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https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#1
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27888461/inhibitory-effects-of-bee-venom-and-its-components-against-viruses-in-vitro-and-in-vivo
#2
Md Bashir Uddin, Byeong-Hoon Lee, Chamilani Nikapitiya, Jae-Hoon Kim, Tae-Hwan Kim, Hyun-Cheol Lee, Choul Goo Kim, Jong-Soo Lee, Chul-Joong Kim
Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV)...
December 2016: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27877159/efficacy-of-antibacterial-peptides-against-peptide-resistant-mrsa-is-restored-by-permeabilization-of-bacteria-membranes
#3
Joshua Ravensdale, Zachary Wong, Frances O'Brien, Keith Gregg
Clinical application of antimicrobial peptides (AMPs), as with conventional antibiotics, may be compromised by the development of bacterial resistance. This study investigated AMP resistance in methicillin resistant Staphylococcus aureus, including aspects related to the resilience of the resistant bacteria toward the peptides, the stability of resistance when selection pressures are removed, and whether resistance can be overcome by using the peptides with other membrane-permeabilising agents. Genotypically variant strains of S...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27808347/clinical-efficacy-of-melittin-in-the-treatment-of-cats-infected-with-the-feline-immunodeficiency-virus
#4
Anja D Hartmann, Natalie Wilhelm, Volker Erfle, Katrin Hartmann
OBJECTIVE: The bee venom melittin shows an antiviral efficacy against the human immunodeficiency virus in cell culture. It was shown to be non-toxic for cats. Aim of this pilot study was to investigate the clinical efficacy and side-effects of melittin in cats naturally infected with feline immunodeficiency virus (FIV). MATERIAL AND METHODS: The study was performed as a prospective, placebo-controlled double-blinded trial. Twenty cats were included, of which 10 cats each were treated with either melittin (500 µg/kg body weight) or phosphate-buffered saline (placebo) subcutaneously twice per week...
November 3, 2016: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/27788004/characterizing-and-controlling-the-loading-and-release-of-cationic-amphiphilic-peptides-onto-and-from-peg-stabilized-lipodisks
#5
Karin Reijmar, Katarina Edwards, Karl Andersson, Victor Agmo Hernandez
Recent studies have identified PEG-stabilized lipid nanodisks (lipodisks) as promising carriers for cationic amphiphilic peptides with antimicrobial and anticancer activity. Using fluorimetric and nanogravimetric methods, we have in this work characterized the parameters describing and controlling the binding of three selected peptides (melittin, LL37 and magainin 2) onto lipodisks. It was found that the affinity of melittin for lipodisks is independent on the disk size and rim charge. On the other hand, the number of binding sites is strongly dependent on both parameters, with the highest loading being obtained for small disks with a negatively charged rim...
October 27, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27772956/effect-of-melittin-treatment-in-a-mouse-model-of-xenobiotic-induced-cholangitis-and-biliary-fibrosis
#6
Hyun-Jung Sung, Kyung-Hyun Kim, Young-In Maeng, Kwan-Kyu Park
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27754384/metabolomic-profiling-of-the-effects-of-melittin-on-cisplatin-resistant-and-cisplatin-sensitive-ovarian-cancer-cells-using-mass-spectrometry-and-biolog-microarray-technology
#7
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin Kyu Park, Jong Woon Jeon, Valerie A Ferro, David G Watson
In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists...
October 13, 2016: Metabolites
https://www.readbyqxmd.com/read/27732908/when-and-how-the-melittin-ion-channel-exhibits-ohmic-behavior
#8
Lucia Becucci, Giovanni Aloisi, Rolando Guidelli
Melittin exhibits an ohmic behavior in a lipid bilayer having a DOPC distal leaflet and interposed between a 2.25nm tetraethyleneoxy chain tethered to a mercury drop and an aqueous solution. This behavior is induced in a pH6.8 buffer solution of 0.8μg/mL melittin by a pretreatment consisting of series of electrochemical impedance spectroscopy measurements at bias potentials varied by 50mV steps over a transmembrane potential range from about +250 to -250mV. This metastable ohmic behavior remains unchanged for hours, even after acidifying the solution to pH3...
