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Peptides for Health Benefits 2019

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 208441

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Guest Editor
Instituto de Investigación en Ciencias de la Alimentación (CIAL), Consejo Superior de Investigaciones Científicas (CSIC). c/ Nicolás Cabrera 9, 28049 Madrid, Spain
Interests: bioactive peptides; food proteins; multifuncionality; digestion; bioavailability; inflammation-associated diseases; chemopreventive activity; peptidomics; antioxidant activity
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain
Interests: grains; peptides; phenolic compounds; nutritional characterization; protein quality and digestibility; bioavailability of food compounds; bioactivity; germination; fermentation; enzymatic treatments
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, peptides have received increased interest by the pharmaceutical industry. The high potency, specificity and good safety profile are the main strengths of bioactive peptides as new and promising therapies that may fill the gap between small molecules and protein drugs. These positive attributes of peptides, along with advances in drug delivery technologies, have afforded a renewed interest in the discovery, optimization and development of peptides as pharmacological therapy. Among bioactive peptides, those released from food protein sources have acquired importance as nutraceutical and active components in functional foods because they are known to possess regulatory functions that can lead to health benefits.

This Special Issue, “Peptides for Health Benefits”, will cover a selection of recent research papers, reviews, short communications, as well as perspectives in the field of bioactive peptides. It aims to cover all aspects of peptide research in relation to health promotion. In particular, this Special Issue emphasizes current knowledge and research trends concerning bioactive peptides, including identification and quantification of peptides from new sources, methods for their production and purification, structure-function relationships, mechanisms of action, development of novel in vitro and in vivo assays for the evaluation of their bioactivity, physiological evidence to support health benefits, and peptide stability, bioavailability, and sensory (or techno-functional) properties. Papers regarding the development of new drugs, functional foods or nutraceuticals based on bioactive peptides will be also taken into consideration.

Dr. Blanca Hernández-Ledesma
Dr. Cristina Martínez-Villaluenga
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Human health
  • Bioactive peptides
  • Food peptides
  • Biological activity
  • Peptidomics
  • In vitro and in vivo assays
  • Identification and characterization
  • Functional foods
  • Peptide-based therapies

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Published Papers (37 papers)

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Editorial

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6 pages, 204 KiB  
Editorial
Peptides for Health Benefits 2019
by Cristina Martínez-Villaluenga and Blanca Hernández-Ledesma
Int. J. Mol. Sci. 2020, 21(7), 2543; https://doi.org/10.3390/ijms21072543 - 6 Apr 2020
Cited by 17 | Viewed by 3341
Abstract
In recent years, peptides have received increased interest in pharmaceutical, food, cosmetics and various other fields [...] Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)

Research

Jump to: Editorial, Review

18 pages, 4250 KiB  
Article
Cryptides Identified in Human Apolipoprotein B as New Weapons to Fight Antibiotic Resistance in Cystic Fibrosis Disease
by Rosa Gaglione, Angela Cesaro, Eliana Dell’Olmo, Rocco Di Girolamo, Luca Tartaglione, Elio Pizzo and Angela Arciello
Int. J. Mol. Sci. 2020, 21(6), 2049; https://doi.org/10.3390/ijms21062049 - 17 Mar 2020
Cited by 24 | Viewed by 3957
Abstract
Chronic respiratory infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients, and are characterized by the development of multidrug resistance (MDR) phenotype and biofilm formation, generally recalcitrant to treatment with conventional antibiotics. Hence, novel effective strategies are urgently [...] Read more.
Chronic respiratory infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients, and are characterized by the development of multidrug resistance (MDR) phenotype and biofilm formation, generally recalcitrant to treatment with conventional antibiotics. Hence, novel effective strategies are urgently needed. Antimicrobial peptides represent new promising therapeutic agents. Here, we analyze for the first time the efficacy of three versions of a cryptide identified in human apolipoprotein B (ApoB, residues 887-922) towards bacterial strains clinically isolated from CF patients. Antimicrobial and anti-biofilm properties of ApoB-derived cryptides have been analyzed by broth microdilution assays, crystal violet assays, confocal laser scanning microscopy and scanning electron microscopy. Cell proliferation assays have been performed to test cryptide effects on human host cells. ApoB-derived cryptides have been found to be endowed with significant antimicrobial and anti-biofilm properties towards Pseudomonas and Burkholderia strains clinically isolated from CF patients. Peptides have been also found to be able to act in combination with the antibiotic ciprofloxacin, and they are harmless when tested on human bronchial epithelial mesothelial cells. These findings open interesting perspectives to cryptide applicability in the treatment of chronic lung infections associated with CF disease. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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14 pages, 2755 KiB  
Article
Whey-Derived Peptides Interactions with ACE by Molecular Docking as a Potential Predictive Tool of Natural ACE Inhibitors
by Yara Chamata, Kimberly A. Watson and Paula Jauregi
Int. J. Mol. Sci. 2020, 21(3), 864; https://doi.org/10.3390/ijms21030864 - 29 Jan 2020
Cited by 45 | Viewed by 7012
Abstract
Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to [...] Read more.
Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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14 pages, 2341 KiB  
Article
Inhibitory Effects of Peptide Lunasin in Colorectal Cancer HCT-116 Cells and Their Tumorsphere-Derived Subpopulation
by Samuel Fernández-Tomé, Fei Xu, Yanhui Han, Blanca Hernández-Ledesma and Hang Xiao
Int. J. Mol. Sci. 2020, 21(2), 537; https://doi.org/10.3390/ijms21020537 - 14 Jan 2020
Cited by 26 | Viewed by 5030
Abstract
The involvement of cancer stem-like cells (CSC) in the tumor pathogenesis has profound implications for cancer therapy and chemoprevention. Lunasin is a bioactive peptide from soybean and other vegetal sources with proven protective activities against cancer and other chronic diseases. The present study [...] Read more.
The involvement of cancer stem-like cells (CSC) in the tumor pathogenesis has profound implications for cancer therapy and chemoprevention. Lunasin is a bioactive peptide from soybean and other vegetal sources with proven protective activities against cancer and other chronic diseases. The present study focused on the cytotoxic effect of peptide lunasin in colorectal cancer HCT-116 cells, both the bulk tumor and the CSC subpopulations. Lunasin inhibited the proliferation and the tumorsphere-forming capacity of HCT-116 cells. Flow cytometry results demonstrated that the inhibitory effects were related to apoptosis induction and cell cycle-arrest at G1 phase. Moreover, lunasin caused an increase in the sub-GO/G1 phase of bulk tumor cells, linked to the apoptotic events found. Immunoblotting analysis further showed that lunasin induced apoptosis through activation of caspase-3 and cleavage of PARP, and could modulate cell cycle progress through the cyclin-dependent kinase inhibitor p21. Together, these results provide new evidence on the chemopreventive activity of peptide lunasin on colorectal cancer by modulating both the parental and the tumorsphere-derived subsets of HCT-116 cells. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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11 pages, 1163 KiB  
Communication
Oral Delivery of a Tetrameric Tripeptide Inhibitor of VEGFR1 Suppresses Pathological Choroid Neovascularization
by Valeria Tarallo, Emanuela Iaccarino, Valeria Cicatiello, Riccardo Sanna, Menotti Ruvo and Sandro De Falco
Int. J. Mol. Sci. 2020, 21(2), 410; https://doi.org/10.3390/ijms21020410 - 9 Jan 2020
Cited by 8 | Viewed by 2914
Abstract
Age-related macular degeneration (AMD) is the primary cause of blindness in advanced countries. Repeated intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents has represented an important advancement for the therapy of wet AMD with significative results in terms of blindness prevention and [...] Read more.
