Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract The capacity of buffalo milk proteins to release bioactive peptides was evaluated and novel bioactive peptides were identified. The sequential similarity between buffalo milk proteins and their cow counterparts was analysed. Buffalo milk proteins were simulated to yield theoretical peptides via in silico proteolysis. The potential of selected proteins to release specific bioactive peptides was evaluated by the A value obtained from the BIOPEP–UWM database (Minkiewicz et al. in Int J Mol Sci 20(23):5978, 2019). Buffalo milk protein is a suitable precursor to produce bioactive peptides, particularly dipeptidyl peptidase IV (DPP-IV) and angiotensin I-converting enzyme (ACE) inhibitory peptides. Two novel ACE inhibitory peptides (KPW and RGP) and four potential DPP-IV inhibitory peptides (RGP, KPW, FPK and KFTW) derived from in silico proteolysis of buffalo milk proteins were screened using different integrated bioinformatic approaches (PeptideRanker, Innovagen, peptide-cutter and molecular docking). The Lineweaver–Burk plots showed that KPW (IC50 = 136.28 ± 10.77 μM) and RGP (104.72 ± 8.37 μM) acted as a competitive inhibitor against ACE. Similarly, KFTW (IC50 = 873.92 ± 32.89 μM) was also a competitive inhibitor of DPP-IV, while KPW and FPK (82.52 ± 10.37 and 126.57 ± 8.45 μM, respectively) were mixed-type inhibitors. It should be emphasized that this study does not involve any clinical trial. PubDate: 2023-01-26
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Laccase is a versatile enzyme widely used for the oxidation of environmental contaminants and exhibits great potential in many others applications; however, it undergoes photo-degradation when irradiated with UVB light. The photo-stability of this biomolecule can be improved by immobilization in different encapsulation media and reverse micelles have been employed with this purpose. The laccase activity using syringaldazine as substrate has been studied in the absence and in the presence of reverse micelles of 0.15 M of sodium 1,4-bis (2-ethylhexyl) sulfosuccinate (AOT) in isooctane at W0 ([H2O]/[AOT]) = 30, before and after irradiation of the enzyme with UVB light. The kinetic parameters, i.e., Michaelis–Menten constant (KM), catalytic constant (kCAT), and catalytic efficiency (kCAT/KM), were determined by spectroscopic measurements in the micellar system and in homogeneous aqueous medium. The distribution of the substrate in two pseudo-phases (micelle and organic solvent) was taking into account in the kinetic parameters’ determinations. The results obtained indicate that the nano-aggregate system confers a solubilization media in the water core of the micelle, both for the enzyme and the substrate, in which the catalytic function of the enzyme is preserved. On the other hand, in homogeneous aqueous medium kCAT/KM value, it is reduced by ~50% after UVB irradiation of the enzyme, while in micellar medium, less than 10% of the activity was affected. This mean that the enzyme achieves a considerably photo-protection when it is irradiated with UVB light in reverse micelles as compared with the homogeneous aqueous medium. This phenomenon can be mainly due to the confinement of the biomolecule inside the micelle. Physical properties of the nano-environment could affect photochemical reactions. PubDate: 2023-01-25
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract We developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method to study the change of plasma levels of free glycine (Gly) in patients with acute ischemic stroke (AIS). Twenty-four patients with AIS confirmed by diffusion-weighted imaging (DWI) were enrolled. During the study period, the patients did not receive any supplemental amino acids therapy that could affect the obtained results. Our results showed that although AIS patients adopted different methods of treatment (thrombolytic and non-thrombolytic), the clinical NIHSS score of AIS showed a downward trend whereas Gly concentration showed increased trend. Moreover, plasma free Gly concentration was positively correlated with ASPECTS score. The correlation between Gly levels and infarct volume showed a statistical significance. That is to say, higher Gly level predicted smaller infarct size. Thus, the change of free Gly level in plasma could be considered as a potential biomarker of AIS. PubDate: 2023-01-25
