Search Results (79,109)

Abstract: Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host’s epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host’s innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally. Full article

This study focuses on refining in vitro propagation protocols for red currant cultivars of the Ribes genus and evaluating the role of LED lighting in the adaptation of microplants. The cultivars ‘Red Lake’, ‘Englische Grosse Weisse’, ‘Marmeladnitsa’, and ‘Podarok Leta’ were successfully introduced into in vitro culture during their dormancy phase using 0.1% HgCl₂ as a sterilizing agent. The period of spring introduction is not very efficient in connection with the intensive development of saprophytic microflora and weak morphogenesis microplants. Using 0.01% C₉H₉HgNaO₂S sterilizer resulted in a decrease in the necrosis percentage, but an increase in mold proportion. The preparation of the plants with 12% H₂O₂ was considered environmentally not effective enough to obtain a large number of healthy microplants. The use of 12% H₂O₂ resulted in increased necrosis rates by 24.76% compared to 0.01% C₉H₉HgNaO₂S and 0.1% HgCl₂ sterilizers. The variety specificity of Ribesia plants in terms of the content of MS and LF nutrient media components was determined by the survival rate of explants, the formation of additional micro-shoots, and the morphological development. The MS medium with the addition of 1 mg∙L⁻¹ BAP decreased the percentage of mold and necrosis infection and provided a high percentage of viable plants with optimal growth and reproduction rate. In contrast, the LF medium with the same concentration of 6-BAP resulted in poor explant quality and leaf chlorosis at later stages. The study also investigated the effects of different LED light spectra on morphological and physiological traits. For ‘Red Lake’ and ‘Englische Grosse Weisse’, RWUV-A (625–740 nm) lighting enhanced biomass and chlorophyll (Chl a and Chl a + b) accumulation, while the White (W) spectrum benefited ‘Podarok Leta’. Conversely, the RW spectrum with minimal green and no ultraviolet light restricted growth and photosynthetic pigment accumulation across all cultivars, promoting compact plant structures. The RWUV-A lighting condition resulted in the highest NDVI values across all cultivars, indicating an improved physiological status and biomass accumulation. These findings underscore the importance of refining the microclonal reproduction protocols for Ribesia subgenus representatives, emphasizing the genotype-specific light modulation during the proliferation stage. The study highlights the utility of the MS medium and tailored light conditions in enhancing the effectiveness of propagation techniques for producing high-quality planting material. Full article

Viral infections remain a major concern, as existing treatments often yield inadequate responses or lead to the development of antiviral resistance in some cases. Fucoidan extracted from Undaria pinnatifida (F) is a natural sulphated polysaccharide that exhibits antiviral action. Despite its potential, the biomedical application of F is limited due to its difficult administration through trans-mucosal, skin, or oral ingestion. The most effective way to solve these problems is to propose novel methods of administration aiming to ensure better contact between the biopolymers and pathogens, leading to their inactivation. In this work, the synthesis of films based on chitosan (Ch)-coupled F is reported, aiming to generate a synergic effect between both biopolymers in terms of their antiviral and antioxidant capability. Biocomposites were prepared by a sonochemical method. They were characterized to infer structural properties, functionality, and possible F-Ch interactions by using Zeta potential, FTIR, and XRD techniques. The biocomposites showed excellent film-forming ability. They also exhibited improved antioxidant activity with respect to F and Ch individually and proved to be non-cytotoxic. These results demonstrate, for the first time, the antiviral activity of F:Ch biocomposites against bovine coronavirus and human viruses (adenovirus, poliovirus, herpes simplex, and respiratory syncytial virus), which could be applied in film form to prevent or treat viral infections. Full article