Age-related macular degeneration (AMD) is the primary cause of blindness in advanced countries. Repeated intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents has represented an important advancement for the therapy of wet AMD with significative results in terms of blindness prevention and partial vision restore. Nonetheless, some patients are not responsive or do not attain significant visual improvement, intravitreal injection may cause serious complications and important side effects have been reported for the prolonged block of VEGF-A. In order to evaluate new anti-angiogenic strategies, we focused our attention on VEGF receptor 1 (VEGFR1) developing a specific VEGFR-1 antagonist, a tetrameric tripeptide named inhibitor of VEGFR 1 (iVR1). We have evaluated its anti-angiogenic activity in the preclinical model of AMD, the laser-induced choroid neovascularization (CNV). iVR1 is able to potently inhibit CNV when delivered by intravitreal injection. Surprisingly, it is able to significantly reduce CNV also when delivered by gavage. Our data show that the specific block of VEGFR1 in vivo represents a valid alternative to the block of VEGF-A and that the inhibition of the pathological neovascularization at ocular level is also possible by systemic delivery of compounds not targeting VEGF-A. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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9 pages, 1755 KiB  
Article
Food-Derived Collagen Peptides, Prolyl-Hydroxyproline (Pro-Hyp), and Hydroxyprolyl-Glycine (Hyp-Gly) Enhance Growth of Primary Cultured Mouse Skin Fibroblast Using Fetal Bovine Serum Free from Hydroxyprolyl Peptide
by Tomoko T. Asai, Fumi Oikawa, Kazunobu Yoshikawa, Naoki Inoue and Kenji Sato
Int. J. Mol. Sci. 2020, 21(1), 229; https://doi.org/10.3390/ijms21010229 - 28 Dec 2019
Cited by 21 | Viewed by 7643
Abstract
Prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) appear in human blood after ingestion of collagen hydrolysate and trigger growth of fibroblasts attached on collagen gel, which has been associated with beneficial effects upon ingestion of collagen hydrolysate, such as improvement of skin and joint conditions. [...] Read more.
Prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) appear in human blood after ingestion of collagen hydrolysate and trigger growth of fibroblasts attached on collagen gel, which has been associated with beneficial effects upon ingestion of collagen hydrolysate, such as improvement of skin and joint conditions. In the present study, inconsistent results were obtained by using different lots of fetal bovine serum (FBS). Fibroblasts proliferated in collagen gel without adding Pro-Hyp and Hyp-Gly and did not respond to addition of Pro-Hyp and Hyp-Gly, which raises doubts about conclusions from prior research. Unexpectedly high levels of hydroxyprolyl peptides, including Pro-Hyp, however, were present in the FBS (approximately 100 µM), and also in other commercially available forms of FBS (70–80 µM). After removal of low molecular weight (LMW, < 6000 Da) compounds from the FBS by size exclusion chromatography, Pro-Hyp and Hyp-Gly again triggered growth of fibroblasts attached on collagen and increased the number of fibroblasts migrated from mouse skin. These results indicate the presence of bioactive hydroxyprolyl peptides in commercially available FBS, which can mask effects of Pro-Hyp and Hyp-Gly supplementation; our work confirms that Pro-Hyp and Hyp-Gly do play crucial roles in proliferation of fibroblasts. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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23 pages, 1238 KiB  
Article
BIOPEP-UWM Database of Bioactive Peptides: Current Opportunities
by Piotr Minkiewicz, Anna Iwaniak and Małgorzata Darewicz
Int. J. Mol. Sci. 2019, 20(23), 5978; https://doi.org/10.3390/ijms20235978 - 27 Nov 2019
Cited by 505 | Viewed by 17206
Abstract
The BIOPEP-UWM™ database of bioactive peptides (formerly BIOPEP) has recently become a popular tool in the research on bioactive peptides, especially on these derived from foods and being constituents of diets that prevent development of chronic diseases. The database is continuously updated and [...] Read more.
The BIOPEP-UWM™ database of bioactive peptides (formerly BIOPEP) has recently become a popular tool in the research on bioactive peptides, especially on these derived from foods and being constituents of diets that prevent development of chronic diseases. The database is continuously updated and modified. The addition of new peptides and the introduction of new information about the existing ones (e.g., chemical codes and references to other databases) is in progress. New opportunities include the possibility of annotating peptides containing D-enantiomers of amino acids, batch processing option, converting amino acid sequences into SMILES code, new quantitative parameters characterizing the presence of bioactive fragments in protein sequences, and finding proteinases that release particular peptides. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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18 pages, 3362 KiB  
Article
Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma
by Ewelina Russjan, Kryspin Andrzejewski, Dorota Sulejczak, Patrycja Kleczkowska and Katarzyna Kaczyńska
Int. J. Mol. Sci. 2019, 20(23), 5935; https://doi.org/10.3390/ijms20235935 - 26 Nov 2019
Cited by 8 | Viewed by 3164
Abstract
We examined anti-inflammatory potency of hybrid peptide-PK20, composed of neurotensin (NT) and endomorphin-2 (EM-2) pharmacophores in a murine model of non-atopic asthma induced by skin sensitization with 2,4-dinitrofluorobenzene and intratracheal challenge of cognate hapten. Mice received intraperitoneally PK20, equimolar mixture of its structural [...] Read more.
We examined anti-inflammatory potency of hybrid peptide-PK20, composed of neurotensin (NT) and endomorphin-2 (EM-2) pharmacophores in a murine model of non-atopic asthma induced by skin sensitization with 2,4-dinitrofluorobenzene and intratracheal challenge of cognate hapten. Mice received intraperitoneally PK20, equimolar mixture of its structural elements (MIX), dexamethasone (DEX), or NaCl. Twenty-four hours following hapten challenge, the measurements of airway responsiveness to methacholine were taken. Bronchoalveolar lavage (BALF) and lungs were collected for further analyses. Treatment with PK20, similarly to dexamethasone, reduced infiltration of inflammatory cells, concentration of mouse mast cell protease, IL-1β, IL-12p40, IL-17A, CXCL1, RANTES in lungs and IL-1α, IL-2, IL-13, and TNF-α in BALF. Simple mixture of NT and EM-2 moieties was less potent. PK20, DEX, and MIX significantly decreased malondialdehyde level and secretory phospholipase 2 activity in lungs. Intensity of NF-κB immunoreactivity was diminished only after PK20 and DEX treatments. Neither PK20 nor mixture of its pharmacophores were as effective as DEX in alleviating airway hyperresponsiveness. PK20 effectively inhibited hapten-induced inflammation and mediator and signaling pathways in a manner seen with dexamethasone. Improved anti-inflammatory potency of the hybrid over the mixture of its moieties shows its preponderance and might pose a promising tool in modulating inflammation in asthma. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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14 pages, 3986 KiB  
Article
Cytoprotective Effect of Antioxidant Pentapeptides from the Protein Hydrolysate of Swim Bladders of Miiuy Croaker (Miichthys miiuy) against H2O2-Mediated Human Umbilical Vein Endothelial Cell (HUVEC) Injury
by Shi-Ying Cai, Yu-Mei Wang, Yu-Qin Zhao, Chang-Feng Chi and Bin Wang
Int. J. Mol. Sci. 2019, 20(21), 5425; https://doi.org/10.3390/ijms20215425 - 31 Oct 2019
Cited by 40 | Viewed by 3575
Abstract
In our previous research, ten antioxidant pentapeptides including FYKWP, FTGMD, GFEPY, YLPYA, FPPYERRQ, GFYAA, FSGLR, FPYLRH, VPDDD, and GIEWA were identified from the hydrolysate of miiuy croaker (Miichthys miiuy) swim bladder. In this work, their protective function on H2O [...] Read more.
