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1.
NPJ Syst Biol Appl ; 10(1): 115, 2024 Oct 04.
Article de Anglais | MEDLINE | ID: mdl-39367008

RÉSUMÉ

Peptides are promising drug development frameworks that have been hindered by intrinsic undesired properties including hemolytic activity. We aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and data mining. Metadata networks (METNs) were useful to characterize and find general patterns associated with hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), represented the hemolytic peptide space. The best candidate HSPNs were used to extract various subsets of hemolytic peptides (scaffolds) considering network centrality and peptide similarity. These scaffolds have been proved to be useful in developing robust similarity-based model classifiers. Finally, using an alignment-free approach, we reported 47 putative hemolytic motifs, which can be used as toxic signatures when developing novel peptide-based drugs. We provided evidence that the number of hemolytic motifs in a sequence might be related to the likelihood of being hemolytic.


Sujet(s)
Fouille de données , Hémolyse , Peptides , Fouille de données/méthodes , Hémolyse/effets des médicaments et des substances chimiques , Humains , Biologie informatique/méthodes
2.
J Phys Chem B ; 128(41): 10272-10285, 2024 Oct 17.
Article de Anglais | MEDLINE | ID: mdl-39378314

RÉSUMÉ

Predicting the interfacial properties of peptides is important for replacing oil-derived surfactants in cosmetics, oil, and agricultural applications. This work validated experimentally the estimations of surface tension at the critical micelle concentration (STCMC) of six peptides performed through a random forest (RF) model in a previous contribution. In silico interfacial tensions of the peptides were obtained in the system decane-water, and dilational experiments were applied to elucidate the foaming potential. The RF model accurately classified the peptides into high and low potential to reduce the STCMC. The simulations at the decane-water interface correctly identified peptides with high, intermediate, and low interfacial properties, and the dilational rheology allowed the estimation of the possible potential of three peptides to produce foams. This study sets the basis for identifying surface-active peptides, but future work is necessary to improve the estimations and the correlation between dilational properties and foam stabilization.


Sujet(s)
Peptides , Tension superficielle , Eau , Peptides/composition chimique , Eau/composition chimique , Micelles , Alcanes/composition chimique , Simulation numérique , Tensioactifs/composition chimique
4.
Molecules ; 29(19)2024 Sep 24.
Article de Anglais | MEDLINE | ID: mdl-39407463

RÉSUMÉ

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.


Sujet(s)
Antinéoplasiques , Carcinome épidermoïde , Prolifération cellulaire , Tumeurs de la bouche , Venins de scorpion , Humains , Prolifération cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Tumeurs de la bouche/traitement médicamenteux , Tumeurs de la bouche/anatomopathologie , Venins de scorpion/pharmacologie , Venins de scorpion/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Animaux , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Peptides/pharmacologie , Peptides/composition chimique , Peptides/synthèse chimique , Apoptose/effets des médicaments et des substances chimiques , Scorpions/composition chimique , Potentiel de membrane mitochondriale/effets des médicaments et des substances chimiques , Cycle cellulaire/effets des médicaments et des substances chimiques
5.
Nutrients ; 16(19)2024 Oct 08.
Article de Anglais | MEDLINE | ID: mdl-39408370

RÉSUMÉ

BACKGROUND/OBJECTIVES: The oral administration of hydrolyzed collagen peptides is a scientifically validated intervention for enhancing skeletal muscle health and performance. This integrative review consolidates the evidence supporting the use of low molecular weight collagen peptides (2000-3500 daltons) for their superior bioavailability and absorption. Our objective was to review the effects of collagen peptide or hydrolyzed collagen supplementation on muscle damage, recovery, and construction related to physical exercise. METHODS: A bibliographic search was conducted in major English-language databases, including PubMed/Medline, using terms like "Peptides Collagen and Damage" and "collagen peptides AND Soreness Muscle". This review followed PRISMA guidelines, with bias risk assessed via the PEDro scale. The inclusion criteria were (a) randomized clinical trials, (b) randomized studies in humans with a control or placebo group, (c) studies assessing muscle damage or delayed onset muscle soreness via physiological markers or strength performance tests, and (d) studies using hydrolyzed collagen or collagen peptides. RESULTS: Initially, 752 articles were identified. After applying the inclusion and exclusion criteria, including duplicate removal, eight articles with 286 participants were included. Of these, 130 participants received collagen peptide supplementation, while 171 received a placebo or control. CONCLUSION: This integrative review supports the potential of collagen peptide supplementation to mitigate muscle stress from acute strenuous resistance training. However, due to the methodological heterogeneity among the studies, further clinical trials are needed to clarify the mechanisms underlying muscle improvement with collagen supplementation.