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most common causes of bacterial foodborne infections worldwide. It has an extensive host range, including birds and humans, making it one of the most adaptable Salmonella serovars. This study aims to define the virulence gene profile of S. Enteritidis and identify genes critical to its host specificity. Currently, there is limited understanding of the molecular mechanisms that allow S. Enteritidis to continue as an important foodborne pathogen. To better understand the genes that may play a role in the host-specific virulence and/or fitness of S. Enteritidis, we first compiled a virulence gene profile-based genome analysis of sequenced S. Enteritidis strains isolated from shell eggs in our laboratory. This analysis was subsequently used to compare the representative genomes of Salmonella serovars with varying host ranges and S. Enteritidis genomes. The study involved a comprehensive and direct examination of the conservation of virulence and/or fitness factors, especially in a host-specific manner—an area that has not been previously explored. Key findings include the identification of 10 virulence-associated clusters of orthologous genes (COGs) specific to poultry-colonizing serovars and 12 virulence-associated COGs unique to human-colonizing serovars. Virulence/fitness-associated gene analysis identified more than 600 genes. The genome sequences of the two S. Enteritidis isolates were compared to those of the other serovars. Genome analysis revealed a core of 2817 COGs that were common to all the Salmonella serovars examined. Comparative genome analysis revealed that 10 virulence-associated COGs were specific to poultry-colonizing serovars, whereas 12 virulence-associated COGs were present in all human-colonizing serovars. Phylogenetic analyses further highlight the evolution of host specificity in S. Enteritidis. This study offers the first comprehensive analysis of genes that may be unique to and possibly essential for the colonization and/or pathogenesis of S. Enteritidis in various and specific hosts. Full article

Infections by the major opportunistic pathogen of human Candida albicans are commonly treated with echinocandin (ECN) drugs. However, C. albicans can adapt to grow in the presence of certain amounts of ECNs. Prior studies by several laboratories have defined multiple genes, as well as mechanisms involving induced aneuploidy, that can govern this. Still, the mechanisms of ECN adaptation are not fully understood. Here, we use genome-wide profiling of chromatin accessibility by ATAC-seq to determine if ECN adaptation is reflected in changes in the chromatin landscape in the absence of aneuploidy. We find that drug adaptation is coupled with multiple changes in chromatin accessibility genome-wide, which occur predominantly in gene promoter regions. Areas of increased accessibilities in promoters are enriched with the binding motifs for at least two types of transcription factors: zinc finger and basic leucine zipper. We also find that chromatin changes are often associated with differentially expressed genes including genes with functions relevant to the ECN-adapted phenotype, such as cell wall biosynthesis. Consistent with this, we find that the cell wall is remodeled in ECN-adapted mutants, with chitin up and glucan down and increased cell surface exposure. A full understanding of ECN adaptation processes is of critical importance for the prevention of clinical resistance. Full article

Background: Since Legionella pneumophila (Lp) is widely present in natural and artificial water environments, it has a high potential risk of outbreak. Diarrhea caused by Lp pulmonary infection is an important symptom of Legionnaires’ disease (LD); however, the underlying mechanism of the diarrhea has not yet been revealed. This not only has a negative impact on clinical diagnosis and treatment, but may also cause misdiagnosis. Methods: In the present study, a mouse model of enteritis caused by pulmonary infection of Lp was established. By using this mouse model, we explored the underlying mechanisms of the enteritis caused by Lp pulmonary infection. Results: The results indicated that the systemic inflammatory response played a very important role in the enteritis phenotype caused by a strong-virulence strain of Lp. Furthermore, we found that the expression of Bcl-2 was downregulated by IL-6 through the p53 signaling pathway, thereby activating the caspase 3 of intestinal epithelial cells (IECs), causing the apoptosis of IECs, and ultimately leading to the enteritis phenotype. Conclusions: The IL-6–caspase 3 axis plays an important role in enteritis caused by Lp pulmonary infection. Full article

Fungal infections are a significant global health challenge, causing approximately 3.8 million deaths annually, with immunocompromised populations particularly at risk. Traditional antifungal therapies, including azoles, echinocandins, and polyenes, face limitations due to rising antifungal resistance, toxicity, and inadequate treatment options. This review explores innovative strategies for preventing and managing fungal infections, such as vaccines, antifungal peptides, nanotechnology, probiotics, and immunotherapy. Vaccines offer promising avenues for long-term protection, despite difficulties in their development due to fungal complexity and immune evasion mechanisms. Antifungal peptides provide a novel class of agents with broad-spectrum activity and reduced resistance risk, whilst nanotechnology enables targeted, effective drug delivery systems. Probiotics show potential in preventing fungal infections, particularly vulvovaginal candidiasis, by maintaining microbial balance. Immunotherapy leverages immune system modulation to enhance antifungal defenses, and omics technologies deliver comprehensive insights into fungal biology, paving the way for novel therapeutic and vaccine targets. While these approaches hold immense promise, challenges such as cost, accessibility, and translational barriers remain. A coordinated effort among researchers, clinicians, and policymakers is critical to advancing these strategies and addressing the global burden of fungal infections effectively. Full article

