqueous medium...
May 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29774408/possible-association-of-cag-repeat-polymorphism-in-kcnn3-encoding-the-potassium-channel-sk3-with-oxaliplatin-induced-neurotoxicity
#9
Benjamin Anon, Bérenger Largeau, Alban Girault, Aurélie Chantome, Morgane Caulet, Clémence Perray, Driffa Moussata, Christophe Vandier, Chantal Barin-Le Guellec, Thierry Lecomte
INTRODUCTION: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. MATERIALS AND METHODS: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density...
May 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29769518/a-cell-penetrating-artificial-metalloenzyme-regulates-a-gene-switch-in-a-designer-mammalian-cell
#10
Yasunori Okamoto, Ryosuke Kojima, Fabian Schwizer, Eline Bartolami, Tillmann Heinisch, Stefan Matile, Martin Fussenegger, Thomas R Ward
Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29768434/plasma-membrane-insertion-of-kca2-3-sk3-is-dependent-upon-the-snare-proteins-syntaxin-4-and-snap23
#11
Claudia A Bertuccio, Tony T Wang, Kirk L Hamilton, Diego J Rodriguez-Gil, Steven B Condliffe, Daniel C Devor
We previously demonstrated endocytosis of KCa2.3 is caveolin-1-, dynamin II- and Rab5-dependent. KCa2.3 then enters Rab35/EPI64C- and RME-1-containing recycling endosomes and is returned to the plasma membrane (PM). Herein, we report on the mechanism by which KCa2.3 is inserted into the PM during recycling and following exit from the Golgi. We demonstrate KCa2.3 colocalizes with SNAP-23 and Syntaxin-4 in the PM of HEK and endothelial cells by confocal immunofluorescence microscopy. We further show KCa2.3 can be co-immunoprecipitated with SNAP-23 and Syntaxin-4...
2018: PloS One
https://www.readbyqxmd.com/read/29767559/g-protein-pathway-suppressor-2-gps2-enhanced-the-renal-large-conductance-ca2-activated-potassium-channel-expression-via-inhibiting-erk-1-2-signaling-pathway
#12
Zhizhi Zhuang, Jia Xiao, Xinxin Chen, Xiaohan Hu, Ruidian Li, Shan Chen, Xiuyan Feng, Saier Shen, He-Ping Ma, Jieqiu Zhuang, Hui Cai
G-protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G-protein mitogen-activated protein kinase (MAPK) signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large conductance Ca2+ activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In HEK BK stably-expressing cells transfected with either GPS2 or its pCMV vector control, a single cell recording showed that GPS2 significantly increased BK channel activity (NPo), increasing BK open probability (Po) and channel number (N) compared to the control...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29761913/functional-variants-in-the-lc3b-gene-promoter-in-acute-myocardial-infarction
#13
Feng Gao, Qiang Su, Wentao Yang, Shuchao Pang, Shuai Wang, Yinghua Cui, Jinguo Zhang, Bo Yan
Acute myocardial infarction (AMI) is a common disease mainly caused by atherosclerosis, for which genetic causes remain largely unknown. Recently, low frequency and rare genetic variants have been proposed as risk factors. Autophagy has been involved in many cellular processes, such as lipid metabolism and inflammation, and implicated in human diseases, including cardiovascular diseases. In previous studies, we have reported reduced levels of LC3B, a core protein and a marker for autophagy, in AMI patients...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29761267/porcine-fc%C3%AE%C2%B5ri-mediates-porcine-reproductive-and-respiratory-syndrome-virus-multiplication-and-regulates-the-inflammatory-reaction
#14
Peidian Shi, Lilin Zhang, Jiashun Wang, Dong Lu, Yi Li, Jie Ren, Menglu Shen, Lei Zhang, Jinhai Huang
Porcine reproductive and respiratory syndrome virus (PRRSV) shows characteristic antibody-dependent enhancement (ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction; however, the role of porcine FcεRI in ADE is still unclear. In this study, the expression of different Fc receptors (FcRs) on macrophages was investigated in a PRRSV 3D4/21 cell infection model in the presence or absence of PRRSV antibody. The transcription level of FcγII and FcεRI was significantly up-regulated under PRRSV-antibody complex infection...
