Search Results (9)

Traditional doubanjiang was investigated to identify endogenous peptides that may contribute to taste maintenance under salt-reduction conditions. Peptidomics identified 1230 peptides at −10logP ≥ 15. UMPred-FRL predicted 161 potential umami peptides, and molecular docking showed that 141 of these peptides could enter the binding site of the T1R1/T1R3 receptor. The successfully docked sequences were mainly short oligopeptides containing three to five amino acid residues. Based on docking scores, six representative candidate peptides were screened, namely EESP, SCPH, SSSGF, PDTE, SYH, and DYDS. Docking and MM-GBSA analyses suggested that these peptides mainly bound within the VFT cavity of T1R1/T1R3, and the interacting residues were dominated by polar residues such as Ser, Asn, Gln, and His and hydrophobic residues such as Tyr, Ile, Leu, and Val. MM-GBSA further suggested that vdW was the major favorable contributor, while Lipo supported complex stability. The umami thresholds of the six peptides ranged from 0.14 to 1.09 mmol/L. Experimental validation by threshold determination and sensory addition showed that all six peptides significantly increased saltiness, whereas their effects on umami differed. PDTE showed the strongest umami-enhancing effect, while SSSGF, SYH, and SCPH exhibited more pronounced saltiness synergy. These results suggest that the screened peptides do not necessarily amplify umami in complex food systems, but may contribute to taste maintenance under salt-reduction conditions through umami support, saltiness synergy, and taste-structure remodeling. Full article

Dietary intervention is the basis for the treatment of diabetes mellitus. This study employed Ganoderma lucidum (GL) mycelium to ferment a compound medium of oat and purple potato (OPP), optimized fermentation conditions to increase the triterpene content in the resulting product (F-OPPF), and systematically investigated the impact of fermentation on the nutritional quality, structural characteristics, and functional properties of OPP. The results indicated that the triterpene content in F-OPPF significantly increased from 8.53 mg/g to 17.23 mg/g under optimal conditions (temperature: 28 °C, inoculum size: 10%, material quantity: 36 g/250 mL, and fermentation time: day 13). Fermentation resulted in enhanced nutritional quality, with increased contents of protein, soluble protein, crude fiber, ash, mineral elements, essential amino acids, polysaccharides, flavonoids, and total phenols. Mycelium not only enveloped the OPP surface but also penetrated its interior, forming a porous honeycomb-like structure. The types of reactive groups and crystals (C + V-type) were not changed after fermentation, while the crystallinity increased. F-OPPF exhibited positive changes in thermogravimetric properties, antioxidant and hypoglycemic activities, and adsorption capacity of insoluble dietary fiber. Additionally, incorporating F-OPPF into the diet markedly reduced fasting blood glucose levels and promoted weight gain in T2DM rats induced by a high-fat diet and streptozotocin. The fermented groups exhibited improvements in glyco- and lipo-metabolism, oxidative stress, and the function and pathological morphology of the pancreas, liver, and kidneys compared to the unfermented group. Collectively, these findings suggested that GL mycelium fermentation enhanced the nutritional and functional values of OPP, and F-OPPF holds potential as a raw material for developing diabetic-friendly foods. Full article

Because ceramide-like lipo-amino acid cholesteryl derivatives can exert a bound water-holding function due to their lamellae-forming properties, in this study, we determined if topical application of those derivatives to atopic dry skin would elicit an ameliorative effect on skin symptoms, at least on its water-holding function. In this clinical study, daily treatment with a nano-emulsion containing 10% phytosteryl/octyldodecyl lauroyl glutamate (POLG) significantly (p < 0.0001) improved skin symptoms, including dryness/scaling, itchiness and stimulus sensations, in the non-lesional skin of patients with atopic dermatitis (AD) at 3 and at 6 weeks compared with week 0. Those significant improvements in skin symptoms were accompanied by a significantly enhanced water content (conductance) and a significant improvement of roughness (SESC) and smoothness (SESM) values measured using a Visioscan at 3 and 6 weeks. Those effects appeared concomitant with a significantly increased corneocyte size, a significantly down-regulated degree of thick abrasions, and a significant impairment of the corneocyte lipid envelope at 6 weeks. Thus, our clinical study suggests, for the first time, that topical application of the POLG nano-emulsion has the distinct potential to ameliorate atopic dry skin symptoms, particularly scaling and itchiness, in the skin of patients with AD. Those effects result from alleviation of the disrupted water-holding function probably due to the increased supply of lamellae structures into the stratum corneum despite the failure to improve barrier function. Full article

The ‘core’ metabolome of the Bacteroidetes genus Chitinophaga was recently discovered to consist of only seven metabolites. A structural relationship in terms of shared lipid moieties among four of them was postulated. Here, structure elucidation and characterization via ultra-high resolution mass spectrometry (UHR-MS) and nuclear magnetic resonance (NMR) spectroscopy of those four lipids (two lipoamino acids (LAAs), two lysophosphatidylethanolamines (LPEs)), as well as several other undescribed LAAs and N-acyl amino acids (NAAAs), identified during isolation were carried out. The LAAs represent closely related analogs of the literature-known LAAs, such as the glycine-serine dipeptide lipids 430 (2) and 654. Most of the here characterized LAAs (1, 5–11) are members of a so far undescribed glycine-serine-ornithine tripeptide lipid family. Moreover, this study reports three novel NAAAs (N-(5-methyl)hexanoyl tyrosine (14) and N-(7-methyl)octanoyl tyrosine (15) or phenylalanine (16)) from Olivibacter sp. FHG000416, another Bacteroidetes strain initially selected as best in-house producer for isolation of lipid 430. Antimicrobial profiling revealed most isolated LAAs (1–3) and the two LPE ‘core’ metabolites (12, 13) active against the Gram-negative pathogen M. catarrhalis ATCC 25238 and the Gram-positive bacterium M. luteus DSM 20030. For LAA 1, additional growth inhibition activity against B. subtilis DSM 10 was observed. Full article

Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface of protein receptors (e.g., GCPR), which take part in cell-to-cell communications either directly or via the intermediary of hormones or signalling molecules. To confer on aptamers the same sort of conformational rigidity that characterises an antibody binding site, aptamers are often constructed in the form of cyclic peptides, on the assumption that this will encourage stronger binding interactions than would occur if the aptamers were simply linear chains. However, no formal studies have been conducted to confirm the hypothesis that linear peptides will engage in stronger binding interactions with cyclic peptides than with other linear peptides. In this study, the interaction of a model cyclic decamer with a series of linear peptide constructs was compared with that of a linear peptide with the same sequence, showing that the cyclic configuration does confer benefits by increasing the strength of binding. Full article

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography–mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (r_S = 0.28), FFAs (r_S = 0.42), glucose Rd (r_S = −0.33) and glycerol Ra (r_S = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (r_S > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (r_S = −0.31), glycine (r_S = −0.44) and branched chain AA (r_S = −0.32), and directly correlated with saturated (r_S = 0.41) and monounsaturated FFAs (r_S = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD. Full article

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C₁₂ chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming L_α lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*. Full article

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis. Full article

Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules. Full article