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract The protonation constants are one of the most fundamental properties of biological molecules. The determination of the constants of the dipeptide is interesting and necessary for a full understanding of its activities in biological process. In this study, the protonation constants of some aliphatic alanine dipeptides (alanyl-alanine, alanyl-phenylalanine, alanyl-valine, alanyl-leucine, and alanyl-methionine) were studied in water and ethanol–water mixtures (20%ethanol–80%water;40%ethanol–60%water;60%ethanol–40%water, (v/v)) at 25 ± 0.1 °C under nitrogen atmosphere and ionic strength at 0.10 mol L−1 by potentiometry. The constants of the systems were calculated using Best computer program. The effects of the different amino acids bound to the alanine on the acidity of the alanyl dipeptides were investigated. The constants were influenced by changes in solvent composition and their variations were discussed in terms of solvent and structural properties. PubDate: 2023-01-24
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract To find out the dietary leucine requirement of fingerling Channa punctatus (5.24 ± 0.07 g), six purified experimental diets (45% CP and 14.73 kJ/g DE) with various leucine concentrations (0.5, 1.0,1.5, 2.0, 2.5 and 3.0% diet) were fed to apparent satiation to triplicate groups for 12 weeks (714/02/a/CPCSEA). Absolute weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio, protein and leucine retention efficiency, and RNA/DNA ratio improved up to 2.0% leucine in the diet. Carcass protein and fat increased significantly with increasing leucine levels up to a 2.0% dry diet. Moisture content showed a reverse pattern. Red blood corpuscles hemoglobin and hematocrit increased with incremental levels of leucine up to 2.0% diet. Significant changes were also noted in serum total protein, superoxide dismutase, aspartate aminotransferase, alanine aminotransferase, and lysozyme activity. Serum protein, superoxide dismutase and lysozyme activity were positively correlated with increasing leucine levels up to 2.0% diet, whereas aspartate aminotransferase and alanine aminotransferase showed the opposite trend. Based on the quadratic regression analysis of absolute weight gain, specific growth rate, feed conversion ratio, protein, and leucine retention efficiency, inclusion of 2.0% leucine is recommended for optimum growth of fingerling C. punctatus. PubDate: 2023-01-22
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Infection with the nematode Haemonchus contortus causes host malnutrition and gastrointestinal injuries. The objective of this study was to investigate the effects of H. contortus infection on gastrointestinal contents of free amino acids (AA), the expression of AA transporters and microbiota with a focus on amino acid metabolism. Twenty-four Xiangdong black goats (13 ± 1.5 kg, 6 months old) were randomly assigned into the control group (n = 8) and the infected group (n = 16). The results showed that H. contortus infection increased (P < 0.05) the free AA contents in jejunum and ileum digesta. The concentrations of blood threonine, phenylalanine and tyrosine were lower (P < 0.05) in the infected group as compared to the control group. In the jejunum and ileum epithelium, H. contortus infection significantly (P < 0.05) down-regulated the expression of AA transporter b0,+AT/rBAT and B0AT1, but up-regulated (P < 0.05) the expression of transporter CAT2 and xCT. Furthermore, microbiota in both jejunum (Bifidobacteriaceae, Lachnospiraceae, Bacteroidaceae, Enterobacteriaceae, and Micrococcaceae) and ileum (Acidaminococcaceae, Desulfovibrionaceae, Bacteroidaceae, and Peptostreptococcaceae) were also altered at the family level by H. contortus infection. The commensal bacteria of jejunum showed a close correlation with amino acids, AA transporters, and amino acid metabolism, especially cystine. In conclusion, H. contortus infection affected the intestinal AA contents and the expression of intestinal AA transporters, suggesting altered AA metabolism and absorption, which were accompanied by changes in the relative abundances of gut bacteria that mediate amino acid metabolism. PubDate: 2023-01-17
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract L-Tryptophan (Trp) was shown to improve the gut barrier and growth of weaning piglets. However, whether excessive dietary Trp regulates amino acids (AAs) metabolism and gut serotonin (5-HT) homeostasis in piglets with gut inflammation is not clear yet. We hypothesize that excessive dietary Trp alleviates acetate-induced colonic inflammation and gut barrier damage in weaning piglets partially through the regulation of colonic AAs metabolism and 5-HT signaling. Fifty-four 21-day-old weaned piglets were divided into six groups: control, acetate, 0.2%Trp, 0.2%Trp + acetate, 0.4% Trp, and 0.4%Trp + acetate. Piglets were fed a basal diet supplemented with 0%, 0.2%, or 0.4% of Trp throughout the 12-day experiment. During days 0–7, all piglets had free access to diet and drinking water. On day 