May 14, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/29760652/cadherins-interact-with-synaptic-organizers-to-promote-synaptic-differentiation
#15
Masahito Yamagata, Xin Duan, Joshua R Sanes
Classical cadherins, a set of ~20 related recognition and signaling molecules, have been implicated in many aspects of neural development, including the formation and remodeling of synapses. Mechanisms underlying some of these steps have been studied by expressing N-cadherin ( cdh2 ), a Type 1 cadherin, in heterologous cells, but analysis is complicated because widely used lines express cdh2 endogenously. We used CRISPR-mediated gene editing to generate a Human embryonic kidney (HEK)293 variant lacking Cdh2, then compared the behavior of rodent cortical and hippocampal neurons co-cultured with parental, cdh2 mutant and cdh2 -rescued 293 lines...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29757938/piezo1-channel-is-a-potential-regulator-of-synovial-sarcoma-cell-viability
#16
Takahisa Suzuki, Yukiko Muraki, Noriyuki Hatano, Hiroka Suzuki, Katsuhiko Muraki
Detection of mechanical stress is essential for diverse biological functions including touch, audition, and maintenance of vascular myogenic tone. PIEZO1, a mechano-sensing cation channel, is widely expressed in neuronal and non-neuronal cells and is expected to be involved in important biological functions. Here, we examined the possibility that PIEZO1 is involved in the regulation of synovial sarcoma cell-viability. Application of a PIEZO1 agonist Yoda1 effectively induced Ca2+ response and cation channel currents in PIEZO1 -expressing HEK (HEK-Piezo1) cells and synovial sarcoma SW982 (SW982) cells...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29757659/bone-marrow-derived-mesenchymal-stem-cells-promoted-cutaneous-wound-healing-by-regulating-keratinocyte-migration-via-the-%C3%AE-2-adrenergic-receptor-signaling
#17
Jiahui Huo, Sujing Sun, Zhijun Geng, Wei Sheng, Runkai Chen, Kui Ma, Xiaoyan Sun, Xiaobing Fu
Mesenchymal stem cells (MSCs) play an important role in the cutaneous wound healing; however, the functional mechanisms involved in the healing process are poorly understood. A series of studies indicate that keratinocytes which migrate into the wound bed rely on an epithelial-mesenchymal transition (EMT)-like process to initiate re-epithelialization. We therefore examined whether bone marrow-derived MSCs (BMSCs) could affect biological behavior and induce EMT-like characteristics in the human epidermal keratinocytes (HEKs) and in the immortalized human keratinocyte cell line HaCaT cells; and we investigated the signaling pathways of BMSC-mediated phenotypic changes...
May 14, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29755599/nuclear-lamin-protein-c-is-linked-to-lineage-specific-whole-cell-mechanical-properties
#18
Rafael D González-Cruz, Jessica S Sadick, Vera C Fonseca, Eric M Darling
INTRODUCTION: Lamin proteins confer nuclear integrity and relay external mechanical cues that drive changes in gene expression. However, the influence these lamins have on whole-cell mechanical properties is unknown. We hypothesized that protein expression of lamins A, B1, and C would depend on the integrity of the actin cytoskeleton and correlate with cellular elasticity and viscoelasticity. METHODS: To test these hypotheses, we examined the protein expression of lamins A, B1, and C across five different cell lines with varied mechanical properties...
April 2018: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/29753785/lactoferrin-inhibits-aflatoxin-b1-and-aflatoxin-m1-induced-cytotoxicity-and-dna-damage-in-caco-2-hek-hep-g2-and-sk-n-sh-cells
#19
Nan Zheng, Huan Zhang, Songli Li, Jiaqi Wang, Jia Liu, Hui Ren, Yanan Gao
Aflatoxins, including aflatoxin B1 (AFB1 ) and M1 (AFM1 ), are natural potent carcinogens produced by Aspergillus spp. These compounds, which can often be detected in dairy foods, can cause diseases in human beings. However, the molecular mechanisms involved in cytotoxicity, as well as methods for intervention, remain largely unexplored. For example, it is unclear whether lactoferrin (LF), a major antioxidant in milk, can inhibit the cytotoxicity of AFB1 and AFM1 . In this study, we assessed AFB1 - and AFM1 -induced cell toxicity by measuring cell viability, membrane permeability, and genotoxicity, and then investigated the ability of LF to protect cells against AFB1 and AFM1 ...
May 10, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29752618/tritium-labeled-agonists-as-tools-for-studying-adenosine-a-2b-receptors
#20
Sonja Hinz, Wessam M Alnouri, Ulrich Pleiss, Christa E Müller
A selective agonist radioligand for A2B adenosine receptors (A2B ARs) is currently not available. Such a tool would be useful for labeling the active conformation of the receptors. Therefore, we prepared BAY 60-6583, a potent and functionally selective A2B AR (partial) agonist, in a tritium-labeled form. Despite extensive efforts, however, we have not been able to establish a radioligand binding assay using [3 H]BAY 60-6583. This is probably due to its high non-specific binding and its moderate affinity, which had previously been overestimated based on functional data...
May 11, 2018: Purinergic Signalling
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