Sujet(s)
Collagène , Compléments alimentaires , Muscles squelettiques , Myalgie , Humains , Muscles squelettiques/effets des médicaments et des substances chimiques , Myalgie/traitement médicamenteux , Peptides/pharmacologie , Peptides/administration et posologie , Entraînement en résistance , Fatigue musculaire/effets des médicaments et des substances chimiques , Essais contrôlés randomisés comme sujet , Force musculaire/effets des médicaments et des substances chimiques , Mâle , Adulte , Femelle , Exercice physique
6.
Int J Mol Sci ; 25(17)2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39273238

RÉSUMÉ

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, this study underscores the importance of understanding peptide interactions in digestion. The greatest contribution to the antioxidant activity was exerted by the low molecular weight peptides with ORAC values for the <3 kDa fraction of HES, GD-HES, and GID-HES of 0.74 ± 0.03, 0.72 ± 0.004, and 0.56 ± 0.01 (µmol TE/mg protein, respectively). GD-HES and GID-HES exhibited immunomodulatory effects, promoting the release of NO up to 18.52 and 8.58 µM, respectively. The findings of this study highlighted the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.


Sujet(s)
Antioxydants , Digestion , Erythrina , Peptides , Protéines végétales , Hydrolyse , Protéines végétales/métabolisme , Protéines végétales/composition chimique , Peptides/composition chimique , Peptides/métabolisme , Erythrina/composition chimique , Antioxydants/pharmacologie , Antioxydants/composition chimique , Antioxydants/métabolisme , Humains , Subtilisines/métabolisme , Subtilisines/composition chimique , Stress oxydatif , Tube digestif/métabolisme
7.
Int J Mol Sci ; 25(17)2024 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-39273592

RÉSUMÉ

Bioinformatics has emerged as a valuable tool for screening drugs and understanding their effects. This systematic review aimed to evaluate whether in silico studies using anti-obesity peptides targeting therapeutic pathways for obesity, when subsequently evaluated in vitro and in vivo, demonstrated effects consistent with those predicted in the computational analysis. The review was framed by the question: "What peptides or proteins have been used to treat obesity in in silico studies?" and structured according to the acronym PECo. The systematic review protocol was developed and registered in PROSPERO (CRD42022355540) in accordance with the PRISMA-P, and all stages of the review adhered to these guidelines. Studies were sourced from the following databases: PubMed, ScienceDirect, Scopus, Web of Science, Virtual Heath Library, and EMBASE. The search strategies resulted in 1015 articles, of which, based on the exclusion and inclusion criteria, 7 were included in this systematic review. The anti-obesity peptides identified originated from various sources including bovine alpha-lactalbumin from cocoa seed (Theobroma cacao L.), chia seed (Salvia hispanica L.), rice bran (Oryza sativa), sesame (Sesamum indicum L.), sea buckthorn seed flour (Hippophae rhamnoides), and adzuki beans (Vigna angularis). All articles underwent in vitro and in vivo reassessment and used molecular docking methodology in their in silico studies. Among the studies included in the review, 46.15% were classified as having an "uncertain risk of bias" in six of the thirteen criteria evaluated. The primary target investigated was pancreatic lipase (n = 5), with all peptides targeting this enzyme demonstrating inhibition, a finding supported both in vitro and in vivo. Additionally, other peptides were identified as PPARγ and PPARα agonists (n = 2). Notably, all peptides exhibited different mechanisms of action in lipid metabolism and adipogenesis. The findings of this systematic review underscore the effectiveness of computational simulation as a screening tool, providing crucial insights and guiding in vitro and in vivo investigations for the discovery of novel anti-obesity peptides.


Sujet(s)
Simulation numérique , Obésité , Peptides , Animaux , Humains , Agents antiobésité/composition chimique , Agents antiobésité/pharmacologie , Biologie informatique , Simulation de docking moléculaire , Obésité/traitement médicamenteux , Obésité/métabolisme , Peptides/composition chimique , Peptides/pharmacologie
8.
An Acad Bras Cienc ; 96(suppl 1): e20231375, 2024.
Article de Anglais | MEDLINE | ID: mdl-39319835