In our previous research, ten antioxidant pentapeptides including FYKWP, FTGMD, GFEPY, YLPYA, FPPYERRQ, GFYAA, FSGLR, FPYLRH, VPDDD, and GIEWA were identified from the hydrolysate of miiuy croaker (Miichthys miiuy) swim bladder. In this work, their protective function on H2O2-induced oxidative damage to human umbilical vein endothelial cells (HUVECs) was studied. Results indicated that there was no significant difference in the HUVEC viability between the normal group and the treated groups with the 10 pentapeptides at the concentration of 100 μM for 24 h (p < 0.05). Furthermore, FPYLRH of 100 μg/mL extremely significantly (p < 0.001) increased the viability (80.58% ± 5.01%) of HUVECs with H2O2-induced oxidative damage compared with that of the model group. The protective mechanism indicated that FPYLRH could extremely significantly (p < 0.001) increase the levels of superoxide dismutase (SOD) (211.36 ± 8.29 U/mg prot) and GSH-Px (53.06 ± 2.34 U/mg prot) and decrease the contents of reactive oxygen species (ROS) (139.1 ± 11.8% of control), malondialdehyde (MDA) (13.66 ± 0.71 nM/mg), and nitric oxide (NO) (4.36 ± 0.32 µM/L) at the concentration of 100 μM in HUVECs with H2O2-induced oxidative damage compared with those of the model group. In addition, FPYLRH dose-dependently protected DNA in oxidative damage HUVECs model. These results suggested that FPYLRH could significantly attenuate the H2O2-induced stress injury in HUVECs and might be used as a potential natural antioxidant in the functional food industries. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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22 pages, 2938 KiB  
Article
Gender Differences in the Pharmacological Actions of Pegylated Glucagon-Like Peptide-1 on Endothelial Progenitor Cells and Angiogenic Precursor Cells in a Combination of Metabolic Disorders and Lung Emphysema
by Olga Victorovna Pershina, Angelina Vladimirovna Pakhomova, Darius Widera, Natalia Nicolaevna Ermakova, Anton Alexandrovich Epanchintsev, Edgar Sergeevich Pan, Vyacheslav Andreevich Krupin, Olga Evgenevna Vaizova, Olesia Dmitrievna Putrova, Lubov Alexandrovna Sandrikina, Irina Vitalevna Kurochkina, Sergey Georgievich Morozov, Aslan Amirkhanovich Kubatiev, Alexander Mikhaylovich Dygai and Evgenii Germanovich Skurikhin
Int. J. Mol. Sci. 2019, 20(21), 5414; https://doi.org/10.3390/ijms20215414 - 30 Oct 2019
Cited by 4 | Viewed by 3533
Abstract
In clinical practice, the metabolic syndrome (MetS) is often associated with chronic obstructive pulmonary disease (COPD). Although gender differences in MetS are well documented, little is known about sex-specific differences in the pathogenesis of COPD, especially when combined with MetS. Consequently, it is [...] Read more.
In clinical practice, the metabolic syndrome (MetS) is often associated with chronic obstructive pulmonary disease (COPD). Although gender differences in MetS are well documented, little is known about sex-specific differences in the pathogenesis of COPD, especially when combined with MetS. Consequently, it is not clear whether the same treatment regime has comparable efficacy in men and women diagnosed with MetS and COPD. In the present study, using sodium glutamate, lipopolysaccharide, and cigarette smoke extract, we simulated lipid metabolism disorders, obesity, hyperglycemia, and pulmonary emphysema (comorbidity) in male and female C57BL/6 mice. We assessed the gender-specific impact of lipid metabolism disorders and pulmonary emphysema on angiogenic precursor cells (endothelial progenitor cells (EPC), pericytes, vascular smooth muscle cells, cells of the lumen of the nascent vessel), as well as the biological effects of pegylated glucagon-like peptide 1 (pegGLP-1) in this experimental paradigm. Simulation of MetS/COPD comorbidity caused an accumulation of EPC (CD45CD31+CD34+), pericytes, and vascular smooth muscle cells in the lungs of female mice. In contrast, the number of cells involved in the angiogenesis decreased in the lungs of male animals. PegGLP-1 had a positive effect on lipids and area under the curve (AUC), obesity, and prevented the development of pulmonary emphysema. The severity of these effects was stronger in males than in females. Furthermore, PegGLP-1 stimulated regeneration of pulmonary endothelium. At the same time, PegGLP-1 administration caused a mobilization of EPC (CD45CD31+CD34+) into the bloodstream in females and migration of precursors of angiogenesis and vascular smooth muscle cells to the lungs in male animals. Gender differences in stimulatory action of pegGLP-1 on CD31+ endothelial lung cells in vitro were not observed. Based on these findings, we postulated that the cellular mechanism of in vivo regeneration of lung epithelium was at least partly gender-specific. Thus, we concluded that a pegGLP-1-based treatment regime for metabolic disorder and COPD should be further developed primarily for male patients. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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14 pages, 1247 KiB  
Article
How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3
by Adenrele Oludiran, David S. Courson, Malia D. Stuart, Anwar R. Radwan, John C. Poutsma, Myriam L. Cotten and Erin B. Purcell
Int. J. Mol. Sci. 2019, 20(21), 5289; https://doi.org/10.3390/ijms20215289 - 24 Oct 2019
Cited by 15 | Viewed by 3730
Abstract
The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the [...] Read more.
The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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18 pages, 3541 KiB  
Article
The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3)
by Francesca Caccuri, Antonella Bugatti, Silvia Corbellini, Sara Roversi, Alberto Zani, Pietro Mazzuca, Stefania Marsico, Arnaldo Caruso and Cinzia Giagulli
Int. J. Mol. Sci. 2019, 20(21), 5287; https://doi.org/10.3390/ijms20215287 - 24 Oct 2019
Cited by 9 | Viewed by 3712
Abstract
In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic [...] Read more.
