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https://www.readbyqxmd.com/read/29332931/proteasome-inhibitor-carbobenzoxy-l-leucyl-l-leucyl-l-leucinal-mg132-enhances-therapeutic-effect-of-paclitaxel-on-breast-cancer-by-inhibiting-nuclear-factor-nf-%C3%AE%C2%BAb-signaling
#1
Yunjing Zhang, Bin Yang, Jinping Zhao, Xiaoli Li, Long Zhang, Zhenhua Zhai
BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde proteasome inhibitor, can inhibit tumor progression by inactivating nuclear factor (NF)-κB signaling. Paclitaxel (PTX) is part of a routine regimen for the treatment of breast cancer. However, activation of the NF-κB pathway after treatment with PTX confers insensitivity to this drug. This study investigated the potential effect of MG132 as a co-treatment with PTX against breast cancer, and clarifies the underlying molecular mechanisms...
January 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29299161/n-ac-l-leu-pei-mediated-mir-34a-delivery-improves-osteogenic-differentiation-under-orthodontic-force
#2
Wenwen Yu, Yi Zheng, Zhujun Yang, Hongbo Fei, Yang Wang, Xu Hou, Xinhua Sun, Yuqin Shen
Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the in vitro and in vivo effects of miR-34a on osteogenic differentiation under orthodontic force using an N-acetyl-L-leucine-modified polyethylenimine (N-Ac-l-Leu-PEI) carrier. N-Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of Runx2 and ColI, Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain in vitro...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29260462/agglomerated-novel-spray-dried-lactose-leucine-tailored-as-a-carrier-to-enhance-the-aerosolization-performance-of-salbutamol-sulfate-from-dpi-formulations
#3
Carlos Molina, Waseem Kaialy, Qiao Chen, Daniel Commandeur, Ali Nokhodchi
Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition)...
December 19, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29240717/a-novel-antibiotic-mechanism-of-l-cyclopropylalanine-blocking-the-biosynthetic-pathway-of-essential-amino-acid-l-leucine
#4
Bingji Ma, Jinwen Shen, Wandee Yindeeyoungyeon, Yuan Ruan
The unusual amino acid l-cyclopropylalanine was isolated from the mushroom Amanita virgineoides after detection in an anti-fungal screening test. l-Cyclopropylalanine was found to exhibit broad-spectrum inhibition against fungi and bacteria. The anti-fungal activity was found to be abolished in the presence of the amino acid l-leucine, but not any other amino acids, indicating that l-cyclopropylalanine may block the biosynthesis of the essential amino acid l-leucine, thereby inhibiting fungal and bacteria growth...
December 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29212719/a-novel-pathway-of-nutrient-absorption-in-crustaceans-branchial-amino-acid-uptake-in-the-green-shore-crab-carcinus-maenas
#5
Tamzin A Blewett, Greg G Goss
Estuaries are environments enriched with dissolved nutrients such as amino acids. To date, marine arthropods are the only invertebrate group that have not been demonstrated to access this potentially important nutrient resource. Using in vitro gill perfusion techniques, we sought to investigate the ability of the green shore crab (Carcinus maenas) to take up the amino acid l-leucine directly from the water. Investigation of the concentration-dependent transport kinetics of radiolabelled l-leucine showed that there are two specific transport pathways across Carcinus gills, one with high affinity and low capacity, and the other with high capacity and low affinity...
December 6, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29200902/jph203-a-selective-l-type-amino-acid-transporter-1-inhibitor-induces-mitochondria-dependent-apoptosis-in-saos2-human-osteosarcoma-cells
#6
Dae Woo Choi, Do Kyung Kim, Yoshikatsu Kanai, Michael F Wempe, Hitoshi Endou, Jong-Keun Kim
Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29191128/suppressive-effect-of-nobiletin-and-epicatechin-gallate-on-fructose-uptake-in-human-intestinal-epithelial-caco-2-cells
#7
Hideo Satsu, Sohei Awara, Tomonori Unno, Makoto Shimizu
Inhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters...
December 1, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29183324/novel-essential-amino-acid-supplements-enriched-with-l-leucine-facilitate-increased-protein-and-energy-intakes-in-older-women-a-randomised-controlled-trial
#8
Theocharis Ispoglou, Kevin Deighton, Roderick Fgj King, Helen White, Matthew Lees
BACKGROUND: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. METHODS: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7...
