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Veterinary Research Feb 2024In mammary glands, the formation of less-permeable tight junctions (TJs) and the production of antimicrobial compounds like lactoferrin and defensins are important for...
In mammary glands, the formation of less-permeable tight junctions (TJs) and the production of antimicrobial compounds like lactoferrin and defensins are important for preventing mastitis. Resveratrol, a polyphenol contained in red grapes, is known to protect mammary epithelial cells (MECs) from oxidative stress; however, oral administration of resveratrol causes a decrease in certain biological processes through conjugation and metabolic conversion. In this study, we determined the beneficial effects of resveratrol on TJs and antimicrobial compounds in cultured goat MECs by adding it to the medium, and in lactating goat mammary glands by topical application for percutaneous absorption. TJ barrier function was evaluated by transepithelial resistance and expression or localization pattern of claudins for culture model in vitro and by somatic cell count, Na, albumin, and IgG in milk for topical application in vivo. Concentrations of antimicrobial compounds and cytokines were measured using ELISA. Activation of STAT3 was evaluated by Western blotting. Resveratrol strengthened TJ barrier function by upregulating claudin-3 in cultured MECs and topical application to udders reduced somatic cell count, Na, albumin, and IgG in milk. Resveratrol increased β-defensin and S100A7 levels in cultured MECs and milk. In addition, resveratrol down-regulated cytokine production and STAT3 pathway. These findings suggest that the topical application of resveratrol to udders may be effective in preventing mastitis.
Topics: Female; Animals; Tight Junctions; Lactation; Resveratrol; Epithelial Cells; Milk; Mammary Glands, Animal; Mastitis; Anti-Infective Agents; Goats; Albumins; Immunoglobulin G; Goat Diseases
PubMed: 38365712
DOI: 10.1186/s13567-024-01276-z -
Molecules (Basel, Switzerland) Feb 2024The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical...
The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects.
Topics: Mice; Animals; Muramidase; Zingiber officinale; Claudin-1; alpha-Defensins; Diarrhea; Anti-Bacterial Agents; Sugars
PubMed: 38338475
DOI: 10.3390/molecules29030732 -
Nutrients Jan 2024Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal... (Randomized Controlled Trial)
Randomized Controlled Trial
A 14-Day Double-Blind, Randomized, Controlled Crossover Intervention Study with Anti-Bacterial Benzyl Isothiocyanate from Nasturtium () on Human Gut Microbiome and Host Defense.
Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing their composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium () is known for its antimicrobial activity and is used for the treatment of infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question of whether a 14 d nasturtium intervention (3 g daily, N = 30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak but significant antibacterial effect against . A significant increase in human beta defensin 1 as a parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did the circulating serum metabolome. On an individual level, some large changes were observed between sampling points, however. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species.
Topics: Female; Humans; Gastrointestinal Microbiome; Tropaeolum; Nasturtium; Isothiocyanates; Bacteria; Escherichia coli; Metabolome
PubMed: 38337658
DOI: 10.3390/nu16030373 -
Journal of Clinical Medicine Feb 2024(1) Background: Developing and implementing strategies for local wound care focused on improving the quality of life related to health status and reducing treatment...