RÉSUMÉ

Recent research has demonstrated the increasing interest in using insects for the extraction of bioactive compounds, particularly peptides. These compounds offer a spectrum of beneficial physiological effects. The aim of this study was to standardize a methodology for obtaining bioactive peptides from Tenebrio molitor and evaluate its physicochemical characterization, antioxidant, and antimicrobial potential. Six assays were carried out to hydrolyse larvae protein, with variations in Alcalase concentration (0.04 to 0.08%) and reaction time (3 to 8 h). The results indicated that the process applied to defatted mealworm flour was effective in reducing lipids by 82.5%. Consequently, it was an observed increase of 38.4% in protein content. Additionally, an increase in glycogen content was found in defatted mealworm flour (177 µmol glucose g-1 sample) and peptides (152.81 µmol glucose g-1 sample). The degree of hydrolysis was higher in assays with longer hydrolysis durations (8.14 - 8.38%). The antioxidant capacity was 12 to 14% lower in assays with an incubation time of 8h. In this sense, the methodology proposed in the present study proved to be efficient in obtaining bioactive peptides from T. molitor.


Sujet(s)
Antioxydants , Peptides , Tenebrio , Tenebrio/composition chimique , Animaux , Antioxydants/pharmacologie , Antioxydants/analyse , Antioxydants/composition chimique , Peptides/analyse , Peptides/composition chimique , Peptides/pharmacologie , Peptides/isolement et purification , Anti-infectieux/pharmacologie , Anti-infectieux/composition chimique , Anti-infectieux/analyse , Tests de sensibilité microbienne
9.
Molecules ; 29(17)2024 Sep 07.
Article de Anglais | MEDLINE | ID: mdl-39275099

RÉSUMÉ

Peptides are receiving significant attention in pharmaceutical sciences due to their applications as anti-inflammatory drugs; however, many aspects of their interactions and mechanisms at the molecular level are not well-known. This work explores the molecular structure of two peptides-(i) cysteine (Cys)-asparagine (Asn)-serine (Ser) (CNS) as a molecule in the gas phase and solvated in water in zwitterion form, and (ii) the crystal structure of the dipeptide serine-asparagine (SN), a reliable peptide indication whose experimental cell parameters are well known. A search was performed by means of atomistic calculations based on density functional theory (DFT). These calculations matched the experimental crystal structure of SN, validating the CNS results and useful for assignments of our experimental spectroscopic IR bands. Our calculations also explore the intercalation of CNS into the interlayer space of montmorillonite (MNT). Our quantum mechanical calculations show that the conformations of these peptides change significantly during intercalation into the confined interlayer space of MNT. This intercalation is energetically favorable, indicating that this process can be a useful preparation for therapeutic anti-inflammatory applications and showing high stability and controlled release processes.


Sujet(s)
Anti-inflammatoires , Bentonite , Cystéine , Théorie de la fonctionnelle de la densité , Sérine , Bentonite/composition chimique , Anti-inflammatoires/composition chimique , Anti-inflammatoires/pharmacologie , Cystéine/composition chimique , Sérine/composition chimique , Asparagine/composition chimique , Modèles moléculaires , Peptides/composition chimique , Intercalants/composition chimique
10.
BMC Genomics ; 25(1): 884, 2024 Sep 20.
Article de Anglais | MEDLINE | ID: mdl-39304820

RÉSUMÉ

BACKGROUND: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further. RESULTS: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting ß-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties. CONCLUSIONS: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir.


Sujet(s)
Maladie d'Alzheimer , Génome bactérien , Kéfir , Lactobacillus , Microbiote , Peptides , Kéfir/microbiologie , Lactobacillus/génétique , Brésil , Peptides/composition chimique , Peptides/pharmacologie , Humains , Simulation de docking moléculaire , Peptides bêta-amyloïdes/métabolisme , Peptides bêta-amyloïdes/génétique , Amyloid precursor protein secretases/métabolisme , Aspartic acid endopeptidases/génétique , Aspartic acid endopeptidases/métabolisme , Métagénomique/méthodes
11.
Molecules ; 29(16)2024 Aug 09.
Article de Anglais | MEDLINE | ID: mdl-39202855

