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https://www.readbyqxmd.com/read/29928669/cholecystokinin-receptor-targeted-polyplex-nanoparticle-inhibits-growth-and-metastasis-of-pancreatic-cancer
#1
Julian Burks, Sandeep Nadella, Abdullah Mahmud, Charoen Mankongpaisarnrung, Juan Wang, Jong-In Hahm, Robin D Tucker, Narayan Shivapurkar, Stephan T Stern, Jill P Smith
Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) remains the most aggressive malignancy with the lowest 5-year survival rate of all cancers in part owing to the lack of tumor-specific therapy and the rapid metastatic nature of this cancer. The gastrointestinal peptide gastrin is a trophic peptide that stimulates growth of PDAC in an autocrine fashion by interaction with the cholecystokinin receptor that is overexpressed in this malignancy. Methods: We developed a therapeutic novel polyplex nanoparticle (NP) that selectively targets the cholecystokinin receptor on PDAC...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29927319/dietary-fat-stimulates-pancreatic-cancer-growth-and-promotes-fibrosis-of-the-tumor-microenvironment-through-the-cholecystokinin-receptor
#2
Sandeep Nadella, Julian Burks, Abdulhameed Al-Sabban, Gloria Inyang, Juan Wang, Robin D Tucker, Marie E Zamanis, William Bukowski, Narayan Shivapurkar, Jill P Smith
The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat to aid in digestion, and plasma CCK levels are elevated with the consumption of high fat diets. CCK is also a trophic peptide for the pancreas and has also been shown to stimulate growth of pancreatic cancer. In the current investigation, we studied the influence of a diet high in saturated fat on growth of pancreatic cancer in syngeneic murine models before the mice became obese to exclude the confounding factors associated with obesity...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29925682/enhancing-igg-distribution-to-lung-mucosal-tissue-improves-protective-effect-of-anti-pseudomonas-aeruginosa-antibodies
#3
M Jack Borrok, Antonio DiGiandomenico, Nurten Beyaz, Gabriela M Marchetti, Arnita S Barnes, Kristen J Lekstrom, Sandrina S Phipps, Michael P McCarthy, Herren Wu, William F Dall'Acqua, Ping Tsui, Ruchi Gupta
IgG antibodies are abundantly present in the vasculature but to a much lesser extent in mucosal tissues. This contrasts with antibodies of the IgA and IgM isotype that are present at high concentration in mucosal secretions due to active delivery by the polymeric Ig receptor (pIgR). IgG is the preferred isotype for therapeutic mAb development due to its long serum half-life and robust Fc-mediated effector function, and it is utilized to treat a diverse array of diseases with antigen targets located in the vasculature, serosa, and mucosa...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29921321/extracellular-release-of-virulence-factor-major-surface-protease-via-exosomes-in-leishmania-infantum-promastigotes
#4
Skye Marshall, Patrick H Kelly, Brajesh K Singh, R Marshall Pope, Peter Kim, Bayan Zhanbolat, Mary E Wilson, Chaoqun Yao
BACKGROUND: The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment...
June 19, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29915220/predicta-chip-based-high-resolution-diagnosis-of-rhinovirus-induced-wheeze
#5
Katarzyna Niespodziana, Katarina Stenberg-Hammar, Spyridon Megremis, Clarissa R Cabauatan, Kamila Napora-Wijata, Phyllis C Vacal, Daniela Gallerano, Christian Lupinek, Daniel Ebner, Thomas Schlederer, Christian Harwanegg, Cilla Söderhäll, Marianne van Hage, Gunilla Hedlin, Nikolaos G Papadopoulos, Rudolf Valenta
Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology...