(1) Background: Developing and implementing strategies for local wound care focused on improving the quality of life related to health status and reducing treatment costs for this patient group poses a challenge to contemporary healthcare systems. The utilization of Maggot Debridement Therapy (MDT) is one potential form of local therapy for preparing wounds for the healing process. The debridement of the wound bed with medical maggots is highly precise, and the defensins produced by the larvae eliminate bacteria and stimulate tissue regeneration. However, the presence of larvae in the wound may lead to the occurrence of pain symptoms. The aim of the study was to assess the intensity of pain during larval therapy in patients with chronic wounds treated in outpatient settings. (2) Patients and Methods: The study employed a diagnostic survey and estimation; the tool consisted of a research protocol comprising three parts (questionnaires). Inclusion criteria for the study were voluntary consent to participate (completion of the MDT acceptance questionnaire), chronic wounds of vascular etiology or pressure injuries, full-thickness skin or deep tissue damage, and pain intensity not exceeding four on the NRS (Numerical Rating Scale: 0-no pain, 10-the most severe pain) at the time of the study. Patient observation during the 3-day treatment was conducted by a wound care clinic nurse, assessing pain intensity once every 24 h during the larval dressing changes. (3) Results: Out of 348 individuals who qualified for MDT during the study period, 215 individuals participated in the study: 94 women (43.7%) and 121 men (56.3%). The age of the participants ranged from 28 to 97 years (mean 69.87 ± 12.95). Each participant experienced mild pain (2.26 ± 1.60 on the NRS) on the day of qualification for the study. An increase in pain intensity, according to subjective assessments, was reported by 29.3% of participants (n = 63). On the third day of MDT therapy, an increase in pain intensity was observed, reaching a mean value of 4.79 ± 2.12 ( < 0.0001). Participants with pressure injuries showed the lowest pain intensity, which increased in consecutive days for all types of wounds. Additionally, the increase in pain intensity in patients with vascular etiology wounds was greater compared to patients with pressure injuries ( < 0.001). (4) Conclusions: Local wound therapy with larvae increases pain intensity in the consecutive days of treatment. The wound area and the time since its occurrence may determine pain symptoms.
PubMed: 38337579
DOI: 10.3390/jcm13030884 -
Cells Feb 2024Cathepsin B (CatB) is thought to be essential for the induction of lipopolysaccharide ( LPS)-induced Alzheimer's disease-like pathologies in mice, including...
Cathepsin B (CatB) is thought to be essential for the induction of lipopolysaccharide ( LPS)-induced Alzheimer's disease-like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.
Topics: Humans; beta-Defensins; Cathepsin B; I-kappa B Kinase; Inflammasomes; Interleukin-1beta; Lipopolysaccharides; Microglia; NF-kappa B; NF-KappaB Inhibitor alpha; NLR Family, Pyrin Domain-Containing 3 Protein; Virulence Factors
PubMed: 38334675
DOI: 10.3390/cells13030283 -
Heliyon Feb 2024The seaweeds are in focus for their immunity and gut health-stimulating potentials in humans and farm animals, but their potential as a gut health-promoting agent and...
The seaweeds are in focus for their immunity and gut health-stimulating potentials in humans and farm animals, but their potential as a gut health-promoting agent and performance booster to replace antibiotic growth promoters (AGP) in broiler chicken-feed remains to be evaluated. feeding experiments were conducted on commercial broiler chickens (1-42 days post-hatch) to evaluate dried aqueous exact of red seaweed (referred to as PBD 5). Each of the three test diets (basal diet with three dosing regimens of PBD5, 0.25 g kg for 0-6 weeks, 0.25 g kg for 0-4 weeks or 1.0 g kg for 0-2 weeks), along with an AGP supplemented diet (Virginiamycin (V), 20 ppm in basal diet), and a control diet was fed to 13 pen replicates of five chicks in each. PBD5 at 1.0 g kg diet for 0-2 weeks improved (P < 0.05) cumulative feed efficiency (4.65 % improvement at 28 d, and 3.74 % at 35 d) than the control and comparable to the V group and the trend in improvement persisted up to 42 d. The group fed with PBD5 @ 1.0 g kg for 0-2 weeks had significantly (P < 0.05) higher serum IgG level, glutathione peroxidase levels, fat digestibility, and expression of occludin and avian beta-defensin 4 gene in the gut and a trend of increased expression of growth hormone receptor gene in the liver as compared to the control with no significant effect on body weight, phytohemagglutinin response or haemagglutination inhibition titer. At d 25 of age, fecal count was significantly (P < 0.01) lower in the seaweed extract groups and the V group as compared to the control. It can be concluded that dried aqueous extract of at 1 g kg diet for 0-2 weeks can be used as an alternative to antibiotic growth promoter in broiler chickens to improve feed efficiency and reduce gut pathogen load, and the improved performance was associated with increased expression of gut immunity and growth hormone receptor genes.
PubMed: 38333794
DOI: 10.1016/j.heliyon.2024.e25219 -
Hepatology International Jun 2024Experimental studies linked dysfunctional Farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling to liver disease. This study investigated key...
