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Frontiers in Immunology 2023The mechanism underlying radiation-induced gut microbiota dysbiosis is undefined. This study examined the effect of radiation on the intestinal Paneth cell α-defensin...
INTRODUCTION
The mechanism underlying radiation-induced gut microbiota dysbiosis is undefined. This study examined the effect of radiation on the intestinal Paneth cell α-defensin expression and its impact on microbiota composition and mucosal tissue injury and evaluated the radio-mitigative effect of human α-defensin 5 (HD5).
METHODS
Adult mice were subjected to total body irradiation, and Paneth cell α-defensin expression was evaluated by measuring α-defensin mRNA by RT-PCR and α-defensin peptide levels by mass spectrometry. Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. HD5 was administered in a liquid diet 24 hours before or after irradiation. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by cytokine expression. Systemic inflammation was evaluated by measuring plasma cytokine levels.
RESULTS
Ionizing radiation reduced the Paneth cell α-defensin expression and depleted α-defensin peptides in the intestinal lumen. α-Defensin down-regulation was associated with the time-dependent alteration of gut microbiota composition, increased gut permeability, and endotoxemia. Administration of human α-defensin 5 (HD5) in the diet 24 hours before irradiation (prophylactic) significantly blocked radiation-induced gut microbiota dysbiosis, disruption of intestinal epithelial tight junction and adherens junction, mucosal barrier dysfunction, and mucosal inflammatory response. HD5, administered 24 hours after irradiation (treatment), reversed radiation-induced microbiota dysbiosis, tight junction and adherens junction disruption, and barrier dysfunction. Furthermore, HD5 treatment also prevents and reverses radiation-induced endotoxemia and systemic inflammation.
CONCLUSION
These data demonstrate that radiation induces Paneth cell dysfunction in the intestine, and HD5 feeding prevents and mitigates radiation-induced intestinal mucosal injury, endotoxemia, and systemic inflammation.
Topics: Humans; Adult; Animals; Mice; Paneth Cells; alpha-Defensins; Dysbiosis; Endotoxemia; RNA, Ribosomal, 16S; Radiation Injuries; Cytokines; Inflammation
PubMed: 37638013
DOI: 10.3389/fimmu.2023.1174140 -
International Journal of Molecular... Sep 2023Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to... (Meta-Analysis)
Meta-Analysis Review
Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to preventing further oral damage and the associated health complications. This study offers a systematic review of the literature published up to April 2023, and aims to clearly explain the role of proteomics in identifying salivary biomarkers for periodontitis. Comprehensive searches were conducted on PubMed and Web of Science to shortlist pertinent studies. The inclusion criterion was those that reported on mass spectrometry-driven proteomic analyses of saliva samples from periodontitis cohorts, while those on gingivitis or other oral diseases were excluded. An assessment for risk of bias was carried out using the Newcastle-Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies or the NIH quality assessment tool, and a meta-analysis was performed for replicable candidate biomarkers, i.e., consistently reported candidate biomarkers (in specific saliva samples, and periodontitis subgroups, reported in ≥2 independent cohorts/reports) were identified. A Gene Ontology enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resources, which consistently expressed candidate biomarkers, to explore the predominant pathway wherein salivary biomarkers consistently manifested. Of the 15 studies included, 13 were case-control studies targeting diagnostic biomarkers for periodontitis participants (periodontally healthy/diseased, = 342/432), while two focused on biomarkers responsive to periodontal treatment ( = 26 participants). The case-control studies were considered to have a low risk of bias, while the periodontitis treatment studies were deemed fair. Summary estimate and confidence/credible interval, etc. determination for the identified putative salivary biomarkers could not be ascertained due to the low number of studies in each case. The results from the included case-control studies identified nine consistently expressed candidate biomarkers (from nine studies with 230/297 periodontally healthy/diseased participants): (i) those that were upregulated: alpha-amylase, serum albumin, complement C3, neutrophil defensin, profilin-1, and S100-P; and (ii) those that were downregulated: carbonic anhydrase 6, immunoglobulin J chain, and lactoferrin. All putative biomarkers exhibited consistent regulation patterns. The implications of the current putative marker proteins identified were reviewed, with a focus on their potential roles in periodontitis diagnosis and pathogenesis, and as putative therapeutic targets. Although in its early stages, mass spectrometry-based salivary periodontal disease biomarker proteomics detection appeared promising. More mass spectrometry-based proteomics studies, with or without the aid of already available clinical biochemical approaches, are warranted to aid the discovery, identification, and validation of periodontal health/disease indicator molecule(s). Protocol registration number: CRD42023447722; supported by RD-02-202410 and GRF17119917.
