Search Results (8)

We previously isolated a cDNA clone for galactosylceramide expression factor 1, which is the rat homologue of hepatocyte-growth-factor-regulated tyrosine kinase substrate (HGS) and induces galactosylceramide expression and morphological changes in COS-7 cells, and reported that overexpression of HGS induced morphological changes in canine kidney epithelial MDCK cells. HGS is a component of the endosomal sorting complexes required for transport machinery that mediates endosomal multivesicle body formation. In this study, the overexpression of HGS induced epithelial–mesenchymal transition and caused transformation in MDCK cells, whereas the overexpression of a coiled-coil domain of HGS inhibited induction of epithelial–mesenchymal transition by HGF stimulation. The overexpression of HGS in mouse melanoma B16 cells and human colorectal cancer COLO205 cells promoted cancer characteristic anchorage-independent cell growth ability and tumor growth, whereas the overexpression of the coiled-coil domain of HGS in these cells suppressed them. The oligopeptide OP12-462 constituting the coiled-coil domain suppressed the anchorage-independent cell growth ability and tumor growth of COLO205 cells. The coiled-coil domain of HGS and OP12-462 are novel tumor growth inhibitors that do not directly destroy cancer cells but rather inhibit only the anchorage-independent cell growth ability of cancer cells. Full article

The dietary presence of feed additives is crucial for boosting fish growth and immunity. Accordingly, this feeding trial aimed to investigate the effects of the separate and concurrent dietary supplementation of Spirulina platensis (SP) and bitter lemon (Citrus limon) peel essential oil (LEO) on the growth, immunity, antioxidant capacity, and intestinal health of Nile tilapia (Oreochromis niloticus). Four groups of male Nile tilapia were employed. The first group (control) was given the basal diet, while the second and third groups received the basal diet supplemented with LEO extract (1%) and SP (1 g/kg diet), respectively. The fourth group received the basal diet supplemented with a mix of LEO (1%) and SP at 1 g/kg. After two months of feeding, using LEO or/and SP improved the overall growth and immunological parameters, with their combination yielding the best outcomes. The supplementation of LEO or/and SP improved the Nile tilapia’s growth metrics and transcriptomic levels of growth-regulating genes such as (oligo-peptide transporter 1 (Pep1), growth hormone receptors 1 (GHR1), and insulin-like growth factor (IGF1). The improved growth performance was linked to significant increases in the expression levels of mucin and fat metabolism-related genes. Moreover, fish supplemented with LEO, SP, or their combination showed enhanced non-specific immunological measures, including phagocytic and lysozyme activities and the mRNA copies of its regulating genes. Additionally, remarkable increases in the antioxidant enzyme activities and the mRNA levels of their related genes were detected. The complement (C3) gene’s transcriptomic level was also significantly increased. Furthermore, the dietary supplementation of LEO, SP, or their combination improved the histological structures of the spleen, hepatopancreas, and intestine. The enhanced effects of LEO, SP, or their combination on fish immunity and growth are suggested to be due to their contents of bioactive compounds with anti-inflammatory, antioxidant, and antimicrobial properties. Thus, using the LOE and SP blends as feed additives is recommended for better growth and immunity of Nile tilapia. Full article

Cell-penetrating peptides (CPPs) are small peptides capable of translocating through biological membranes carrying various attached cargo into cells and even into the nucleus. They may also participate in transcellular transport. Our in silico study intends to model several peptides and their conjugates. We have selected three CPPs with a linear backbone, including penetratin, a naturally occurring oligopeptide; two of its modified sequence analogues (6,14-Phe-penetratin and dodeca-penetratin); and three natural CPPs with a cyclic backbone: Kalata B1, the Sunflower trypsin inhibitor 1 (SFT1), and Momordica cochinchinensis trypsin inhibitor II (MCoTI-II). We have also built conjugates with the small-molecule drug compounds doxorubicin, zidovudine, and rasagiline for each peptide. Molecular dynamics (MD) simulations were carried out with explicit membrane models. The analysis of the trajectories showed that the interaction of penetratin with the membrane led to spectacular rearrangements in the secondary structure of the peptide, while cyclic peptides remained unchanged due to their high conformational stability. Membrane–peptide and membrane–conjugate interactions have been identified and compared. Taking into account well-known examples from the literature, our simulations demonstrated the utility of computational methods for CPP complexes, and they may contribute to a better understanding of the mechanism of penetration, which could serve as the basis for delivering conjugated drug molecules to their intracellular targets. Full article

