Search Results (703)

The mudflat crab (H. tientsinensis) is a dominant species in coastal tidal flat areas, primarily inhabiting the high tide region of the intertidal zone, and possesses significant ecological and economic value. Vibrio species are one of the main bacterial pathogens responsible for diseases in marine organisms, and they are widely distributed in seawater and estuarine environments. However, the immune mechanisms employed by H. tientsinensis in response to Vibrio infections remain unclear. This study aims to investigate the physiological and immune mechanisms by analyzing the structural changes and differential gene expression in the gill and hepatopancreas following Vibrio parahaemolyticus infection. The results indicate that V. parahaemolyticus infection causes cellular damage, with structural alterations observed in the gills (epithelial cell edema in the gill filaments, and aneurysm formation) and the hepatopancreas (changes in lumen size, nuclear condensation, and modifications in connective tissue morphology). Transcriptome analysis revealed 9766 differentially expressed genes (DEGs) in the gills of the experimental group, with 4687 upregulated and 5079 downregulated genes. These DEGs are primarily involved in different ribosomal subunits. In the hepatopancreas, 1594 DEGs were identified, with 834 upregulated and 760 downregulated. These DEGs are predominantly associated with energy-coupled proton transmembrane transport, electron transport-coupled proton transport, and lipid transporter activity. H. tientsinensis gene annotation and KEGG enrichment analysis revealed that chemical carcinogens DNA adducts, amino acid metabolism, and some immune pathways play key roles in the ability of H. tientsinensis to defend against V. parahaemolyticus infection. The findings of this study contribute to a deeper understanding of the immune mechanisms of H. tientsinensis against V. parahaemolyticus infection and provide new insights for aquaculture management. Full article

The cellular membrane is a dynamic structure composed of lipids and proteins organized into specialized domains that facilitate interactions between extracellular molecules and the intracellular environment. Tetraspanins are a family of transmembrane proteins involved in diverse cellular processes, including membrane stabilization and fusion, endocytosis, extracellular vesicle formation, and the organization of proteins and lipids at specific membrane sites known as Tetraspanin-Enriched Microdomains (TEMs). These lipid–protein interactions play a critical role in the replicative cycle of Orthoflavivirus, including dengue, Zika, and West Nile, by facilitating viral entry, replication, assembly, and egress. In addition, tetraspanins also regulate the biogenesis and function of extracellular vesicles, contributing to viral dissemination, persistent infection, and immune evasion. This review summarizes the current knowledge on the structural and functional aspects of tetraspanins, their interplay with lipids, and their emerging roles in the Orthoflavivirus replicative cycle. We also discuss how these insights may inform the development of antiviral strategies targeting membrane organization and virus–host interactions. Full article

Serum sickness-like reaction (SSLR) is a rare immune-mediated condition that typically affects the skin and joints after exposure to certain drugs, infections, or vaccines. Although it shares clinical similarities with serum sickness (SS), SSLR differs in its underlying mechanisms, histopathology, and causes. Despite its generally benign and self-limiting nature, SSLR is frequently misdiagnosed and may lead to unnecessary hospitalization. This narrative review summarizes current knowledge on epidemiology, pathophysiology, clinical features, diagnosis, treatment, and long-term considerations related to SSLR. The condition is most often associated with antibiotics, monoclonal antibodies, and vaccines, particularly in pediatric populations. Its pathogenesis remains incompletely understood, but proposed mechanisms include immune complex formation, altered drug metabolism, lymphocyte toxicity, and the development of anti-drug antibodies. Diagnosis is primarily clinical, although novel diagnostic tools are emerging. Management involves discontinuation of the offending agent and supportive care, such as antihistamines or nonsteroidal anti-inflammatory drugs (NSAIDs) in mild cases, and corticosteroids in more severe cases. Long-term management, especially in cases requiring potential re-exposure to the causative agent, remains challenging. Skin testing and graded oral challenges appear promising within a structured clinical framework. Increased awareness of SSLR is essential for timely recognition and appropriate care, and further research is needed to elucidate its mechanisms and inform evidence-based management strategies. Full article