RÉSUMÉ

Plant peptidase inhibitors play crucial roles in plant defence mechanisms and physiological processes. In this study, we isolated and characterised a Kunitz trypsin inhibitor from Enterolobium gummiferum seeds named EgPI (E. gummiferum peptidase inhibitor). The purification process involved two chromatography steps using size exclusion and hydrophobic resins, resulting in high purity and yield. EgPI appeared as a single band of ~20 kDa in SDS-PAGE. Under reducing conditions, the inhibitor exhibited two polypeptide chains, with 15 and 5 kDa. Functional characterisation revealed that EgPI displayed an inhibition stoichiometry of 1:1 against trypsin, with a dissociation constant of 8.4 × 10-9 mol·L-1. The amino-terminal sequencing of EgPI revealed the homology with Kunitz inhibitors. Circular dichroism analysis provided insights into the secondary structure of EgPI, which displayed the signature typical of Kunitz inhibitors. Stability studies demonstrated that EgPI maintained the secondary structure necessary to exhibit its inhibitory activity up to 70 °C and over a pH range from 2 to 8. Microbiological screening revealed that EgPI has antibiofilm properties against pathogenic yeasts at 1.125 µmol·L-1, and EgPI reduced C. albicans biofilm formation by 82.7%. The high affinity of EgPI for trypsin suggests potential applications in various fields. Furthermore, its antibiofilm properties recommended its usefulness in agriculture and antimicrobial therapy research, highlighting the practical implications of our research.


Sujet(s)
Biofilms , Fabaceae , Protéines végétales , Graines , Inhibiteurs trypsiques , Graines/composition chimique , Biofilms/effets des médicaments et des substances chimiques , Fabaceae/composition chimique , Inhibiteurs trypsiques/pharmacologie , Inhibiteurs trypsiques/composition chimique , Inhibiteurs trypsiques/isolement et purification , Protéines végétales/pharmacologie , Protéines végétales/composition chimique , Protéines végétales/isolement et purification , Candida albicans/effets des médicaments et des substances chimiques , Antifongiques/pharmacologie , Antifongiques/composition chimique , Antifongiques/isolement et purification , Séquence d'acides aminés , Peptides
12.
Int J Mol Sci ; 25(15)2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39125644

RÉSUMÉ

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.


Sujet(s)
Marqueurs biologiques , Maladie de Machado-Joseph , Humains , Maladie de Machado-Joseph/génétique , Maladie de Machado-Joseph/métabolisme , Maladie de Machado-Joseph/anatomopathologie , Ataxine-3/génétique , Ataxine-3/métabolisme , Protéines neurofilamenteuses/métabolisme , Peptides/métabolisme , Évolution de la maladie , Stress oxydatif
13.
Nutrients ; 16(15)2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39125276

RÉSUMÉ

Bioinformatics has expedited the screening of new efficient therapeutic agents for diseases such as diabetes mellitus (DM). The objective of this systematic review (SR) was to understand naturally occurring proteins and peptides studied in silico and subsequently reevaluated in vivo for treating DM, guided by the question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The RS protocol was registered in the International Prospective Register of Systematic Reviews database. Articles meeting the eligibility criteria were selected from the PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library (VHL), and EMBASE databases. Five studies that investigated peptides or proteins analyzed in silico and in vivo were selected. Risk of bias assessment was conducted using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. A diverse range of assessed proteins and/or peptides that had a natural origin were investigated in silico and corresponding in vivo reevaluation demonstrated reductions in glycemia and/or insulin, morphological enhancements in pancreatic ß cells, and alterations in the gene expression of markers associated with DM. The in silico studies outlined offer crucial insights into therapeutic strategies for DM, along with promising leads for screening novel therapeutic agents in future trials.


Sujet(s)
Simulation numérique , Diabète , Peptides , Animaux , Humains , Glycémie/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Biologie informatique/méthodes , Diabète/traitement médicamenteux , Hypoglycémiants/composition chimique , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Insuline , Peptides/composition chimique , Peptides/pharmacologie , Peptides/usage thérapeutique , Protéines
14.
Chem Res Toxicol ; 37(9): 1562-1573, 2024 Sep 16.
Article de Anglais | MEDLINE | ID: mdl-39105764

RÉSUMÉ

The oxidation of proteins and, in particular, of tryptophan (Trp) residues leads to chemical modifications that can affect the structure and function. The oxidative damage to proteins in photochemical processes is relevant in the skin and eyes and is related to a series of pathologies triggered by exposure to electromagnetic radiation. In this work, we studied the photosensitized formation of N-formylkynurenine (NFKyn) from Trp in different reaction systems. We used two substrates: free Trp and a peptide of nine amino acid residues, with Trp being the only oxidizable residue. Two different photosensitizers were employed: Rose Bengal (RB) and pterin (Ptr). The former is a typical type II photosensitizer [acts by producing singlet oxygen (1O2)]. Ptr is the parent compound of oxidized or aromatic pterins, natural photosensitizers that accumulate in human skin under certain pathological conditions and act mainly through type I mechanisms (generation of radicals). Experimental data were collected in steady photolysis, and the irradiated solutions were analyzed by chromatography (HPLC). Results indicate that the reaction of Trp with 1O2 initiates the process leading to NFKyn, but different competitive pathways take place depending on the photosensitizer and the substrate. In Ptr-photosensitization, a type I mechanism is involved in secondary reactions accelerating the formation of NFKyn when free Trp is the substrate.