November 28, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/29167357/how-fish-eggs-are-preadapted-for-the-evolution-of-matrotrophy
#9
Keenan R Morrison, Vyvian Ngo, Richard A Cardullo, David N Reznick
Teleost fishes evolved livebearing via egg retention 14 times. Matrotrophy has evolved within 12 of those lineages. By contrast, squamate reptiles evolved livebearing over 115 times, but only two to four of those lineages are known to have evolved matrotrophy. Is the discrepancy between these organisms in the probability of this transition caused by differences in their eggs? We show that the eggs of oviparous species in the superorder Atherinomorpha can acquire small organic molecules from their surrounding environment against a concentration gradient via mechanisms of active transport...
November 29, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29162837/l-leucine-and-spns1-coordinately-ameliorate-dysfunction-of-autophagy-in-mouse-and-human-niemann-pick-type-c-disease
#10
Hiroko Yanagisawa, Tomohiro Ishii, Kentaro Endo, Emiko Kawakami, Kazuaki Nagao, Toshiyuki Miyashita, Keiko Akiyama, Kazuhiko Watabe, Masaaki Komatsu, Daisuke Yamamoto, Yoshikatsu Eto
Lysosomal storage disorders are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. 573C10 is a Schwann cell line derived from a mouse model of Niemann-Pick type C disease-1, NPC (-/-). Under serum-starved conditions, NPC (-/-) cells manifested impaired autophagy accompanied by an increase in the amount of p62 and lysosome enlargement. Addition of L-leucine to serum-starved NPC (-/-) cells ameliorated the enlargement of lysosomes and the p62 accumulation...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138359/comparative-effects-of-intraduodenal-amino-acid-infusions-on-food-intake-and-gut-hormone-release-in-healthy-males
#11
Robert E Steinert, Sina S Ullrich, Nori Geary, Lori Asarian, Marco Bueter, Michael Horowitz, Christine Feinle-Bisset
In contrast to the many studies of the effects of individual amino acids (AAs) on eating, no studies have compared the effects of different AAs on eating and underlying preabsorptive gastrointestinal mechanisms. To compare the effects of intraduodenal infusions of l-tryptophan (TRP), l-leucine (LEU), l-phenylalanine (PHE) and l-glutamine (GLN) on appetite, gastrointestinal hormone responses (including ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 [GLP-1]), glycemia (glucagon, insulin and glucose) and test meal size in healthy males, we retrospectively analyzed data from four published independent, randomized, double-blind, placebo-controlled studies of 90-min intraduodenal infusions of the individual AAs...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29137790/thermal-and-morphological-properties-of-nanocomposite-materials-based-on-graphene-oxide-and-l-leucine-containing-poly-benzimidazole-amide-prepared-by-ultrasonic-irradiation
#12
Mohammad Dinari, Elahe Salehi, Amir Abdolmaleki
A new poly(benzimidazole-amide) (PBIA) was fabricated by polycondensation of 1,3-bis(5-amino-1H-benzimidazole-2-yl)benzene with chiral diacid under green media by using tetra-n-butylammonium bromide as a cheap commercially available molten ionic salt at 120°C. The affection of reaction time on the polymer yield and viscosity was tested and optimized for PBIA. Inherent viscosity value of the prepared PBIA under optimized conditions is 0.31dL/g. Then to acquire a uniformly dispersion of graphene oxide (GO) in the PBIA matrix, GO was prepared through strong oxidation procedure...
March 2018: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/29136406/the-interaction-between-androgen-receptor-and-semenogelin-i-a-synthetic-lxxll-peptide-antagonist-inhibits-the-growth-of-prostate-cancer-cells
#13
Peng Li, Jinbo Chen, Eiji Kashiwagi, Taichi Mizushima, Bin Han, Satoshi Inoue, Hiroki Ide, Koji Izumi, Hiroshi Miyamoto
BACKGROUND: We previously demonstrated that a seminal plasma protein, semenogelin I (SgI), functioned as an androgen receptor (AR) coactivator. Meanwhile, several short sequence motifs in AR coregulators, such as LxxLL (L=leucine), have been shown to mediate specific interactions with AR. METHODS: We investigated the role of the LxxLL motif within SgI in the interactions with AR and cell growth in prostate cancer lines in vitro. RESULTS: A full-length SgI with mutations in the motif (i...
November 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29119997/dimeric-camptothecin-loaded-rgd-modified-targeted-cationic-polypeptide-based-micelles-with-high-drug-loading-capacity-and-redox-responsive-drug-release-capability
#14
Zhaopei Guo, Xingzhi Zhou, Mengze Xu, Huayu Tian, Xuesi Chen, Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-l-lysine (ε-Lys(Z)) and l-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide...