October 6, 2016: Bioelectrochemistry
https://www.readbyqxmd.com/read/27718471/pyrazole-derived-ultra-short-antimicrobial-peptidomimetics-with-potent-anti-biofilm-activity
#9
Mija Ahn, Pethaiah Gunasekaran, Ganesan Rajasekaran, Eun Young Kim, Soo-Jae Lee, Geul Bang, Kun Cho, Jae-Kyung Hyun, Hyun-Ju Lee, Young Ho Jeon, Nam-Hyung Kim, Eun Kyoung Ryu, Song Yub Shin, Jeong Kyu Bang
In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin...
September 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27693786/melittin-ameliorates-cvb3-induced-myocarditis-via-activation-of-the-hdac2-mediated-gsk-3%C3%AE-nrf2-are-signaling-pathway
#10
Tuanjie Wang, Jian Zhang, Aiju Xiao, Weiqing Liu, Yun Shang, Jindou An
Viral myocarditis (VMC) is characterized as an inflammatory process of the myocardium and can be fatal in infants and children. Melittin is a major polypeptide in honey bee venom that has been traditionally used against inflammation. However, its effect on VMC and the underlying molecular mechanism has not been reported. In this study, BALB/c mice were intraperitoneally injected with CVB3 to build a VMC model and treated with melittin. The results showed that melittin increased the mice's body weight and inhibited CVB3 replication...
September 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27677623/application-of-bee-venom-and-its-main-constituent-melittin-for-cancer-treatment
#11
Cui-Cui Liu, Ding-Jun Hao, Qian Zhang, Jing An, Jing-Jing Zhao, Bo Chen, Ling-Ling Zhang, Hao Yang
Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles...
September 27, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27666985/one-step-purification-of-melittin-derived-from-apis-mellifera-bee-venom
#12
Angela Ching Ling Teoh, Kyoung-Hwa Ryu, Eun Gyo Lee
The concern of the use of melittin in honey bee venom due to its adverse reaction caused by allergens such as phospholipase A2 (PLA₂) and hyaluronidase (HYA) has been an obstacle towards its usage. We developed a novel single-step method for melittin purification and the removal of PLA₂ and HYA. This study explores the influence of pH, buffer compositions, salt concentration and types of cation-exchange chromatography resins on the recovery of melittin and the removal of both HYA and PLA₂. Melittin can be readily purified with a strong cation-exchange resin at pH 6...
September 23, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27651455/phosphorylation-specific-status-of-rnai-triggers-in-pharmacokinetic-and-biodistribution-analyses
#13
Vladimir S Trubetskoy, Jacob B Griffin, Anthony L Nicholas, Eric M Nord, Zhao Xu, Ryan M Peterson, Christine I Wooddell, David B Rozema, Darren H Wakefield, David L Lewis, Steven B Kanner
The RNA interference (RNAi)-based therapeutic ARC-520 for chronic hepatitis B virus (HBV) infection consists of a melittin-derived peptide conjugated to N-acetylgalactosamine for hepatocyte targeting and endosomal escape, and cholesterol-conjugated RNAi triggers, which together result in HBV gene silencing. To characterize the kinetics of RNAi trigger delivery and 5'-phosphorylation of guide strands correlating with gene knockdown, we employed a peptide-nucleic acid (PNA) hybridization assay. A fluorescent sense strand PNA probe binding to RNAi duplex guide strands was coupled with anion exchange high performance liquid chromatography to quantitate guide strands and metabolites...
September 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27631466/use-of-ultraviolet-photodissociation-coupled-with-ion-mobility-mass-spectrometry-to-determine-structure-and-sequence-from-drift-time-selected-peptides-and-proteins
#14
Alina Theisen, Bin Yan, Jeffery M Brown, Michael Morris, Bruno Bellina, Perdita E Barran
We demonstrate the capabilities of a laser-coupled ion mobility mass spectrometer for analysis of peptide sequence and structure showing ultraviolet photodissociation (UVPD) spectra of mass and mobility selected ions. A Synapt G2-S mass spectrometer has been modified to allow photointeraction of ions post the mobility cell. For this work, we have employed a single wavelength laser, which irradiates at 266 nm. We present the unique capabilities of this instrument and demonstrate several key features. Irradiation of luteinizing hormone releasing hormone (LHRH), growth hormone releasing hexapeptide (GHRP-6), and TrpCage (sequence NLYIQWLKDGGPSSGRPPPS) yields extensive b- and y-type fragmentation as well as a- and c-type ions...