June 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29915147/proteomics-reveals-scope-of-mycolactone-mediated-sec61-blockade-and-distinctive-stress-signature
#6
Jean-David Morel, Anja O Paatero, Jiajie Wei, Jonathan W Yewdell, Laure Guenin-Macé, Delphi Van Haver, Francis Impens, Natalia Pietrosemoli, Ville O Paavilainen, Caroline Demangel
Mycolactone is a bacteria-derived macrolide that blocks the biogenesis of a large array of secretory and integral transmembrane proteins (TMP) through potent inhibition of the Sec61 translocon. Here, we used quantitative proteomics to delineate the direct and indirect effects of mycolactone-mediated Sec61 blockade in living cells. In T lymphocytes, dendritic cells and sensory neurons, Sec61 substrates downregulated by mycolactone were in order of incidence: secretory proteins (with a signal peptide but no transmembrane domain), TMPs with a signal peptide (Type I) and TMPs without signal peptide and a cytosolic N-terminus (Type II)...
June 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29910937/engineering-thermoresponsive-phase-separated-vesicles-formed-via-emulsion-phase-transfer-as-a-content-release-platform
#7
Kaiser Karamdad, James W Hindley, Guido Bolognesi, Mark S Friddin, Robert V Law, Nicholas J Brooks, Oscar Ces, Yuval Elani
Giant unilamellar vesicles (GUVs) are a well-established tool for the study of membrane biophysics and are increasingly used as artificial cell models and functional units in biotechnology. This trend is driven by the development of emulsion-based generation methods such as Emulsion Phase Transfer (EPT), which facilitates the encapsulation of almost any water-soluble compounds (including biomolecules) regardless of size or charge, is compatible with droplet microfluidics, and allows GUVs with asymmetric bilayers to be assembled...
June 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29909197/plasmonic-au-nanostar-raman-probes-coupling-with-highly-ordered-tio-2-au-nanotube-arrays-as-the-reliable-sers-sensing-platform-for-chronic-myeloid-leukemia-drug-evaluation
#8
Shengping Wen, Yu Su, Rong Wu, Shiwei Zhou, Qianhao Min, Gao-Chao Fan, Li-Ping Jiang, Rong-Bin Song, Jun-Jie Zhu
The accurate therapeutic evaluation for chronic myeloid leukemia (CML) drug is of great importance to minimize side effects and enhance efficacy. Herein, a facile and precise surface-enhanced scattering (SERS) approach based on coupled plasmonic field has been introduced to evaluate the therapeutic outcomes of antileukemia drug through ultrasensitive assay of caspase-3 activity in apoptotic cells. Caspase-3 as an apoptosis indicator could specifically cleave the N-terminus of biotinylated DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Gly-Cys) immobilized on the Au nanoparticle-decorated TiO2 nanotube arrays (TiO2 /Au NTAs) substrate...
June 2, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29906285/murine-leukemia-virus-p12-tethers-the-capsid-containing-pre-integration-complex-to-chromatin-by-binding-directly-to-host-nucleosomes-in-mitosis
#9
Madushi Wanaguru, David J Barry, Donald J Benton, Nicola J O'Reilly, Kate N Bishop
The murine leukaemia virus (MLV) Gag cleavage product, p12, is essential for both early and late steps in viral replication. The N-terminal domain of p12 binds directly to capsid (CA) and stabilises the mature viral core, whereas defects in the C-terminal domain (CTD) of p12 can be rescued by addition of heterologous chromatin binding sequences (CBSs). We and others hypothesised that p12 tethers the pre-integration complex (PIC) to host chromatin ready for integration. Using confocal microscopy, we have observed for the first time that CA localises to mitotic chromatin in infected cells in a p12-dependent manner...
June 15, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29902373/characterization-of-disulfide-linkages-in-proteins-by-193-nm-ultraviolet-photodissociation-uvpd-mass-spectrometry
#10
M Montana Quick, Christopher M Crittenden, Jake A Rosenberg, Jennifer S Brodbelt
Deciphering disulfide bond patterns in proteins remains a significant challenge. In the present study, inter-linked disulfide bonds connecting peptide chains are homolytically cleaved with 193 nm ultraviolet photodissociation (UVPD). Analysis of insulin showcased the ability of UVPD to cleave multiple disulfide bonds and provide sequence coverage of the peptide chains in the same MS/MS event. For proteins containing more complex disulfide bonding patterns, an approach combining partial reduction and alkylation mitigated disulfide scrambling and alloed assignment of the array of disulfide bonds...