November 9, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29111711/formal-total-synthesis-of-c9-deoxyomuralide-from-l-leucine-using-a-double-sacrificial-chirality-transfer-approach
#15
Philip C Bulman Page, Ross L Goodyear, Alexandra E Horton, Yohan Chan, Rehana Karim, Maria A O'Connell, Christopher Hamilton, Alexandra M Z Slawin, Benjamin R Buckley, Steven Mark Allin
Formal stereocontrolled syntheses of (±)- and (+)-C9-deoxyomuralide is reported, constituting one of the shortest routes to the full carbon skeleton reported to date.
November 7, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29111706/17o-mas-nmr-correlation-spectroscopy-at-high-magnetic-fields
#16
Eric G Keeler, Vladimir K Michaelis, Michael T Colvin, Ivan Hung, Peter L Gor'kov, Timothy A Cross, Zhehong Gan, Robert G Griffin
The structure of two protected amino acids, FMOC-L-leucine and FMOC-L-valine, and a dipeptide, N-acetyl-L-valyl-L-leucine (N-Ac-VL), were studied via one- and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy. Utilizing 17O magic-angle spinning (MAS) NMR at multiple magnetic fields (17.6-35.2 T/750-1500 MHz for 1H) the 17O quadrupolar and chemical shift parameters were determined for the two oxygen sites of each FMOC-protected amino acids and the three distinct oxygen environments of the dipeptide...
November 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29108956/the-mouse-gm853-gene-encodes-a-novel-enzyme-leucine-decarboxylase
#17
Ana Lambertos, Bruno Ramos-Molina, David Cerezo, Andrés J López-Contreras, Rafael Peñafiel
Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently incorporated into the ODC/AZINs family is the murine Gm853, which is located in the same chromosome as AZIN2, and whose biochemical function is still unknown. By means of transfection assays of HEK293T cells with a plasmid containing the coding region of Gm853, we show here that unlike ODC, GM853 was a stable protein that was not able to decarboxylate l-ornithine or l-lysine and that did not act as an antizyme inhibitor...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29095657/redispersible-spray-dried-lipid-core-nanocapsules-intended-for-oral-delivery-the-influence-of-the-particle-number-on-redispersibility
#18
Diego Fontana de Andrade, Branko Vukosavljevic, Edilson Valmir Benvenutti, Adriana Raffin Pohlmann, Sílvia Stanisçuaski Guterres, Maike Windbergs, Ruy Carlos Ruver Beck
This study proposes a new approach to produce easily redispersible spray-dried lipid-core nanocapsules (LNC) intended for oral administration, evaluating the influence of the particle number density of the fed sample. The proposed approach to develop redispersible spray-dried LNC formulations intended for oral route is innovative, evidencing the needing of an optimization of the initial particle number density in the liquid suspension of nanocapsules. A mixture of maltodextrin and L-leucine (90:10 w/w) was used as drying adjuvant...
November 2, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29064707/l-carnosine-derived-fmoc-tripeptides-forming-ph-sensitive-and-proteolytically-stable-supramolecular-hydrogels
#19
Rita Das Mahapatra, Joykrishna Dey, Richard G Weiss
A series of β-amino acid containing tripeptides has been designed and synthesized in order to develop oligopeptide-based, thermoreversible, pH-sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9-methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown that the Fmoc group plays an important role in the gelation process. Also a dependence of gelation ability on hydrophobicity of the side chain of the Fmoc-protected α-amino acid was observed...
November 3, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29062971/characterization-of-the-metallo-dependent-amidohydrolases-responsible-for-auxiliary-leucinyl-removal-in-the-biosynthesis-of-2-2-bipyridine-antibiotics
#20
Ming Chen, Bo Pang, Ya-Nan Du, Yi-Peng Zhang, Wen Liu
2,2'-Bipyridine (2,2'-BiPy) is an attractive core structure present in a number of biologically active natural products, including the structurally related antibiotics caerulomycins (CAEs) and collismycins (COLs). Their biosynthetic pathways share a similar key 2,2'-BiPy-l-leucine intermediate, which is desulfurated or sulfurated at C5, arises from a polyketide synthase/nonribosomal peptide synthetase hybrid assembly line. Focusing on the common off-line modification steps, we here report that the removal of the "auxiliary" l-leucine residue relies on the metallo-dependent amidohydrolase activity of CaeD or ColD...
June 2017: Synthetic and Systems Biotechnology
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