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Carlos Lopez-Abarrategui,1 Viviana Figueroa-Espi,2 Maria B Lugo-Alvarez,1 Caroline D Pereira,3 Hilda Garay,4 João ARG Barbosa,5 Rosana Falcão,6 Linnavel Jiménez-Hernández,2 Osvaldo Estévez-Hernández,2,7 Edilso Reguera,8 Octavio L Franco,3,9 Simoni C Dias,3 Anselmo J Otero-Gonzalez1 1Faculty of Biology, Center for Protein Studies, 2Lab of Structural Analysis, Institute of Materials Science and Technology, Havana University, La Habana, Havana, Cuba; 3Center for Biochemical and Proteomics Analyses, Catholic University of Brasilia, Brasilia, Brazil; 4Laboratory of Peptide Analysis and Synthesis, Center of Genetic Engineering and Biotechnology, La Habana, Havana, Cuba; 5Department of Cellular Biology, Laboratory of Biophysics, Institute of Biological Science, University of Brasilia, 6Brazilian Agricultural Research Corporation (EMBRAPA), Center of Genetic Resources and Biotechnology (CENARGEN), Brasilia DF, Brazil; 7Instituto de Ciencia y Tecnología de Materiales (IMRE), Universidad de La Habana, Cuba; 8Research Center for Applied Science and Advanced Technology (CICATA), National Polytechnic Institute (IPN), Lagaria Unit, Mexico DF, Mexico; 9S-Inova Biotech, Post-Graduate in Biotechnology, Universidade Catolica Dom Bosco, Campo Grande, Brazil Abstract: Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid-modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 µg/mL. However, the nanoparticles were not capable of inhibiting Gram-negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 µg/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity. Keywords: nanoparticles, conjugation, antifungal, Cm-p5 peptide

Amanda CM Saúde,1 Alicia S Ombredane,1 Osmar N Silva,1 João ARG Barbosa,1,2 Susana E Moreno,3 Ana Claudia Guerra Araujo,4 Rosana Falcão,4 Luciano P Silva,4 Simoni C Dias,1 Octávio L Franco1,3 1Programa de Pós Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, FD, Brazil; 2Laboratório de Biofísica-Departamento de Biologia Celular-IB, Universidade de Brasília – UNB, DF, Brazil; 3Universidade Católica Dom Bosco – UCDB, Campo Grande, MS, Brazil; 4Empresa Brasileira de Pesquisa Agropecuária – EMBRAPA – Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil Abstract: Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections. Keywords: peptides, antimicrobial, nanoparticles, nanobiotechnology

El artículo describe y analiza la circulación de prácticas y discursos asociados con la espiritualidad Nueva Era en circuitos que promueven la cultura emprendedora. Para ello se avanza en un análisis de los discursos de oradores/as y su marco de enunciación en dos eventos públicos en la ciudad argentina de Córdoba, interesados en la difusión del “espíritu emprendedor”: Experiencia Endeavor y 7 Reinas – Movimiento de Motivación Femenina. Los resultados, aunque tentativos, permiten reflexionar sobre las miradas convencionales que conciben al ámbito económico como racional y secular. Asimismo, dan cuenta de un proceso de reactualización y renovación del discurso gerencial contemporáneo a través de la incorporación de prácticas y discursos asociados con la espiritualidad Nueva Era.

Since the new millennium, Political Science and International Relations around the world have evidenced a growing interest in religious phenomena. In Argentina, however, the same impact has not been noticed: the continuous increase in studies on religion seems to come mainly from disciplines such as Sociology and Anthropology. Thus, it is necessary to explore the situation that are facing Argentina’s Political Science and International Relations on the renewed interest in religious phenomena. We did a systematic review of articles published between 1990 and the first semester of 2017 (n = 71), in eight Argentine scientific journals whose scope has a focus on Political Science and International Relations’ topics. The paper considers some bibliometric indicators as those of productivity and authorship, and we also present a textual content analysis to discuss the ways in which religion is presented in the most recognized local circuit of publications from both disciplines.