Sujet(s)
Cynurénine , Oxydoréduction , Photosensibilisants , Rose de Bengale , Tryptophane , Tryptophane/composition chimique , Cynurénine/composition chimique , Cynurénine/analogues et dérivés , Cynurénine/métabolisme , Photosensibilisants/composition chimique , Rose de Bengale/composition chimique , Peptides/composition chimique , Oxygène singulet/composition chimique , Ptérines/composition chimique , Chromatographie en phase liquide à haute performance , Photolyse , Humains
15.
Mar Drugs ; 22(8)2024 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-39195485

RÉSUMÉ

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.


Sujet(s)
Antiviraux , Virus de la dengue , Microalgues , Virus de la dengue/effets des médicaments et des substances chimiques , Antiviraux/pharmacologie , Antiviraux/composition chimique , Animaux , Hydrolysats de protéines/pharmacologie , Hydrolysats de protéines/composition chimique , Dengue/traitement médicamenteux , Dengue/virologie , Peptides/pharmacologie , Peptides/composition chimique , Sérogroupe , Chlorocebus aethiops , Humains , Aedes/effets des médicaments et des substances chimiques , Cellules Vero
16.
Food Chem ; 460(Pt 2): 140653, 2024 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-39089038

RÉSUMÉ

Multifunctional peptides derived from various food sources, including ancestral grains, hold significant promise for managing metabolic syndrome. These bioactive peptides exhibit diverse properties that collectively contribute to improving the components of metabolic syndrome. In this study, we investigated the in vitro multifunctionality of six peptides (PW, PM, SW, PPG, PW, and IW) identified through in silico analysis and chemically synthesized. These peptides were evaluated for their potential to address metabolic syndrome-related activities such as antidiabetic, antiobesity, antihypertensive, and antioxidative properties. Assessment included their capacity to inhibit key enzymes associated with these activities, as well as their free radical scavenging and cellular antioxidative activities. Principal component analysis was employed to cluster the peptides according to their multifunctionality. Our results revealed that peptides containing tryptophan (SW, PW, and IW) exhibited the most promising multifunctional attributes, with SW showing particularly high potential. This multifunctional peptide represents a promising avenue for addressing metabolic syndrome.


Sujet(s)
Syndrome métabolique X , Peptides , Syndrome métabolique X/traitement médicamenteux , Syndrome métabolique X/métabolisme , Peptides/composition chimique , Peptides/pharmacologie , Humains , Hypoglycémiants/composition chimique , Hypoglycémiants/pharmacologie , Antioxydants/composition chimique , Antioxydants/pharmacologie , Animaux , Antihypertenseurs/composition chimique , Antihypertenseurs/pharmacologie , Agents antiobésité/composition chimique , Agents antiobésité/pharmacologie
17.
Nutrients ; 16(15)2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39125394

RÉSUMÉ

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.


Sujet(s)
Agents gastro-intestinaux , Peptides , Enregistrements , Syndrome de l'intestin court , Humains , Syndrome de l'intestin court/traitement médicamenteux , Femelle , Mâle , Adulte d'âge moyen , Peptides/usage thérapeutique , Adulte , Sujet âgé , Agents gastro-intestinaux/usage thérapeutique , Insuffisance intestinale/traitement médicamenteux , Résultat thérapeutique , Maladie de Crohn/traitement médicamenteux
18.
Toxins (Basel) ; 16(8)2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39195752

RÉSUMÉ

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202's ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.


