Search Results (110)

The American cockroach (Periplaneta americana) serves as an exemplary model for regeneration research due to its exceptional regenerative capabilities, particularly in appendage regeneration. In this study, regenerated coxa tissue underwent histological analysis through H & E straining. Microscopic examination revealed the progression of regeneration. To elucidate the underlying mechanisms, a comparative transcriptomic analysis was conducted between regenerating legs and non-amputated control legs. This analysis identified 2343 differentially expressed genes (DEGs) between 0 days post-amputation (0 dpa) and 7 dpa, 2963 DEGs between 14 dpa and 0 dpa, and 3135 DEGs between 14 dpa and 7 dpa. Significantly, several DEGs are associated with growth- or regeneration-related processes, including extracellular matrix (different collagen, Pro-resilin isoforms, integrin beta (itgb) and matrix metalloproteinase (mmp)), immune-related genes (Toll-like receptor 13 (tlr13), defensin (def), drosomycin-like defensin (dld), Polyphenoloxidases2 (ppo2), cytochrome P450 (p450), peptidoglycan recognition protein (pgrp) and secreted C-type lectin (sClec)), insulin-like growth factor (IGF) and Epidermal Growth Factor Receptor (EGFR). Functional validation through RNA interference (RNAi) further suggested that EGFR and a specific C-type lectin (Regenectin) regulate leg regeneration in Periplaneta americana. These findings enhance our understanding of the molecular mechanisms governing regeneration in this species. Full article

Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains. Full article

Monkeypox virus (MPXV) has caused 148,892 confirmed cases and 341 deaths from 137 countries worldwide, as reported by the World Health Organization (WHO), highlighting the urgent need for effective vaccines to prevent the spread of MPXV. Traditional vaccine development is low-throughput, expensive, time consuming, and susceptible to reversion to virulence. Alternatively, a reverse vaccinology approach offers a rapid, efficient, and safer alternative for MPXV vaccine design. Here, MPXV proteins associated with viral infection were analyzed for immunogenic epitopes to design multi-epitope vaccines based on B-cell, CD4+, and CD8+ epitopes. Epitopes were selected based on allergenicity, antigenicity, and toxicity parameters. The prioritized epitopes were then combined via peptide linkers and N-terminally fused to various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal protein L7/12, RS-09, and the cholera toxin B subunit (CTB). All vaccine constructs were computationally validated for physicochemical properties, antigenicity, allergenicity, safety, solubility, and structural stability. The three-dimensional structure of the selected construct was also predicted. Moreover, molecular docking and molecular dynamics (MD) simulations between the vaccine and the TLR-4 immune receptor demonstrated a strong and stable interaction. The vaccine construct was codon-optimized for high expression in the E. coli and was finally cloned in silico into the pET21a (+) vector. Collectively, these results could represent innovative tools for vaccine formulation against MPXV and be transformative for other infectious diseases. Full article

Background/Objectives: The role of intestinal dysbiosis as an important driver of inflammation in metabolic disorders is becoming increasingly evident. Beta-defensin 2 is an antimicrobial peptide that contributes to innate immunity, while recently it has been suggested as a novel biomarker of gut dysbiosis. However, its role in obesity remains unexplored. This study aimed to compare circulating beta-defensin 2 levels between individuals with overweight and obesity and lean controls. An additional objective was to explore potential correlations between beta-defensin 2 and other inflammatory markers in this population. Methods: The study population consisted of 81 participants (61.7% females) divided into obesity (n = 27), overweight (n = 34), and normal body mass index (n = 20) groups. All participants were free of infection and diabetes mellitus. Beta-defensin 2, interleukin-6, presepsin, high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated in the study groups. Results: We did not find significant differences in beta-defensin 2 levels between the groups (p = 0.936). In contrast, hs-CRP levels were higher in people with obesity compared to the sum of participants in the overweight and control groups (p = 0.044), after adjusting for the effects of age, sex, smoking, and vitamin D status. Furthermore, a positive correlation was established between beta-defensin 2 and presepsin values (p = 0.012). Conclusions: The results of the present study demonstrate that obesity is characterized by an aggravation of inflammation, as expressed by elevated hs-CRP levels. Although the study design cannot prove causal relationships, our findings also suggest that beta-defensin 2 levels correlate with the magnitude of systemic inflammation in infection-free individuals living with obesity. The value of the combined evaluation of different biomarkers in obesity-related outcomes warrants further investigation by larger studies. Full article

