-
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0246393.].
Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.
[This corrects the article DOI: 10.1371/journal.pone.0246393.].
PubMed: 38809824
DOI: 10.1371/journal.pone.0304732 -
Journal of Developmental Biology May 2024Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and...
BACKGROUND
Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and immunomodulation are represented by specific markers; therefore, the aim of this study was to determine the expression of matrix metalloproteinase-2 (MMP2), tissue inhibitor of metalloproteinases-2 (TIMP2), CD34, vascular endothelial growth factor (VEGF), and human β-defensin 2 (HBD2) in preterm and full-term human umbilical cord tissue.
METHODS
Samples of umbilical cord tissue were obtained from 17 patients and divided into two groups: very preterm and moderate preterm birth umbilical cords; late preterm birth and full-term birth umbilical cords. Routine histology examination was conducted. Marker-positive cells were detected using the immunohistochemistry method. The number of positive structures was counted semi-quantitatively using microscopy. Statistical analysis was carried out using the SPSS Statistics 29 program.
RESULTS
Extraembryonic mesenchyme cells are the most active cell producers, expressing MMP2, TIMP2, VEGF, and HBD2 at notable levels in preterm and full-term umbilical cord tissue. Statistically significant differences in the expression of CD34, MMP2, and TIMP2 between the two patient groups were found. The expression of VEGF was similar in both patient groups, with the highest number of VEGF-positive cells seen in the extraembryonic mesenchyme. The expression of HBD2 was the highest in the extraembryonic mesenchyme and the amniotic epithelium, where mostly moderate numbers of HBD2-positive cells were detected.
CONCLUSIONS
Extracellular matrix remodeling in preterm and term umbilical cords is strongly regulated, and tissue factors MMP2 and TIMP2 take part in this process. The expression of VEGF is not affected by the umbilical cord's age; however, individual patient factors can affect the production of VEGF. Numerous CD34-positive cells in the endothelium of the umbilical arteries suggest a significant role of progenitor cells in very preterm and moderate preterm birth umbilical cords. Antimicrobial activity provided by HBD2 is essential and constant in preterm and full-term umbilical cords.
PubMed: 38804433
DOI: 10.3390/jdb12020013 -
Developmental and Comparative Immunology Sep 2024Defensins are antimicrobial peptides involved in innate immunity, and gene number differs amongst eutherian mammals. Few studies have investigated defensins in...
Defensins are antimicrobial peptides involved in innate immunity, and gene number differs amongst eutherian mammals. Few studies have investigated defensins in marsupials, despite their potential involvement in immunological protection of altricial young. Here we use recently sequenced marsupial genomes and transcriptomes to annotate defensins in nine species across the marsupial family tree. We characterised 35 alpha and 286 beta defensins; gene number differed between species, although Dasyuromorphs had the largest repertoire. Defensins were encoded in three gene clusters within the genome, syntenic to eutherians, and were expressed in the pouch and mammary gland. Marsupial beta defensins were closely related to eutherians, however marsupial alpha defensins were more divergent. We identified marsupial orthologs of human DEFB3 and 6, and several marsupial-specific beta defensin lineages which may have novel functions. Marsupial predicted mature peptides were highly variable in length and sequence composition. We propose candidate peptides for future testing to elucidate the function of marsupial defensins.
Topics: Animals; Marsupialia; Phylogeny; beta-Defensins; Humans; Multigene Family; Immunity, Innate; Defensins; Transcriptome; Genome; alpha-Defensins; Amino Acid Sequence; Evolution, Molecular
PubMed: 38797458
DOI: 10.1016/j.dci.2024.105207 -
The Journal of Nutrition May 2024Gut dysbiosis and increased intestinal permeability have been reported to precede type 1 diabetes-related autoimmunity. The role of gut inflammation in autoimmunity is...
BACKGROUND
Gut dysbiosis and increased intestinal permeability have been reported to precede type 1 diabetes-related autoimmunity. The role of gut inflammation in autoimmunity is not understood.
OBJECTIVES
This study aimed to assess whether gut inflammation markers are associated with risk of islet autoimmunity and whether diet is associated with gut inflammation markers.
METHODS
A nested case-control sample of 75 case children with islet autoimmunity and 88 control children was acquired from the Finnish Type 1 Diabetes Prediction and Prevention cohort. Diet was assessed with 3-d food records, and calprotectin and human β-defensin-2 (HBD-2) were analyzed from stool samples at 6 and 12 mo of age. Conditional logistic regression analysis was used in a matched case-control setting to assess risk of autoimmunity. Analysis of variance, independent samples t test, and a general linear model were used in secondary analyses to test associations of background characteristics and dietary factors with inflammation markers.
