Search Results (760)

Staphylococcus aureus (S. aureus) is a common pathogen that threatens healthcare and food safety. Vine tea extract (VTE) and its major active component, dihydromyricetin (DMY), show antibacterial activity. However, their mechanisms of action are not fully understood. In this study, we combined proteomics and lipidomics, with RT–qPCR validation of selected differentially expressed genes, to investigate how DMY and VTE affect S. aureus. Proteomics identified 210 and 535 differentially expressed proteins (DEPs) in the DMY-treated and VTE-treated groups, respectively. These DEPs were mainly enriched in cell wall- and membrane-associated pathways. DMY markedly increased proteins involved in fatty acid degradation, glyceride metabolism, and cell wall synthesis. In contrast, VTE increased proteins related to heme/iron acquisition and cell wall degradation. In addition, VTE altered proteins involved in pyrimidine metabolism and aminoacyl-tRNA biosynthesis, suggesting that non-DMY components in VTE may contribute to the antibacterial activity through additional pathways. Lipidomics further indicated membrane lipid remodeling, including increased fatty acid unsaturation and shorter acyl chain length. Collectively, DMY and VTE may inhibit S. aureus growth by remodeling membrane lipids and disturbing cell wall–cell membrane homeostasis. These findings provide mechanistic support for further development of DMY and VTE as natural antimicrobial candidates. Full article

Dendritic cells (DCs) are essential for antiviral immunity but are also susceptible to HIV-1 infection. Although sensing and restriction pathways in DCs are well described, the mechanisms underlying latent infection and its functional consequences remain unclear. In this study, we performed transcriptomic profiling of monocyte-derived DCs harboring transcriptionally active (Active-HIV) or latent HIV-1 (Latent-HIV) proviruses using a dual-reporter virus. Gene set enrichment analysis revealed suppression of metabolic and stress-modulatory programs in Active-HIV compared to unexposed DCs. In contrast, Latent-HIV showed broad downregulation of pathways, including interferon and innate responses and metabolic programs, indicating a hyporesponsive and dampened antiviral state despite the absence of differentially expressed genes (DEGs). DEG analysis of Active-HIV versus Latent-HIV showed that active transcription associates with cellular stress, cytoskeletal remodeling, and RNA processing. Functional analyses further demonstrated the activation of RNA processes, the suppression of antigen-presentation pathways, and altered membrane and cytoskeletal signaling in Active-HIV. These pathways suggest that transcriptionally active HIV-1 is linked to cellular programs supporting replication, coinciding with a metabolically strained yet immunologically engaged state that may impair antigen presentation. Conversely, latently infected DCs display a hyporesponsive state consistent with proviral silencing. This dichotomy reveals distinct mechanisms of DC dysfunction that may facilitate HIV-1 persistence and immune evasion. Full article

This study investigated the metabolic mechanisms driving physiological functional remodeling in RFM by analyzing plasma biochemical parameters and metabolomic profiles at key peripartum timepoints (21 and 7 d prepartum and 4 h postpartum), integrated with placental and fetal membrane metabolic characteristics. The results revealed that RFM cows exhibited significant negative energy balance (NEB) as early as 21 days before parturition, characterized by elevated plasma levels of non-esterified fatty acids, β-hydroxybutyrate, and malondialdehyde, alongside reduced activity of antioxidant enzymes (GSH-Px, CAT) (p ≤ 0.05). Metabolomic analysis demonstrated persistent lipid metabolism dysregulation, amino acid imbalance, and nucleotide metabolism disturbances in RFM cows from 21 days prepartum to 4 h postpartum, indicating premature mobilization of adipose and muscle tissues. Further metabolomic analyses of the placenta and fetal membranes confirmed that metabolic dysfunction compromises energy supply during parturition, adversely affecting immune homeostasis and extracellular matrix degradation in the placenta and fetal membranes of RFM dairy cows. These physiological dysfunctions have the potential to impede the timely expulsion of fetal membranes after calving. In conclusion, RFM is closely associated with early-onset metabolic dysfunction during the periparturient period, where insufficient energy supply due to NEB, oxidative stress, and immune-endocrine disruptions collectively impair normal fetal membrane detachment. Full article