Background: Resistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges., Major Conclusions: Here we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 μmol L -1 . It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties., General Significance: This study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Skeletal muscle is a highly adaptive tissue, capable of responding to different physiological and functional demands, even in situations that may cause instability., Objectives: To evaluate how partial calcaneal tendon (CT) injuries affect the remodeling and plasticity of the gastrocnemius muscle over time., Methods and Results: The study was carried out with Wistar rats randomly divided into five groups. The control group comprised animals not subjected to partial CT damage. The remaining four groups were subjected to partial CT damage and were further categorized based on the time of euthanasia: 3, 14, 28, and 55 days after injury. The gastrocnemius muscle was collected and used for gene expression analysis, zymography, flow cytometry, and morphology. The calcaneal tendon was analyzed only to verify the presence of the partial injury., Results: The impact of partial CT injury on the gastrocnemius homeostasis, particularly on gene expression, was more pronounced in the 3-day group compared to the other groups, especially the control group. Cytokine profile and morphologic alterations occurred in the 55 days group when compared to the other groups., Conclusions: The data reported here suggest that partial injury can negatively affect intracellular signaling and degradation pathways, disturbing the muscular extracellular matrix regulatory mechanisms and communication with the tendon. However, skeletal muscle seems to mitigate these harmful effects in comparison with lesions that affect muscle and tendon., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Poultry meat production and exportation contribute significantly to the global economy. However, various infections affect poultry production and consequently affect the economy. Nowadays, antibiotics are widely used in infection treatment and prevention. Antibiotic overuse is problematic because may cause antimicrobial resistance, which can be transferred to humans directly or indirectly, affecting public health. In addition, since antibiotics for animal growth stimulation are banned, it is important to search for new molecules to overcome these difficulties. As an alternative, antimicrobial peptides (AMPs) can show immunomodulatory, antimicrobial, and growth stimulation, which makes these molecules interesting as alternatives to antibiotic use. Studying AMPs can provide new ideas for treating the most important infections that affect poultry. Besides, this can assist in reducing the resistance problem. This review aims to examine recent studies about AMPs used against pathogens that can affect the poultry industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g., tuberculosis and bacterial pneumonia), (2) bacterial infection is a consequence of disease and worsens the disease prognosis (e.g., cystic fibrosis), and (3) bacteria-triggered inflammation propagates the disease (e.g., chronic obstructive pulmonary disease). Current approaches to combat infections generally include long and aggressive antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of infections that cannot be treated with conventional antibiotics is rapidly increasing, and novel therapies are urgently needed. In this context, antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress inflammation and provide other host defense functions (motivating the alternative term host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this, AMP delivery systems have recently attracted attention. For airway infections, the currently investigated delivery approaches range from aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating bacterial infections in the airways.

Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Streptococcus pneumoniae, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This systematic review aimed to compile various research designs, including experimental, longitudinal, cross-sectional, and case studies in humans and experimental studies in rodents, to examine changes in Akkermansia muciniphila abundance in response to exercise. This comprehensive approach can improve our understanding of A. muciniphila response to physical exercise and highlight gaps in the literature, providing valuable insights for future microbiome research. Four databases (Web of Science, PubMed, Scopus, and Sports Discuss) were searched in the literature. Quality assessment was conducted independently and in duplicate using two risk-of-bias tools (Downs and Black for human studies and SYRCLE's risk of bias for animal studies). 3,901 studies were identified, with thirteen human studies and nine animal studies included after screening. Of the thirteen human studies analysed, five (38.5%) were cross-sectional, seven (53.8%) were longitudinal/experimental, and one (7.7%) was a case study. These studies included 522 participants, among whom 157 were athletes, such as rugby players, marathon runners, triathletes, and skiers. Six studies reported an increase in A. muciniphila, five showed a decrease, and two found no significant differences. Regarding interventions, two studies used a combination of moderate-intensity strength and aerobic training, while seven used low to moderate-intensity aerobic exercises. In the nine rodent studies, eight (88.9%) were conducted on mice and one (11.1%) on rats, with all being experimental. These studies involved 310 animals. Eight studies reported a substantial increase in A. muciniphila, while one found no differences. Among these, eight employed moderate-intensity aerobic exercises as the intervention, and one utilised low-to-moderate-intensity strength training. The studies summarised in this review indicate that the impact of various physical exercise protocols on A. muciniphila abundance in humans remains controversial. However, rodent studies provide strong evidence that aerobic exercise increases A. muciniphila abundance in faecal pellets of both healthy and diseased models.

Bacterial resistance has become a serious public health problem in recent years, thus encouraging the search for new antimicrobial agents. Here, we report an antimicrobial peptide (AMP), called PEPAD, which was designed based on an encrypted peptide from a Kunitz-type plant peptidase inhibitor. PEPAD was capable of rapidly inhibiting and eliminating numerous bacterial species at micromolar concentrations (from 4μM to 10 μM), with direct membrane activity. It was also observed that the peptide can act synergistically with ciprofloxacin and showed no toxicity in the G. mellonella in vivo assay. Circular dichroism assays revealed that the peptide's secondary structure adopts different scaffolds depending on the environment in which it is inserted. In lipids mimicking bacterial cell membranes, PEPAD adopts a more stable α-helical structure, which is consistent with its membrane-associated mechanism of action. When in contact with lipids mimicking mammalian cells, PEPAD adopts a disordered structure, losing its function and suggesting cellular selectivity. Therefore, these findings make PEPAD a promising candidate for future antimicrobial therapies with low toxicity to the host., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

