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Juxin Yin, Jianjian Zhuang, Shaowu Lv, Ying Mu
Excessive reactive oxygen species (ROS) levels are harmful to the body. The peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant enzymes for preventing ROS-induced damage. Se-CuZn-65P is an enzyme mimetic with dual GPx and SOD antioxidant function. However, currently, its production is mainly based on the cysteine auxotrophic expression technique, which is inefficient, expensive, and time consuming. In this study, we combined protein engineering and the chemical mutation method to synthesize Se-CuZn-65P...
April 15, 2018: Journal of Molecular Recognition: JMR
Yoshitaka J Sei, Jungho Ahn, Taeyoung Kim, Eunjung Shin, Angel J Santiago-Lopez, Seung Soon Jang, Noo Li Jeon, Young C Jang, YongTae Kim
High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through its native roles like reverse cholesterol transport. The reconstitution of this natural nanoparticle (NP) has become a nexus between nanomedicine and multi-disease therapies, for which a major portion of HDL functionality is attributed to its primary scaffolding protein, apolipoprotein A1 (apoA1). ApoA1-mimetic peptides were formulated as cost-effective alternatives to apoA1-based therapies; reverse-4F (r4F) is one such peptide used as part of a nanoparticle platform...
April 6, 2018: Biomaterials
Qingqing Yao, Yangxi Liu, Balaranjan Selvaratnam, Ranjit T Koodali, Hongli Sun
Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF)...
April 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jesus Campagna, Kanagasabai Vadivel, Barbara Jagodzinska, Michael Jun, Tina Bilousova, Patricia Spilman, Varghese John
The aspartyl protease BACE1 (BACE) has emerged as an appealing target for reduction of amyloid-β (Aβ) in Alzheimer's disease (AD). The clinical fate of active-site BACE inhibitors may depend on potential side effects related to enzyme- and substrate-selectivity. One strategy to reduce this risk is through development of allosteric inhibitors that interact with and modulate the Loop F region unique to BACE1. Previously, a BACE-inhibiting antibody (Ab) was shown by co-crystallization to bind and induce conformational changes of Loop F, resulting in backbone perturbations at the distal S6 and S7 subsites, preventing proper binding of a long APP-like substrate to BACE and inhibiting its cleavage...
April 9, 2018: Journal of Molecular Biology
Camila M Mano, Thais Guaratini, Karina H M Cardozo, Pio Colepicolo, Etelvino J H Bechara, Marcelo P Barros
Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that affords many benefits to human health. ASTA is particularly effective against radical-mediated lipid peroxidation, and recent findings hypothesize a "mitochondrial-targeted" action of ASTA in cells. Therefore, we examined the protective effects of ASTA against lipid peroxidation in zwitterionic phosphatidylcholine liposomes (PCLs) and anionic phosphatidylcholine: phosphatidylglycerol liposomes (PCPGLs), at different pHs (6...
April 12, 2018: Marine Drugs
Alexey B Mantsyzov, Oleg Y Savelyev, Polina M Ivantcova, Stefan Bräse, Konstantin V Kudryavtsev, Vladimir I Polshakov
Synthetic β-peptides are potential functional mimetics of native α-proteins. A recently developed, novel, synthetic approach provides an effective route to the broad group of β-proline oligomers with alternating patterns of stereogenic centers. Conformation of the pyrrolidine ring, Z / E isomerism of β-peptide bonds, and hindered rotation of the neighboring monomers determine the spatial structure of this group of β-proline oligopeptides. Preferences in their structural organization and corresponding thermodynamic properties are determined by NMR spectroscopy, restrained molecular dynamics and quantum mechanics...