The oxidative state of intestinal tracts of healthy animals were investigated after short-term intake of half-fin anchovy hydrolysates (HAHp) and their thermal or Maillard reaction products (MRPs). After one month of continuous oral gavage of HAHp, HAHp-heated products (HAHp-H), the MRPs of HAHp with 3% of glucose (HAHp-3%G MRPs), and the MRPs of HAHp with 3% of fructose (HAHp-3%F MRPs) at a dose of 1.0 g/kg of body weight per day into healthy ICR male mice, the concentrations of serum low-density and high-density lipoprotein cholesterol did not significantly change compared to the control group (CK, gavage with saline). Similar results were found for the interleukin-6 concentrations of all groups. By comparison, HAHp-H, HAHp-3%G MRPs, and HAHp-3%F MRPs administration decreased serum tumor necrosis factor-α concentration as compared to the CK group (p < 0.05). No histological damage was observed in the jejunum, ileum, and colonic tissues of all groups. However, HAHp-H treatment induced higher upregulation of Kelch-like ECH-associated protein 1, transcription factors Nrf-2, associated protective phase-II enzymes of NAD(P)H: quinine oxidoreductase-1, and hemoxygenase-1 in colon tissue, as well as higher upregulation of endogenous antioxidant enzymes, including copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase 2 than other groups (p < 0.05). Additionally, increases in Nε-carboxymethyllysine expression in the colonic tissues of all groups were consistent with their increased oligopeptide transporter 1 expressions. Our results suggest that the thermal products of HAHp might have a broad application prospect in improving antioxidant defense in vivo in healthy animals. Full article

The nutritional functions of tributyrin (TB) have been extensively studied, but questions remain regarding its influence on the growth of juvenile grass carp (Ctenopharyngodon idellus) and the regulation pathway to PepT1 in the intestine of grass carp. To answer the remaining questions, feeding trials, cell trials, and peritoneal injection trials were conducted in this study. The results showed that an appropriate level of TB (0.5 g/kg and 1.0 g/kg) supplementation in feed significantly promoted the growth performance of juvenile grass carp. The expressions of intestine genes (CDX2, SP1 and PepT1) related to oligopeptide transportation increased in the 0.5 g/kg TB group of feeding trials and both the 5 mM and 10 mM TB groups of the intestine cell trials, respectively. Subsequently, the injection trials of inhibitors CDX2 and SP1 demonstrated that the inhibition of CDX2 or SP1 decreased the mRNA expression of PepT1. Finally, the results of independent or combined treatments of TB and the inhibitors suggested that CDX2/SP1 mediated TB regulation on PepT1. These findings may help us to better understand the functions of TB on growth and PepT1 oligopeptide transportation, which could be modulated by dietary TB through the CDX2/SP1-PepT1 pathway in juvenile grass carp. Full article

Self-assembling peptides are a promising class of biomaterials with desirable biocompatibility and versatility. In particular, the oligopeptide (RADA)₄, consisting of arginine (R), alanine (A), and aspartic acid (D), self-assembles into nanofibers that develop into a three-dimensional hydrogel of up to 99.5% (w/v) water; yet, the organization of water within the hydrogel matrix is poorly understood. Importantly, peptide concentration and polarity are hypothesized to control the internal water structure. Using variable temperature deuterium solid-state nuclear magnetic resonance (²H NMR) spectroscopy, we measured the amount of bound water in (RADA)₄-based hydrogels, quantified as the non-frozen water content. To investigate how peptide polarity affects water structure, five lysine (K) moieties were appended to (RADA)₄ to generate (RADA)₄K₅. Hydrogels at 1 and 5% total peptide concentration were prepared from a 75:25 (w/w) blend of (RADA)₄:(RADA)₄K₅ and similarly analyzed by ²H NMR. Interestingly, at 5% peptide concentration, there was lower mobile water content in the lysinated versus the pristine (RADA)₄ hydrogel. Regardless of the presence of lysine, the 5% peptide concentration had higher non-frozen water content at temperatures as low as 217 ± 1.0 K, suggesting that bound water increases with peptide concentration. The bound water, though non-frozen, may be strongly bound to the charged lysine moiety to appear as immobilized water. Further understanding of the factors controlling water structure within hydrogels is important for tuning the transport properties of bioactive solutes in the hydrogel matrix when designing for biomedical applications. Full article

GE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis. Mutations that inactivate the Opp system and confer GE81112 resistance arise spontaneously with a frequency of ca. 1 × 10⁻⁶, similar to that of the mutants resistant to tri-l-ornithine, a known Opp substrate. On the contrary, cells expressing extrachromosomal copies of the opp genes are extremely sensitive to GE81112 in rich medium and GE81112-resistant mutations affecting the molecular target of the antibiotic were not detected upon examining >10⁹ cells of this type. However, some mutations introduced in the 16S rRNA to confer kasugamycin resistance were found to reduce the sensitivity of the cells to GE81112. Full article

A series of amino acid monoester prodrugs of floxuridine was synthesized and evaluated for the improvement of oral bioavailability and the feasibility of target drug delivery via oligopeptide transporters. All floxuridine 5′-amino acid monoester prodrugs exhibited PEPT1 affinity, with inhibition coefficients of Gly-Sar uptake (IC50) ranging from 0.7 – 2.3 mM in Caco-2 and 2.0 – 4.8 mM in AsPC-1 cells, while that of floxuridine was 7.3 mM and 6.3 mM, respectively. Caco-2 membrane permeabilities of floxuridine prodrugs (1.01 – 5.31 x 10^-6 cm/sec) and floxuridine (0.48 x 10^-6 cm/sec) were much higher than that of 5-FU (0.038 x 10^-6 cm/sec). MDCK cells stably transfected with the human oligopeptide transporter PEPT1 (MDCK/hPEPT1) exhibited enhanced cell growth inhibition in the presence of the prodrugs. This prodrug strategy offers great potential, not only for increased drug absorption but also for improved tumor selectivity and drug efficacy. Full article