To evaluate the effects of the association of host defence peptide IDR-1002 and ciprofloxacin on human dental pulp cells (hDPSCs). hDPSCs were stimulated with ciprofloxacin and IDR-1002. Cell viability (by MTT assay), migration capacity (by scratch assay), production of inflammatory and anti-inflammatory mediators by hDPSCs (RT-PCR) and osteogenic differentiation (alizarin red staining) were evaluated. Phenotypic profile of hDPSCs demonstrated 97% for positive marked mesenchymal stem cell. Increased pulp cell migration and proliferation were observed after 24 and 48 h of exposure to IDR-1002 with ciprofloxacin. Mineral matrix formation by hDPSCs was observed of the association while its reduction was observed in the presence of peptide. After 24 h, the association between ciprofloxacin and IDR-1002 significantly downregulated TNFRSF-1, IL-1β, IL-8, IL-6 and IL-10 gene expression (p ≤ 0.0001). The association between the IDR-1002 and ciprofloxacin showed favourable immunomodulatory potential, emerging as a promising option for pulp revascularisation processes., (© 2024 Australian Society of Endodontology Inc.)

The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI, and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared with Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI, and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Many factors contribute to bacterial membrane stabilization, including steric effects between lipids, membrane spontaneous curvature, and the difference in the number of neighboring molecules. This forum provides an overview of the physicochemical properties associated with membrane curvature and how this parameter can be tuned to design more effective antimicrobial peptides., Competing Interests: Declaration of interests C.F-N. provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L., Peptidus, and Phare Bio. C.F-N. is also on the Advisory Board of the Peptide Drug Hunting Consortium (PDHC). The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. C.F-N. is on the Advisory Board of Cell Reports Physical Science., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diverse computational approaches have been widely used to assist in designing antimicrobial peptides with enhanced activities. This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro-adrenomedullin N-terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an α-helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C-terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal-isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic α-helical arrangement with the conserved C-terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences., (© 2024 John Wiley & Sons Ltd.)

Gut peptides play a role in signaling appetite control in the hypothalamus. Limited knowledge exists regarding the release of these peptides in individuals with obesity before and during external stimuli. We hypothesize that the expression of gut peptides is different in the fasting and postprandial states in the scenario of obesity. PubMed/MEDLINE, Scopus, and Science Direct electronic databases were searched. The meta-analysis was performed using Review Manager Software. Randomized controlled trials that measured gut peptides in both obese and lean subjects were included in the analysis. A total of 552 subjects with obesity were enrolled in 25 trials. The gut peptide profile did not show any significant difference between obese and lean subjects for glucagon-like peptide 1 (95% confidence interval [CI], -1.21 to 0.38; P = .30), peptide YY (95% CI, -1.47 to 0.18; P = .13), and cholecystokinin (95% CI, -1.25 to 1.28; P = .98). Gut peptides are decreased by an increased high-fat, high-carbohydrate diet and by decreased chewing. There is no statistically significant difference in gut peptides between individuals with obesity and leanness in a fasting state. However, the release of gut peptides is affected in individuals with obesity following external stimuli, such as dietary interventions and chewing. Further studies are necessary to investigate the relationship between various stimuli and the release of gut peptides, as well as their impact on appetite regulation in subjects with obesity., Competing Interests: Author Declarations The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bovine mastitis is a mammary gland inflammation that can occur due to infectious pathogens, Staphylococcus aureus and Escherichia coli , which are, respectively, the most prevalent Gram-positive and Gram-negative bacteria associated with this disease. Currently, antibiotic treatment has become more complicated due to the presence of resistant pathogens. This review, therefore, aims to identify the most common resistance genes reported for these strains in the last four years. During the review, it was noted that bla Z , bla SHV, bla TEM , and bla ampC are the most reported genes for S. aureus and E. coli, associated with drug inactivation, mainly β-lactamases. They are characterized by generating bacterial resistance to β-lactam antibiotics, the most common treatment in animal and human bacterial treatments (penicillins and cephalosporins, among others). Genes associated with efflux systems were also present in the two strains and included norA, tetA, tetC , and tetK , which generate resistance to macrolide and tetracycline antibiotics. Additionally, the effects of spreading resistance between animals and humans through direct contact (such as consumption of contaminated milk) or indirect contact (through environmental contamination) has been deeply discussed, emphasizing the importance of having adequate sanitation and antibiotic control and administration protocols.

Investigations involving high-intensity interval training (HIIT) have proven to be efficient in controlling diabesity. This study aimed to assess the impact of discontinuing HIIT and retraining within the context of diabesity. 75 C57BL6 mice went through 5 stages: baseline, induction of diabesity with Western diet, training, detraining, and retraining (6 weeks each period). Detraining led to elevated adiposity, exacerbated metabolic parameters and intestinal health, and altered gut microbiota composition. Retraining restored blood glucose regulation and enhanced intestinal health yet did not induce fat reduction. While both training and retraining exerted an effect on the composition of the gut microbiota, the impact of diet demonstrates a more substantial potency compared to that of exercise concerning intestinal health and microbiome. These findings may contribute to a broader understanding of diabesity management and introduce perspectives for the use of specific physical training to enhance patient outcomes and intestine health., Competing Interests: There are no conflicts of interest to disclose., (© 2024 The Authors.)