2018: Frontiers in Chemistry
Christoph P Sager, Brigitte Fiege, Pascal Zihlmann, Raghu Vannam, Said Rabbani, Roman P Jakob, Roland C Preston, Adam Zalewski, Timm Maier, Mark W Peczuh, Beat Ernst
Seven-membered ring mimetics of mannose were studied as ligands for the mannose-specific bacterial lectin FimH, which plays an essential role in the first step of urinary tract infections (UTI). A competitive binding assay and isothermal titration calorimetry (ITC) experiments indicated an approximately ten-fold lower affinity for the seven-membered ring mannose mimetic 2- O-n -heptyl-1,6-anhydro-d- glycero -d-galactitol ( 7 ) compared to n -heptyl α-d-mannopyranoside ( 2 ), resulting exclusively from a loss of conformational entropy...
January 21, 2018: Chemical Science
Di Wu, Yitian Gao, Yining Tan, Yuzhang Liu, Lei Wang, Mei Zhou, Xinping Xi, Chengbang Ma, Olaf R P Bininda-Emonds, Tianbao Chen, Chris Shaw
Amphibian skin secretions are an important treasure house of bioactive antimicrobial peptides (AMPs). Despite having been the focus of decades of research in this context, investigations of phyllomedusine frogs continue to identify new AMPs from their skin secretions. In this study, the prototype of a novel family of AMP distinctin-like-peptide-PH (DLP-PH) was identified from the skin secretion of the otherwise well-studied Tiger-Legged Tree Frog Phyllomedusa hypochondrialis through cloning of its precursor-encoding cDNA from a skin secretion-derived cDNA library by a 3'-rapid amplification of cDNA ends (RACE) strategy...
2018: Frontiers in Microbiology
Mohammadhasan Hedayati, Matt J Kipper
Blood vessels present a dense, non-uniform, polysaccharide-rich layer, called the endothelial glycocalyx. The polysaccharides in the glycocalyx include polyanionic glycosaminoglycans (GAGs). This polysaccharide-rich surface has excellent and unique blood compatibility. We report new methods for preparing and characterizing dense GAG surfaces that can serve as models of the vascular endothelial glycocalyx. The GAG-rich surfaces are prepared by adsorbing heparin or chondroitin sulfate-containing polyelectrolyte complex nanoparticles (PCNs) to chitosan-hyaluronan polyelectrolyte multilayers (PEMs)...
June 15, 2018: Carbohydrate Polymers
Federico Biglioli, Federico Bolognesi, Fabiana Allevi, Dimitri Rabbiosi, Silvia Cupello, Antonino Previtera, Alessandro Lozza, Valeria M A Battista, Claudio Marchetti
Recent facial paralyses, in which fibrillations of the mimetic muscles are still detectable by electromyography (EMG), allow facial reanimation based on giving new neural stimuli to musculature. However, if more time has elapsed, mimetic muscles can undergo irreversible atrophy, and providing a new neural stimulus is simply not effective. In these cases function is provided by transferring free flaps into the face or transposing masticatory muscles to reinstitute major movements, such as eyelid closure and smiling...
March 14, 2018: Journal of Cranio-maxillo-facial Surgery
Koichi Fujisawa, Kazusa Hara, Taro Takami, Sae Okada, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans...
April 6, 2018: Stem Cell Research & Therapy
Laia Montoliu-Gaya, Sandra D Mulder, Maaike A C Herrebout, Johannes C Baayen, Sandra Villegas, Robert Veerhuis
An imbalance between production and clearance of soluble amyloid-β (Aβ) initiates the pathological process in sporadic Alzheimer's disease (AD). Aβ-specific antibodies seemed promising as therapeutic option in AD mouse models. In patients, however, vascular side-effects and Aβ-antibody complex-induced microglial and/or perivascular macrophage inflammatory responses were encountered. To prevent inflammatory reactions, we designed a single chain variable fragment (scFv-h3D6), based on monoclonal antibody bapineuzumab (mAb-h3D6), but lacking the Fc region...
April 3, 2018: Molecular and Cellular Neurosciences
Ding Li, Stacey D Finley
Multiple promoters and inhibitors mediate angiogenesis, the formation of new blood vessels, and these factors represent potential targets for impeding vessel growth in tumors. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor targeted in anti-angiogenic cancer therapies. In addition, thrombospondin-1 (TSP1) is a major endogenous inhibitor of angiogenesis, and TSP1 mimetics are being developed as an alternative type of anti-angiogenic agent. The combination of bevacizumab, an anti-VEGF agent, and ABT-510, a TSP1 mimetic, has been tested in clinical trials to treat advanced solid tumors...