RESULTS
In unadjusted analyses, calprotectin was not associated with risk of islet autoimmunity, whereas HBD-2 in the middle (odds ratio [OR]: 3.23; 95% confidence interval [CI]: 1.03, 10.08) or highest tertile (OR: 3.02; 95% CI: 1.05, 8.69) in comparison to the lowest at 12 mo of age showed borderline association (P-trend = 0.063) with higher risk of islet autoimmunity. Excluding children with cow milk allergy in sensitivity analyses strengthened the association of HBD-2 with islet autoimmunity, whereas adjusting for dietary factors and maternal education weakened it. At age 12 mo, higher fat intake was associated with higher HBD-2 (β: 0.219; 95% CI: 0.110, 0.328) and higher intake of dietary fiber (β: -0.294; 95% CI: -0.510, -0.078), magnesium (β: -0.036; 95% CI: -0.059, -0.014), and potassium (β: -0.003; 95% CI: -0.005, -0.001) with lower HBD-2.
CONCLUSIONS
Higher HBD-2 in infancy may be associated with higher risk of islet autoimmunity. Dietary factors play a role in gut inflammatory status.
PubMed: 38795745
DOI: 10.1016/j.tjnut.2024.05.015 -
International Journal of Molecular... May 2024Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical...
Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical phenotypes of CRS. Our aim was to use detected IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, Ki 67, HBD-2, HBD-3, and LL-37 to classify specific inflammatory endotypes in chronic rhinosinusitis with the tissue of nasal polyps (CRSwNP). Samples from 35 individuals with primary and recurrent CRSwNP were taken during surgery. The tissues were stained for the previously mentioned biomarkers immunohistochemically. A hierarchical cluster analysis was performed. The clinical parameters were compared between clusters. Five clusters had significantly different biomarkers between groups. There were no significant differences in the clinical parameters, except for the Lund-Mackay score, which was significantly higher in cluster 4 compared to that of cluster 1 ( = 0.024). Five endotypes of (CRSwNP) are characterized by different combinations of type 1, type 2, and type 3 tissue inflammation patterns. In the Latvian population, endotypes associated with neutrophilic inflammation or a combination of neutrophilic inflammation and type 2 inflammation are predominant. Increased proliferation marker Ki 67 values are not associated with more severe inflammation in the tissue samples of chronic rhinosinusitis with nasal polyps.
Topics: Humans; Nasal Polyps; Sinusitis; Chronic Disease; Female; Male; Rhinitis; Middle Aged; Adult; Latvia; Biomarkers; Aged; Recurrence; Cytokines; Inflammation; Rhinosinusitis
PubMed: 38791197
DOI: 10.3390/ijms25105159 -
Probiotics and Antimicrobial Proteins May 2024Commensal-derived peptidoglycan (PG) or lipoteichoic acid (LTA) can improve the growth, immunity, and intestinal health of fish, but it is not clear whether the two...
Commensal Bacillus pumilus SE5-Derived Peptidoglycan and Lipoteichoic Acid Showed Synergistic Effects in Improving Growth, Immunity, and Intestinal Health of Grouper (Epinephelus coioides).
Commensal-derived peptidoglycan (PG) or lipoteichoic acid (LTA) can improve the growth, immunity, and intestinal health of fish, but it is not clear whether the two components have synergistic effects. To clarify this, grouper (Epinephelus coioides) was fed basal diet (CG) or diets containing 1.0 × 10 CFU/g heat-inactivated SE5 (HIB), PG (21.30 mg/kg), LTA (6.70 mg/kg), mixture (PL1) of PG (10.65 mg/kg) and LTA (3.35 mg/kg), and mixture (PL2) of PG (21.30 mg/kg) and LTA (6.70 mg/kg). Improved growth performance and feed utilization were observed in groups PG, LTA, PL1, and PL2, and the optimum growth performance was recorded in group PL1. Furthermore, improved serum alkaline phosphatase (AKP) activity and immunoglobulin M (IgM) and complement C3 (C3) contents were observed in all treatments, and the AKP activity in group PL1 was significantly superior to that of groups PG and LTA. Although PG and LTA alone or in combination exert comparable effects on intestinal microbiota and physical structure, obviously enhanced intestinal protease activity was observed in group PL1. The combined efficacy of PL1 could further potentiate the immune response by modulating the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and upregulating the expression of antimicrobial peptides (epinecidin-1, hepcidin-1, and β-defensin) as well as IgM. At the same time, group PL1 could further mitigate intestinal inflammation by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. In conclusion, probiotic B. pumilus SE5-derived PG and LTA mixture (10.65 mg/kg PG and 3.35 mg/kg LTA) exhibits better potential for improving the growth performance, intestinal health, and immune function compared to another mixture (21.30 mg/kg PG and 6.70 mg/kg LTA) and PG or LTA alone in grouper.