Bacterial infections pose a significant threat to human health, constituting a major challenge for healthcare systems. Antibiotic resistance is particularly concerning in the context of treating staphylococcal infections. In addressing this challenge, antimicrobial peptides (AMPs), characterized by their hydrophobic and cationic properties, unique mechanism of action, and remarkable bactericidal and immunomodulatory capabilities, emerge as promising alternatives to conventional antibiotics for tackling bacterial multidrug resistance. This study focuses on the Cry10Aa protein as a template for generating AMPs due to its membrane-penetrating ability. Leveraging the Joker algorithm, six peptide variants were derived from α-helix 3 of Cry10Aa, known for its interaction with lipid bilayers. In vitro, antimicrobial assays determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) required for inhibiting the growth of Staphylococcus aureus , Escherichia coli , Acinetobacter baummanii , Enterobacter cloacae , Enterococcus facallis , Klebsiella pneumonia , and Pseudomonas aeruginosa . Time-kill kinetics were performed using the parental peptide AMPCry10Aa, as well as AMPCry10Aa_1 and AMPCry10Aa_5, against E. coli ATCC, S. aureus 111 and S. aureus ATCC strains showing that AMPCry10Aa_1 and AMPCry10Aa_5 peptides can completely reduce the initial bacterial load with less than 2 h of incubation. AMPCry10Aa_1 and AMPCry 10Aa_5 present stability in human serum and activity maintenance up to 37 °C. Cytotoxicity assays, conducted using the MTT method, revealed that all of the tested peptides exhibited cell viability >50% (IC50). The study also encompassed evaluations of the structure and physical-chemical properties. The three-dimensional structures of AMPCry10Aa and AMPCry10Aa_5 were determined through nuclear magnetic resonance (NMR) spectroscopy, indicating the adoption of α-helical segments. Electron paramagnetic resonance (EPR) spectroscopy elucidated the mechanism of action, demonstrating that AMPCry10Aa_5 enters the outer membranes of E. coli and S. aureus , causing substantial increases in lipid fluidity, while AMPCry10Aa slightly increases lipid fluidity in E. coli . In conclusion, the results obtained underscore the potential of Cry10Aa as a source for developing antimicrobial peptides as alternatives to conventional antibiotics, offering a promising avenue in the battle against antibiotic resistance., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I 5 , R 8 ], mastoparan-MO, and [I 5 , R 8 ] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I 5 , R 8 ] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I 5 , R 8 ] mastoparan. Mastoparan-MO and [I 5 , R 8 ] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I 5 , R 8 ] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.

Background and Aim: Fructooligosaccharide (FOS) supplementation can stimulate beneficial intestinal bacteria growth, but little is known about its influence on training performance. Therefore, this study analyzed FOS and exercise effects on gut microbiota and intestinal morphology of C57Bl/6 mice., Methods: Forty male mice were divided into four groups: standard diet-sedentary (SDS), standard diet-exercised (SDE), FOS supplemented (7.5% FOS)-sedentary (FDS), and FOS supplemented-exercised (FDE), n = 10 each group. Exercise training consisted of 60 min/day, 3 days/week, for 12 weeks., Results: SDE and FDE groups had an increase in aerobic performance compared to the pretraining period and SDS and FDS groups (P < 0.01), respectively. Groups with FOS increased colonic crypts size (P < 0.05). The FDE group presented rich microbiota (α-diversity) compared to other groups. The FDE group also acquired a greater microbial abundance (β-diversity) than other groups. The FDE group had a decrease in the Ruminococcaceae (P < 0.002) and an increase in Roseburia (P < 0.003), Enterorhabdus (P < 0.004) and Anaerotruncus (P < 0.006)., Conclusions: These findings suggest that aerobic exercise associated with FOS supplementation modulates gut microbiota and can increase colonic crypt size without improving endurance exercise performance., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide's secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu 2+ , Ni 2+ , and Zn 2+ , give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brango-Vanegas, Leite, Macedo, Cardoso and Franco.)