June 14, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29899427/treating-the-intestine-with-oral-apoa-i-mimetic-tg6f-reduces-tumor-burden-in-mouse-models-of-metastatic-lung-cancer
#11
Arnab Chattopadhyay, Xinying Yang, Pallavi Mukherjee, Dawoud Sulaiman, Hannah R Fogelman, Victor Grijalva, Steven Dubinett, Tonya C Wasler, Manash K Paul, Ramin Salehi-Rad, Julia J Mack, M Luisa Iruela-Arispe, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy
Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29895785/a-novel-shk-like-toxic-peptide-from-the-transcriptome-of-the-cnidarian-palythoa-caribaeorum-displays-neuroprotection-and-cardioprotection-in-zebrafish
#12
Qiwen Liao, Guiyi Gong, Shirley Weng In Siu, Clarence Tsun Ting Wong, Huidong Yu, Yu Chung Tse, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee
Palythoa caribaeorum (class Anthozoa) is a zoantharian which, together with other cnidarians, like jellyfishes, hydra, and sea anemones, possesses specialized structures in its tissues, the cnidocytes, which deliver an array of toxins in order to capture prey and deter predators. The whole transcriptome of P. caribaeroum was deep sequenced, and a diversity of toxin-related peptide sequences were identified, and some retrieved for functional analysis. In this work, a peptide precursor containing a ShK domain, named PcShK3, was analyzed by means of computational processing, comprising structural phylogenetic analysis, model prediction, and dynamics simulation of peptide-receptor interaction...
June 12, 2018: Toxins
https://www.readbyqxmd.com/read/29890117/peptide-amyloids-in-the-origin-of-life
#13
REVIEW
Jason Greenwald, Witek Kwiatkowski, Roland Riek
How life can emerge from non-living matter is one of the fundamental mysteries of the universe. A bottom-up approach to this problem focuses on the potential chemical precursors of life, in particular the nature of the first replicative molecules. Such thinking has led to the currently most popular idea: that a RNA-like molecule played a central role as the first replicative and catalytic molecule. Here, we review an alternative hypothesis that has recently gained experimental support, focusing on the role of amyloidogenic peptides rather than nucleic acids, in what has been by some termed "the amyloid-world" hypothesis...
June 8, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29888302/sex-differences-after-chronic-stress-in-the-expression-of-opioid-stress-and-neuroplasticity-related-genes-in-the-rat-hippocampus
#14
Matthew Randesi, Yan Zhou, Sanoara Mazid, Shannon C Odell, Jason D Gray, J Correa da Rosa, Bruce S McEwen, Teresa A Milner, Mary Jeanne Kreek
Opioid peptides and their receptors re-organize within hippocampal neurons of female, but not male, rats following chronic immobilization stress (CIS) in a manner that promotes drug-related learning. This study was conducted to determine if there are also sex differences in gene expression in the hippocampus following CIS. Adult female and male rats were subjected to CIS (30 min/day) for 10 days. Twenty-four hours after the last stressor, the rats were euthanized, the brains were harvested and the medial (dentate gyrus/CA1) and lateral (CA2/CA3) dorsal hippocampus were isolated...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29886535/mapping-amyloid-regions-in-gad-m-1-with-peptide-arrays
#15
Rosa Sánchez, Javier Martínez, Laura Montoya, Milagros Castellanos, Maria Gasset
Amyloid formation is basically featured by a protein-protein interaction in which the reacting regions are the segments assembling into cross β-sheets. To identify these segments both theoretical and experimental tools have been developed. Here, we focus on the use of peptide arrays to probe the binding of several amyloid-specific probes such as the OC and A11 anti-amyloid conformation-selective antibodies and of monomers and preformed fibrils. These arrays use libraries containing partly overlapping peptides derived from the sequence of Gad m 1, the major allergen from Atlantic cod, which forms amyloids under gastrointestinal relevant conditions...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29885883/microrna-125a-regulates-mhc-i-expression-on-esophageal-adenocarcinoma-cells-associated-with-suppression-of-anti-tumor-immune-response-and-poor-outcomes-of-patients
#16
Luigi Mari, Sanne J M Hoefnagel, Domenico Zito, Marian van de Meent, Peter van Endert, Silvia Calpe, Maria Del Carmen Sancho Serra, Mirjam H M Heemskerk, Hanneke W M van Laarhoven, Maarten C C M Hulshof, Susanne S Gisbertz, Jan Paul Medema, Mark I van Berge Henegouwen, Sybren L Meijer, Jacques J G H M Bergman, Francesca Milano, Kausilia K Krishnadath
BACKGROUND & AIMS: Immune checkpoint inhibition may affect growth or progression of highly aggressive cancers, such as esophageal adenocarcinoma (EAC). We investigated the regulation of expression of major histocompatibility complex, class 1 (MHC-I) proteins (encoded by HLA-A, HLA-B, and HLA-C) and the immune response to EACs in patient samples. METHODS: We performed quantitative PCR array analyses of OE33 cells and OE19 cells, which express different levels of the ATP binding cassette subfamily B member 1 (TAP1) and TAP2, required for antigen presentation by MHC-I, to identify microRNAs that regulate their expression...
