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https://www.readbyqxmd.com/read/28549557/aberrant-distribution-of-the-trochlear-nerve-a-cadaveric-study-supported-by-immunohistochemistry
#1
Kojiro Takezawa, Grant Townsend, Jim Manavis, Mounir Ghabriel
The trochlear nerve is generally considered to be a purely motor nerve supplying one extraocular muscle, the superior oblique. In the current study, 28 orbits were dissected and in one orbit (3.6%), the trochlear nerve divided into two main branches. The medial branch followed the classical course, entered the superior oblique muscle and was presumed to be motor in function. However, before entering the muscle, it partially fused with the frontal nerve, and gave a bundle of nerve fibres to the frontal nerve...
May 23, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/28549350/an-anti-cancer-wxxxe-containing-azurin-polypeptide-inhibits-rac1-dependent-stat3-and-erk-gsk-3%C3%AE-signaling-in-breast-cancer-cells
#2
Zhe Zhang, Zhiyong Luo, Wenpu Min, Lin Zhang, Yaqun Wu, Xiaopeng Hu
In our previous study, we characterized a mycoplasmal small GTPase-like polypeptide of 240 amino acids that possesses an N-terminal WVLGE sequence. The N-terminal WVLGE sequence promotes activation of Rac1 and subsequent host cancer cell proliferation. To investigate the function of the WxxxE motif in the interaction with Rac1 and host tumor progression, we synthesized a 35-amino acid WVLGE-containing polypeptide derived from a cell-penetrating peptide derived from the azurin protein. We verified that the WVLGE-containing polypeptide targeted MCF-7 cells rather than MCF-10A cells...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544965/nrgd-modified-lycobetaine-and-octreotide-combination-delivery-system-to-overcome-multiple-barriers-and-enhance-anti-glioma-efficacy
#3
Tijia Chen, Xu Song, Ting Gong, Yao Fu, Liuqing Yang, Zhirong Zhang, Tao Gong
For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544962/effect-of-immobilization-on-the-antimicrobial-activity-of-a-cysteine-terminated-antimicrobial-peptide-cecropin-p1-tethered-to-silica-nanoparticle-against-e-coli-o157-h7-edl933
#4
Xi Wu, Pei-Hsun Wei, Xiao Zhu, Mary J Wirth, Arun Bhunia, Ganesan Narsimhan
Antimicrobial peptides (AMPs) have the ability to penetrate the cell membrane, form pores which eventually lead to cell death. Immobilization of AMP on nanoparticles can play a major role in antimicrobial materials, biosensors for pathogen detection and in food safety. The minimum inhibitory concentration (MIC) of free Cecropin P1 (CP1, sequence SWLSTAKKLENSAKKRLSEGIAIAIQGGPR) and adsorbed on silica nanoparticle against E. coli O157:H7 EDL933 were 0.78μg/ml. This was found to be consistent with preservation of α-helical secondary structure of CP1 upon adsorption as indicated by circular dichroism (CD)...
May 17, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28536357/glycosylated-triterpenoids-as-endosomal-escape-enhancers-in-targeted-tumor-therapies
#5
REVIEW
Hendrik Fuchs, Nicole Niesler, Alexandra Trautner, Simko Sama, Gerold Jerz, Hossein Panjideh, Alexander Weng
Protein-based targeted toxins play an increasingly important role in targeted tumor therapies. In spite of their high intrinsic toxicity, their efficacy in animal models is low. A major reason for this is the limited entry of the toxin into the cytosol of the target cell, which is required to mediate the fatal effect. Target receptor bound and internalized toxins are mostly either recycled back to the cell surface or lysosomally degraded. This might explain why no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date although more than 500 targeted toxins have been developed within the last decades...
March 29, 2017: Biomedicines
https://www.readbyqxmd.com/read/28534613/flashbody-a-next-generation-fluobody-with-fluorescence-intensity-enhanced-by-antigen-binding
#6
Devina Wongso, Jinhua Dong, Hiroshi Ueda, Tetsuya Kitaguchi
Fluorescent probes are valuable tools for visualizing the spatiotemporal dynamics of molecules in living cells. Here we developed a genetically-encoded antibody probe with antigen-dependent fluorescence intensity called "Flashbody". We first created a fusion of EGFP to the single chain variable region fragment (scFv) of antibody against seven amino acids of the bone Gla protein C-terminus (BGPC7) called BGP Fluobody, which successfully showed the intracellular localization of BGPC7-tagged protein. To generate BGP Flashbody, circularly permuted GFP was inserted in between two variable region fragments, and the linkers were optimized, resulting in fluorescence intensity increase of 300% upon binding with BGPC7 in a dose-dependent manner...
May 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28532244/virucidal-activity-of-cell-penetrating-peptides-of-viral-origin
#7
Nawal Abd El-Baky, Vladimir N Uversky, Elrashdy M Redwan
No abstract text is available yet for this article.