Topics: Humans; Proteomics; Periodontitis; Mass Spectrometry; Biomarkers; Proteins; Periodontal Diseases; Saliva
PubMed: 37834046
DOI: 10.3390/ijms241914599 -
Journal of Reproductive Immunology Dec 2023Chronic endometritis has a high incidence in infertile women, which is caused by endometrial microbiome infection. In response to microbial infection, the role of...
Chronic endometritis has a high incidence in infertile women, which is caused by endometrial microbiome infection. In response to microbial infection, the role of defensins during chronic endometritis need explored. Besides, the expression of estrogen and its receptors vary in different menstrual cycles, but their roles in chronic endometritis are still unclear. In this study, we used the human endometrial tissues to examine the expression of antimicrobial peptides (AMPs) α-defensin hNP-1 and β-defensins hBD-1, hBD-2, hBD-3, hBD-4 and LCN2. We found the expression of hBD-1 and LCN2 were downregulated in endometritis tissues, while the expressions of hBD-2, hBD-3, hBD-4, hNP-1, and estrogen and ERα were upregulated in chronic endometritis tissues compared to normal tissues. The expression and phosphorylation of STING, which is a crucial mediator of mammalian innate immunity in response to pathogens, was regulated with the treatment of ERα inhibitor raloxifene (Rx). Furthermore, using with the estrogen receptor inhibitor Rx and STING inhibitor H-151 significantly decreases the LCN2 expression. Taken together, these results suggested ERα was upregulated to modulate STING expression inducing LCN2 antimicrobial peptide expression to modulate the mucosal immunity during chronic endometritis.
Topics: Animals; Female; Humans; Defensins; Down-Regulation; Endometritis; Estrogen Receptor alpha; Estrogens; Infertility, Female; Lipocalin-2; Mammals; Receptors, Estrogen
PubMed: 37952294
DOI: 10.1016/j.jri.2023.104167 -
Frontiers in Immunology 2023High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many...
High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.
Topics: Animals; Chiroptera; beta-Defensins; Antimicrobial Peptides; Antimicrobial Cationic Peptides; Cathelicidins
PubMed: 37822944
DOI: 10.3389/fimmu.2023.1250229 -
Cureus Jun 2024Filamentous fungal keratitis is a particularly serious eye infection that often results in ulceration, corneal perforation, and blindness. The cornea acts as a natural... (Review)
Review
Filamentous fungal keratitis is a particularly serious eye infection that often results in ulceration, corneal perforation, and blindness. The cornea acts as a natural barrier against harmful agents due to the close connection of its epithelial cells. In addition, on its surface, there is a large number of substances with anti-inflammatory and bactericidal properties, such as secretory IgA and mucin glycoproteins, and antimicrobial peptides (AMPs), such as human β-defensin 2 (HBD-2) and LL-37, which are especially increased in filamentous fungal keratitis. The interaction between pathogenic fungi and the host's immune mechanisms is a complex process: pathogen-associated molecular pattern (PAMP) molecules (chitin, β-glucan, and mannan) found in the fungal cell wall are recognized by pattern recognition receptors (PRRs) (toll-like receptors {TLRs}, C-type lectin receptors {CLRs}, nucleotide-binding oligomerization domain-like receptors {NLRs}, and scavenger receptors {SR}) found in host defense cells, triggering the secretion of various types of cytokines, such as interleukins (IL), tumor necrosis factors (TNFs), and chemokines, which recruit macrophages and neutrophils to migrate to the site of infection and activate inflammatory responses. In addition, the interaction of hyphae and corneal epithelial cells can activate cluster of differentiation (CD) 4+ T cells, CD8+ T cells, and B cells and induce secretion of T-helper (Th)-type cytokines 2 (IL-4 and IL-13) and IgG.