Background/Objectives: Silver sulfadiazine (AgSD) is widely used in the topical treatment of burns and infected wounds, but its conventional formulations present drawbacks such as poor water solubility, the need for multiple daily applications, and patient discomfort. To overcome these limitations, this study aimed to develop and evaluate Laponite^® (LAP)-based hydrogels loaded with AgSD for controlled release and enhanced antimicrobial and antibiofilm efficacy, offering a promising alternative for the treatment of contaminated or biofilm-forming wounds. Methods: Laponite^®-based hydrogels containing 1% and 1.2% AgSD (LAP@AgSD) were prepared using a one-pot method. The formulations were characterized rheologically, thermally, and structurally. In vitro drug release was assessed using Franz diffusion cells, and mathematical modeling was applied to determine release kinetics. Antibacterial and antibiofilm activities were evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using standardized microbiological methods. Results: LAP@AgSD hydrogels exhibited pseudoplastic behavior, high structural integrity, and enhanced thermal stability. In vitro release assays revealed a sustained release profile, best fitted by the Weibull model, indicating diffusion-controlled mechanisms. Antibacterial assays demonstrated concentration-dependent activity, with LAP@AgSD 1.2% showing superior efficacy over LAP@AgSD 1% and comparable performance to the commercial silver sulfadiazine cream (CC-AgSD). Biofilm inhibition was significant for all formulations, with CC-AgSD 1% exhibiting the highest immediate activity, while LAP@AgSD 1.2% provided sustained antibiofilm potential. Conclusions: LAP-based hydrogels are promising smart delivery systems for AgSD, combining mechanical robustness, controlled drug release, and effective antibacterial and antibiofilm activities. These findings support their potential use in topical therapies for infected and chronic wounds, particularly where biofilm formation is a challenge. Full article

This study reports, for the first time, lanthanum oxide (La₂O₃) nanoparticles (NPs) that simultaneously suppress osteosarcoma MG63 cell proliferation and promote normal Vero cell viability, a dual effect not previously documented for La₂O₃ or similar metal oxide NPs. Physico-chemical characterization revealed a unique needle-like morphology, cubic crystallinity, and dispersion stability in DMSO without acidic dispersants, properties that can influence cellular uptake, ROS modulation, and biocompatibility. Comprehensive characterization (fluorescence spectroscopy, particle size/zeta potential, Raman, XRD, TGA, ATR-FTIR, and TEM) confirmed structural stability and surface chemistry relevant to biological interactions.La₂O₃ NPs exhibited broad-spectrum antibacterial activity (Gram-positive Streptococcus pyogenes, Bacillus cereus; Gram-negative Escherichia coli, Pseudomonas aeruginosa) and strong enzymatic/non-enzymatic antioxidant capacity, supporting potential use in implant coatings and infection control. MTT assays demonstrated dose-dependent cytotoxicity in MG63 cells, with enhanced proliferation in Vero cells. In zebrafish embryos, developmental toxicity assays yielded an LC₅₀ of 2.6 mg/mL higher (less toxic) than values reported for Ag NPs (~0.3–1 mg/mL) with normal development at lower concentrations and dose-dependent malformations (e.g., impaired somite formation and skeletal deformities) at higher doses. Collectively, these findings position La₂O₃ NPs as a multifunctional platform for oncology and regenerative medicine, uniquely combining selective anticancer activity, normal cell support, antimicrobial and antioxidant functions, and a defined developmental safety margin. Full article