The increasing contamination of agricultural soils with microplastics (MPs) represents an emerging environmental challenge. While conventional plastics such as low-density polyethylene (LDPE) persist for decades, biodegradable alternatives like polybutylene adipate terephthalate (PBAT) are promoted as eco-friendly solutions. However, their environmental safety for crop plants and soil microbiota remains poorly understood. In this study, we evaluated the effects of LDPE and PBAT microplastics (1% w/w) on the growth and physiological state of winter wheat (Triticum aestivum L.) cultivated in soil, either alone or in combination with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and the plant-beneficial fungus Trichoderma citrinoviride. Growth parameters (root and shoot length and mass), germination index, chlorophyll content, antioxidant enzyme activity, and lipidomic profiles of wheat were assessed. PBAT stimulated biomass accumulation but simultaneously triggered oxidative stress and remodeled membrane phospholipids, indicating physiological disturbance. T. citrinoviride enhanced wheat growth and mitigated oxidative stress under non-contaminated conditions; however, its beneficial effect was generally suppressed in the presence of PBAT and/or 2,4-D. The results suggest that, despite its biodegradability, PBAT may pose a higher phytotoxic potential than conventional LDPE, particularly by altering oxidative balance and membrane lipid composition in wheat. Full article

Phosphatidylserine (PS) externalization is a conserved membrane stress signal that becomes chronically dysregulated in cancer cells and tumor-associated endothelium. In vivo, PS does not exist as a free lipid signal but is presented in specific membrane-associated forms, including apoptotic or stressed cell surfaces, PS-rich extracellular vesicles, and circulating lipid particles. Unlike apoptosis-associated transient PS exposure, malignant PS externalization arises from metabolic rewiring, oxidative stress, epigenetic silencing of flippases, and microenvironmental cues, creating an immunosuppressive interface across the tumor–host boundary. This review synthesizes mechanistic, immunological, and clinical evidence on PS biology, including its roles in tumor immune evasion, extracellular vesicle-mediated systemic suppression, and vascular remodeling. We further summarize the development and evaluation of PS-targeted therapeutic platforms—such as bavituximab, SapC-DOPS/BXQ-350, and PS-directed imaging agents—and highlight their translational potential in combination with radiotherapy, chemotherapy, and checkpoint inhibitors. Chronic PS externalization, as manifested through distinct cellular and vesicular carriers, represents a unifying biomarker of tumor stress, immune suppression, and therapeutic vulnerability, offering a next-generation axis for theragnostic cancer management. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Background/Objectives: Ocular graft-versus-host disease (oGVHD) is a chronic, immune-mediated complication of allogeneic hematopoietic stem cell transplantation that can progress to corneal ulceration or perforation. These cases are often refractory to standard therapy and present a high risk of graft failure after keratoplasty. We report a case of oGVHD-related corneal perforation successfully managed with a novel amniotic membrane-assisted “envelope” technique during corneal transplantation. Case Report: A 42-year-old man with chronic oGVHD and a full-thickness corneal perforation underwent urgent repair with a lamellar patch graft completely wrapped in cryopreserved amniotic membrane, followed by penetrating keratoplasty (PKP) using an amniotic membrane envelope surrounding the donor lenticule. Results: The amniotic membrane provided a 360° biological barrier that isolated graft antigens from the inflammatory environment while supporting epithelial healing and stromal remodeling. Despite recurrent inflammatory episodes and multiple procedures—including cataract extraction, pars plana vitrectomy, and multilayer amniotic membrane transplantation—the graft remained clear and stable at 12-month follow-up, achieving a best-corrected visual acuity of 20/40. Conclusions: The amniotic membrane envelope technique may represent a valuable adjunct in managing high-risk corneal perforations secondary to oGVHD. By combining immune modulation and regenerative support, this approach can enhance tectonic stability, reduce rejection risk, and promote durable surface recovery, potentially delaying or avoiding keratoprosthesis in refractory cases. Full article