Sujet(s)
Anticonvulsivants , Modèles animaux de maladie humaine , Crises épileptiques , Animaux , Mâle , Anticonvulsivants/pharmacologie , Anticonvulsivants/usage thérapeutique , Souris , Crises épileptiques/traitement médicamenteux , Crises épileptiques/induit chimiquement , Pilocarpine , Acide kaïnique/analogues et dérivés , Peptides/pharmacologie , Peptides/usage thérapeutique , Peptides/administration et posologie , Épilepsie temporale/traitement médicamenteux , Épilepsie temporale/induit chimiquement
19.
Int J Mol Sci ; 25(16)2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39201622

RÉSUMÉ

Previous reports have demonstrated that the peptide derived from LfcinB, R-1-R, exhibits anti-Candida activity, which is enhanced when combined with an extract from the Bidens pilosa plant. However, the mechanism of action remains unexplored. In this research, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both the SC5314 strain and a fluconazole-resistant isolate of Candida albicans after incubation with R-1-R. The proteomic data revealed that treatment with R-1-R led to the up-regulation of most differentially expressed proteins compared to the controls in both strains. These proteins are primarily involved in membrane and cell wall biosynthesis, membrane transport, oxidative stress response, the mitochondrial respiratory chain, and DNA damage response. Additionally, proteomic analysis of the C. albicans parental strain SC5314 treated with R-1-R combined with an ethanolic extract of B. pilosa was performed. The differentially expressed proteins following this combined treatment were involved in similar functional processes as those treated with the R-1-R peptide alone but were mostly down-regulated (data are available through ProteomeXchange with identifier PXD053558). Biological assays validated the proteomic results, evidencing cell surface damage, reactive oxygen species generation, and decreased mitochondrial membrane potential. These findings provide insights into the complex antifungal mechanisms of the R-1-R peptide and its combination with the B. pilosa extract, potentially informing future studies on natural product derivatives.


Sujet(s)
Antifongiques , Bidens , Candida albicans , Extraits de plantes , Protéomique , Antifongiques/pharmacologie , Protéomique/méthodes , Bidens/composition chimique , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Candida albicans/effets des médicaments et des substances chimiques , Synergie des médicaments , Protéines fongiques/métabolisme , Peptides/pharmacologie , Peptides/composition chimique , Tests de sensibilité microbienne , Résistance des champignons aux médicaments/effets des médicaments et des substances chimiques , Fluconazole/pharmacologie
20.
Curr Microbiol ; 81(10): 319, 2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39167225

RÉSUMÉ

With the emergence of multidrug-resistant microorganisms, microbial agents have become a serious global threat, affecting human health and various plants. Therefore, new therapeutic alternatives, such as chitin-binding proteins, are necessary. Chitin is an essential component of the fungal cell wall, and chitin-binding proteins exhibit antifungal activity. In the present study, chitin-binding peptides isolated from Capsicum chinense seeds were characterized and evaluated for their in vitro antimicrobial effect against the growth of Candida and Fusarium fungi. Proteins were extracted from the seeds and subsequently the chitin-binding proteins were separated by chitin affinity chromatography. After chromatography, two fractions, Cc-F1 (not retained on the column) and Cc-F2 (retained on the column), were obtained. Electrophoresis revealed major protein bands between 6.5 and 26.6 kDa for Cc-F1 and only a ~ 6.5 kDa protein band for Cc-F2, which was subsequently subjected to mass spectrometry. The protein showed similarity with hevein-like and endochitinase and was then named Cc-Hev. Data are available via ProteomeXchange with identifier PXD054607. Next, we predicted the three-dimensional structure of the peptides and performed a peptide docking with (NAG)3. Subsequently, growth inhibition assays were performed to evaluate the ability of the peptides to inhibit microorganism growth. Cc-Hev inhibited the growth of C. albicans (up to 75% inhibition) and C. tropicalis (100% inhibition) and induced a 65% decrease in cell viability for C. albicans and 100% for C. tropicalis. Based on these results, new techniques to combat fungal diseases could be developed through biotechnological applications; therefore, further studies are needed.


Sujet(s)
Antifongiques , Candida , Capsicum , Chitine , Chitinase , Fusarium , Graines , Graines/composition chimique , Antifongiques/pharmacologie , Antifongiques/isolement et purification , Antifongiques/composition chimique , Antifongiques/métabolisme , Chitine/métabolisme , Chitine/pharmacologie , Fusarium/effets des médicaments et des substances chimiques , Chitinase/pharmacologie , Chitinase/métabolisme , Chitinase/composition chimique , Chitinase/isolement et purification , Candida/effets des médicaments et des substances chimiques , Candida/enzymologie , Lectines végétales/pharmacologie , Lectines végétales/composition chimique , Lectines végétales/isolement et purification , Tests de sensibilité microbienne , Peptides/pharmacologie , Peptides/composition chimique , Peptides/isolement et purification , Peptides/métabolisme , Simulation de docking moléculaire , Protéines végétales/pharmacologie , Protéines végétales/composition chimique , Protéines végétales/isolement et purification , Protéines végétales/métabolisme , Peptides antimicrobiens cationiques
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