Chronic wounds and post-operative complications generate significant biomedical challenges due to impaired tissue regeneration and persistent microbial infections, often aggravated by biofilm formation and antibiotic resistance. To address these issues, this study investigates the development and in vitro evaluation of electrospun polyvinylpyrrolidone (PVP) scaffolds embedded with silver nanoparticles (AgNPs), designed as multifunctional bioactive platforms for wound healing and implant applications. AgNPs were synthesized and uniformly incorporated into the PVP matrix using optimized electrospinning parameters, harnessing their antimicrobial and anti-inflammatory properties alongside the hydrophilicity, biocompatibility, and chemical stability of PVP. Structural and mechanical characterization, including Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), homogenous nanoparticle dispersion, and favorable mechanical properties, such as Young’s modulus. In vitro cytotoxicity assays with fibroblast cell lines demonstrated good biocompatibility, while antibiofilm activity against Staphylococcus aureus revealed significant microbial inhibition. Overall, electrospun PVP+AgNPs scaffolds demonstrate strong potential as multifunctional biomaterials for wound healing and implant coating due to their synergistic capacity to support tissue regeneration and inhibit infection. These promising results highlight the need for further in vitro and in vivo investigation to confirm their therapeutic efficacy, biocompatibility, and long-term stability in physiological environments. Full article

Vascular grafts have a significant role in the artery replacement, aneurysm repair, and hemodialysis treatments. Synthetic grafts that have been mostly used in the clinic include ePTFE and Dacron; however, their use has been associated with a range of complications that include clot formation, intimal hyperplasia, and infections. Corrugated Biopolymeric grafts are one of the promising options that were introduced in the market due to their relatively higher biocompatibility and mechanical advantages. There is still a need to find the right choice regarding mechanical strength, fluid flow, and effective antimicrobial activity. The given research explores the mechanical response of the physiological pressure in corrugated biopolymeric grafts in order to improve antimicrobial activity. These grafts were manufactured and stimulated with the help of COMSOL Multiphysics ^® 6.2 with an aim to determine the pattern of stress distribution, resistance to pulsatile pressure, and fatigue behavior during dynamic flow. The result was that the corrugated structure showed superior mechanical strength and had better compliance with natural blood vessels, which consequently might improve antimicrobial activity. Full article

The dengue virus (DENV) exploits host cell exosome pathways to disseminate and evade immunity. However, the host factors enabling this process remain poorly defined. Here, we demonstrate that DENV infection robustly induces expression of the short isoform of Reticulon 3 (RTN3S) in hepatic (Huh7) and monocytic cells, and that RTN3S is a critical driver of infectious exosome biogenesis. RTN3S physically associates with double-stranded viral RNA and the DENV non-structural protein 3 (NS3) in infected cells, indicating its integration into the viral replication complex. Loss of RTN3 markedly reduced exosome production and the exosomal export of viral RNA and proteins, demonstrating that RTN3S is required for efficient exosome-mediated viral release. Conversely, overexpression of full-length RTN3S dramatically increased the release of infectious virus-containing exosomes; truncation of the RTN3S C-terminal domain abolished this enhancement, confirming the essential role of the C-terminus in RTN3S’s pro-viral exosomal function. In DENV-infected monocytes, we observed a shift toward a CD16-positive intermediate phenotype, accompanied by the upregulation of genes involved in vesicle biogenesis and stress response. These infected monocytes also secreted higher levels of inflammatory cytokines. Similarly, monocytes from Dengue patients exhibited high RTN3 expression, which correlated with an expansion of intermediate (CD16⁺) subsets and enriched expression of vesicle trafficking machinery genes. These findings reveal a previously unrecognized mechanism by which DENV hijacks RTN3S to promote the formation of infectious exosomes, thereby facilitating viral dissemination and immune evasion. RTN3S thus represents a novel element of the Dengue pathogenesis and a potential target for host-directed antiviral strategies. Full article