Marathon running exerts physical stress and may lead to transient immune dysregulation, increasing susceptibility to airway inflammation and exercise-induced bronchoconstriction (EIB). This study investigated systemic levels of antimicrobial peptides in athletes and their association with EIB. Serum concentrations of angiogenin, human beta-defensin 2 (hBD-2), major basic protein (MBP), S100A8, and S100A8/A9 were measured in 34 marathoners and 36 half-marathoners at baseline, immediately after a race, and seven days postrace using enzyme-linked immunosorbent assays and compared with 30 sedentary controls. Lung function was assessed by spirometry to identify bronchoconstriction. Levels of hBD-2 and S100A8/A9 were significantly elevated postrace in runners compared to baseline and controls, returning to baseline during recovery. During recovery, S100A8 levels remained slightly elevated in marathoners with EIB. Similarly, human beta-defensin 2 was modestly increased in runners who developed bronchoconstriction. Notably, S100A8 levels correlated negatively with lung function parameters, including forced expiratory volume and mid-expiratory flows. These findings suggest that endurance running induces systemic inflammatory responses and modulates innate immune peptides, particularly in individuals prone to bronchoconstriction. These peptides may serve as biomarkers of respiratory stress and help guide personalized strategies in endurance sports. Full article

Infectious laryngotracheitis (ILT) is a severe upper respiratory disease highly contagious in chickens that causes a huge economic impact on the poultry industry all over the world. The current study aimed to design a multi-epitope-based vaccine candidate using envelope glycoprotein B and glycoprotein D of the ILT virus using an immune informatics approach. The glycoproteins B and D are crucial for attachment as well as entry of ILT virus inside the cell, which makes them a potential option for designing vaccine candidates. The prediction of epitopes, viz. helper T lymphocyte, cytotoxic T lymphocyte and interferon-gamma producing epitopes, was performed and high-scoring predicted epitopes were joined in an organized manner using suitable linkers to design the final vaccine candidate. The avian beta-defensin 1 was included as an adjuvant in the amino-terminal of the vaccine design that possesses antimicrobial activity and histidine residues at the carboxy-terminal for the purpose of purification. The final vaccine candidate was evaluated for its physicochemical characteristics, solubility, antigenicity, stability, and allergenicity and validated for its modeling. Molecular docking, binding affinity, and interacting residues between the vaccine candidate and immune receptors, viz. TLR 3, MHC Class I and Class II were assessed. Further, to assess the immune response profile generated by the final vaccine design, an insilico immune simulation study was also performed. The findings of this study revealed that the final vaccine candidate was antigenic, nonallergenic, stable, interacted with immune receptors, and able to produce antibodies as well as cellular immune responses against ILTV infection. Full article

Background/Objectives: β-defensins are a family of classical endogenous antimicrobial peptides involved in innate immune response. β-defensins are encoded by a large number of loci and known to show extensive copy number variations (CNVs) that may be useful as DNA markers for host resilience against pathogenic infections. Methods: We developed a quantitative PCR-based method to estimate the genomic copy numbers of 13 pig β-defensin (pBD) genes and analyzed the range and extent of CNVs across several commercial pig breeds. Results: We assessed 38 animals from four pure breeds and a crossbreed and observed CNVs ranging from two to five genomic copies from pBD114, pBD115, pBD119, pBD124, pBD128, and pBD129, indicating extensive individual variations of gene copy numbers of these genes within each breed. The mean copy numbers of these pBDs were lower in Landrace and higher in Berkshire than in other breeds. We also observed a strong correlation between the genomic copy number and their expression levels with the correlation coefficient (r) > 0.9 for pBD114, pBD119, and pBD129 in the kidney, with these genes being highly expressed. Conclusions: Although we only analyzed 13 pBDs among 29 reported genes, our results showed the presence of extensive CNVs in β-defensins from pigs. The genomic copy number of β-defensins may contribute to improving animal resilience against pathogenic infections and other associated phenotypes. Full article