In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid, PDT) is a synthetic dipeptide, which possesses immunomodulatory properties and exerts a well-defined pharmacological activity against infections, but its real mechanism of action is still undefined. Here, we show that PDT is capable of activating tyrosine phosphorylation-based cell signaling in human primary monocytes and triggering rapid adhesion and chemotaxis. PDT-induced monocyte migration requires the activation of the PI3K/Akt signaling pathway and chemokine receptor CXCR3. Indeed, a mAb to CXCR3 and a specific receptor inhibitor suppressed significantly PDT-dependent chemotaxis, and CXCR3-silenced primary monocytes lost responsiveness to PDT chemoattraction. Moreover, our results highlighted that the PDT-induced migratory activity is sustained by the CXCR3A isoform, since CXCR3-transfected L1.2 cells acquired responsiveness to PDT stimulation. Finally, we show that PDT, as CXCR3 ligands, is also able to direct the migration of IL-2 activated T cells, which express the highest levels of CXCR3 among CXCR3-expressing cells. In conclusion, our study defines a chemokine-like activity for PDT through CXCR3A and points on the possible role that this synthetic dipeptide may play in leukocyte trafficking and function. Since recent studies have highlighted diverse therapeutic roles for molecules which activates CXCR3, our findings call for an exploration of using this dipeptide in different pathological processes. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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17 pages, 2522 KiB  
Article
In Silico and In Vitro Assessment of Portuguese Oyster (Crassostrea angulata) Proteins as Precursor of Bioactive Peptides
by Honey Lyn R. Gomez, Jose P. Peralta, Lhumen A. Tejano and Yu-Wei Chang
Int. J. Mol. Sci. 2019, 20(20), 5191; https://doi.org/10.3390/ijms20205191 - 20 Oct 2019
Cited by 32 | Viewed by 4330
Abstract
In this study, the potential bioactivities of Portuguese oyster (Crassostrea angulata) proteins were predicted through in silico analyses and confirmed by in vitro tests. C. angulata proteins were characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and identified by proteomics [...] Read more.
In this study, the potential bioactivities of Portuguese oyster (Crassostrea angulata) proteins were predicted through in silico analyses and confirmed by in vitro tests. C. angulata proteins were characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and identified by proteomics techniques. Hydrolysis simulation by BIOPEP-UWM database revealed that pepsin (pH > 2) can theoretically release greatest amount of bioactive peptides from C. angulata proteins, predominantly angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitory peptides, followed by stem bromelain and papain. Hydrolysates produced by pepsin, bromelain and papain have shown ACE and DPP-IV inhibitory activities in vitro, with pepsin hydrolysate (PEH) having the strongest activity of 78.18% and 44.34% at 2 mg/mL, respectively. Bioactivity assays of PEH fractions showed that low molecular weight (MW) fractions possessed stronger inhibitory activity than crude hydrolysate. Overall, in vitro analysis results corresponded with in silico predictions. Current findings suggest that in silico analysis is a rapid method to predict bioactive peptides in food proteins and determine suitable enzymes for hydrolysis. Moreover, C. angulata proteins can be a potential source of peptides with pharmaceutical and nutraceutical application. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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13 pages, 1550 KiB  
Article
Protective Effects of Novel Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler Against Oxidative Stress in Chang Liver Cells In Vitro and in a Zebrafish Model In Vivo
by Yuling Ding, Seok-Chun Ko, Sang-Ho Moon and Seung-Hong Lee
Int. J. Mol. Sci. 2019, 20(20), 5187; https://doi.org/10.3390/ijms20205187 - 19 Oct 2019
Cited by 44 | Viewed by 3644
Abstract
Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective [...] Read more.
Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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12 pages, 3546 KiB  
Article
Beneficial Effects of Neurotensin in Murine Model of Hapten-Induced Asthma
by Ewelina Russjan and Katarzyna Kaczyńska
Int. J. Mol. Sci. 2019, 20(20), 5025; https://doi.org/10.3390/ijms20205025 - 11 Oct 2019
Cited by 12 | Viewed by 2534
Abstract
Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB/c mice by [...] Read more.
Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal hapten provocation. The mice were treated intraperitoneally with NT, SR 142948 (NTR1 receptor antagonist) + NT or NaCl. Twenty-four hours after the challenge, airway responsiveness to nebulized methacholine was measured. Bronchoalveolar lavage fluid (BALF) and lungs were collected for biochemical and immunohistological analysis. NT alleviated airway hyperreactivity and reduced the number of inflammatory cells in BALF. These beneficial effects were inhibited by pretreatment with the NTR1 antagonist. Additionally, NT reduced levels of IL-13 and TNF-α in BALF and IL-17A, IL12p40, RANTES, mouse mast cell protease and malondialdehyde in lung homogenates. SR 142948 reverted only a post-NT TNF-α decrease. NT exhibited anti-inflammatory activity in the hapten-induced asthma. Reduced leukocyte accumulation and airway hyperresponsiveness indicate that this beneficial NT action is mediated through NTR1 receptors. A lack of effect by the NTR1 blockade on mast cell activation, oxidative stress marker and pro-inflammatory cytokine production suggests that other pathways can be involved, which requires further research. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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17 pages, 3691 KiB  
Article
Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities
by Mihee Jang, Jieun Kim, Yujin Choi, JeongKyu Bang and Yangmee Kim
Int. J. Mol. Sci. 2019, 20(19), 4895; https://doi.org/10.3390/ijms20194895 - 2 Oct 2019
Cited by 17 | Viewed by 3842
Abstract
Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with [...] Read more.
Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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16 pages, 2010 KiB  
Article
The Bactericidal Activity of Temporin Analogues Against Methicillin Resistant Staphylococcus aureus
by Anna Golda, Paulina Kosikowska-Adamus, Aleksandra Kret, Olena Babyak, Kinga Wójcik, Ewelina Dobosz, Jan Potempa, Adam Lesner and Joanna Koziel
Int. J. Mol. Sci. 2019, 20(19), 4761; https://doi.org/10.3390/ijms20194761 - 25 Sep 2019
Cited by 10 | Viewed by 3234
Abstract
Staphylococcus aureus is a major infectious agent responsible for a plethora of superficial skin infections and systemic diseases, including endocarditis and septic arthritis. Recent epidemiological data revealed the emergence of resistance to commonly used antibiotics, including increased numbers of both hospital- and community-acquired [...] Read more.
Staphylococcus aureus is a major infectious agent responsible for a plethora of superficial skin infections and systemic diseases, including endocarditis and septic arthritis. Recent epidemiological data revealed the emergence of resistance to commonly used antibiotics, including increased numbers of both hospital- and community-acquired methicillin-resistant S. aureus (MRSA). Due to their potent antimicrobial functions, low potential to develop resistance, and immunogenicity, antimicrobial peptides (AMPs) are a promising alternative treatment for multidrug-resistant strains. Here, we examined the activity of a lysine-rich derivative of amphibian temporin-1CEb (DK5) conjugated to peptides that exert pro-proliferative and/or cytoprotective activity. Analysis of a library of synthetic peptides to identify those with antibacterial potential revealed that the most potent agent against multidrug-resistant S. aureus was a conjugate of a temporin analogue with the synthetic Leu-enkephalin analogue dalargin (DAL). DAL-PEG-DK5 exerted direct bactericidal effects via bacterial membrane disruption, leading to eradication of both planktonic and biofilm-associated staphylococci. Finally, we showed that accumulation of the peptide in the cytoplasm of human keratinocytes led to a marked clearance of intracellular MRSA, resulting in cytoprotection against invading bacteria. Collectively, the data showed that DAL-PEG-DK5 might be a potent antimicrobial agent for treatment of staphylococcal skin infections. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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20 pages, 4112 KiB  
Article
Systematical Analysis of the Protein Targets of Lactoferricin B and Histatin-5 Using Yeast Proteome Microarrays
by Pramod Shah, Wei-Sheng Wu and Chien-Sheng Chen
Int. J. Mol. Sci. 2019, 20(17), 4218; https://doi.org/10.3390/ijms20174218 - 28 Aug 2019
Cited by 8 | Viewed by 3028
Abstract
Antimicrobial peptides (AMPs) have potential antifungal activities; however, their intracellular protein targets are poorly reported. Proteome microarray is an effective tool with high-throughput and rapid platform that systematically identifies the protein targets. In this study, we have used yeast proteome microarrays for systematical [...] Read more.