Bovine mastitis is a frequent infection in lactating cattle, causing great economic losses. Staphylococcus aureus represents the main etiological agent, which causes recurrent and persistent intramammary infections because conventional antibiotics are ineffective against it. Mastoparan-like peptides are multifunctional molecules with broad antimicrobial potential, constituting an attractive alternative. Nevertheless, their toxicity to host cells has hindered their therapeutic application. Previously, our group engineered three mastoparan-L analogs, namely mastoparan-MO, mastoparan-R1, and [I 5 , R 8 ] MP, to improve cell selectivity and potential. Here, we were interested in comparing the antibacterial efficacy of mastoparan-L and its analogs against bovine mastitis isolates of S. aureus strains, making a correlation with the physicochemical properties and structural arrangement changes promoted by the sequence modifications. As a result, the analog's hemolytic and/or antimicrobial activity was balanced. All the peptides displayed α-helical folding in hydrophobic and membrane-mimetic environments, as determined by circular dichroism. The peptide [I 5 , R 8 ] MP stood out for its enhanced selectivity and antibacterial features related to mastoparan-L and the other derivatives. Biophysical approaches revealed that [I 5 , R 8 ] MP rapidly depolarizes the bacterial membrane of S. aureus , causing cell death by subsequent membrane disruption. Our results demonstrated that the [I 5 , R 8 ] MP peptide could be a starting point for the development of peptide-based drugs for the treatment of bovine mastitis, with the advantage of no residue in milk, which would help reduce the use of classical antibiotics.IMPORTANCE Staphylococcus aureus is a leading cause of mastitis, the world's most important dairy cattle disease. The multidrug resistance and zoonotic potential of S. aureus , besides the likelihood of antibiotic residues in milk, are of critical concern to public and animal health. Antimicrobial peptides offer a novel antimicrobial strategy. Here, we demonstrate that [I 5 , R 8 ] MP is a potent and selective peptide, which acts on S. aureus by targeting the bacterial membrane. Therefore, understanding the physicochemical determinants and the modes of action of this class of antimicrobials opens novel prospects for peptide development with enhanced activities in the bovine mastitis context., Competing Interests: The authors declare no conflict of interest.

Inflammation contributes to the onset and exacerbation of numerous age-related diseases, often manifesting as a chronic condition during aging. Given that cellular senescence fosters local and systemic inflammation, senotherapeutic interventions could potentially aid in managing or even reducing inflammation. Here, we investigated the immunomodulatory effects of the senotherapeutic Peptide 14 (Pep 14) in human peripheral blood mononuclear cells (PBMCs), monocytes, and macrophages. We found that, despite failing to significantly influence T cell activation and proliferation, the peptide promoted a Th2/Treg gene expression and cytokine signature in PBMCs, characterized by increased expression of the transcription factors GATA3 and FOXP3 , as well as the cytokines IL-4 and IL-10. These observations were partially confirmed through ELISA, in which we observed increased IL-10 release by resting and PHA-stimulated PBMCs. In monocytes from the U-937 cell line, Pep 14 induced apoptosis in lipopolysaccharide (LPS)-stimulated cells and upregulated IL-10 expression. Furthermore, Pep 14 prevented LPS-induced activation and promoted an M2-like polarization in U-937-derived macrophages, evidenced by decreased expression of M1 markers and increased expression of M2 markers. We also showed that the conditioned media from Pep 14-treated macrophages enhanced fibroblast migration, indicative of a functional M2 phenotype. Taken together, our findings suggest that Pep 14 modulates immune cell function towards an anti-inflammatory and regenerative phenotype, highlighting its potential as a therapeutic intervention to alleviate immunosenescence-associated dysregulation.

Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 μmol L -1 , also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents., Competing Interests: Declaration of competing interest The authors declare no competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lactic acid (LA) production has seen significant progress over the past ten years. LA has seen increased economic importance due to its broadening use in different sectors such as the food, medicine, polymer, cosmetic, and pharmaceutical industries. LA production bioprocesses using microorganisms are economically viable compared to chemical synthesis and can benefit from metabolic engineering for improved productivity, purity, and yield. Strategies to optimize LA productivity in microorganisms on the strain improvement end include modifying metabolic routes, adding gene coding for lactate transporters, inducing tolerance to organic acids, and choosing cheaper carbon sources as fuel. Many of the recent advances in this regard have involved the metabolic engineering of yeasts and filamentous fungi to produce LA due to their versatility in fuel choice and tolerance of industrial-scale culture conditions such as pH and temperature. This review aims to compile and discuss metabolic engineering innovations in LA production in yeasts and filamentous fungi over the 2013-2023 period, and present future directions of research in this area, thus bringing researchers in the field up to date with recent advances.

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 μM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells., Competing Interests: Declaration of competing interest The authors declare no competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mastoparans are cationic peptides with multifunctional pharmacological properties. Mastoparan-R1 and mastoparan-R4 were computationally designed based on native mastoparan-L from wasps and have improved therapeutic potential for the control of bacterial infections. Here, we evaluated whether these peptides maintain their activity against Escherichia coli strains under a range of salt concentrations. We found that mastoparan-R1 and mastoparan-R4 preserved their activity under the conditions tested, including having antibacterial activities at physiological salt concentrations. The overall structure of the peptides was investigated using circular dichroism spectroscopy in a range of solvents. No significant changes in secondary structure were observed (random coil in aqueous solutions and α-helix in hydrophobic and anionic environments). The three-dimensional structures of mastoparan-R1 and mastoparan-R4 were elucidated through nuclear magnetic resonance spectroscopy, revealing amphipathic α-helical segments for Leu3-Ile13 (mastoparan-R1) and Leu3-Ile14 (mastoparan-R4). Possible membrane-association mechanisms for mastoparan-R1 and mastoparan-R4 were investigated through surface plasmon resonance and leakage studies with synthetic POPC and POPC/POPG (4:1) lipid bilayers. Mastoparan-L had the highest affinity for both membrane systems, whereas the two analogs had weaker association, but improved selectivity for lysing anionic membranes. This finding was also supported by molecular dynamics simulations, in which mastoparan-R1 and mastoparan-R4 were found to have greater interactions with bacteria-like membranes compared with model mammalian membranes. Despite having a few differences in their functional and structural profiles, the mastoparan-R1 analog stood out with the highest activity, greater bacteriostatic potential, and selectivity for lysing anionic membranes. This study reinforces the potential of mastoparan-R1 as a drug candidate., (© 2023 Federation of European Biochemical Societies.)