Magnetic nanoparticles (MNPs) are widely applied in biomedicine, including bioimaging, drug delivery, and cell tracking. As central mediators of immune surveillance, macrophages phagocytize foreign substances, rendering their interactions with MNPs particularly consequential. During MNP uptake, macrophages undergo cytoplasmic remodeling that can lead to morphological alterations. Although prior studies have predominantly focused on MNP uptake efficiency and cytotoxicity, systematic quantitative assessments of macrophage morphological alterations following MNP treatment remain scarce. In this study, phase-contrast microscopy images of macrophages before and after MNP treatment were analyzed using unsupervised variational autoencoder (VAE)-based frameworks. Specifically, the β-VAE, β-total correlation VAE, and multi-encoder VAE frameworks were employed to extract latent representations of cellular morphology. The analysis revealed that MNP-treated macrophages exhibited pronounced structural alterations, including membrane expansion, central density shifts, and shape distortions. These findings were further substantiated through quantitative evaluations, including effect size analysis, kernel density estimation, latent traversal, and difference mapping. Collectively, these results demonstrate that VAE-based unsupervised learning provides a robust framework for detecting subtle morphological responses of macrophages to nanoparticle exposure and highlights its broader applicability across varied cell types, treatment conditions, and imaging platforms. Full article

The liver stage of Plasmodium infection represents a critical bottleneck in malaria pathogenesis and a unique interface between parasite development and hepatocyte-intrinsic immunity. Recent evidence suggests that hepatocytes do not eliminate liver-stage parasites through canonical xenophagy, as previously assumed, but instead employ a noncanonical autophagy response known as the conjugation of ATG8 to single membranes (CASM). CASM drives rapid lipidation of LC3 onto the parasitophorous vacuole membrane (PVM) via a V-ATPase-ATG16L1-dependent mechanism, thereby activating the Plasmodium-associated autophagy-related (PAAR) response. This process represents a major hepatocyte-intrinsic mechanism that limits early liver-stage parasite development. Plasmodium liver-stage parasites have evolved specialized strategies to counteract this host defense. The PVM proteins UIS3 and UIS4 enable parasite evasion by sequestering LC3 and remodeling perivacuolar actin, thereby preventing endolysosomal fusion and inhibiting PAAR execution. In parallel, parasites selectively exploit host autophagy components—particularly GABARAP paralogs—to activate TFEB, promoting lysosomal biogenesis and improving access to host-derived nutrients. These interactions highlight autophagy as both a protective and parasite-supportive pathway, depending on the molecular context. Understanding how CASM, PAAR, and parasite evasion mechanisms intersect is crucial for designing pathway-selective interventions that amplify hepatocyte-intrinsic clearance while avoiding the inadvertent enhancement of parasite-supportive autophagy programs. Selective modulation of noncanonical autophagy offers a promising avenue for host-directed therapies that restrict liver-stage development while limiting the emergence of antimalarial resistance. This review synthesizes recent advances in the mechanistic interplay between Plasmodium liver stages and hepatocyte autophagy, identifies major knowledge gaps, and outlines future directions for translating these discoveries into therapeutic innovation. Full article

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disorder characterized by submucosal cartilaginous and osseous nodules of the tracheobronchial tree, typically sparing the posterior membranous wall. Involvement of the vocal cords is exceedingly rare and may result in critical airway obstruction. The underlying genetic and molecular mechanisms of TO remain largely unexplored. Case presentation: We report a rare case of TO extending from the vocal cords to the bronchi in a 76-year-old man who initially presented with pneumonia and later developed acute respiratory failure due to severe airway narrowing, necessitating emergency tracheostomy. Bronchoscopy and computed tomography revealed diffuse calcified nodules involving the anterior and lateral airway walls, including the subglottic region. Histopathology demonstrated chronic inflammatory cell infiltration with squamous metaplasia. To explore the molecular basis of this condition, whole-genome sequencing (WGS) was performed using peripheral blood samples—the first such application in TO. WGS identified 766 germline mutations (including 27 high-impact variants) and 66 structural variations. Candidate genes were implicated in coagulation and inflammation (KNG1), arachidonic acid metabolism and extracellular matrix remodeling (PLA2G4D), ciliary dysfunction and mineralization (TMEM67), vascular calcification (CDKN2B-AS1), smooth muscle function (MYLK4), abnormal calcification (TRPV2, SPRY2, BAZ1B), fibrotic signaling (AHNAK2), and mucosal barrier integrity (MUC12/MUC19). Notably, despite systemic germline mutations, calcification was restricted to the airway. Conclusions: This case highlights that TO with vocal cord involvement can progress beyond a benign course to cause life-threatening airway obstruction. Integrating clinical, histological, and genomic findings, we propose a novel pathophysiological model in which systemic genetic susceptibility interacts with local immune cell infiltration and fibroblast-driven extracellular matrix remodeling, resulting in airway-restricted dystrophic calcification. This first genomic characterization of TO provides new insights into its pathogenesis and suggests that multi-omics approaches may enable future precision medicine strategies for this rare airway disease. Full article