Antimicrobial peptides (AMPs) have potential antifungal activities; however, their intracellular protein targets are poorly reported. Proteome microarray is an effective tool with high-throughput and rapid platform that systematically identifies the protein targets. In this study, we have used yeast proteome microarrays for systematical identification of the yeast protein targets of Lactoferricin B (Lfcin B) and Histatin-5. A total of 140 and 137 protein targets were identified from the triplicate yeast proteome microarray assays for Lfcin B and Histatin-5, respectively. The Gene Ontology (GO) enrichment analysis showed that Lfcin B targeted more enrichment categories than Histatin-5 did in all GO biological processes, molecular functions, and cellular components. This might be one of the reasons that Lfcin B has a lower minimum inhibitory concentration (MIC) than Histatin-5. Moreover, pairwise essential proteins that have lethal effects on yeast were analyzed through synthetic lethality. A total of 11 synthetic lethal pairs were identified within the protein targets of Lfcin B. However, only three synthetic lethal pairs were identified within the protein targets of Histatin-5. The higher number of synthetic lethal pairs identified within the protein targets of Lfcin B might also be the reason for Lfcin B to have lower MIC than Histatin-5. Furthermore, two synthetic lethal pairs were identified between the unique protein targets of Lfcin B and Histatin-5. Both the identified synthetic lethal pairs proteins are part of the Spt-Ada-Gcn5 acetyltransferase (SAGA) protein complex that regulates gene expression via histone modification. Identification of synthetic lethal pairs between Lfcin B and Histatin-5 and their involvement in the same protein complex indicated synergistic combination between Lfcin B and Histatin-5. This hypothesis was experimentally confirmed by growth inhibition assay. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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15 pages, 10326 KiB  
Article
Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies
by Sara María Martínez-Sánchez, Horacio Pérez-Sánchez, José Antonio Gabaldón, José Abellán-Alemán and Silvia Montoro-García
Int. J. Mol. Sci. 2019, 20(17), 4204; https://doi.org/10.3390/ijms20174204 - 28 Aug 2019
Cited by 11 | Viewed by 3134
Abstract
Food peptides contain a very wide range of diversified structures, which explains their diverse range of functional activities. Proatherogenic endothelium is related to vasoconstriction, inflammation, and oxidative stress. In this line, four synthetic bioactive peptides from dry-cured pork ham, previously identified according to [...] Read more.
Food peptides contain a very wide range of diversified structures, which explains their diverse range of functional activities. Proatherogenic endothelium is related to vasoconstriction, inflammation, and oxidative stress. In this line, four synthetic bioactive peptides from dry-cured pork ham, previously identified according to their Angiotensin I Converting Enzyme (ACE) inhibitory capacity and high bioavailability, were tested. Among them, KPVAAP displayed an estimated IC50 of 59.22 µM for human ACE inhibition, and docking simulations demonstrated the consistency of the noncompetitive binding with the protein. The addition of synthetic peptides to human endothelial cells significantly prevents the expression of genes related to endothelial dysfunction and inflammation (eNOS, ICAM-1, VCAM-1, IL-6) and lowers NF-κB activation (all p < 0.05). In silico dockings showed that the four bioactive peptides interact with the regulatory subunit NEMO of the NF-κB transcription factor at the same site as other characterized inhibitors (CC2-LZ region). This is the first study linking experimental and computational approaches that shows NF-κB to be the target of biopeptides of food origin. These multifunctional peptides from dry-cured pork ham make them good candidates for further research into their therapeutic or preventive use to attenuate the inflammatory atherosclerotic process. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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17 pages, 2377 KiB  
Article
Hydrolysed Collagen from Sheepskins as a Source of Functional Peptides with Antioxidant Activity
by Arely León-López, Lucía Fuentes-Jiménez, Alma Delia Hernández-Fuentes, Rafael G. Campos-Montiel and Gabriel Aguirre-Álvarez
Int. J. Mol. Sci. 2019, 20(16), 3931; https://doi.org/10.3390/ijms20163931 - 13 Aug 2019
Cited by 57 | Viewed by 6946
Abstract
The extraction and enzymatic hydrolysis of collagen from sheepskins at different times of hydrolysis (0, 10, 15, 20, 30 min, 1, 2, 3 and 4 h) were investigated in terms of amino acid content (hydroxyproline), isoelectric point, molecular weight (Mw) by sodium dodecyl [...] Read more.
The extraction and enzymatic hydrolysis of collagen from sheepskins at different times of hydrolysis (0, 10, 15, 20, 30 min, 1, 2, 3 and 4 h) were investigated in terms of amino acid content (hydroxyproline), isoelectric point, molecular weight (Mw) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, viscosity, Fourier-transform infrared (FTIR) spectroscopy, antioxidant capacity by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, thermal properties (Differential Scanning Calorimetry) and morphology by scanning electron microscopy (SEM) technique. The kinetics of hydrolysis showed an increase in the protein and hydroxyproline concentration as the hydrolysis time increased to 4 h. FTIR spectra allowed us to identify the functional groups of hydrolysed collagen (HC) in the amide I region for collagen. The isoelectric point shifted to lower values compared to the native collagen precursor. The change in molecular weight and viscosity from time 0 min to 4 h promoted important antioxidant activity in the resulting HC. The lower the Mw, the greater the ability to donate an electron or hydrogen to stabilize radicals. From the SEM images it was evident that HC after 2 h had a porous and spongy structure. These results suggest that HC could be a good alternative to replace HC from typical sources like pigs, cows and fish. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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14 pages, 3056 KiB  
Article
Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis
by Josep Nácher-Juan, María Carmen Terencio, María José Alcaraz and María Luisa Ferrándiz
Int. J. Mol. Sci. 2019, 20(16), 3845; https://doi.org/10.3390/ijms20163845 - 7 Aug 2019
Cited by 11 | Viewed by 3521
Abstract
In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether [...] Read more.
In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 μg/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of RORγt+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1β, IL-2, IL-6, IL-17, and tumor necrosis factor-α in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-κB ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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12 pages, 3710 KiB  
Article
Intragenic Antimicrobial Peptide Hs02 Hampers the Proliferation of Single- and Dual-Species Biofilms of P. aeruginosa and S. aureus: A Promising Agent for Mitigation of Biofilm-Associated Infections
by Lucinda J. Bessa, Julia R. Manickchand, Peter Eaton, José Roberto S. A. Leite, Guilherme D. Brand and Paula Gameiro
Int. J. Mol. Sci. 2019, 20(14), 3604; https://doi.org/10.3390/ijms20143604 - 23 Jul 2019
Cited by 17 | Viewed by 4550
Abstract
Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in a large variety of infections. Their co-occurrence in the same site of infection has been frequently reported and is linked to enhanced virulence and difficulty of treatment. Herein, the antimicrobial and antibiofilm [...] Read more.
Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in a large variety of infections. Their co-occurrence in the same site of infection has been frequently reported and is linked to enhanced virulence and difficulty of treatment. Herein, the antimicrobial and antibiofilm activities of an intragenic antimicrobial peptide (IAP), named Hs02, which was uncovered from the human unconventional myosin 1H protein, were investigated against several P. aeruginosa and S. aureus strains, including multidrug-resistant (MDR) isolates. The antibiofilm activity was evaluated on single- and dual-species biofilms of P. aeruginosa and S. aureus. Moreover, the effect of peptide Hs02 on the membrane fluidity of the strains was assessed through Laurdan generalized polarization (GP). Minimum inhibitory concentration (MIC) values of peptide Hs02 ranged from 2 to 16 μg/mL against all strains and MDR isolates. Though Hs02 was not able to hamper biofilm formation by some strains at sub-MIC values, it clearly affected 24 h preformed biofilms, especially by reducing the viability of the bacterial cells within the single- and dual-species biofilms, as shown by confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM) images. Laurdan GP values showed that Hs02 induces membrane rigidification in both P. aeruginosa and S. aureus. Peptide Hs02 can potentially be a lead for further improvement as an antibiofilm agent. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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15 pages, 1538 KiB  
Article
Alterations in Galanin-Like Immunoreactivity in the Enteric Nervous System of the Porcine Stomach Following Acrylamide Supplementation
by Katarzyna Palus, Krystyna Makowska and Jarosław Całka
Int. J. Mol. Sci. 2019, 20(13), 3345; https://doi.org/10.3390/ijms20133345 - 8 Jul 2019
Cited by 16 | Viewed by 2972
Abstract
In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), especially among young people has been noted. The present study was created to establish the impact of acrylamide supplementation, in tolerable daily intake [...] Read more.
In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), especially among young people has been noted. The present study was created to establish the impact of acrylamide supplementation, in tolerable daily intake (TDI) dose and a dose ten times higher than TDI, on the population of galanin-like immunoreactive (GAL-LI) stomach neurons in pigs. Additionally, in the present study, the possible functional co-operation of GAL with other neuroactive substances and their role in acrylamide intoxication was investigated. Using double-labelling immunohistochemistry, alterations in the expression of GAL were examined in the porcine stomach enteric neurons after low and high doses of acrylamide supplementation. Generally, upregulation in GAL-LI immunoreactivity in both myenteric and submucous plexuses was noted in all stomach fragments studied. Additionally, the proportion of GAL-expressing cell bodies simultaneously immunoreactive to vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and cocaine- and amphetamine- regulated transcript peptide (CART) also increased. The results suggest neurotrophic or/and neuroprotective properties of GAL and possible co-operation of GAL with VIP, nNOS, CART in the recovery processes in the stomach enteric nervous system (ENS) neurons following acrylamide intoxication. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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21 pages, 3302 KiB  
Article
EDB-FN Targeted Peptide–Drug Conjugates for Use against Prostate Cancer
by Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang and Rakesh Kumar Tiwari
Int. J. Mol. Sci. 2019, 20(13), 3291; https://doi.org/10.3390/ijms20133291 - 4 Jul 2019
Cited by 16 | Viewed by 4692
Abstract
Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that [...] Read more.
Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can differentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buffered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 h. Confocal microscopy studies demonstrated increased binding of ligand 8 to EDB-FN compared to ligand 1. Therefore, we hypothesized that the EDB-FN targeted peptides (1 and 8) conjugated with an anticancer drug via a hydrolyzable linker would provide selective cytotoxicity to the cancer cells. To test our hypothesis, we selected both the normal prostate cell line, RWPE-1, and the cancerous prostate cell lines, PC3, DU-145, LNCaP, and C4-2, to evaluate the anticancer activity of synthesized peptide–drug conjugates. Docetaxel (Doce) and doxorubicin (Dox) were used as anticancer drugs. Dox conjugate 13 containing disulfide linkage showed comparable cytotoxicity versus Dox after 72 h incubation in all the cancer cell lines, whereas it was found to be less cytotoxic on RWPE-1, suggesting that it can act as a Dox prodrug. Doce conjugate 14 was found to be less cytotoxic in all the cell lines as compared to drug alone. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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11 pages, 1327 KiB  
Article
Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors
by Lilia Y. Kucheryavykh, Jescelica Ortiz-Rivera, Yuriy V. Kucheryavykh, Astrid Zayas-Santiago, Amanda Diaz-Garcia and Mikhail Y. Inyushin
Int. J. Mol. Sci. 2019, 20(10), 2482; https://doi.org/10.3390/ijms20102482 - 20 May 2019
Cited by 14 | Viewed by 5349
Abstract
Immunostaining with specific antibodies has shown that innate amyloid beta (Aβ) is accumulated naturally in glioma tumors and nearby blood vessels in a mouse model of glioma. In immunofluorescence images, Aβ peptide coincides with glioma cells, and enzyme-linked immunosorbent assay (ELISA) have shown [...] Read more.
Immunostaining with specific antibodies has shown that innate amyloid beta (Aβ) is accumulated naturally in glioma tumors and nearby blood vessels in a mouse model of glioma. In immunofluorescence images, Aβ peptide coincides with glioma cells, and enzyme-linked immunosorbent assay (ELISA) have shown that Aβ peptide is enriched in the membrane protein fraction of tumor cells. ELISAs have also confirmed that the Aβ(1–40) peptide is enriched in glioma tumor areas relative to healthy brain areas. Thioflavin staining revealed that at least some amyloid is present in glioma tumors in aggregated forms. We may suggest that the presence of aggregated amyloid in glioma tumors together with the presence of Aβ immunofluorescence coinciding with glioma cells and the nearby vasculature imply that the source of Aβ peptides in glioma can be systemic Aβ from blood vessels, but this question remains unresolved and needs additional studies. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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16 pages, 1690 KiB  
Article
Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study
by Paraskevi L. Tsiolaki, Aikaterini D. Katsafana, Fotis A. Baltoumas, Nikolaos N. Louros and Vassiliki A. Iconomidou
Int. J. Mol. Sci. 2019, 20(9), 2274; https://doi.org/10.3390/ijms20092274 - 8 May 2019
Cited by 9 | Viewed by 4748
Abstract
Human apolipoprotein E (apoE) is a major component of lipoprotein particles, and under physiological conditions, is involved in plasma cholesterol transport. Human apolipoprotein E found in three isoforms (E2; E3; E4) is a member of a family of apolipoproteins that under pathological conditions [...] Read more.
