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https://www.readbyqxmd.com/read/28816044/action-of-gold-nanospikes-based-nanoradiosensitizers-cellular-internalization-radiotherapy-and-autophagy
#1
Ningning Ma, Peidang Liu, Nongyue He, Ning Gu, Fu-Gen Wu, Zhan Chen
A major challenge to achieve effective X-ray radiation therapy is to use a relatively low and safe radiation dose. Various radiosensitizers, which can significantly enhance the radiotherapeutic performance, have been developed. Gold-based nanomaterials, as a new type of nanoparticle-based radiosensitizers, have been extensively used in researches involving cancer radiotherapy. However, the cancer therapeutic effect using the gold nanoparticle-based radiotherapy is usually not significant because of the low cellular uptake efficiency and the autophagy-inducing ability of these gold nanomaterials...
August 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28807436/simple-and-efficient-knockdown-of-his-tagged-proteins-by-ternary-molecules-consisting-of-a-his-tag-ligand-a-ubiquitin-ligase-ligand-and-a-cell-penetrating-peptide
#2
Takayuki Hattori, Koyo Okitsu, Norikazu Yamazaki, Nobumichi Ohoka, Norihito Shibata, Takashi Misawa, Masaaki Kurihara, Yosuke Demizu, Mikihiko Naito
We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin-proteasome system (UPS)...
August 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28804533/in-vivo-radioprotective-activity-of-cell-permeable-bifunctional-antioxidant-enzyme-gst-tat-sod-against-whole-body-ionizing-irradiation-in-mice
#3
Jianru Pan, Huocong He, Ying Su, Guangjin Zheng, Junxin Wu, Shutao Liu, Pingfan Rao
GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28780039/disruption-of-5-ht2a-pdz-protein-interaction-differently-affects-the-analgesic-efficacy-of-ssri-snri-and-tca-in-the-treatment-of-traumatic-neuropathic-pain-in-rats
#4
Anne-Sophie Wattiez, Amandine Dupuis, Anne-Marie Privat, Maryse Chalus, Eric Chapuy, Youssef Aissouni, Alain Eschalier, Christine Courteix
Antidepressants remain one of the first line treatments prescribed to neuropathic pain patients despite their limited efficacy and/or their numerous side effects. More and more, pharmacotherapy for neuropathic pain has evolved towards the use of therapeutic combinations. The goal of the present study was to assess the efficacy of the combination of antidepressants - selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors-with a peptide (TAT-2ASCV) able to disrupt the interaction between serotonin type 2A (5-HT2A) receptors and associated PDZ proteins...
August 2, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28775288/a-polypeptide-from-the-junction-region-sequence-of-ews-fli1-inhibits-ewing-s-sarcoma-cells-interacts-with-the-ews-fli1-and-partner-proteins
#5
Krishna Priya Thangaretnam, Gopal Gopisetty, Priya Ramanathan, Thangarajan Rajkumar
The EWS-FLI1 chimeric protein uniquely expressed in Ewing's sarcoma has an obligate role in its aetiology. In our previous report we showed that ectopic expression of the DNA sequences form the junction region (a.a 251-280) can inhibit Ewing's sarcoma cell growth. In the present report, we introduced a peptide (TAT/NLS/EWS-PEP) comprising of thirty amino acids spanning the junction in conjunction with HIV-1-trans-activating (TAT) and nuclear localization signal sequence (NLS). Peptide uptake and localization studies revealed presence of peptide in ~99% of transduced cells and in the nucleus...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#6
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28765221/signal-peptide-hydrophobicity-modulates-interaction-with-the-twin-arginine-translocase
#7
Qi Huang, Tracy Palmer
The general secretory pathway (Sec) and twin-arginine translocase (Tat) operate in parallel to export proteins across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of plant chloroplasts. Substrates are targeted to their respective machineries by N-terminal signal peptides that share a tripartite organization; however, Tat signal peptides harbor a conserved and almost invariant arginine pair that is critical for efficient targeting to the Tat machinery. Tat signal peptides interact with a membrane-bound receptor complex comprised of TatB and TatC components, with TatC containing the twin-arginine recognition site...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28733898/d-cycloserine-ameliorates-autism-like-deficits-by-removing-glua2-containing-ampa-receptors-in-a-valproic-acid-induced-rat-model
#8
Han-Fang Wu, Po See Chen, Ya-Ting Hsu, Chi-Wei Lee, Tzu-Feng Wang, Yi-Ju Chen, Hui-Ching Lin
Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist D-cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28721013/a-novel-local-anesthetic-system-transcriptional-transactivator-peptide-decorated-nanocarriers-for-skin-delivery-of-ropivacaine
#9
Chuanyu Chen, Peijun You
PURPOSE: Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). METHODS: In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28717424/low-active-loading-of-cargo-into-engineered-extracellular-vesicles-results-in-inefficient-mirna-mimic-delivery
#10
Dhruvitkumar S Sutaria, Jinmai Jiang, Ola A Elgamal, Steven M Pomeroy, Mohamed Badawi, Xiaohua Zhu, Ryan Pavlovicz, Ana Clara P Azevedo-Pouly, Jeffrey Chalmers, Chenglong Li, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28713906/chronic-administration-of-sumo%C3%A2-1-has-negative-effects-on-novel-object-recognition-memory-as-well-as-cell-proliferation-and-neuroblast-differentiation-in-the-mouse-dentate-gyrus
#11
Dae Young Yoo, Dae Won Kim, Hyun Jung Kwon, Hyo Young Jung, Sung Min Nam, Jong Whi Kim, Jin Young Chung, Moo-Ho Won, Yeo Sung Yoon, Soo Young Choi, In Koo Hwang
Post‑translational modifications have been associated with developmental and aging processes, as well as in the pathogenesis of certain diseases. The present study aimed to investigate the effects of small ubiquitin‑like modifier 1 (SUMO‑1) on hippocampal dependent memory function, cell proliferation and neuroblast differentiation. To facilitate the delivery of SUMO‑1 into hippocampal neurons, a transactivator of transcription (Tat)‑SUMO‑1 fusion protein was constructed and mice were divided into two groups: A vehicle (Tat peptide)‑treated group and a Tat‑SUMO‑1‑treated group...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#12
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28699828/glioma-targeted-delivery-strategy-of-doxorubicin-loaded-liposomes-by-dual-ligand-modification
#13
Wei Han, Guangfu Yin, Ximing Pu, Xianchun Chen, Xiaoming Liao, Zhongbing Huang
The blood-brain barrier (BBB) is the protective parclose of brain safety, but it is also the main obstacle of the drug delivery to cerebral parenchyma, which hamper therapy for brain diseases. In this work, a glioma targeted drug delivery system was developed through loading doxorubicin into Angiopep-2 and TAT peptide dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor-related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding efficiency...