PubMed: 38855487
DOI: 10.7759/cureus.61954 -
Journal of Ethnopharmacology Dec 2023Man has used honey to treat diseases since ancient times, perhaps even before the history of medicine itself. Several civilizations have utilized natural honey as a... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Man has used honey to treat diseases since ancient times, perhaps even before the history of medicine itself. Several civilizations have utilized natural honey as a functional and therapeutic food to ward off infections. Recently, researchers worldwide have been focusing on the antibacterial effects of natural honey against antibiotic-resistant bacteria.
AIM OF THE STUDY
This review aims to summarize research on the use of honey properties and constituents with their anti-bacterial, anti-biofilm, and anti-quorum sensing mechanisms of action. Further, honey's bacterial products, including probiotic organisms and antibacterial agents which are produced to curb the growth of other competitor microorganisms is addressed.
MATERIALS AND METHODS
In this review, we have provided a comprehensive overview of the antibacterial, anti-biofilm, and anti-quorum sensing activities of honey and their mechanisms of action. Furthermore, the review addressed the effects of antibacterial agents of honey from bacterial origin. Relevant information on the antibacterial activity of honey was obtained from scientific online databases such as Web of Science, Google Scholar, ScienceDirect, and PubMed.
RESULTS
Honey's antibacterial, anti-biofilm, and anti-quorum sensing activities are mostly attributed to four key components: hydrogen peroxide, methylglyoxal, bee defensin-1, and phenolic compounds. The performance of bacteria can be altered by honey components, which impact their cell cycle and cell morphology. To the best of our knowledge, this is the first review that specifically summarizes every phenolic compound identified in honey along with their potential antibacterial mechanisms of action. Furthermore, certain strains of beneficial lactic acid bacteria such as Bifidobacterium, Fructobacillus, and Lactobacillaceae, as well as Bacillus species can survive and even grow in honey, making it a potential delivery system for these agents.
CONCLUSION
Honey could be regarded as one of the best complementary and alternative medicines. The data presented in this review will enhance our knowledge of some of honey's therapeutic properties as well as its antibacterial activities.
Topics: Bees; Animals; Honey; Bacteria; Anti-Bacterial Agents; Biofilms; Quorum Sensing
PubMed: 37400003
DOI: 10.1016/j.jep.2023.116830 -
Biopharmaceutics & Drug Disposition Oct 2023α-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported...
α-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported that a decrease in α-defensin 5 level in the human small intestine is a risk of inflammatory bowel disease (IBD). Furthermore, P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter superfamily, encoded by the ABCB1/MDR1 gene, plays an important role in the front line of host defense by protecting the gastrointestinal barrier from xenobiotic accumulation and may contribute to the development and persistence of IBD. Therefore, we examined the relationship between α-defensin 5 and the expression and function of P-gp using a human gastrointestinal model cell line (Caco-2). We found that MDR1 mRNA and P-gp protein level were increased in Caco-2 cells as well as α-defensin 5 secretion corresponded with the duration of cell culture. Exposure to α-defensin 5 peptide and recombinant tumor necrosis factor-α (TNF-α) significantly increased the expression and function P-gp. The mRNA levels of interleukin (IL)-8, IL-6, TNF-α, IL-1β, and IL-2 were also increased following exposure to TNF-α, similar to α-defensin 5 treatment. These results suggest that α-defensin 5 regulates P-gp expression and function by increasing TNF-α expression in Caco-2 cells.
Topics: Humans; ATP Binding Cassette Transporter, Subfamily B, Member 1; Caco-2 Cells; alpha-Defensins; Tumor Necrosis Factor-alpha; ATP Binding Cassette Transporter, Subfamily B; Inflammatory Bowel Diseases; RNA, Messenger
PubMed: 37277970
DOI: 10.1002/bdd.2367 -
BioRxiv : the Preprint Server For... May 2024Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins...