BACKGROUND AND AIMS
Experimental studies linked dysfunctional Farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling to liver disease. This study investigated key intersections of the FXR-FGF19 pathway along the gut-liver axis and their link to disease severity in patients with cirrhosis.
METHODS
Patients with cirrhosis undergoing hepatic venous pressure gradient measurement (cohort-I n = 107, including n = 53 with concomitant liver biopsy; n = 5 healthy controls) or colonoscopy with ileum biopsy (cohort-II n = 37; n = 6 controls) were included. Hepatic and intestinal gene expression reflecting FXR activation and intestinal barrier integrity was assessed. Systemic bile acid (BA) and FGF19 levels were measured.
RESULTS
Systemic BA and FGF19 levels correlated significantly (r = 0.461; p < 0.001) and increased with cirrhosis severity. Hepatic SHP expression decreased in patients with cirrhosis (vs. controls; p < 0.001), indicating reduced FXR activation in the liver. Systemic FGF19 (r = -0.512, p < 0.001) and BA (r = -0.487, p < 0.001) levels correlated negatively with hepatic CYP7A1, but not SHP or CYP8B1 expression, suggesting impaired feedback signaling in the liver. In the ileum, expression of FXR, SHP and FGF19 decreased in patients with cirrhosis, and interestingly, intestinal FGF19 expression was not linked to systemic FGF19 levels. Intestinal zonula occludens-1, occludin, and alpha-5-defensin expression in the ileum correlated with SHP and decreased in patients with decompensated cirrhosis as compared to controls.
CONCLUSIONS
FXR-FGF19 signaling is dysregulated at essential molecular intersections along the gut-liver axis in patients with cirrhosis. Decreased FXR activation in the ileum mucosa was linked to reduced expression of intestinal barrier proteins. These human data call for further mechanistic research on interventions targeting the FXR-FGF19 pathway in patients with cirrhosis.
CLINICAL TRIAL NUMBER
NCT03267615.
Topics: Humans; Fibroblast Growth Factors; Male; Female; Liver Cirrhosis; Receptors, Cytoplasmic and Nuclear; Middle Aged; Signal Transduction; Liver; Bile Acids and Salts; Intestinal Mucosa; Adult; Aged; Ileum
PubMed: 38332428
DOI: 10.1007/s12072-023-10636-4 -
Physiological Reports Feb 2024Antimicrobial peptides (AMPs) constitute a complex network of 10-100 amino acid sequence molecules widely distributed in nature. While over 300 AMPs have been described...
Antimicrobial peptides (AMPs) constitute a complex network of 10-100 amino acid sequence molecules widely distributed in nature. While over 300 AMPs have been described in mammals, cathelicidins and defensins remain the most extensively studied. Some publications have explored the role of AMPs in COVID-19, but these findings are preliminary, and in vivo studies are still lacking. In this study, we report the plasma levels of five AMPs (LL-37, α-defensin 1, α-defensin 3, β-defensin 1, and β-defensin 3), using the ELISA technique (MyBioSource, San Diego, CA, United States, kits MBS2601339 (beta-defensin 1), MBS2602513 (beta-defensin 3), MBS703879 (alpha-defensin 1), MBS706289 (alpha-defensin 3), MBS7234921 (LL37)), and the measurement of six cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, interferon-γ, and monocyte chemoattractant protein-1), through the magnetic bead immunoassay Milliplex® and the MAGPIX® System (MilliporeSigma, Darmstadt, Germany, kit HCYTOMAG-60 K (cytokines)), in 15 healthy volunteers, 36 COVID-19 patients without Acute Kidney Injury (AKI) and 17 COVID-19 patients with AKI. We found increased levels of α-defensin 1, α-defensin 3 and β-defensin 3, in our COVID-19 population, when compared to healthy controls, along with higher levels of interleukin-6, interleukin-10, interferon-γ, and monocyte chemoattractant protein-1. These findings suggest that these AMPs and cytokines may play a crucial role in the systemic inflammatory response and tissue damage characterizing severe COVID-19. The levels of α-defensin 1 and α-defensin 3 were significantly higher in COVID-19 AKI group in comparison to the non-AKI group. Furthermore, IL-10 and the product IL-10 × IL-1B showed excellent performance in discriminating AKI, with AUCs of 0.86 and 0.88, respectively. Among patients with COVID-19, AMPs may play a key role in the inflammation process and disease progression. Additionally, α-defensin 1 and α-defensin 3 may mediate the AKI process in these patients, representing an opportunity for further research and potential therapeutic alternatives in the future.