The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved., Objectives: Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1., Methods: An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020., Results: K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1., Conclusions: Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During carcinogenesis, neoplastic cells accumulate mutations in genes important for cellular homeostasis, producing defective proteins. Viral infections occur when viral capsid proteins bind to the host cell receptor, allowing the virus to enter the cells. In both cases, proteins play important roles in cancer development and viral infection, so these targets can be exploited to develop alternative treatments. mRNA display technology is a very powerful tool for the development of peptides capable of acting on specific targets in neoplastic cells or on viral capsid proteins. mRNA display technology allows the selection and evolution of peptides with desired functional properties from libraries of many nucleic acid variants. Among other advantages of this technology, the use of flexizymes allows the production of peptides with unnatural amino acid residues, which can enhance the activity of these molecules. From target immobilization, peptides with greater specificity for the targets of interest are generated during the selection rounds. Herein, we will explore the use of mRNA display technology for the development of active peptides after successive rounds of selection, using proteins present in neoplastic cells and viral particles as targets., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Antimicrobial peptides (AMPs) are considered a promising therapeutic approach against multi-drug resistant microorganisms. Besides their advantages, there are limitations to be overcome so that these molecules can become market competitive. One of the biggest limitations is proteolytic susceptibility, which could be overcome by structural modifications such as cyclization, especially for helix-constraining strategies. Over the years, many helix stabilization techniques have arisen, such as lactam-bridging, triazole-based, N-alkylation and all-hydrocarbon stapling. All-hydrocarbon stapling takes advantage of modified amino acid residues and olefinic cross-linking to constrain peptide helices. Despite being a well-established strategy and presenting efficient stability results, there are different limitations especially related to toxicity. In this review, recent studies on stapled AMPs for antimicrobial usage are explored with the aim of understanding the future of these molecules as putative antimicrobial agents.

Chagas disease, sleeping sickness and malaria are infectious diseases caused by protozoan parasites that kill millions of people worldwide. Here, we performed in vitro assays of Pa-MAP , Pa-MAP1.9 , and Pa-MAP2 synthetic polyalanine peptides derived from the polar fish Pleuronectes americanus toward Trypanosoma cruzi , T. brucei gambiense and Plasmodium falciparum activities. We demonstrated that the peptides Pa-MAP1.9 and Pa-MAP2 were effective to inhibit T. brucei growth. In addition, structural analyses using molecular dynamics (MD) studies showed that Pa-MAP2 penetrates deeper into the membrane and interacts more with phospholipids than Pa-MAP1.9 , corroborating the previous in vitro results showing that Pa-MAP1.9 acts within the cell, while Pa-MAP2 acts via membrane lysis. In conclusion, polyalanine Pa-MAP1.9 and Pa-MAP2 presented activity against bloodstream forms of T. b. gambiense , thus encouraging further studies on the application of these peptides as a treatment for sleeping sickness.

The intricate, tightly controlled mechanism of wound healing that is a vital physiological mechanism is essential to maintaining the skin's natural barrier function. Numerous studies have focused on wound healing as it is a massive burden on the healthcare system. Wound repair is a complicated process with various cell types and microenvironment conditions. In wound healing studies, novel therapeutic approaches have been proposed to deliver an effective treatment. Nanoparticle-based materials are preferred due to their antibacterial activity, biocompatibility, and increased mechanical strength in wound healing. They can be divided into six main groups: metal NPs, ceramic NPs, polymer NPs, self-assembled NPs, composite NPs, and nanoparticle-loaded hydrogels. Each group shows several advantages and disadvantages, and which material will be used depends on the type, depth, and area of the wound. Better wound care/healing techniques are now possible, thanks to the development of wound healing strategies based on these materials, which mimic the extracellular matrix (ECM) microenvironment of the wound. Bearing this in mind, here we reviewed current studies on which NPs have been used in wound healing and how this strategy has become a key biotechnological procedure to treat skin infections and wounds., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Antimicrobial peptides (AMPs) are components of natural immunity against invading pathogens. They are polymers that fold into a variety of three-dimensional structures, enabling their function, with an underlying sequence that is best represented in a non-flat space. The structural data of AMPs exhibits non-Euclidean characteristics, which means that certain properties, e.g., differential manifolds, common system of coordinates, vector space structure, or translation-equivariance, along with basic operations like convolution, in non-Euclidean space are not distinctly established. Geometric deep learning (GDL) refers to a category of machine learning methods that utilize deep neural models to process and analyze data in non-Euclidean settings, such as graphs and manifolds. This emerging field seeks to expand the use of structured models to these domains. This review provides a detailed summary of the latest developments in designing and predicting AMPs utilizing GDL techniques and also discusses both current research gaps and future directions in the field., Competing Interests: CF-N provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L. and Phare Bio. The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fernandes, Cardoso, Gil-Ley, Luchi, da Silva, Macedo, de la Fuente-Nunez and Franco.)