Human apolipoprotein E (apoE) is a major component of lipoprotein particles, and under physiological conditions, is involved in plasma cholesterol transport. Human apolipoprotein E found in three isoforms (E2; E3; E4) is a member of a family of apolipoproteins that under pathological conditions are detected in extracellular amyloid depositions in several amyloidoses. Interestingly, the lipid-free apoE form has been shown to be co-localized with the amyloidogenic Aβ peptide in amyloid plaques in Alzheimer’s disease, whereas in particular, the apoE4 isoform is a crucial risk factor for late-onset Alzheimer’s disease. Evidence at the experimental level proves that apoE self-assembles into amyloid fibrilsin vitro, although the misfolding mechanism has not been clarified yet. Here, we explored the mechanistic insights of apoE misfolding by testing short apoE stretches predicted as amyloidogenic determinants by AMYLPRED, and we computationally investigated the dynamics of apoE and an apoE–Αβ complex. Our in vitro biophysical results prove that apoE peptide–analogues may act as the driving force needed to trigger apoE aggregation and are supported by the computational apoE outcome. Additional computational work concerning the apoE–Αβ complex also designates apoE amyloidogenic regions as important binding sites for oligomeric Αβ; taking an important step forward in the field of Alzheimer’s anti-aggregation drug development. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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16 pages, 2323 KiB  
Article
Prediction of Bioactive Peptides from Chlorella sorokiniana Proteins Using Proteomic Techniques in Combination with Bioinformatics Analyses
by Lhumen A. Tejano, Jose P. Peralta, Encarnacion Emilia S. Yap, Fenny Crista A. Panjaitan and Yu-Wei Chang
Int. J. Mol. Sci. 2019, 20(7), 1786; https://doi.org/10.3390/ijms20071786 - 11 Apr 2019
Cited by 51 | Viewed by 6885
Abstract
Chlorella is one of the most nutritionally important microalgae with high protein content and can be a good source of potential bioactive peptides. In the current study, isolated proteins from Chlorella sorokiniana were subjected to in silico analysis to predict potential peptides with [...] Read more.
Chlorella is one of the most nutritionally important microalgae with high protein content and can be a good source of potential bioactive peptides. In the current study, isolated proteins from Chlorella sorokiniana were subjected to in silico analysis to predict potential peptides with biological activities. Molecular characteristics of proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and proteomics techniques. A total of eight proteins were identified by proteomics techniques from 10 protein bands of the SDS-PAGE. The predictive result by BIOPEP’s profile of bioactive peptides tools suggested that proteins of C. sorokiniana have the highest number of dipeptidyl peptidase-IV (DPP IV) inhibitors, with high occurrence of other bioactive peptides such as angiotensin-I converting enzyme (ACE) inhibitor, glucose uptake stimulant, antioxidant, regulating, anti-amnestic and antithrombotic peptides. In silico analysis of enzymatic hydrolysis revealed that pepsin (pH > 2), bromelain and papain were proteases that can release relatively larger quantity of bioactive peptides. In addition, combinations of different enzymes in hydrolysis were observed to dispense higher numbers of bioactive peptides from proteins compared to using individual proteases. Results suggest the potential of protein isolated from C. sorokiniana could be a source of high value products with pharmaceutical and nutraceutical application potential. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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12 pages, 2210 KiB  
Article
Development of a Soy Protein Hydrolysate with an Antihypertensive Effect
by Eric Banan-Mwine Daliri, Fred Kwame Ofosu, Ramachandran Chelliah, Mi Houn Park, Jong-Hak Kim and Deog-Hwan Oh
Int. J. Mol. Sci. 2019, 20(6), 1496; https://doi.org/10.3390/ijms20061496 - 25 Mar 2019
Cited by 53 | Viewed by 6164
Abstract
In this study, we combined enzymatic hydrolysis and lactic acid fermentation to generate an antihypertensive product. Soybean protein isolates were first hydrolyzed by Prozyme and subsequently fermented with Lactobacillus rhamnosus EBD1. After fermentation, the in vitro angiotensin-converting enzyme (ACE) inhibitory activity of the [...] Read more.
In this study, we combined enzymatic hydrolysis and lactic acid fermentation to generate an antihypertensive product. Soybean protein isolates were first hydrolyzed by Prozyme and subsequently fermented with Lactobacillus rhamnosus EBD1. After fermentation, the in vitro angiotensin-converting enzyme (ACE) inhibitory activity of the product (P-SPI) increased from 60.8 ± 2.0% to 88.24 ± 3.2%, while captopril (a positive control) had an inhibitory activity of 94.20 ± 5.4%. Mass spectrometry revealed the presence of three potent and abundant ACE inhibitory peptides, PPNNNPASPSFSSSS, GPKALPII, and IIRCTGC in P-SPI. Hydrolyzing P-SPI with gastrointestinal proteases did not significantly affect its ACE inhibitory ability. Also, oral administration of P-SPI (200 mg/kg body weight) to spontaneous hypertensive rats (SHRs) for 6 weeks significantly lowered systolic blood pressure (−19 ± 4 mm Hg, p < 0.05) and controlled body weight gain relative to control SHRs that were fed with physiological saline. Overall, P-SPI could be used as an antihypertensive functional food. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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Review

Jump to: Editorial, Research

31 pages, 1615 KiB  
Review
Evolving a Peptide: Library Platforms and Diversification Strategies
by Krištof Bozovičar and Tomaž Bratkovič
Int. J. Mol. Sci. 2020, 21(1), 215; https://doi.org/10.3390/ijms21010215 - 27 Dec 2019
Cited by 51 | Viewed by 9655
Abstract
Peptides are widely used in pharmaceutical industry as active pharmaceutical ingredients, versatile tools in drug discovery, and for drug delivery. They find themselves at the crossroads of small molecules and proteins, possessing favorable tissue penetration and the capability to engage into specific and [...] Read more.
Peptides are widely used in pharmaceutical industry as active pharmaceutical ingredients, versatile tools in drug discovery, and for drug delivery. They find themselves at the crossroads of small molecules and proteins, possessing favorable tissue penetration and the capability to engage into specific and high-affinity interactions with endogenous receptors. One of the commonly employed approaches in peptide discovery and design is to screen combinatorial libraries, comprising a myriad of peptide variants of either chemical or biological origin. In this review, we focus mainly on recombinant peptide libraries, discussing different platforms for their display or expression, and various diversification strategies for library design. We take a look at well-established technologies as well as new developments and future directions. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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23 pages, 2704 KiB  
Review
Expression and Function of Host Defense Peptides at Inflammation Sites
by Suhanya V. Prasad, Krzysztof Fiedoruk, Tamara Daniluk, Ewelina Piktel and Robert Bucki
Int. J. Mol. Sci. 2020, 21(1), 104; https://doi.org/10.3390/ijms21010104 - 22 Dec 2019
Cited by 64 | Viewed by 9010
Abstract
There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to [...] Read more.
There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to understand their function because some HDPs play opposing pro-inflammatory and anti-inflammatory roles, depending on their expression level within the site of inflammation. While it is known that HDPs maintain constitutive host protection against invading microorganisms, the inducible nature of HDPs in various cells and tissues is an important aspect of the molecular events of inflammation. This review outlines the biological functions and emerging roles of HDPs in different inflammatory conditions. We further discuss the current data on the clinical relevance of impaired HDPs expression in inflammation and selected diseases. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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41 pages, 2901 KiB  
Review
A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases
by Carmen Martínez, Yasmina Juarranz, Irene Gutiérrez-Cañas, Mar Carrión, Selene Pérez-García, Raúl Villanueva-Romero, David Castro, Amalia Lamana, Mario Mellado, Isidoro González-Álvaro and Rosa P. Gomariz
Int. J. Mol. Sci. 2020, 21(1), 65; https://doi.org/10.3390/ijms21010065 - 20 Dec 2019
Cited by 34 | Viewed by 10713
Abstract
The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in [...] Read more.