May 23, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28530637/cell-penetrating-peptides-selectively-targeting-smad3-inhibit-profibrotic-tgf-%C3%AE-signaling
#8
Jeong-Han Kang, Mi-Yeon Jung, Xueqian Yin, Mahefatiana Andrianifahanana, Danielle M Hernandez, Edward B Leof
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28528116/ph-controllable-cell-penetrating-polypeptide-possessing-cancer-targeting
#9
DaeYong Lee, IlKoo Noh, Jisang Yoo, N Sanoj Rejinold, Yeu-Chun Kim
Helical peptides were naturally-occurring ordered conformations that mediated various biological functions essential for biotechnology. However, it was difficult for natural helical polypeptides to be applied in biomedical fields due to low bioavailability. To avoid these problems, synthetic alpha-helical polypeptides have recently been introduced by further modifying pendants in the side chain. In spite of an attractive biomimetic helical motif, these systems could not be tailored for targeted delivery mainly due to nonspecific binding events...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28528024/structure-diverse-phylomer-libraries-as-a-rich-source-of-bioactive-hits-from-phenotypic-and-target-directed-screens-against-intracellular-proteins
#10
REVIEW
Paul M Watt, Nadia Milech, Shane R Stone
Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the delivery of a wide range of biologics...
May 18, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28525708/affinity-based-assembly-of-peptides-on-plasmonic-nanoparticles-delivered-intracellularly-with-light-activated-control
#11
Demosthenes P Morales, William Wonderly, Xiao Huang, Meghan McAdams, Amanda Chron, Norbert O Reich
We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and internalization peptide attachment are an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol labeled scaffolds terminated with the affinity partner...
May 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28524768/anti-microrna-targeting-using-peptide-based-nanocomplexes-to-inhibit-differentiation-of-human-pancreatic-stellate-cells
#12
Jonas Schnittert, Praneeth R Kuninty, Tomasz F Bystry, Roland Brock, Gert Storm, Jai Prakash
AIM: To develop novel peptide-based nanocomplexes (NCs) for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells (hPSCs), precursors of cancer-associated fibroblasts. MATERIALS & METHODS: NCs of anti-miRNA oligonucleotides and cell-penetrating peptides (different variants) were formed and characterized. The effects of anti-miR-199a delivery on hPSC differentiation and 3D heterospheroid formation were investigated. RESULTS: Dimeric cell-penetrating peptide based NCs (NC-2) showed 130-fold higher uptake by hPSCs compared with monomer-based NCs (NC-1) and tenfold higher uptake compared with general fibroblasts and different pancreatic tumor cells...
May 19, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28523591/assessment-of-the-neuroprotective-effects-of-arginine-rich-protamine-peptides-poly-arginine-peptides-r12-cyclic-r22-and-arginine-tryptophan-containing-peptides-following-in-vitro-excitotoxicity-and-or-permanent-middle-cerebral-artery-occlusion-in-rats
#13
Bruno P Meloni, Diego Milani, Jane L Cross, Vince W Clark, Adam B Edwards, Ryan S Anderton, David J Blacker, Neville W Knuckey
We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke...
May 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28522994/new-potent-membrane-targeting-antibacterial-peptides-from-viral-capsid-proteins
#14
Susana A Dias, João M Freire, Clara Pérez-Peinado, Marco M Domingues, Diana Gaspar, Nuno Vale, Paula Gomes, David Andreu, Sónia T Henriques, Miguel A R B Castanho, Ana S Veiga
The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28522193/ph-triggered-re-assembly-of-nanosphere-to-nanofiber-the-role-of-peptide-conformational-change-for-enhanced-cancer-therapy
#15
Peiqing Liang, Junjiong Zheng, Shulin Dai, Jiayu Wang, Zhaoqing Zhang, Ting Kang, Changyun Quan
pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28521201/validation-of-the-use-of-an-artificial-mitochondrial-reporter-dna-vector-containing-a-cytomegalovirus-promoter-for-mitochondrial-transgene-expression
#16
Yuma Yamada, Takuya Ishikawa, Hideyoshi Harashima
Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system...
May 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28517007/generation-of-a-cell-permeable-cycloheptapeptidyl-inhibitor-against-the-peptidyl-prolyl-isomerase-pin1
#17
Walaa Bedewy, Hui Liao, Nageh A Abou-Taleb, Sherif F Hammad, Tamer Nasr, Dehua Pei
Cyclic peptides are capable of binding and modulating challenging drug targets including protein-protein interactions. However, their lack of membrane permeability prevents their application against intracellular targets. In this study, we show that it is possible to design a cell-permeable and biologically active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl-prolyl isomerase Pin1 by integrating cell-penetrating and target-binding sequences.
May 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28512335/arginine-rich-cell-penetrating-peptide-modified-extracellular-vesicles-for-active-macropinocytosis-induction-and-efficient-intracellular-delivery
#18
Ikuhiko Nakase, Kosuke Noguchi, Ayako Aoki, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505457/molecular-and-biocompatibility-characterization-of-red-blood-cell-membrane-targeted-and-cell-penetrating-peptide-modified-polymeric-nanoparticles
#19
Kaustuv Sahoo, Sriharsha Karumuri, Rangika S Hikkaduwa Koralege, Nicholas H Flynn, Steve Hartson, Jing Liu, Joshua D Ramsey, Kaan Kalkan, Carey Pope, Ashish Ranjan
Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug encapsulated nanoparticles (NPs) to GPA, and modification with cell penetration peptide (CPP) will impact binding, oxygenation and induce cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single chain variable antibody (scFv TER-119, SNPs), and low molecular weight protamine based CPP (LNPs) and determine their biocompatibility using a variety of complementary high-throughput in vitro assays...
May 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28503153/investigating-engineered-ribonucleoprotein-particles-to-improve-oral-rnai-delivery-in-crop-insect-pests
#20
François-Xavier Gillet, Rayssa A Garcia, Leonardo L P Macedo, Erika V S Albuquerque, Maria C M Silva, Maria F Grossi-de-Sa
Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil (Anthonomus grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect...
2017: Frontiers in Physiology
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