8, piglets were intrarectal administered with 10 mL of 10% acetate saline solution or 0.9% saline. During days 8–12, all piglets were pair-fed the same amount of feed per kg bodyweight. Results showed that excessive dietary Trp alleviated acetate-induced reductions in daily weight gain and increase in feed/gain ratio. Trp restored (P < 0.05) acetate-induced increase in concentrations of free aspartate, glutamate/glutamine, glycine, 5-HT, and 3-methylindole in the colon, downregulation of zonula occludens-1 and 5-HT reuptake transporter (SERT) expression and upregulation of IL-1β, IL-8, TLR4, and 5-HT receptor 2A (HTR2A) expression, and the increase in ratios of p-STAT3/ STAT3 and p-p65/p65 in the colon. The above findings suggested that excessive dietary Trp in the proper amount regulated colonic AAs metabolism, 5-HT homeostasis, and signaling that may contribute as important regulators of gut inflammation during the weaning transition. PubDate: 2023-01-17
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Type-2 diabetes (T2D) is characterised by a dysregulation of metabolism, including skeletal muscle insulin resistance, mitochondrial dysfunction, and oxidative stress. Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor β-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10 mM carnosine, 10 mM β-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (p = 0.016 and p = 0.005). Treatment with 10 mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (p = 0.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (p = 0.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle. PubDate: 2023-01-13
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn’s disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis. PubDate: 2023-01-10
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract To design and develop novel antimicrobial agents, a series of phthalimide–triazine-based derivatives (6a–6e) were synthesized, characterized and evaluated for their potential antibacterial activities. The compounds were prepared through reaction of 6-phenyl-1,3,5-triazine-2,4-diamine with phthalimide moiety containing aliphatic amino acid. Structural analysis of the synthesized compounds was carried out by various characterization techniques such as FT-IR, 1H and 13C-NMR and mass spectroscopy. After the confirmation of the structure, the antibacterial screening of the synthesized compounds was performed against two strains of Gram-positive (Staphylococcus aureus, and Bacillus subtilis) and two strains of Gram-negative (Escherichia coli and Salmonella enteritidis) bacteria. The results of antimicrobial activity showed that compound 6d was the most active against all the tested strains of microorganisms with the MIC value 1.25 µg/µl. The synthesized compounds were docked into the binding sites of E. coli–DNA gyrase B and S. aureus–DNA gyrase complex to explore their theoretically binding mode and possible interactions of these ligands with these two targets. Docking study showed the importance of both hydrogen bonding and hydrophobic interactions as a key interaction with the targets. Based on the obtained results, the hybrid derivatives of triazine and phthalimide could be regarded as efficient candidates for further molecular developments of antimicrobial agents. PubDate: 2023-01-08
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Peptide engineering has gained attraction as a source of new cationicity-enhanced analogues with high potential for the design of next-generation antibiotics. In this context, cruzioseptin-1 (CZS-1), a peptide identified from Cruziohyla calcarifer, is recognized for its antimicrobial potency. However, this amidated-peptide is moderately hemolytic. In order to reduce toxicity and increase antimicrobial potency, 3 peptide analogues based on cruzioseptin-1 were designed and evaluated. [K4K15]CZS-1, an analogue with increased cationicity and reduced hydrophobicity, showed antibacterial, antifungal and antiproliferative properties. In addition, [K4K15]CZS-1 is less hemolytic than CZS-1. The in silico and scanning electron microscopy analysis reveal that [K4K15]CZS-1 induces a membranolytic effect on bacteria. Overall, these results confirm the potential of CZS-1 as source of inspiration for design new selective antimicrobial analogues useful for development of new therapeutic agents. PubDate: 2023-01-06