The physiological functions of newborn calves are undeveloped, especially the immune system, making them susceptible to infections. In recent years, the theory of trained immunity has attracted attention and provided new strategies to prevent unknown infections in animals. This study investigated the effects of feeding yeast β-glucan on the intestinal and respiratory health of calves during the suckling period. Newborn Holstein calves (average birth weight: 36.18 ± 0.61 kg, mean ± SE) were randomly assigned to two groups: the PO (Per Os) group (n = 22) and the CON (Control) group (n = 22). Calves in the PO group were fed a yeast β-glucan solution (0.1 g/mL, 65 mg/kg body weight) at 3 and 6 days of age, respectively, while calves in the CON group received equal volumes of sterile saline orally at the same time. Blood and fecal samples were collected at 7 and 30 days of age, respectively. The results showed that (1) Compared to the CON group, being fed yeast β-glucan resulted in an inflammatory response after 24 h of the second administration, including increased gene expression of interleukin-6 (IL-6, p < 0.01), interleukin-1 beta (IL-1β, p < 0.01), and malonaldehyde (MDA, p < 0.001) content. Also, stimulation with β-glucan increased the concentrations of secreted immunoglobulin A (sIgA, p < 0.01) and defensins (p < 0.05) in the rectal feces. (2) Pre-stimulation with yeast β-glucan effectively reduced the incidence of diarrhea (p < 0.05) and bovine respiratory disease (BRD, p < 0.05) from day 31 to day 60. (3) At 30 days of age, the pre-stimulated calves had significantly lower serum DAO (p < 0.001) and MDA levels (p < 0.05), while they had higher levels of serum IL-6 (p < 0.01) and fecal slgA (p < 0.05) than calves in the CON group. (4) Pre-stimulation with yeast β-glucan altered the intestinal bacterial community; the Beta diversity results showed that the CON group and the PO group were clustered separately in the principal coordinate analysis (PCoA) graph. Obviously, the PO group sample points were more clustered. In conclusion, this study highlights the potential of yeast β-glucan-induced trained immunity to improve calf health during the suckling period. The findings offer new insights into the prevention of intestinal and respiratory infections in calves. Full article

Antimicrobial peptides, such as beta-defensin 2 (BD2), are vital in controlling infections and immune responses. In this study, we investigated the expression and role of BD2 in the amniotic membrane and human amniotic epithelial cells (hAECs) from patients with preterm birth and chorioamnionitis, focusing on its regulation of inflammatory cytokines and its protective effect on the epithelial barrier. Our results show increased BD2 expression in chorioamnionitis, and Lipopolysaccharide (LPS)-induced inflammation increased BD2 release from hAECs in a dose- and time-dependent manner. BD2 treatment effectively modulated the inflammatory response by reducing pro-inflammatory cytokines (IL-6, IL-1β) and enhancing the release of the anti-inflammatory cytokine IL-10. Additionally, BD2 helps preserve epithelial barrier integrity by restoring E-cadherin expression and reducing Snail expression in inflamed hAECs. In an LPS-induced preterm birth mouse model, BD2 treatment delayed preterm delivery and reduced inflammatory cytokine levels. These results suggest that BD2 plays a protective role in preventing preterm birth by regulating inflammation and maintaining epithelial barrier function, highlighting its therapeutic potential for inflammation-related preterm birth. Full article

During the postpartum period, domestic ruminants suffer elevated endogenous cortisol levels, which are associated with an increased risk of uterine infections. Selenium is a trace mineral nutrient with beneficial impacts on animals. The study aimed to investigate whether selenium yeast (SeY) could attenuate Escherichia coli (E. coli)-induced endometrial injury in goats with high cortisol background. Goats were examined after oral SeY administration for 21 days and were treated with glacial acetic acid, E. coli, and hydrocortisone to establish an endometritis model with high cortisol background. The results showed that endometrial injury caused by E. coli was aggravated under high cortisol background. Supplementation with SeY alleviated endometrial inflammation and serum LDH content. The mRNA expression of pro-inflammatory cytokines and defensin beta 2 and the phosphorylation level of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-b (NF-κB) signaling pathways were decreased by SeY supplementation. Total antioxidant capacity and antioxidant enzymes activities were increased by SeY supplementation, but malondialdehyde and 4-hydroxynonenal content were decreased. Moreover, nuclear factor erythroid-2 related factor 2 (NRF2) in the nucleus, heme oxygenase-1, and NAD(P)H quinone dehydrogenase 1 were increased by SeY supplementation. So, supplementation with SeY alleviated E. coli-induced endometritis in goats by activating the NRF2 pathway and inhibiting the activation of the MAPK and NF-κB pathways under postpartum stress. Full article