UNLABELLED
Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins can increase rather than block infection by certain prominent bacterial and viral pathogens in cell culture and . We have shown previously that exposure of mouse and human adenoviruses (HAdVs) to α-defensins is able to overcome competitive inhibitors that block cell binding, leading us to hypothesize a defensin-mediated binding mechanism that is independent of known viral receptors. To test this hypothesis, we used genetic approaches to demonstrate that none of several primary receptors nor integrin co-receptors are needed for human α-defensin-mediated binding of HAdV to cells; however, infection remains integrin dependent. Thus, our studies have revealed a novel pathway for HAdV binding to cells that bypasses viral primary receptors. We speculate that this pathway functions in parallel with receptor-mediated entry and contributes to α-defensin-enhanced infection of susceptible cells. Remarkably, we also found that in the presence of α-defensins, HAdV tropism is expanded to non-susceptible cells, even when viruses are exposed to a mixture of both susceptible and non-susceptible cells. Therefore, we propose that in the presence of sufficient concentrations of α-defensins, such as in the lung or gut, integrin expression rather than primary receptor expression will dictate HAdV tropism . In summary, α-defensins may contribute to tissue tropism not only through the neutralization of susceptible viruses but also by allowing certain defensin-resistant viruses to bind to cells independently of previously described mechanisms.
AUTHOR SUMMARY
In this study, we demonstrate a novel mechanism for binding of human adenoviruses (HAdVs) to cells that is dependent upon interactions with α-defensin host defense peptides but is independent of known viral receptors and co-receptors. To block normal receptor-mediated HAdV infection, we made genetic changes to both host cells and HAdVs. Under these conditions, α-defensins restored cell binding; however, infection still required the function of HAdV integrin co-receptors. This was true for multiple types of HAdVs that use different primary receptors and for cells that are either naturally devoid of HAdV receptors or were engineered to be receptor deficient. These observations suggest that in the presence of concentrations of α-defensins that would be found naturally in the lung or intestine, there are two parallel pathways for HAdV binding to cells that converge on integrins for productive infection. Moreover, these binding pathways function independently, and both operate in mixed culture. Thus, we have found that viruses can co-opt host defense molecules to expand their tropism.
PubMed: 38854108
DOI: 10.1101/2024.05.30.596681 -
Journal of Functional Biomaterials Dec 2023Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may... (Review)
Review
Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may affect the dental implant surface's chemical inertness, cell adhesion, and antibacterial characteristics. Different surface coatings and mechanical surface changes have been studied to improve osseointegration and decrease peri-implantitis. The surface medication increases surface energy, leading to enhanced cell proliferation and growth factors, and, consequently, to a rise in the osseointegration process. This review provides a comprehensive update on the numerous biomimetic coatings used to improve the surface characteristics of dental implants and their applications in two main categories: coating to improve osseointegration, including the hydroxyapatite layer and nanocomposites, growth factors (BMPs, PDGF, FGF), and extracellular matrix (collagen, elastin, fibronectin, chondroitin sulfate, hyaluronan, and other proteoglycans), and coatings for anti-bacterial performance, covering drug-coated dental implants (antibiotic, statin, and bisphosphonate), antimicrobial peptide coating (GL13K and human beta defensins), polysaccharide antibacterial coatings (natural chitosan and its coupling agents) and metal elements (silver, zinc, and copper).
PubMed: 38248682
DOI: 10.3390/jfb15010015 -
International Journal of Molecular... May 2024Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a... (Review)
Review
Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a mixture of important compounds, such as proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, and polyphenols, that underlie the remarkable biological and therapeutic activities of RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, the major royal jelly proteins, and specific peptides such as apisimin, royalisin, royalactin, apidaecin, defensin-1, and jelleins are characteristic ingredients of RJ. RJ shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, RJ may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing. This article provides an overview of the molecular mechanisms underlying the beneficial effects of RJ in various diseases, aging, and aging-related complications, with special emphasis on the bioactive components of RJ and their health-promoting properties. The data presented should be an incentive for future clinical studies that hopefully will advance our knowledge about the therapeutic potential of RJ and facilitate the development of novel RJ-based therapeutic opportunities for improving human health and well-being.
Topics: Humans; Fatty Acids; Animals; Anti-Inflammatory Agents
PubMed: 38892209
DOI: 10.3390/ijms25116023