April 6, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Kaushik Mukherjee, Qichao Ruan, Steven Nutt, Jinhui Tao, James J De Yoreo, Janet Moradian-Oldak
The gradual discovery of functional domains in native enamel matrix proteins has enabled the design of smart bioinspired peptides for tooth enamel mimetics and repair. In this study, we expanded upon the concept of biomineralization to design smaller amelogenin-inspired peptides with conserved functional domains for clinical translation. The synthetic peptides displayed a characteristic nanostructured scaffold reminiscent of 'nanospheres' seen in the enamel matrix and effectively controlled apatite nucleation in vitro resulting in the formation of smaller crystallites...
March 31, 2018: ACS Omega
Shi-Cong Tao, Shang-Chun Guo, Chang-Qing Zhang
Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation...
February 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Luis R Castillo-Menendez, Kristen Witt, Nicole Espy, Amy Princiotto, Navid Madani, Beatriz Pacheco, Andrés Finzi, Joseph Sodroski
The mature envelope glycoprotein (Env) spike on the surface of human immunodeficiency virus (HIV-1) infected cells and virions is derived by proteolytic cleavage of a trimeric gp160 glycoprotein precursor. In these studies, we compared the conformations of cleaved and uncleaved membrane Envs with truncated cytoplasmic tails to those of stabilized soluble gp140 SOSIP.664 Env trimers. Deletion of the gp41 cytoplasmic tail did not significantly affect the sensitivity of viruses with the HIV-1AD8 Env to inhibition by antibodies or a CD4-mimetic compound...
April 4, 2018: Journal of Virology
Susan D Finkbeiner, Patricio A Salazar, Sofía Nogales, Cassidi E Rush, Adriana D Briscoe, Ryan I Hill, Marcus R Kronforst, Keith R Willmott, Sean P Mullen
Despite more than a century of biological research on the evolution and maintenance of mimetic signals, the relative frequencies of models and mimics necessary to establish and maintain Batesian mimicry in natural populations remain understudied. Here we investigate the frequency-dependent dynamics of imperfect Batesian mimicry, using predation experiments involving artificial butterfly models. We use two geographically distinct populations of Adelpha butterflies that vary in their relative frequencies of a putatively defended model ( Adelpha iphiclus ) and Batesian mimic ( Adelpha serpa )...
April 11, 2018: Proceedings. Biological Sciences
Amy M Princiotto, Vladimir D Vrbanac, Bruno Melillo, Jongwoo Park, Andrew M Tager, Amos B Smith, Joseph Sodroski, Navid Madani
Background: Small-molecule CD4-mimetic compounds (CD4mc) inhibit human immunodeficiency virus (HIV-1) entry by blocking binding to the CD4 receptor and by premature triggering of the viral envelope glycoprotein (Env) spike. Methods: The efficacy of a CD4mc in protecting bone-marrow-liver-thymus (BLT) humanized mice from vaginal HIV-1 challenge was evaluated. Results: Intravaginal application of the CD4mc JP-III-48, either prior to or simultaneously with virus challenge, protected BLT humanized mice from HIV-1JR-CSF infection in a dose-dependent manner...
March 29, 2018: Journal of Infectious Diseases
Kristy L Jackson, Francine Z Marques, Kyungjoon Lim, Pamela J Davern, Geoffrey A Head
Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS) and reactive oxygen species (ROS) reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle...
2018: Frontiers in Physiology
Chao Liu, Tianxu Han, David L Stachura, Huawei Wang, Boris L Vaisman, Jungsu Kim, Richard L Klemke, Alan T Remaley, Tariq M Rana, David Traver, Yury I Miller
Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish...
April 3, 2018: Nature Communications
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