This study assessed the effects of thymol and yeast Saccharomyces cerevisiae on the growth performance, antioxidant capacity and immunological responses and gut immunological transcripts in rainbow trout, Oncorhynchus mykiss. Two hundred and seventy fish (6.62 ± 0.18 g) were distributed in 18 aquaria (15 fish per aquarium) as a 2 × 3 factorial design. The fish were fed on diets containing 0 and 1 × 10⁸ cfu/g of yeast and 0, 250 and 500 mg/kg of thymol for 60 days. The results showed that dietary yeast supplementation led to significantly improved fish weight gain and feed efficiency (p < 0.05). Thymol and yeast supplementation affected the hepatic antioxidant status, leading to lower lipid peroxidation and higher glutathione reserves (p < 0.05). Thymol and yeast supplementation led to significantly lowered plasma aspartate aminotransferase levels (p < 0.05). Dietary yeast supplementation led to significantly elevated plasma and mucus lysozyme, plasma alternative complement, immunoglobulin and mucus alkaline phosphatase levels. In contrast, thymol supplementation led to significantly increased plasma lysozyme and mucus alkaline phosphatase levels (p < 0.05), whereas it had no significant effects on other immunological parameters. The mucus bactericidal activities were improved by dietary yeast but both supplements enhanced the plasma bactericidal activity (p < 0.05). Thymol and yeast supplementation significantly up-regulated the expression of tumor necrosis factor-alpha, interleukin-1 beta, transforming growth factor-beta, beta-defensin and heat shock protein-70 in the hindgut (p < 0.05). In conclusion, dietary yeast supplementation was particularly effective in enhancing fish growth performance and non-specific immunity, while thymol supplementation primarily led to improved antioxidant capacity. Notably, a dietary dose of 250 mg/kg of thymol alone failed to affect the gut transcription as much as 500 mg/kg; however, the co-supplementation of 250 mg/kg of thymol and yeast led to comparable results. Full article

Background: Numerous studies have shown the presence of multiple defence factors in placental tissue, although their role is partially understood; therefore, the aim of this study was to evaluate the expression of nuclear factor-kappa B (NF-κB); human beta-defensin 2, 3, and 4 (HBD-2,3,4); cathelicidine (LL-37); heat shock protein 60 (HSP60); and interleukin 10 (IL-10) in dissimilar gestational week placental tissue and display correlations between immunoreactive cells. Methods: A total of 15 human placental tissue samples were acquired from mothers with different gestational weeks: 28, 31, and 40. Routine staining and immunohistochemistry for the samples were executed. The evaluation of data was performed with semi-quantitative methods, and, for statistical analysis, the Kruskal–Wallis test was used. Spearman’s rank correlation was used for calculating correlations. Results: NF-κB, HBD- 2,3,4, HSP60, and IL-10 expression were discovered in every examined placental tissue cell type. LL-37 expression was found only in Hofbauer cells. A rise in expression with higher gestational weeks was noted in LL-37-positive Hofbauer cells (p = 0.03), HBD-3-positive cytotrophoblasts (p = 0.007), endothelial cells (p = 0.024), extraembryonic mesodermal cells (p = 0.004), and HBD-4-positive endothelial cells (p = 0.001). Numerous statistically significant moderate and strong positive correlations between defence factors were discovered. Conclusions: The persistence of Hofbauer cell accumulations underlines the growing significance of placental macrophages in placental protection. The expression of positive defence factors and a rise in expression in tissue protection factors (HBD-3, LL-37, HBD-4) in higher gestational weeks may indicate these factors as the most significant protectors of the placenta in ontogenetic aspects. The high number of statistically significant positive and negative correlations between positive cells show a strong network to sustain distressed placental growth and therefore pregnancy. Full article