October 3, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27618890/the-protective-effect-of-melittin-on-renal-fibrosis-in-an-animal-model-of-unilateral-ureteral-obstruction
#15
Hyun-Jin An, Jung-Yeon Kim, Woon-Hae Kim, Sang-Mi Han, Kwan-Kyu Park
Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-β1 (TGF-β1)...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27615014/selective-activation-of-anticancer-chemotherapy-by-cancer-associated-fibroblasts-in-the-tumor-microenvironment
#16
Mi-Gyeong Kim, Yuna Shon, Jinyoung Kim, Yu-Kyoung Oh
BACKGROUND: The tumor microenvironment has recently emerged as a new target of anticancer chemotherapy. Selective activation of anticancer chemotherapy in the tumor microenvironment would further reduce the toxicity of anticancer drugs toward normal tissues. Fibroblast activation protein (FAP) is known to be selectively overexpressed on cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Here, we designed an anticancer chemotherapeutic system based on promelittin, a peptide toxin that is selectively converted from an inactive form to the pore-forming melittin upon cleavage by FAP in the tumor microenvironment...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27554435/staphylokinase-has-distinct-modes-of-interaction-with-antimicrobial-peptides-modulating-its-plasminogen-activation-properties
#17
Leonard T Nguyen, Hans J Vogel
Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakΔN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27551823/large-scale-recombinant-expression-and-purification-of-human-tyrosinase-suitable-for-structural-studies
#18
Xuelei Lai, Montserrat Soler-Lopez, Harry J Wichers, Bauke W Dijkstra
Human tyrosinase (TYR) is a glycoprotein that initiates the first two reactions in the melanin biosynthesis pathway. Mutations in its encoding gene cause Oculocutaneous Albinism type I (OCA1), the most severe form of albinism, which is a group of autosomal recessive disorders characterized by reduced or absent production of melanin in skin, hair and eyes. Despite extensive structural and characterization studies of its homologues in lower eukaryotic organisms, the catalytic mechanism of human TYR and the molecular basis of OCA1 are largely unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27526681/the-interaction-of-melittin-with-dimyristoyl-phosphatidylcholine-dimyristoyl-phosphatidylserine-lipid-bilayer-membranes
#19
Durgesh K Rai, Shuo Qian, William T Heller
Membrane-active peptides (MAPs), which interact directly with the lipid bilayer of a cell and include toxins and host defense peptides, display lipid composition-dependent activity. Phosphatidylserine (PS) lipids are anionic lipids that are found throughout the cellular membranes of most eukaryotic organisms where they serve as both a functional component and as a precursor to phosphatidylethanolamine lipids. The inner leaflet of the plasma membrane contains more PS than the outer one, and the asymmetry is actively maintained...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27506246/self-assembly-and-the-hemolysis-effect-of-monodisperse-n-n-diethylacrylamide-acrylic-acid-nanogels-with-high-contents-of-acrylic-acid
#20
Xueting Li, Di Zhao, Xiaodi Shi, Gao Qiu, Xihua Lu
Monodisperse temperature/pH sensitive poly(N,N-diethylacrylamide/acrylic acid) (P(DEA/AAc)) nanogels with high contents of AAc up to 40 wt% have been prepared. In this study, it was unexpectedly found that the polydispersity of the nanogels with 40 wt% AAc strongly depended on the initiator concentration. Monodisperse P(DEA/AA) nanogels were synthesized only at a very low concentration of initiator. The phase transition behavior of the nanogels in water can be tuned by pH and temperature. Due to low polydispersity, the nanogels self-assembled into colloidal crystals at different temperatures below the volume phase transition temperature (VPTT)...
September 21, 2016: Soft Matter
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