Host defense peptides (HDPs) are naturally occurring polypeptide sequences that, in addition to being active against bacteria, fungi, viruses, and other parasites, may stimulate immunomodulatory responses. Cathelicidins, a family of HDPs, are produced by diverse animal species, such as mammals, fish, birds, amphibians, and reptiles, to protect them against pathogen infections. These peptides have variable C-terminal domains responsible for their antimicrobial and immunomodulatory activities and a highly conserved N-terminal pre-pro region homologous to cathelin. Although cathelicidins are the major components of innate immunity, the molecular basis by which they induce an immune response is still unclear. In this review, we will address the role of the LL-37 domain and its SK-24, IV-20, FK-13 and LL-37 fragments in the immunity response. Other cathelicidins also share structural and functional characteristics with the LL-37 domain, suggesting that these fragments may be responsible for interaction between these peptides and receptors in humans. Fragments of the LL-37 domain can give us clues about how homologous cathelicidins, in general, induce an immune response., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Host Defense Peptides (HDPs) have, in previous studies, been demonstrating antimicrobial, anti-inflammatory, and immunomodulatory capacity, important factors in the repair process. Knowing these characteristics, this article aims to evaluate the potential of HDPs IDR1018 and DJK-6 associated with MTA extract in the repair process of human pulp cells. Antibacterial activity of HDPs, MTA and HDPs combined with MTA in Streptococcus mutans planktonic bacteria and antibiofilm activity was evaluated. Cell toxicity was assayed with MTT and cell morphology was observed by scanning electron microscopy (SEM). Proliferation and migration of pulp cells were evaluated by trypan blue and wound healing assay. Inflammatory and mineralization related genes were evaluated by qPCR (IL-6, TNFRSF, DSPP, TGF-β). Alkaline phosphatase, phosphate quantification and alizarin red staining were also verified. The assays were performed in technical and biological triplicate (n = 9). Results were submitted for the calculation of the mean and standard deviation. Then, normality verification by Kolmogorov Smirnov test, analyzing one-way ANOVA. Analyses were considered at a 95% significance level, with a p-value < 0.05. Our study demonstrated that HDPs combined with MTA were able to reduce biofilms performed in 24 h and biofilm performed over 7 days S. mutans biofilm (p < 0.05). IDR1018 and MTA, as well as their combination, down-regulated IL-6 expression (p < 0.05). Tested materials were not cytotoxic to pulp cells. IDR1018 induced high cell proliferation and combined with MTA induced high cellular migration rates in 48 h (p < 0.05). Furthermore, the combination of IDR1018 and MTA also induced high expression levels of DSPP, ALP activity, and the production of calcification nodules. So, IDR-1018 and its combination with MTA could assist in pulp-dentine complex repair process in vitro., (© 2023. The Author(s).)

Throughout evolution, plants have developed a highly complex defense system against different threats, including phytopathogens. Plant defense depends on constitutive and induced factors combined as defense mechanisms. These mechanisms involve a complex signaling network linking structural and biochemical defense. Antimicrobial and pathogenesis-related (PR) proteins are examples of this mechanism, which can accumulate extra- and intracellular space after infection. However, despite their name, some PR proteins are present at low levels even in healthy plant tissues. When they face a pathogen, these PRs can increase in abundance, acting as the first line of plant defense. Thus, PRs play a key role in early defense events, which can reduce the damage and mortality caused by pathogens. In this context, the present review will discuss defense response proteins, which have been identified as PRs, with enzymatic action, including constitutive enzymes, β-1,3 glucanase, chitinase, peroxidase and ribonucleases. From the technological perspective, we discuss the advances of the last decade applied to the study of these enzymes, which are important in the early events of higher plant defense against phytopathogens.