PubMed: 38789900
DOI: 10.1007/s12602-024-10291-7 -
Antibiotics (Basel, Switzerland) Apr 2024Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical...
Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, have led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small-molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We found antifungal activity at low concentrations for many pathogens, which indicates that further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for the development of effective antifungal agents.
PubMed: 38786134
DOI: 10.3390/antibiotics13050405 -
Analytica Chimica Acta Nov 2023Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections...
BACKGROUND
Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections (PJI) remain a serious complication, necessitating extensive interventions and prolonged antimicrobial treatments. The aging population is expected to lead to a rise in TJA cases, subsequently increasing the incidence of PJI, particularly in the elderly who face higher mortality rates. Current diagnostic methods for suspected PJI, such as radiographs and biochemical markers like CRP and ESR, exhibit limited sensitivity. Therefore, there is a critical need for a specific synovial fluid biomarker assay to enhance PJI diagnosis using specific SF-based assay.
RESULTS
This study introduces a novel microfluidic chip with a paper-based aptamer-sandwich assay for the quantitative detection of HNP 1, a crucial PJI biomarker, in synovial fluid. The assay leverages the advantages of aptamers over antibodies, demonstrating high selectivity and affinity for target molecules. The integration of a nitrocellulose (NC) membrane onto the microfluidic platform represents a significant advancement, reducing background signals and simplifying the assay procedure without intricate procedure and pre-treatment. The NC membrane-based microfluidic device offers rapid, cost-effective, and highly sensitive detection of HNP 1, with a limit of detection of 0.5 mg L. The microfluidic device demonstrates exceptional performance, detecting up to four clinical samples in approximately 42 min on a single chip with 100 % accuracy, as confirmed by analysis of 12 clinical samples and comparison with "gold-standard". Moreover, the assay exhibits a wide dynamic range of 0.5-100 mg L-1, underscoring its potential as a powerful tool for PJI diagnosis in clinical settings.
SIGNIFICANCE
This work introduces a paper-based microfluidic system tailored for rapid HNP 1 detection using synovial fluid near joint region (and not serum via blood) for better diagnosis. The innovative paper-based aptamer-sandwich assay yields results within 42-min. Significantly, it boasts a wide dynamic range, detecting levels from an impressive 0.5 mg L-1, crucial in the 2.6 mg L-1 threshold region. This heightened sensitivity and expansive detection capability establish our assay as a leader in PJI diagnostics, promising unmatched precision and efficiency in clinical applications.
Topics: Humans; Aptamers, Nucleotide; Biomarkers; Lab-On-A-Chip Devices; Limit of Detection; Microfluidic Analytical Techniques; Paper; Prosthesis-Related Infections; Synovial Fluid; alpha-Defensins
PubMed: 38783735
DOI: 10.1016/j.aca.2023.341879 -
Cellular and Molecular Life Sciences :... May 2024Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly...
Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis, which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed DvirARP) with differences from its parent gene in its pattern of expression, structure and function. DvirARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 3 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. DvirARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. DvirARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the DvirARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that DvirARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection.
Topics: Drosophila; Defensins; Drosophila Proteins; Animals; Gene Deletion; Gene Duplication; Female; Protein Folding; Amino Acid Motifs; Bacterial Toxins; Staphylococcus aureus
PubMed: 38780625
DOI: 10.1007/s00018-024-05273-5 -
Life Sciences Jul 2024Defensins are a class of small antimicrobial peptides that play a crucial role against pathogens. However, recent research has highlighted defensins exhibit the ability... (Review)
Review
Defensins are a class of small antimicrobial peptides that play a crucial role against pathogens. However, recent research has highlighted defensins exhibit the ability to influence cell cycle checkpoints, promoting or inhibiting specific phases such as G1 arrest or S/M transition. By regulating the cell cycle, defensins impact the proliferation of normal and cancerous cells, with implications for cancer development and progression. Dysregulation of defensin expression can disrupt the delicate balance of cell cycle regulation, leading to uncontrolled cell growth and an increased risk of tumor formation. Defensins contribute to the resolution of inflammation, stimulate angiogenesis, and enhance the migration and proliferation of cells involved in tissue repair. Furthermore, The ability of defensins to respond to microenvironmental changes further demonstrates the significance of these peptides in host defense mechanisms and immune function. By adjusting their expression, defensins continue to combat pathogens effectively and maintain homeostasis within the body. This review highlights the multifaceted role of defensins in regulating the cell cycle and their broader implications in cancer progression, tissue repair, and microenvironmental response.
Topics: Humans; Defensins; Cell Cycle; Animals; Cell Proliferation; Neoplasms; Cell Division
PubMed: 38777302
DOI: 10.1016/j.lfs.2024.122740