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), involves symptoms or effects that persist for more than 4 weeks after the initial SARS-CoV-2 infection. One contributing factor to this condition is the disruption in the expression of the antioxidant enzyme Nuclear Factor Erythroid-2 (Nrf2) induced by the COVID-19 infection. Apigenin and related flavonoids, known for their diverse pharmacological activities, including potent antioxidant properties, have emerged as promising candidates for Long COVID-19 therapy. These compounds, particularly apigenin, are recognized for their ability to modulate oxidative stress and inflammation, making them potential activators of the Nrf2 pathway. This study aims to predict the activity of apigenin and its related flavonoids as Nrf2 activators using molecular modeling and molecular dynamics (MD) techniques, providing insights into their therapeutic potential in managing Long COVID-19. The findings from the molecular modeling analysis indicate that apigenin has a favorable affinity, with a free energy value (ΔG) of −6.40 kcal/mol. Additionally, MD simulation results demonstrate the strong stability of the Keap1-apigenin complex, with an average Root Mean Square Deviation (RMSD) value below 0.20 nm and the lowest average Root Mean Square Fluctuation (RMSF) value of 0.86 nm. Using the Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculation method, the binding affinity of the Keap1-apigenin complex yields a lower free energy value (ΔG) of −67.039 kJ/mol, consistent with the molecular modeling results. Apigenin also exhibits the ability to inhibit the binding of Nrf2 to the hydrophobic surface of Keap1, with a total energy value of 993.266 kcal/mol and binding affinity value of −1.162 kJ/mol through peptide−receptor docking. In conclusion, the comprehensive results suggest that apigenin has the potential to be a lead compound for developing Nrf2 activators specifically designed for Long COVID-19 therapy. Full article

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of heritability on the proneness as well as infection- and vaccine-induced immune responses have been documented for multiple infections, including tuberculosis, malaria, leprosy, otitis media, polio, mumps, measles, rubella, influenza, hepatitis B, and human papillomavirus infections, and recently, SARS-CoV-2. The current data show the heritable aspect in nearly all infections considered. In this contribution, we review and discuss human twin studies on the heritability of host characteristics in liability and response to IDs. This review emphasizes the importance of considering factors such as sex, disease stages, and disease presentation when assessing heritability and argues that the classical twin design provides a unique circumstance for exploring the genetic contribution as twins share levels of maternal antibodies, ancestral background, often the dates and number of vaccine doses, differences in vaccines’ manufacturing and storage, age, family environment, and other exposures. Additionally, we highlight the value of twin studies and the usefulness of combining the twin model with contemporary genomics technologies and advanced statistical tools to grasp a comprehensive and nuanced understanding of heritability in IDs. Full article