Approximately half of the world population is infected with the human pathogen Helicobacter pylori, which causes gastric inflammation, chronic gastritis, or peptide ulceration. A significant factor in the colonization of the upper digestive system is the helical shape of H. pylori. This helical form is maintained by a complex network of peptidoglycan (PG)-modifying enzymes and cytoskeletal proteins. Among these, the D,D-endopeptidase Csd2 plays a central role, working in conjunction with other cell shape-determining (Csd) proteins. Csd1 and Csd2 have been categorized as members of the M23B metallopeptidase family. These enzymes are classified as D,D-endopeptidases, and their function involves the cleavage of the D-Ala4-mDAP3 bond, which is present in the cross-linked di-mer muropeptides. Despite the fact that the structure of the Csd1:Csd2 complex has been examined via biochemical methods, information on the in vivo localization and dynamics of D,D-endopeptidases is still missing. Here, we use an approach that employs sophisticated different microscopy methods to visualize the spatial temporal localization and dynamics of Csd2, involving both structured illumination microscopy and single-molecule tracking. Our findings thus contribute to refining the existing model for this cellular complex by revealing curvature-dependent spatial organization and temporal dynamics underlying peptidoglycan remodeling processes essential for helical cell shape formation and maintenance. Understanding the dynamics provides insight into the mechanisms that maintain bacterial morphology and potential targets for therapeutic intervention. Full article

Verticillium wilt, caused by Verticillium dahliae, severely threatens various crops and trees worldwide. This study aimed to characterize the function of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum (ER) degradation)-domain-containing protein, VdCUE, in V. dahliae, which exhibits sequence divergence between the defoliating strain XJ592 and the non-defoliating strain XJ511. We generated ∆VdCUE-knockout mutants and evaluated their phenotypes in growth and virulence. Functional analyses included verifying the signal peptide activity of VdCUE, testing its ability to induce cell death or inhibit BAX-induced cell death in Nicotiana benthamiana leaves, and identifying host targets via yeast two-hybrid screening. The ∆VdCUE mutants showed reduced formation of melanized microsclerotia but no other obvious growth defects. Cotton plants infected with the ∆VdCUE mutants exhibited a significantly lower disease index and defoliation rate. VdCUE was confirmed to be secreted via a functional signal peptide, but it neither triggered cell death nor inhibited BAX-induced cell death. Three putative host targets were identified and supported by AI-based three-dimensional structural modeling, including tRNA-specific 2-thiouridylase, peptidyl-prolyl cis-trans isomerase, and 40S ribosomal protein, which may mediate VdCUE-dependent virulence regulation. These findings reveal VdCUE as a key virulence factor in V. dahliae, contributing to our understanding of its pathogenic mechanism. Full article

P23-77 is a thermophilic bacteriophage that infects Thermus thermophilus bacteria. The genome of the virus is enclosed in an icosahedral capsid. This capsid is made of the small major capsid protein (VP16), the large major capsid protein (VP17), and the minor capsid protein (VP11). In addition to these three structural proteins, membrane-associated proteins (VP15, VP19, VP20, VP22, and VP23) have been identified in the virus and may serve as scaffold proteins to help with viral assembly. Previous studies have expressed VP11, VP16, and VP17 in E. coli. A mixture of these proteins can lead to the formation of complexes. However, the potential to express membrane-associated proteins has never been explored. Here, we demonstrated, for the first time, the expression and co-expression of some membrane-associated proteins with capsid (coat) proteins, both in the natural host and in E. coli. Co-expression of these proteins did not result in the assembly of virus-like particles. We explored further strategies to express and purify some of the proteins for future studies. We observed that the insertion of a purification tag (Strep-II tag, but not a histidine tag) significantly reduced the expression levels of some of the proteins. Six of the eight structural proteins were successfully purified to homogeneity using different approaches. We showed that VP20 and VP22 migrated on SDS PAGE gel at sizes larger than their predicted molecular weights. Predicted 3D structures of the proteins show that most of them are helical in nature with disordered regions. The work presented here will help pave the way for the expression and purification of these proteins. This will help determine their 3D structures and may shed light on the requirements for viral assembly. Full article

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) matrix; they form by sticking to a surface, growing in number, spreading out, developing fully, and breaking apart. Biofilm represents a risk of infections linked to healthcare environments. It can be one of the leading causes of nosocomial infections, which can colonize the surface of medical equipment, including respirators, urinary and central venous catheters, prosthetic heart valves, and orthopaedic devices. Biofilm formation in urinary catheters is the most common and plays a role in multidrug resistance, especially in patients with catheter-associated urinary tract infections. The supply of antibiotics for the treatment of biofilm bacteria is still inadequate due to continued antibiotic resistance, and the search for a cure for biofilm bacteria in urinary catheters is still under development. Most research currently focuses on preventing biofilm bacteria from adhering to the urinary catheter. This review discusses biofilm bacteria that form with catheter-associated urinary tract infection mechanisms and pathogenesis. In addition, the factors affecting the biofilm development by catheter-associated urinary tract infections were explained. Full article