Novel treatments toward Gram-negative bacteria are urgently needed to prevent even higher mortality levels associated with resistant bacterial infections. Predatory bacteria have been studied as a new type of treatment against pathogenic bacteria, including resistant species. However, because of limitations related to eradication efficacy, combination therapy using predatory bacteria with other agents has also been tested. Here, we discuss recent advances in the use of predatory bacteria to treat infections and propose novel combinatory strategies with antivirulence compounds., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Most antimicrobial peptides (AMPs) exert their microbicidal activity through membrane permeabilization. The designed AMP EcDBS1R4 has a cryptic mechanism of action involving the membrane hyperpolarization of Escherichia coli , suggesting that EcDBS1R4 may hinder processes involved in membrane potential dissipation. We show that EcDBS1R4 can sequester cardiolipin, a phospholipid that interacts with several respiratory complexes of E. coli . Among these, F 1 F O ATP synthase uses membrane potential to fuel ATP synthesis. We found that EcDBS1R4 can modulate the activity of ATP synthase upon partition to membranes containing cardiolipin. Molecular dynamics simulations suggest that EcDBS1R4 alters the membrane environment of the transmembrane F O motor, impairing cardiolipin interactions with the cytoplasmic face of the peripheral stalk that binds the catalytic F 1 domain to the F O domain. The proposed mechanism of action, targeting membrane protein function through lipid reorganization may open new venues of research on the mode of action and design of other AMPs., Competing Interests: Authors declare no competing interests., (© 2023 The Authors.)

Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity. Pep 14 functions via modulation of PP2A, an understudied holoenzyme that promotes genomic stability and is involved in DNA repair and senescence pathways. At the single-cell level, Pep 14 modulates genes that prevent senescence progression by arresting the cell cycle and enhancing DNA repair, which consequently reduce the number of cells progressing to late senescence. When applied on aged ex vivo skin, Pep 14 promoted a healthy skin phenotype with structural and molecular resemblance to young ex vivo skin, decreased the expression of senescence markers, including SASP, and reduced the DNA methylation age. In summary, this work shows the safe reduction of the biological age of ex vivo human skins by a senomorphic peptide., (© 2023. The Author(s).)

Antibiotic-resistant bacterial infections have increased the prevalence of sepsis and septic shock mortality worldwide and have become a global concern. Antimicrobial peptides (AMPs) show remarkable properties for developing new antimicrobial agents and host response modulatory therapies. A new series of AMPs derived from pexiganan (MSI-78) were synthesized. The positively charged amino acids were segregated at their N- and C-termini, and the rest of the amino acids created a hydrophobic core surrounded by positive charges and were modified to simulate the lipopolysaccharide (LPS). The peptides were investigated for their antimicrobial activity and LPS-induced cytokine release inhibition profile. Various biochemical and biophysical methods were used, including attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, microscale thermophoresis (MST), and electron microscopy. Two new AMPs, MSI-Seg-F2F and MSI-N7K, preserved their neutralizing endotoxin activity while reducing toxicity and hemolytic activity. Combining all of these properties makes the designed peptides potential candidates to eradicate bacterial infection and detoxify LPS, which might be useful for sepsis treatment., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria of clinical importance, but its cytotoxicity can represent a problem for its positioning as an effective antimicrobial compound. In contrast, the immunomodulatory peptide IDR-1018 presents low toxicity and a wide regenerative potential due to its ability to reduce apoptotic mRNA expression and promote skin cell proliferation. In the present study, we used human skin cells and a 3D skin equivalent models to analyze the potential of the IDR-1018 peptide to attenuate the cytotoxicity of synoeca-MP, as well as the influence of synoeca-MP/IDR-1018 combination on cell proliferation, regenerative processes, and wound repair. We found that the addition of IDR-1018 significantly improved the biological properties of synoeca-MP on skin cells without modifying its antibacterial activity against S. aureus . Likewise, in both melanocytes and keratinocytes, the treatment with synoeca-MP/IDR-1018 combination induces cell proliferation and migration, while in a 3D human skin equivalent model, it can accelerate wound reepithelization. Furthermore, treatment with this peptide combination generates an up-regulation in the expression of pro-regenerative genes in both monolayer cell cultures and in 3D skin equivalents. This data suggests that the synoeca-MP/IDR-1018 combination possesses a good profile of antimicrobial and pro-regenerative activity, opening the door to the development of new strategies for the treatment of skin lesions.

The co-occurrence of biotic and abiotic stresses in agricultural areas severely affects crop performance and productivity. Drought is one of the most adverse environmental stresses, and its association with root-knot nematodes further limits the development of several economically important crops, such as cowpea. Plant responses to combined stresses are complex and require novel adaptive mechanisms through the induction of specific biotic and abiotic signaling pathways. Therefore, the present work aimed to identify proteins involved in the resistance of cowpea to nematode and drought stresses individually and combined. We used the genotype CE 31, which is resistant to the root-knot nematode Meloidogyne spp. And tolerant to drought. Three biological replicates of roots and shoots were submitted to protein extraction, and the peptides were evaluated by LC-MS/MS. Shotgun proteomics revealed 2345 proteins, of which 1040 were differentially abundant. Proteins involved in essential biological processes, such as transcriptional regulation, cell signaling, oxidative processes, and photosynthesis, were identified. However, the main defense strategies in cowpea against cross-stress are focused on the regulation of hormonal signaling, the intense production of pathogenesis-related proteins, and the downregulation of photosynthetic activity. These are key processes that can culminate in the adaptation of cowpea challenged by multiple stresses. Furthermore, the candidate proteins identified in this study will strongly contribute to cowpea genetic improvement programs.