Background: According to current guidelines, preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting (ERCP/stenting) is often necessary in patients with obstructive jaundice due to pancreatic ductal adenocarcinoma (PDAC), including severe jaundice (bilirubin > 250 umol/l), pruritus, cholangitis, cholestatic liver dysfunction, renal failure, severe malnutrition, or delayed surgery for tumors requiring neoadjuvant chemotherapy. We aimed to investigate the impact of preoperative ERCP/stenting on postoperative and long-term outcomes following pancreaticoduodenectomy (PD) for PDAC. Methods: Clinicopathological data of patients who underwent partial/total PD for PDAC between 2012 and 2019 in two hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We compared patients treated with preoperative ERCP/stenting with those directly undergoing surgery according to postoperative morbidity, postoperative mortality, overall survival (OS) and disease-free survival (DFS). Results: During the study period, 192 patients underwent partial/total PD for PDAC. ERCP/stenting was performed in 105 patients, and 87 patients underwent resection without prior intervention. Postoperative 90-day overall morbidity rate (71% vs. 56%, p = 0.029) and superficial surgical site infection (SSI) rate (39% vs. 17%, p < 0.001) were significantly worse following preoperative ERCP/stenting. Major postoperative morbidity rate (18% vs. 21%, p = 0.650), organ/space SSI rate (7% vs. 14%, p = 0.100), and 90-day postoperative mortality rate (4% vs. 2%, p = 0.549) did not significantly differ between the two groups. After excluding 44 patients for whom the indication for ERCP/stenting was not consistent with current guidelines, ERCP/stenting was associated with a higher superficial SSI rate (36% vs. 17%, p = 0.009) and shorter length of stay (12 vs. 16 days, p = 0.004). Median OS (ERCP/stenting: 18 months vs. no ERCP/stenting: 23 months, p = 0.490) and median DFS (ERCP/stenting: 14 months vs. no ERCP/stenting: 18 months, p = 0.645) were independent from the utilization of ERCP/stenting. Conclusions: Preoperative ERCP/stenting in patients with PDAC can be performed without increasing organ/space SSI, major perioperative morbidity, and mortality rates and without worsening oncologic outcomes. However, it is associated with higher superficial SSI rates. If ERCP/stenting is not performed routinely but according to current guidelines, it is also associated with a shorter length of hospital stay. Further refinement of the indications for preoperative ERCP/stenting may reduce superficial SSI rates. Full article

Malware software has become a pervasive threat in computer and mobile technology attacks. Attackers use this software to obtain information about users of the digital world to obtain benefits by hijacking their data. Antivirus software has been developed to prevent the propagation of malware, but this problem is not yet under control. To develop this software, we have to check the propagation of malware. In this paper, we explore an advanced malware propagation model with a time-delay factor and a variable infection rate. To better understand this model, we use fractal–fractional theory. We use an exponential decay kernel for this. For theoretical purposes (existence, uniqueness, and stability), we use the results from fixed-point theory, and, for numerical purposes, a Lagrange two-point interpolation polynomial is used to develop an algorithm. Matlab R2016a is used for simulation, and the physical significance is assessed. We examine the impact of different fractal and fractional orders for various parameters. Moreover, we compare four different mathematical models (classical, fractional, fractal, and fractal–fractional). Also, constant and variable fractional and fractal orders are compared using graphs. We investigate the idea that significant perturbation in infected nodes might be due to minor changes. This work may help with developing antivirus strategies in real life. Full article

Toxoplasmosis is a significant zoonotic parasitic disease. Currently, there is no effective vaccine available to prevent human infection, and treatment primarily relies on chemotherapy. However, the lack of specific therapeutic agents and the limitations of existing drugs highlight the urgent need for novel, safe, and effective anti-Toxoplasma gondii (T. gondii) medications. In this study, we evaluated the toxicity of ICA (N-(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine) to host cells and assessed its inhibitory and anti-proliferative effects on T. gondii tachyzoites. We further investigated the impact of ICA on the ultrastructure of T. gondii using transmission electron microscopy (TEM). Additionally, we measured alterations in mitochondrial membrane potential, superoxide levels, and ATP levels in T. gondii to assess the effect of ICA on mitochondrial function. Our findings demonstrated that ICA exhibits a safe and effective inhibitory effect on T. gondii, with a selectivity index (SI) of 258.25. Notably, ICA demonstrated a more potent anti-proliferative effect than pyrimethamine (PYR). Ultrastructural observations revealed that ICA induces mitochondrial swelling and membrane rupture in T. gondii. Further investigations confirmed that ICA leads to mitochondrial dysfunction in T. gondii. In conclusion, our results suggest that ICA possesses the potential to serve as a lead compound for the development of novel anti-T. gondii therapies. Full article