July 12, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28698313/hiv-and-hiv-tat-inhibit-lps-induced-il-27-production-in-human-macrophages-by-distinct-intracellular-signaling-pathways
#14
Niranjala Gajanayaka, Shifawn O'Hara, Yulia Konarski, Jason Fernandes, Kar Muthumani, Maya Kozlowski, Jonathan B Angel, Ashok Kumar
Monocyte-derived Mϕs (MDMs) from HIV-infected patients and MDM infected in vitro with HIV exhibit a reduced ability to secrete various cytokines, including IL-12. Recently, IL-27, an IL-12 family cytokine, was shown to inhibit HIV replication in Mϕ. Whether HIV infection or HIV accessory protein(s) impact IL-27 production in Mϕs remains unknown. Herein, we show that in vitro HIV infection, as well as intracellular HIV-Tat (Tat) and Tat peptides, inhibit LPS-induced IL-27 production in human MDMs, suggesting impairment of the TLR4 signaling pathway...
July 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28693996/human-epidermal-growth-factor-coupled-to-different-structural-classes-of-cell-penetrating-peptides-a-comparative-study
#15
Jing Chen, Haibin Li, Jianhua Chen
Human epidermal growth factor (hEGF) plays important roles in wound healing. Due to large molecular weight and hydrophilic nature, cellular uptake and skin permeation of hEGF are very poor, significantly limiting its efficacy. By using recombinant technology, four structural classes of cell penetrating peptides (CPPs) were fused at the C-terminus of hEGF, expressed and purified into homogeneity. Comparative studies were conducted to evaluate their activity, cytotoxicity, cellular uptake and skin permeation...
July 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28687749/inhibition-of-highly-pathogenic-avian-influenza-hpai-virus-by-a-peptide-derived-from-vflip-through-its-direct-destabilization-of-viruses
#16
Ho-Jin Moon, Chamilani Nikapitiya, Hyun-Cheol Lee, Min-Eun Park, Jae-Hoon Kim, Tae-Hwan Kim, Ji-Eun Yoon, Won-Kyung Cho, Jin Yeul Ma, Chul-Joong Kim, Jae U Jung, Jong-Soo Lee
The antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687253/connexin-hemichannel-inhibition-reduces-acetaminophen-induced-liver-injury-in-mice
#17
Michaël Maes, Sara Crespo Yanguas, Joost Willebrords, James L Weemhoff, Tereza Cristina da Silva, Elke Decrock, Margitta Lebofsky, Isabel Veloso Alves Pereira, Luc Leybaert, Anwar Farhood, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen...
August 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28682313/sphingosine-kinase-2-activates-autophagy-and-protects-neurons-against-ischemic-injury-through-interaction-with-bcl-2-via-its-putative-bh3-domain
#18
Dan-Dan Song, Tong-Tong Zhang, Jia-Li Chen, Yun-Fei Xia, Zheng-Hong Qin, Christian Waeber, Rui Sheng
Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release...
July 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28681892/exploring-the-impact-of-the-side-chain-length-on-peptide-rna-binding-events
#19
Lola Sbicca, Alejandro López González, Alexandra Gresika, Audrey Di Giorgio, Jordi Teixido Closa, Roger Estrada Tejedor, Marie-Line Andréola, Stéphane Azoulay, Nadia Patino
The impact of the amino-acid side-chain length on peptide-RNA binding events has been investigated using HIV-1 Tat derived peptides as ligands and the HIV-1 TAR RNA element as an RNA model. Our studies demonstrate that increasing the length of all peptide side-chains improves unexpectedly the binding affinity (KD) but reduces the degree of compactness of the peptide-RNA complex. Overall, the side-chain length appears to modulate in an unpredictable way the ability of the peptide to compete with the cognate TAR RNA partner...
July 6, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28662902/the-use-of-electronic-neutral-penetrating-peptides-cyclosporin-a-to-deliver-pro-apoptotic-peptide-a-possibly-better-choice-than-positively-charged-tat
#20
Wei Gao, Xiucong Yang, Zhiqiang Lin, Bing He, Dong Mei, Dan Wang, Haoran Zhang, Hua Zhang, Wenbing Dai, Xueqing Wang, Qiang Zhang
Cell-penetrating peptides (CPPs) are increasingly important in transporting macromolecules across cell membranes, but their use remains confined to narrow clinical applications due to the systemic toxicity induced by their positive charges. Several newly discovered electronic neutral penetrating peptides are not attracting much attention because their penetrating capacity is normally far less powerful than cationic or amphiphilic CPPs. In this study, we found the electronic neutral cyclic peptide cyclosporin A (CsA) exhibited 5...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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