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Marine Drugs Jan 2024The venoms of various sea anemones are rich in diverse toxins, which usually play a dual role in capturing prey and deterring predators. However, the complex components...
The venoms of various sea anemones are rich in diverse toxins, which usually play a dual role in capturing prey and deterring predators. However, the complex components of such venoms have not been well known yet. Here, venomics of integrating transcriptomic and proteomic technologies was applied for the first time to identify putative protein and peptide toxins from different tissues of the representative sea anemone, . The transcriptomic analysis of identified 728 putative toxin sequences, including 442 and 381 from the tentacles and the column, respectively, and they were assigned to 68 gene superfamilies. The proteomic analysis confirmed 101 protein and peptide toxins in the venom, including 91 in the tentacles and 39 in the column. The integrated venomics also confirmed that some toxins such as the ShK-like peptides and defensins are co-expressed in both the tentacles and the column. Meanwhile, a homology analysis was conducted to predict the three-dimensional structures and potential activity of seven representative toxins. Altogether, this venomics study revealed the venom complexity of which will help deepen our understanding of cnidarian toxins, thereby supporting the in-depth development of valuable marine drugs.
Topics: Animals; Venoms; Sea Anemones; Proteomics; Toxins, Biological; Peptides; Cnidarian Venoms
PubMed: 38393042
DOI: 10.3390/md22020071 -
Virulence Dec 2024(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing...
(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing bovine neutrophil β-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen . In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β in macrophages as well as dendritic cells (DC) and enhanced DC maturation . Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1β, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-β and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.
Topics: Humans; Swine; Animals; Cattle; Immunity, Innate; Actinobacillus pleuropneumoniae; Lymphocytes; Lung; Tumor Necrosis Factor-alpha; Immunosuppression Therapy
PubMed: 38378464
DOI: 10.1080/21505594.2024.2316459 -
Cell & Bioscience Feb 2024Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear...
Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell-cell interactions with cirrhosis decompensation.
PubMed: 38369527
DOI: 10.1186/s13578-024-01209-5 -
Scientific Reports Feb 2024The number of genome-level resources for non-model species continues to rapidly expand. However, frog species remain underrepresented, with up to 90% of frog genera...
The number of genome-level resources for non-model species continues to rapidly expand. However, frog species remain underrepresented, with up to 90% of frog genera having no genomic or transcriptomic data. Here, we assemble the first genomic and transcriptomic resources for the recently described southern stuttering frog (Mixophyes australis). The southern stuttering frog is ground-dwelling, inhabiting naturally vegetated riverbanks in south-eastern Australia. Using PacBio HiFi long-read sequencing and Hi-C scaffolding, we generated a high-quality genome assembly, with a scaffold N50 of 369.3 Mb and 95.1% of the genome contained in twelve scaffolds. Using this assembly, we identified the mitochondrial genome, and assembled six tissue-specific transcriptomes. We also bioinformatically characterised novel sequences of two families of antimicrobial peptides (AMPs) in the southern stuttering frog, the cathelicidins and β-defensins. While traditional peptidomic approaches to peptide discovery have typically identified one or two AMPs in a frog species from skin secretions, our bioinformatic approach discovered 12 cathelicidins and two β-defensins that were expressed in a range of tissues. We investigated the novelty of the peptides and found diverse predicted activities. Our bioinformatic approach highlights the benefits of multi-omics resources in peptide discovery and contributes valuable genomic resources in an under-represented taxon.
Topics: Animals; Antimicrobial Peptides; beta-Defensins; Multiomics; Stuttering; Australia; Cathelicidins; Anura; Chromosomes
PubMed: 38368484
DOI: 10.1038/s41598-024-54522-x -
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