Serratia marcescens is a microorganism that exhibits insecticidal activity against various insects, including the migratory fall armyworm (FAW), Spodoptera frugiperda. This article investigates the insecticidal mechanism of S. marcescens through gastric toxicity. The study involved midgut tissue sectioning, hemolymph observation, and microbiome and transcriptome analysis of both infected and uninfected FAW. The findings revealed that S. marcescens effectively disrupted the structure of the midgut, causing midgut shrinkage and rupture, as well as inducing pseudopodia formation in granulocytes. Moreover, it increased the diversity of gut microbiota. Transcriptome analysis indicated an upregulation of metabolic-related genes and tissue repair genes, while there was a downregulation of fat synthesis genes, some immune genes, hormone synthesis genes, etc. The disruption of the midgut structure negatively affects the metabolism and immune function of the FAW, potentially resulting in midgut rupture, systemic sepsis, and ultimately mortality. In conclusion, our study has elucidated the insecticidal mechanism of S. marcescens against the FAW and demonstrated its potential as a biological control agent for managing this pest. Full article

Toxoplasma gondii is a widely distributed intracellular parasite that disrupts host immune and metabolic homeostasis. Although accumulating evidence highlights the role of gut microbiota in parasitic infections, the effects of acute T. gondii infection on host gut microbial ecology remain poorly understood. In this study, metagenomic sequencing technology was used to systematically analyze the composition and functional alterations of the ileal microbiota in BALB/c mice on day 10 post-infection. Compared to uninfected controls, T. gondii infected mice exhibited a significant reduction in microbial diversity and a pronounced shift in community structure. Notably, there was an expansion of Proteobacteria, particularly the Enterobacteriaceae family, alongside a marked decline in beneficial taxa such as Actinobacteria and Bacillota. Functional annotation using the KEGG and CAZy databases revealed enrichment of metabolic pathways related to glycolysis/gluconeogenesis, O-antigen nucleotide sugar biosynthesis, bacterial secretion systems, and biofilm formation-Escherichia coli in the infected microbiota. These findings provide novel insights into the dysbiosis of gut microbiota and host-microbe interactions during acute T. gondii infection. Full article

Macrophages are critical to the formation of infection- and non-infection-associated immune structures such as cancer spheroids, pathogen-, and non-pathogen-associated granulomas, contributing to the spatiotemporal and chemical immune response and eventual outcome of disease. While well established in cancer immunology, the prevalence of using three-dimensional (3D) cultures to characterize later-stage structural immune response in pathogen-associated granulomas continues to increase, generating valuable insights for empirical and computational analysis. To enable integration of data from 3D in vitro studies with the vast bibliome of standard two-dimensional (2D) tissue culture data, methods that determine concordance between 2D and 3D immune response need to be established. Focusing on macrophage migration and oxidative species production, we develop experimental and computational methods to enable concurrent spatiotemporal and biochemical characterization of 2D versus 3D macrophage–mycobacterium interaction. We integrate standard biological sampling methods, time-lapse confocal imaging, and 4D quantitative image analysis to develop a 3D ex vivo model of Mycobacterium smegmatis infection using bone-marrow-derived macrophages (BMDMs) embedded in reconstituted basement membrane (RBM). Comparing features of 2D to 3D macrophage response that contribute to control and resolution of bacteria infection, we determined that macrophages in 3D environments increased production of reactive species, motility, and differed in cellular volume. Results demonstrate a viable and extensible approach for comparison of 2D and 3D datasets and concurrent biochemical plus spatiotemporal characterization of initial macrophage structural response during infection. Full article