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Doxorubicin (DOX) is a cornerstone of chemotherapy for solid tumors and leukemias. DOX-induced cognitive impairment, termed chemo brain, has been reported in cancer survivors, whereas its mechanism remains poorly understood. Here we initially evaluated the cognitive impairments of mice treated with clinically relevant, long-term, low-dosage of DOX. Using HILIC-MS/MS-based targeted metabolomics, we presented the changes of 21 amino acids across six anatomical brain regions of mice with DOX-induced chemo brain. By mapping the altered amino acids to the human metabolic network, we constructed an amino acid-based network module for each brain region. We identified phenylalanine, tyrosine, methionine, and γ-aminobutyric acid as putative signatures of three regions (hippocampus, prefrontal cortex, and neocortex) highly associated with cognition. Relying on the reported mouse brain metabolome atlas, we found that DOX might perturb the amino acid homeostasis in multiple brain regions, similar to the changes in the aging brain. Correlation analysis suggested the possible indirect neurotoxicity of DOX that altered the brain levels of phenylalanine, tyrosine, and methionine by causing metabolic disorders in the liver and kidney. In summary, we revealed the region-specific amino acid signatures as actionable targets for DOX-induced chemo brain, which might provide safer treatment and improve the quality of life among cancer survivors. PubDate: 2023-01-05
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract L-tryptophan has been used as a feed additive for swine and poultry and as a nutrient supplement for humans. However, some impurities in l-tryptophan have been reported as causative components of eosinophilia-myalgia syndrome. Therefore, from a safety perspective, it is important to analyze meat samples for these impurities. This study aims to develop an analytical method for the simultaneous detection of l-tryptophan impurities in meat products using LC–MS/MS. Among the various impurities, detection methods for (S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid (5-hydroxytryptophan) (HTP), 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]-indole-2-carboxylic acid (PIC), and 1,1′-ethylidenebistryptophan (EBT) and 2-(3-indoylmethyl)-l-tryptophan (IMT) were developed. The developed method allowed simultaneous determination of these four impurities in 5 min. No interferences from the matrix were observed, and the method showed good sensitivity to each analyte. The method detection limit and limit of quantification in meat matrices were below 11.2 and 35.7 μg/kg, respectively. PubDate: 2023-01-02
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Some glycoproteins contain carbohydrates S-linked to cysteine (Cys) residues. However, relatively few S-glycosylated proteins have been detected, due to the lack of an effective research methodology. This work outlines a general concept for the detection of S-glycosylation sites in proteins. The approach was verified by exploratory experiments on a model mixture of β-S-glucosylated polypeptides obtained by the chemical transformation of lysozyme P00698. The model underwent two processes: (1) oxidative hydrolysis of S-glycosidic bonds under alkaline conditions to expose the thiol group of Cys residues; (2) thiol S-alkylation leading to thiol S-adduct formation at the former S-glycosylation sites. Oxidative hydrolysis was conducted in aqueous urea, dimethyl sulfoxide, or trifluoroethanol, with silver nitrate as the reaction promoter, in the presence of triethylamine and/or pyridine. The concurrent formation of stable protein silver thiolates, gluconic acid, and silver nanoclusters was observed. The essential de-metalation of protein silver thiolates using dithiothreitol preceded the S-labeling of Cys residues with 4-vinyl pyridine or a fluorescent reagent. The S-labeled model was sequenced by tandem mass spectrometry to obtain data on the modifications and their distribution over the protein chains. This enabled the efficiency of both S-glycosidic bonds hydrolysis and S-glycosylation site labeling to be evaluated. Suggestions are also given for testing this novel strategy on real proteomic samples. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Replacement of the main chain peptide bond by imidazole ring seems to be a promising tool for the peptide-based drug design, due to the specific prototropic tautomeric as well as amphoteric properties. In this study, we present that both tautomer and pH change can cause a conformational switch of the studied residues of alanine (1–4) and dehydroalanine (5–8) with the C-terminal peptide group replaced by imidazole. The DFT methods are applied and an environment of increasing polarity is simulated. The conformational maps (Ramachandram diagrams) are presented and the stability of possible conformations is discussed. The neutral forms, tautomers τ (1) and π (2), adapt the conformations αRτ (φ, ψ = − 75°, − 114°) and C7eq (φ, ψ = − 75°, 66°), respectively. Their torsion angles ψ differ by about 180°, which results in a considerable impact on the peptide chain conformation. The cation form (3) adapts both these conformations, whereas the anion analogue (4) prefers the conformations C5 (φ, ψ = − 165°, − 178°) and β2 (φ, ψ ~ − 165°, − 3°). Dehydroamino acid analogues, the tautomers τ (5) and π (6) as well as the anion form (8), have a strong tendency toward the conformations β2 (φ, ψ = − 179°, 0°) and C5 (φ, ψ = − 180°, 180°). The preferences of the protonated imidazolium form (7) depend on the environment. The imidazole ring, acting as a donor or acceptor of the hydrogen bonds created within the studied residues, has a profound effect on the type of conformation. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Sulfur-containing amino acids such as methionine and cysteine play critical roles in immune system and redox status. A body of evidence shows that metabolic aspects of supplemented Met and Cys may differ in the body. Therefore, the study aimed to investigate the effects of dietary Met and Cys supplementation in immunologically challenged weaned pigs. Forty weaned piglets (6.5 ± 0.3 kg) were randomly allocated to five treatment groups. The treatment included: (1) sham-challenged control (SCC), (2) challenged control (CC), (3) MET (CC + 0.1% DL-Met), (4) CYS (CC + 0.1% L-Cys), and (5) MET + CYS (CC + 0.1% DL-Met + 0.1% L-Cys). On day 7, all pigs were intramuscularly injected with either Escherichia coli O55:B5 lipopolysaccharides (LPS) or phosphate-buffered saline. Blood, liver, and jejunum samples were analyzed for immune response and redox status. The CC group had lower (P < 0.05) villus surface area and higher (P < 0.05) flux of 4-kDa fluorescein isothiocyanate dextran (FD4) than the SCC group. A lower (P < 0.05) glutathione (GSH) concentration was observed in the jejunum of pigs in the CC group than those in the SCC group. Dietary Cys supplementation increased (P < 0.05) villus surface area, GSH levels, and reduced (P < 0.05) the flux of FD4 in the jejunum of LPS-challenged pigs. Dietary Met supplementation enhanced (P < 0.05) hepatic GSH content. Pigs challenged with LPS in the MET group had lower serum IL-8 concentration than those in the CC group. There was a Met × Cys interaction (P < 0.05) in serum IL-4 and IL-8 concentrations, and Trolox equivalent antioxidant capacity. Dietary L-Cys supplementation restored intestinal integrity and GSH levels that were damaged by lipopolysaccharides administration. Dietary DL-Met supplementation improved hepatic GSH and reduced systemic inflammatory response, but antagonistic interaction with dietary L-Cys supplementation was observed in the inflammatory response and redox status. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract The carnosinase dipeptidase 1 (CNDP1) gene has been reported as a susceptibility locus for the development of diabetic kidney disease (DKD). While the (CTG)5 allele affords protection in the Caucasian population, we have previously shown that this allele is less frequently present in the Chinese population and therefore a protective role for the (CTG)5 allele is difficult to demonstrate. In the present study, we sought to assess if carnosinase-1 (CN-1) concentrations in serum and/or urine are associated with progression of DKD and to what extent CN-1 influences diabetes-associated inflammation. From a total of 622 individuals that enrolled in our study, 247 patients had type 2 diabetes without DKD, 165 patients had DKD and 210 subjects served as healthy controls. Uni- and multivariate regression analyses were performed to identify potential factors predicting urinary albumin creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and CN-1 concentration in serum and urine. The results indicated that serum CN-1 indeed correlated with eGFR (p = 0.001). In addition, urinary CN-1 associated with eGFR and tubular injury indicator: urinary cystatin C (Cys-C) and urinary retinol-binding protein (RBP). Interestingly, serum CN-1 also positively correlated with inflammatory indicators: neutrophils and lymphocytes. With regard to this, a STZ injected C57BL/6 mice model with surgically made skin wound was established for the generation of skin inflammation. This animal model further proved that the expression of CN-1 in liver and kidney increased remarkably in diabetic mice with skin wound as compared to those without. In conclusion, serum and urinary CN-1 significantly related to the surrogates of impaired renal function in diabetic patients; besides, CN-1 expression might also be associated with the process of inflammation. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract The emergence of antimicrobial peptides (AMPs) as a potential alternative to conventional antibiotics has led to the development of efficient computational methods for predicting AMPs. Among all organisms, the presence of multiple genes encoding AMPs in plants demands the development of a plant-based prediction tool. To this end, we developed models based on multiple peptide features like amino acid composition, dipeptide composition, and physicochemical attributes for predicting plant-derived AMPs. The selected compositional models are integrated into a web server termed PTPAMP. The designed web server is capable of classifying a query peptide sequence into four functional activities, i.e., antimicrobial (AMP), antibacterial (ABP), antifungal (AFP), and antiviral (AVP). Our models achieved an average area under the curve of 0.95, 0.91, 0.85, and 0.88 for AMP, ABP, AFP, and AVP, respectively, on benchmark datasets, which were ~ 6.75% higher than the state-of-the-art methods. Moreover, our analysis indicates the abundance of cysteine residues in plant-derived AMPs and the distribution of other residues like G, S, K, and R, which differ as per the peptide structural family. Finally, we have developed a user-friendly web server, available at the URL: http://www.nipgr.ac.in/PTPAMP/. We expect the substantial input of this predictor for high-throughput identification of plant-derived AMPs followed by additional insights into their functions. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Infections induced by fungi, especially the drug-resistant fungi, are difficult clinical problems. Conventional antifungal treatment is effective but due to resistance, treatment failure, and treatment-related toxicity, there is a need for new antifungal drugs. In this study, SA-2 (YYRRLLRVLRRRW) was derived from Cystatin-SA, a saliva protein with a molecular weight of 14 kDa. Meanwhile, the structure–activity of SA-2 and its mutants was also studied. We detected the antimicrobial activity and cytotoxicity of SA-2 and found that SA-2 had a low cytotoxicity toward mammalian cells but a good inhibitory effect on Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans), with MIC values of 16–64 μg/mL and 8–32 μg/mL, respectively. Interestingly, SA-2 effectively killed fluconazole-resistant C. neoformans and C. albicans within 12 h. This antifungal activity against fluconazole-resistant fungi was comparable to that of amphotericin B. In addition, the C. neoformans-infected mice model was established to evaluate the anti-infective activity of SA-2 in vivo. Results showed that SA-2 significantly reduced the counts of fungi in lung and brain tissues to protect fluconazole-resistant C. neoformans-infected mice from death without changing mice body weights. Moreover, the dramatically increased pro-inflammatory cytokines TNF-α, IL-6 and IL-1β induced by intranasal infection of C. neoformans could be obviously declined due to the treatment of SA-2, which may be attributed to the elimination of C. neoformans in time in the infected tissue. For the mode of actions underlying SA-2 against C. neoformans, we found that the cationic peptide SA-2 could adhere to the negatively charged fungal cell membrane to increase the surface potential of C. neoformans in a dose-dependent manner, and finally disrupted the integrity of fungal cell membrane, reflecting as a 60% positive rate of propidium iodide uptake of C. neoformans cells after SA-2 (4 × MIC) treatment. Our study indicated that SA-2 has the potential to develop as a new therapeutic agent against infection induced by drug-resistant fungi. PubDate: 2023-01-01
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract D-Amino acids are regulatory molecules that affect biological processes. Therefore, being able to accurately detect and quantify these compounds is important for understanding their impact on nutrition and health. There is a paucity of information regarding d-amino acids in human milk. We developed a fast method for simultaneous analysis of amino acid enantiomers in human milk using liquid chromatography with tandem mass spectrometry. The method enables the separation of 41 amino acids without chemical derivatization. Our results revealed that human milk from mothers of preterm infants contains concentrations of d-amino acids that range from 0.5 to 45% that of their l-counterparts and that levels of most d-amino acids decrease as the milk production matures. Moreover, we found that Holder pasteurization of milk does not cause racemization of l-amino acids. To our knowledge, this is the first study to describe percentages of d-amino acid levels in human milk; changes in d-amino acid concentration as the milk matures; and the effect of Holder pasteurization on d- and l-amino acid concentrations in human milk. PubDate: 2022-12-29
Hybrid journal (It can contain Open Access articles)