June 7, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29885785/aggregation-of-%C3%AE-and-%C3%AE-caseins-induced-by-peroxyl-radicals-involves-secondary-reactions-of-carbonyl-compounds-as-well-as-di-tyrosine-and-di-tryptophan-formation
#17
Eduardo Fuentes-Lemus, Eduardo Silva, Pablo Barrias, Alexis Aspee, Elizabeth Escobar, Lasse G Lorentzen, Luke Carroll, Fabian Leinisch, Michael J Davies, Camilo López-Alarcón
The present work examined the role of Tyr and Trp in oxidative modifications of caseins, the most abundant milk proteins, induced by peroxyl radicals (ROO• ). We hypothesized that the selectivity of ROO• and the high flexibility of caseins (implying a high exposure of Tyr and Trp residues) would favor radical-radical reactions, and di-tyrosine (di-Tyr) and di-tryptophan (di-Trp) formation. Solutions of α- and β-caseins were exposed to ROO• from thermolysis and photolysis of AAPH (2,2'-azobis(2-methylpropionamidine)dihydrochloride)...
June 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29880633/skin-glands-of-an-aquatic-salamander-vary-in-size-and-distribution-and-release-antimicrobial-secretions-effective-against-chytrid-fungal-pathogens
#18
Kenzie E Pereira, Brian I Crother, David M Sever, Clifford L Fontenot, John A Pojman, Damien B Wilburn, Sarah K Woodley
Amphibian skin is unique among vertebrate classes, containing a large number of multicellular exocrine glands that vary among species and have diverse functions. The secretions of skin glands contain a rich array of bioactive compounds including antimicrobial peptides (AMPs). Such compounds are important for amphibian innate immune responses and may protect some species from chytridiomycosis, a lethal skin disease caused by the fungal pathogens, Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal)...
June 7, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29867843/modes-of-action-of-a-bi-domain-plant-defensin-mtdef5-against-a-bacterial-pathogen-xanthomonas-campestris
#19
Siva L S Velivelli, Kazi T Islam, Eric Hobson, Dilip M Shah
Defensins are small cysteine-rich endogenous host defense peptides expressed in all higher plants. They are thought to be important players in the defense arsenal of plants against fungal and oomycete pathogens. However, little is known regarding the antibacterial activity of these peptides. The genome of the model legume Medicago truncatula contains 63 genes each encoding a defensin with a tetradisulfide array. A unique bi-domain defensin, designated MtDef5, was recently characterized for its potent broad-spectrum antifungal activity...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29867793/antimicrobial-peptides-and-nanotechnology-recent-advances-and-challenges
#20
REVIEW
Lubhandwa S Biswaro, Mauricio G da Costa Sousa, Taia M B Rezende, Simoni C Dias, Octavio L Franco
Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant Staphylococcus aureus (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against Pseudomonas fluorescens than when the antibiotic was alone...
2018: Frontiers in Microbiology
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