The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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18 pages, 1166 KiB  
Review
Humanized Mice as an Effective Evaluation System for Peptide Vaccines and Immune Checkpoint Inhibitors
by Yoshie Kametani, Yusuke Ohno, Shino Ohshima, Banri Tsuda, Atsushi Yasuda, Toshiro Seki, Ryoji Ito and Yutaka Tokuda
Int. J. Mol. Sci. 2019, 20(24), 6337; https://doi.org/10.3390/ijms20246337 - 16 Dec 2019
Cited by 19 | Viewed by 5365
Abstract
Peptide vaccination was developed for the prevention and therapy of acute and chronic infectious diseases and cancer. However, vaccine development is challenging, because the patient immune system requires the appropriate human leukocyte antigen (HLA) recognition with the peptide. Moreover, antigens sometimes induce a [...] Read more.
Peptide vaccination was developed for the prevention and therapy of acute and chronic infectious diseases and cancer. However, vaccine development is challenging, because the patient immune system requires the appropriate human leukocyte antigen (HLA) recognition with the peptide. Moreover, antigens sometimes induce a low response, even if the peptide is presented by antigen-presenting cells and T cells recognize it. This is because the patient immunity is dampened or restricted by environmental factors. Even if the immune system responds appropriately, newly-developed immune checkpoint inhibitors (ICIs), which are used to increase the immune response against cancer, make the immune environment more complex. The ICIs may activate T cells, although the ratio of responsive patients is not high. However, the vaccine may induce some immune adverse effects in the presence of ICIs. Therefore, a system is needed to predict such risks. Humanized mouse systems possessing human immune cells have been developed to examine human immunity in vivo. One of the systems which uses transplanted human peripheral blood mononuclear cells (PBMCs) may become a new diagnosis strategy. Various humanized mouse systems are being developed and will become good tools for the prediction of antibody response and immune adverse effects. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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22 pages, 1345 KiB  
Review
Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications
by Daniel Brady, Alessandro Grapputo, Ottavia Romoli and Federica Sandrelli
Int. J. Mol. Sci. 2019, 20(23), 5862; https://doi.org/10.3390/ijms20235862 - 22 Nov 2019
Cited by 96 | Viewed by 9358
Abstract
The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs), a group of [...] Read more.
The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs), a group of naturally occurring AMPs in insects, and on synthetic Cec-analogs. We describe their action mechanisms and antimicrobial activity against MDR bacteria and other pathogens. We report several data suggesting that Cec and Cec-analog peptides are promising antibacterial therapeutic candidates, including their low toxicity against mammalian cells, and anti-inflammatory activity. We highlight limitations linked to the use of peptides as therapeutics and discuss methods overcoming these constraints, particularly regarding the introduction of nanotechnologies. New formulations based on natural Cecs would allow the development of drugs active against Gram-negative bacteria, and those based on Cec-analogs would give rise to therapeutics effective against both Gram-positive and Gram-negative pathogens. Cecs and Cec-analogs might be also employed to coat biomaterials for medical devices as an approach to prevent biomaterial-associated infections. The cost of large-scale production is discussed in comparison with the economic and social burden resulting from the progressive diffusion of MDR infectious diseases. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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32 pages, 3385 KiB  
Review
Antimicrobial Peptides as Anti-Infective Agents in Pre-Post-Antibiotic Era?
by Tomislav Rončević, Jasna Puizina and Alessandro Tossi
Int. J. Mol. Sci. 2019, 20(22), 5713; https://doi.org/10.3390/ijms20225713 - 14 Nov 2019
Cited by 100 | Viewed by 9174
Abstract
Resistance to antibiotics is one of the main current threats to human health and every year multi-drug resistant bacteria are infecting millions of people worldwide, with many dying as a result. Ever since their discovery, some 40 years ago, the antimicrobial peptides (AMPs) [...] Read more.
Resistance to antibiotics is one of the main current threats to human health and every year multi-drug resistant bacteria are infecting millions of people worldwide, with many dying as a result. Ever since their discovery, some 40 years ago, the antimicrobial peptides (AMPs) of innate defense have been hailed as a potential alternative to conventional antibiotics due to their relatively low potential to elicit resistance. Despite continued effort by both academia and start-ups, currently there are still no antibiotics based on AMPs in use. In this study, we discuss what we know and what we do not know about these agents, and what we need to know to successfully translate discovery to application. Understanding the complex mechanics of action of these peptides is the main prerequisite for identifying and/or designing or redesigning novel molecules with potent biological activity. However, other aspects also need to be well elucidated, i.e., the (bio)synthetic processes, physiological and pathological contexts of their activity, and a quantitative understanding of how physico-chemical properties affect activity. Research groups worldwide are using biological, biophysical, and algorithmic techniques to develop models aimed at designing molecules with the necessary blend of antimicrobial potency and low toxicity. Shedding light on some open questions may contribute toward improving this process. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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22 pages, 1631 KiB  
Review
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties
by Veronika Pražienková, Andrea Popelová, Jaroslav Kuneš and Lenka Maletínská
Int. J. Mol. Sci. 2019, 20(21), 5297; https://doi.org/10.3390/ijms20215297 - 24 Oct 2019
Cited by 22 | Viewed by 6986
Abstract
Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, [...] Read more.
Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10. Special attention is paid to structure-activity relationship studies on PrRP and its analogs as well as to their effect on different physiological functions, mainly their anorexigenic and neuroprotective features and the regulation of the cardiovascular system, pain, and stress. Additionally, the therapeutic potential of this peptide and its analogs is explored. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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11 pages, 2481 KiB  
Review
Detection of Antigen-Specific T Cells Using In Situ MHC Tetramer Staining
by Hadia M. Abdelaal, Emily K. Cartwright and Pamela J. Skinner
Int. J. Mol. Sci. 2019, 20(20), 5165; https://doi.org/10.3390/ijms20205165 - 18 Oct 2019
Cited by 13 | Viewed by 8296
Abstract
The development of in situ major histocompatibility complex (MHC) tetramer (IST) staining to detect antigen (Ag)-specific T cells in tissues has radically revolutionized our knowledge of the local cellular immune response to viral and bacterial infections, cancers, and autoimmunity. IST combined with immunohistochemistry [...] Read more.
The development of in situ major histocompatibility complex (MHC) tetramer (IST) staining to detect antigen (Ag)-specific T cells in tissues has radically revolutionized our knowledge of the local cellular immune response to viral and bacterial infections, cancers, and autoimmunity. IST combined with immunohistochemistry (IHC) enables determination of the location, abundance, and phenotype of T cells, as well as the characterization of Ag-specific T cells in a 3-dimensional space with respect to neighboring cells and specific tissue locations. In this review, we discuss the history of the development of IST combined with IHC. We describe various methods used for IST staining, including direct and indirect IST and IST performed on fresh, lightly fixed, frozen, and fresh then frozen tissue. We also describe current applications for IST in viral and bacterial infections, cancer, and autoimmunity. IST combined with IHC provides a valuable tool for studying and tracking the Ag-specific T cell immune response in tissues. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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18 pages, 314 KiB  
Review
Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors
by Stacey A Krepel and Ji Ming Wang
Int. J. Mol. Sci. 2019, 20(14), 3426; https://doi.org/10.3390/ijms20143426 - 12 Jul 2019
Cited by 32 | Viewed by 4052
Abstract
Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family [...] Read more.
Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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