Background: Excessive body fatness is the basis of many diseases, especially civilization-related ones. The aim of this study is to analyze the body composition and serum levels of selected antimicrobial peptides (AMPs) in patients with basal cell carcinoma (BCC), in comparison to healthy controls (HCs), and investigate whether any specific parameter significantly increases the risk of BCC development. Methods: The body composition and measurements of serum levels of cathelicidin and human-beta-defensin-2 were analyzed in a group of 100 subjects (50 patients with BCC and 50 HCs). Results: There were statistically significant differences between the visceral fat rating (BCC 11.7 vs. control 10.1), cathelicidin (BCC 1022.6 vs. control 428.4), defensin-2 (BCC 1.2 vs. control 0.4), age (BCC 68.7 vs. control 62.4), and the visceral fat/muscle ratio (BCC 0.24 vs. control 0.21). Conclusions: It seems that excessive fat, especially visceral fat, may pose a risk of developing skin cancer. Therefore, it should be taken into account when caring for patients and they should be made aware that losing body weight may be important not only in reducing the risk of hypertension or diabetes but also cancer diseases. There are numerous well-known risk factors for developing skin cancer, but few are modifiable. Among these modifiable factors is the patient’s weight and body composition, so improvaing lifestyle is crucial in the prevention of skin cancers. Full article

Despite the seriousness of the disease carried by ticks, little is known about the Bourbon virus. Only three US states have recorded human cases of Bourbon virus (BRBV) infection; in all cases, a tick bite was connected with the onset of the illness. The Bourbon virus (BRBV) belongs to the Orthomyxoviridae family and Thogotovirus genus, originating in the states of the US, i.e., Kansas, Oklahoma and Missouri. The growing rates of BRBV infections in various parts of the US highlight the necessity for a thorough analysis of the virus’s transmission mechanisms, vector types and reservoir hosts. Currently, there are no vaccines or efficient antiviral therapies to stop these infections. It is imperative to produce a vaccination that is both affordable and thermodynamically stable to reduce the likelihood of future pandemics. Various computational techniques and reverse vaccinology methodologies were employed to identify specific B- and T-cell epitopes. After thorough examination, the linker proteins connected the B- and T-cell epitopes, resulting in this painstakingly constructed vaccine candidate. Furthermore, 3D modeling directed the vaccine construct toward molecular docking to determine its binding affinity and interaction with TLR-4. Human beta-defensin was used as an adjuvant and linked to the N-terminus to boost immunogenicity. Furthermore, the C-IMMSIM simulation resulted in high immunogenic activities, with activation of high interferon, interleukins and immunoglobulin. The results of the in silico cloning process for E. coli indicated that the vaccine construct will try its utmost to express itself in the host, with a codon adaptation CAI value of 0.94. A net binding free energy of −677.7 kcal/mol obtained during docking showed that the vaccine has a high binding affinity for immunological receptors. Further validation was achieved via molecular dynamic simulations, inferring the confirmational changes during certain time intervals, but the vaccine remained intact to the binding site for a 100 ns interval. The thermostability determined using an RMSF score predicted certain changes in the mechanistic insights of the loop region with carbon alpha deviations, but no major changes were observed during the simulations. Thus, the results obtained highlight a major concern for researchers to further validate the vaccine’s efficacy using in vitro and in vivo approaches. Full article

Background/Objectives: Intracranial Epidermoid Cysts (IECs) are rare intracranial tumors primarily treated through surgery. Cyst adherence complicates complete removal, leading to high rates of tumor progression after subtotal resection. The molecular drivers of IEC remain unknown. Consequently, advances in treatment have fallen short. Tumor genetic profiling has revealed potential targets for drug development, including FDA-approved options and reshaping treatment. The genetic landscape of IECs has not been explored. We applied Whole Exome Sequencing (WES) to IECs to gain insights into the mechanisms of oncogenesis and identify potential therapeutic targets. Methods: We performed WES on tumor tissue and matched blood samples, when available. Following GATK best practices, we conducted read processing, quality control, somatic variant calling, and copy-number inference. Data analyses and visualization were conducted in R. Results: Top altered genes are associated with the immune system and tumor microenvironment, suggesting a mechanism of immune evasion. Gene and pathway enrichment revealed a high mutation burden in genes associated with Extracellular Matrix (ECM) and PI3K-AKT-mTOR cascades. Recurrent and deleterious alterations in NOTCH2 and USP8 were identified in 50% and 30% of the cohort, respectively. Frequent amplifications in deubiquitinases and beta-defensins strengthened the involvement of immune mechanisms for oncogenic transformation. Conclusions: Top altered genes and recurrent mutations may play a role in shaping the microenvironment and modulating immune evasion in IECs. USP8 and NOTCH2 may serve as clinically relevant target for IECs. Finally, we present evidence that the crosstalk between the PI3K-Akt-mTOR and ECM signaling pathways may play a role in modulating the immune escape mechanism in IECs. Full article