Tendon injuries, whether resulting from trauma, repetitive strain, or degenerative conditions, present a considerable clinical challenge. The natural healing process, which involves inflammatory, proliferative, and remodeling phases, is often inefficient and leads to excessive scar tissue formation, ultimately compromising the mechanical properties of the tendon compared to its native state. This highlights the critical need for innovative approaches to enhance tendon repair and regeneration. Leveraging the regenerative properties of human amniotic membrane (HAM) and electrospun PCL/gelatin nanofibers, this study aims to develop and assess a novel composite scaffold in a rodent model to facilitate improved tendon healing. This prospective experimental study involved 12 male Sprague Dawley rats (250–300 g), randomly assigned to three groups: Group A (No Treatment/No HAM), Group B (HAM-treated), and Group C (HAM with electrospun nanofibers, HAM-NF). A surgically induced tendon injury was created in the left hind limb, while the right limb served as a control. Following surgery, HAM and HAM-NF (0.5 cm²) were applied to the respective treatment groups, and tendon healing was assessed after six weeks. Gait analysis, including stride length and toe-out angle, was conducted both pre-operatively and six weeks post-operatively. Macroscopic and microscopic evaluations were performed on harvested tendons to assess regeneration, comparing treated groups to the controls. Gait analysis demonstrated that the HAM-NF group showed a significant increase in stride length from 11.70 ± 1.50 cm to 12.79 ± 1.71 cm (p < 0.05), with only a modest change in toe-out angle (14.58 ± 2.96° to 16.27 ± 2.20°). In contrast, the No Treatment group exhibited reduced stride length (10.27 ± 2.17 cm to 8.40 ± 1.67 cm) and a marked increase in toe-out angle (16.33 ± 4.51° to 26.47 ± 5.81°, p < 0.05), while the HAM-only group showed mild changes in both parameters. Macroscopic evaluation showed a significant difference in tendon healing. HAM-NF group had the highest score that indicates more rapid tissue regeneration. Histological analysis after 6 weeks showed that tendons treated with HAM-NF achieved a mean histological score of 5.54 ± 4.14, closely resembling the uninjured tendon (6.67 ± 1.63), indicating substantial regenerative potential. The combination of human amniotic membrane (HAM) and electrospun nanofibers presents significant potential as an effective strategy for tendon regeneration. The HAM/NF group exhibited consistent improvements in gait parameters and histological outcomes, closely mirroring those of uninjured tendons. These preliminary results indicate that this biomaterial-based approach can enhance both functional recovery and structural integrity, providing a promising pathway for advanced tendon repair therapies. Full article

The intensive use of chemical fertilizers in soybean (Glycine max) cultivation has caused significant environmental degradation, underscoring the urgent need for sustainable alternatives. In Argentina, Bradyrhizobium japonicum E109 is widely employed as a liquid bioinoculant, yet its efficiency is limited by loss of viability during storage. This study investigated the physiological and biophysical mechanisms underlying membrane adaptation of B. japonicum E109 under storage stress and evaluated lipid supplementation as a stabilization strategy. During six months of liquid storage at 28 °C, bacterial viability (Log CFU mL⁻¹) declined from 10.0 to 7.7, accompanied by morphological collapse and a 29% reduction in membrane fluorescence polarization, indicating increased fluidity. Fatty acid analysis revealed a drastic decrease of unsaturated 18:1 (from 80% to 40%) and a 300–400% increase in saturated 18:0, reducing the U/S ratio from 4 to 1. Spectral phasor analysis confirmed a shift in the lipid microenvironment from an ordered to a disordered state. Supplementation with 400 µM of stearic acid (18:0) restored membrane rigidity, lowered the U/S ratio to 1.5, and improved thermal tolerance. After one month of storage, 18:0-treated cultures maintained 8.0 Log CFU mL⁻¹ and preserved viability after exposure to 37 °C, whereas controls dropped to 3.8 Log CFU mL⁻¹. These results identify lipid remodeling as a key determinant of B. japonicum stability and demonstrate that exogenous 18:0 supplementation mimics natural adaptation, preventing membrane fluidization and enhancing inoculant shelf-life. This lipid-biophysical approach provides a rational framework for developing next generation, more resilient rhizobia formulations for sustainable agriculture. Full article