Topics: Animals; Humans; beta-Defensins; Interleukin-10; Antimicrobial Cationic Peptides; Chemokine CCL2; SARS-CoV-2; Antimicrobial Peptides; Interleukin-6; alpha-Defensins; Interferon-gamma; Critical Illness; COVID-19; Cytokines; Biomarkers; Acute Kidney Injury; Mammals
PubMed: 38328863
DOI: 10.14814/phy2.15945 -
IScience Feb 2024Inflammation is consistently linked to dysmetabolism. In transgenic mice (Def) model the neutrophilic peptide, alpha defensin, proved atherogenic. This phenotype...
Inflammation is consistently linked to dysmetabolism. In transgenic mice (Def) model the neutrophilic peptide, alpha defensin, proved atherogenic. This phenotype occurred despite favorable cholesterol and glucose levels, and lower body weight and blood pressure. In this study, integration of metabolic&behavioral phenotyping system, endocrine, biochemical and mitochondrial assessment, pathological and immunohistochemical tests, and multiple challenge tests was established to explore the metabolic impact of alpha defensin. Compared to the control group, Def mice exhibited lower total energy expenditure and carbohydrate utilization, and higher fat oxidation. Their ACTH-cortisol and thyroid profiles were intact. Intriguingly, they had low levels of glucagon, with high ammonia, uric acid, triglyceride, and lactate. Mitochondrial evaluations were normal. Overall, defensin-induced hypoglucagonemia is associated with lipolysis, restricted glucose oxidation, and enhanced wasting. Def mice may be a useful model for studying the category of lean, apparently metabolically healthy, and atherosclerotic phenotype, with insight into a potential inflammatory-metabolic link.
PubMed: 38318380
DOI: 10.1016/j.isci.2024.108802 -
Scientific Reports Feb 2024Urinary tract infections (UTIs) are a common comorbidity in hospitalized neonates. The current UTI diagnostics have several limitations including invasive collection of...
Urinary tract infections (UTIs) are a common comorbidity in hospitalized neonates. The current UTI diagnostics have several limitations including invasive collection of urinary samples to ensure sterility, risk of contamination and lack of consensus definitions of UTI based on urine culture. Antimicrobial peptides (AMPs) have been recently utilized as novel biomarkers that can efficiently and accurately diagnose pediatric UTI. However, the concentration of AMPs in neonatal urine is not well-defined. Urine from neonates admitted to a single level IV neonatal intensive care unit was obtained to determine baseline concentration of two AMPs, Ribonuclease 7 (RNase 7) and Beta Defensin-1 (BD-1) and to define the relationship between AMP concentration and gestational age (GA). AMP levels were normalized to urine creatinine. RNase 7 and BD-1 were expressed in neonatal urine (n = 66) regardless of GA and as early as 22 weeks gestation. Urinary concentrations of both AMPs decreased as GA and birthweight increased. The overall median urinary RNase 7/UCr and BD-1/UCr values were 271 ng/mg, and 116 ng/mg, respectively. Median urinary concentrations of RNase 7/UCr for infants born at < 27, 27-32, 33-35 and ≥ 36 weeks were 569, 308, 254, and 124 ng/mg respectively. Similarly, the concentrations of BD-1/UCr at these GA were 166, 115, 108, and 14 ng/mg, respectively. Baseline neonatal urinary concentration of two AMPs (RNase 7 and BD-1) and the variation by GA were identified. This is an essential first step toward the potential utilization of AMPs in improving neonatal UTI diagnostics.
Topics: Infant; Infant, Newborn; Female; Humans; Child; Urinary Tract Infections; Urinalysis; Urinary Tract; Birth Weight; Antimicrobial Peptides; Biomarkers
PubMed: 38316971
DOI: 10.1038/s41598-024-53486-2