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this group, and no studies have examined the vaccination status of patients’ close contacts. Objectives: To assess vaccination rates among patients on biologics and their household contacts, identifying reasons for inadequate vaccination and examining factors influencing vaccination status and attitudes is crucial. Methods: A cross-sectional study was conducted from September 2022 to February 2023 at the two hospitals in Heraklion, Crete, including adult and pediatric patients on biologics. Data were collected through medical records and interviews and analyzed using Microsoft Excel 2016 and MedCalc2006. Results: Among the 446 adults, vaccination rates were as follows: 83% for COVID-19, 73.8% for influenza, 64.5% for the pneumococcal conjugate vaccine, 29.6% for the pneumococcal polysaccharide vaccine, and 4% for Tdap. Among the 26 children included, those with basic immunization schedule coverage exceeded 96%, but rates for the vaccines usually administered at adolescence were lower (Tdap: 47.8%, HPV: 42.1%, MenACWY: 66.7%). COVID-19 vaccination was at 38.5%. Regarding the additional vaccines recommended due to treatment-induced immunosuppression, 69.2% of pediatric patients received the annual influenza vaccine, while only 19.2% received the pneumococcal polysaccharide vaccine. Household contacts demonstrated low vaccination rates (<59%), except for COVID-19 (81%). Female gender (p < 0.007) and older age (by 1 year, p < 0.001) were associated with favorable attitudes and higher coverage in adults, while in pediatric patients, no statistically significant associations were found. A lack of physician recommendation was the primary reported reason for not being vaccinated. Conclusions: Significant vaccination gaps exist among patients on biologics and their close contacts, largely due to inadequate physician recommendations. Raising awareness and strengthening healthcare provider roles are essential to improve coverage in this high-risk group. Full article

Complex wounds pose a significant healthcare challenge due to their susceptibility to infections and delayed healing. This study focuses on developing electrospun polycaprolactone (PCL) nanofiber membranes coated with Type I collagen derived from bovine skin and functionalized with silver nanoparticles (AgNPs) to address these issues. The collagen coating enhances biocompatibility, while AgNPs synthesized through chemical reduction with sodium citrate provide broad-spectrum antimicrobial properties. The physical properties of the membranes were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Results showed the formation of nanofibers without defects and the uniform distribution of AgNPs. A swelling test and contact angle measurements confirmed that the membranes provided an optimal environment for wound healing. In vitro biological assays with murine 3T3 fibroblasts revealed statistically significant (p ≤ 0.05) differences in cell viability among the membranes at 24 h (p = 0.0002) and 72 h (p = 0.022), demonstrating the biocompatibility of collagen-coated membranes and the minimal cytotoxicity of AgNPs. Antibacterial efficacy was evaluated against Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Vancomycin-resistant Enterococcus (VRE), with the significant inhibition of biofilm formation observed for VRE (p = 0.006). Overall, this novel combination of collagen-coated electrospun PCL nanofibers with AgNPs offers a promising strategy for advanced wound dressings, providing antimicrobial benefits. Future in vivo studies are warranted to further validate its clinical and regenerative potential. Full article

Background/Objectives: As the rate of revision total hip arthroplasty (THA) has risen, there has been a drive to improve the technology in the manufacturing of the implants used. One recent advance has been 3-D printing of trabecular titanium implants to improve implant stability and osteointegration. The aim of this study was to review the clinical and radiological outcomes of these acetabular implants in revision THA. Methods: A manual search of the databases of the US National Library of medicine (PubMed/MEDLINE), Embase, and the Cochrane library was performed. The following keywords of “revision total hip arthroplasty” AND “acetabulum” AND “titanium” AND “porous” were utilised. Results: In total, 106 abstracts were identified during manual search of databases. In total, 11 studies reporting 4 different implants, with a total of 597 operated joints in 585 patients were included in this review. There were 349 (59.7%) female patients, and the mean age per study ranged from 56.0 to 78.4 years. The all-cause survival rate was 95.52% (95% CI: 92.37–97.96) at a mean follow up of 3.8 years (95% CI: 2.6–5.1). The 40 cases that required re-operation included 17 (2.8%) for infection, 14 (2.3%) instability, 2 (0.3%) for shell migration and 5 (0.8%) for aseptic loosening. The most commonly used patient reported outcome measure was the Harris Hip Score with the mean post-operative score of 86.7 (95% CI: 84.3–89.1). Conclusion: Trabecular titanium acetabular implants, when used in revision THA, resulted in excellent short- to mid-term outcomes with improved hip specific outcomes and a survivorship of 95.52% over the reported follow-up period. Future prospective studies evaluating long term outcomes are needed to make comparisons between more established solutions used in revision THA. Full article