Lipid raft-associated gangliosides facilitate the early stages of SARS-CoV-2 entry by triggering the exposure of the receptor-binding domain (RBD) within the trimeric spike protein, which is initially sequestered. A broad range of in silico, cryoelectron microscopy and physicochemical approaches indicate that the RBD becomes accessible after a ganglioside-induced conformational rearrangement originating in the N-terminal domain (NTD) of one protomer and propagating to the neighboring RBD. We previously identified a triad of amino acids, Q134-F135-N137, as a strictly conserved element on the NTD. In the present review, we integrate a series of structural and experimental data revealing that this triad may act as a conformational transducer connected to a chain of residues that are capable of transmitting an internal conformational wave within the NTD. This wave is generated at the triad level after physical interactions with lipid raft gangliosides of the host cell membrane. It propagates inside the NTD and collides with the RBD of a neighboring protomer, triggering its unmasking. We also identify a chain of aromatic residues that are capable of controlling electron transfer through the NTD, leading us to hypothesize the existence of a dual conformational/quantum wave. In conclusion, the complete conservation of the Q134-F135-N137 triad despite six years of extensive NTD remodeling underscores its critical role in the viral life cycle. This triad represents a potential Achilles’ heel within the hyper-variable NTD, offering a stable target for therapeutic or vaccinal interventions to disrupt the conformational wave and prevent infection. These possibilities are discussed. Full article

Liver fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins as a wound-healing response to chronic liver injury, leading to tissue scarring and organ dysfunction. Natural compounds, including phytonutrients and polyphenols, have been shown to exert protective effects by reducing profibrotic biomarkers in vitro and in vivo models. Here, we provide the first evidence that the polyphenol hesperidin (HE) can counteract the onset of fibrotic responses in an ex vivo mouse liver fibrosis model induced by Transforming Growth Factor-β1 (TGF-β1) (5 ng/mL). Notably, HE drives early ECM remodeling in the fibrotic mouse liver tissue. Fibrosis-related parameters were assessed at both the transcriptional and translational levels after treatment with HE at increasing concentrations of 50, 75, and 100 µg/mL. Interestingly, HE at 75 µg/mL exerted the strongest beneficial effect, significantly decreasing the gene expression of α-SMA, SERPINH-1, FN-1, VIM and COL1A1 and counteracting the TGF-β1-induced upregulation of key fibrotic markers, including α-SMA, COL1A2, and VIM, reflecting its capacity to attenuate myofibroblast activation and ECM production and modulating membrane lipid peroxidation. Furthermore, HE inhibited SMAD2 phosphorylation, suggesting that its antifibrotic activity may involve the modulation of the TGF-β/SMAD signaling pathway. Moreover, it promoted an anti-inflammatory response, due to a decrease in IL-1β and IL-6 expression. Our study highlights the potential of the ex vivo model as a platform for evaluating the antifibrotic efficacy of natural molecules, and it suggests significant translational implications and new opportunities for developing innovative therapeutic strategies. Full article

Soil salinity is a major constraint on global crop production, disrupting photosynthesis, ion homeostasis, and growth. Beyond the roles of classic osmoprotectants and antioxidant enzymes, flavonoids have emerged as versatile mediators of salt stress tolerance at the interface of redox control, hormone signaling, and developmental plasticity. This review summarizes current evidence on how salinity remodels flavonoid biosynthesis, regulation, and function from cellular to whole-plant scales. We first outline the phenylpropanoid–flavonoid pathway, with emphasis on transcriptional control by MYB, bHLH, and NAC factors and their integration with ABA, JA, and auxin signaling. We then discussed how post-synthetic modifications such as glycosylation and methylation adjust flavonoid stability, compartmentation, and activity under salt stress. Functional sections highlight roles of flavonoids in ROS scavenging, Na⁺/K⁺ homeostasis, membrane integrity, and the modulation of ABA/MAPK/Ca²⁺ cascades and noncoding RNA networks. Spatial aspects, including root–shoot communication and rhizosphere microbiota recruitment, are also considered. Based on this synthesis, we propose a flavonoid-centered stress network (FCSN), in which specific flavonoids function as key nodes that connect metabolic flux with hormonal crosstalk and stress signaling pathways. We argue that reconceptualizing flavonoids as central stress network regulators, rather than generic antioxidants, provides a basis for metabolic engineering, bio-stimulant design, and breeding strategies aimed at improving crop performance on saline soils. Full article