Search Results (1,420)

Background and Clinical Significance: Eczema herpeticum (EH), or Kaposi’s varicelliform eruption, is a dermatologic emergency characterized by the abrupt onset of painful monomorphic vesiculopustules with potential for rapid dissemination. Atopic dermatitis (AD) is the main predisposing condition due to skin barrier dysfunction and impaired antiviral immunity. Early recognition is essential because delayed treatment may result in avoidable complications, including ocular involvement and systemic disease. Current recommendations emphasize immediate systemic acyclovir based on clinical suspicion, without awaiting laboratory confirmation. Case Presentation: A 4-year-old boy with moderate AD presented with a 6-day history of fever, malaise, and a rapidly progressive vesiculopustular eruption involving both eczematous and previously unaffected skin. The patient had a recent AD flare, molluscum contagiosum, and had initially received oral amoxicillin-clavulanate for presumed bacterial superinfection without improvement. Physical examination revealed widespread painful monomorphic umbilicated vesiculopustules with hemorrhagic crusts and mild bilateral conjunctival injection. Oral acyclovir was initiated within one hour of evaluation. Laboratory investigations showed mild inflammatory abnormalities without renal or hepatic involvement. Because lesional PCR was unavailable, complementary blood-based investigations were performed; HSV-1 IgM serology and blood PCR provided additional retrospective findings compatible with HSV-1 infection, while Gram stain and bacterial cultures were negative. Fever resolved within 24 h, no new lesions developed after day 3, and complete re-epithelialization was achieved after a 10-day course of acyclovir. Conclusions: This case highlights the importance of bedside recognition of eczema herpeticum in children with atopic dermatitis, particularly when painful monomorphic vesiculopustules are accompanied by fever and rapid dissemination. Early initiation of systemic acyclovir based on clinical suspicion remains the cornerstone of management. While PCR from vesicular lesions is the preferred diagnostic test when available, laboratory confirmation should not delay treatment. This report also illustrates common real-world challenges, including initial misdiagnosis as bacterial infection and limited access to optimal virological testing. Full article

Regucalcin (RGN), also known as senescence marker protein-30, is a calcium-binding protein without an EF-hand motif that regulates intracellular calcium homeostasis and Ca²⁺-dependent enzyme activity. Its expression is reduced in tumor tissue relative to matched normal tissue across several cancer types, and restoring RGN in cancer cell lines suppresses proliferation, migration, and invasion through cell cycle arrest, reduced expression of matrix metalloproteinases and epithelial–mesenchymal transition regulators, and transcriptional reprogramming involving p53, p21, Rb, c-myc, and β-catenin. Attention has more recently turned to RGN outside the cell. RGN is detectable in serum and interstitial fluid, and recombinant RGN applied to cancer cells reproduces much of the suppression seen upon intracellular overexpression, which has prompted the proposal that extracellular RGN acts within the tumor microenvironment (TME). That proposal, however, rests on evidence that remains incomplete. RGN carries no classical signal peptide and its route of release is undefined; it has been reported in extracellular vesicle preparations but has not been shown to be a bona fide vesicular cargo; no receptor or proximal binding partner has been identified; and its effects on the non-malignant compartment of the TME—fibroblasts, immune cells, and endothelium—have not been tested directly. Here, we review the tumor-suppressive activity of RGN, distinguish demonstrated findings from inferred ones, and outline the experiments required to determine whether extracellular RGN constitutes a signaling axis in the TME or a pharmacological property of a recombinant protein. Full article

Objectives: Heart failure (HF) arises from multiple interrelated pathological processes. Among these, lysosomal impairment and loss of autophagic homeostasis are increasingly recognized as important contributors to myocardial damage and ventricular remodeling. This study sought to identify lysophagy-associated signature genes in HF and to define their biological roles, cellular origins, and potential diagnostic relevance. Methods: Bulk myocardial transcriptome datasets, including GSE16499, GSE57338, and GSE76701, were integrated with the human cardiac single-cell dataset GSE145154. Differential expression analysis was first performed to identify lysophagy-related differentially expressed genes (DEGs). Candidate hub genes were then screened using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression. Functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), immune infiltration assessment, single-cell transcriptomic mapping, and regulatory network analysis were subsequently conducted. The expression profiles of the selected genes were validated in a murine HF model, and VAMP8 overexpression assays were performed in H9c2 cells. Results: Five hub genes, namely VAMP8, STX2, MCOLN1, DERL1, and PTP4A2, were consistently and markedly decreased in failing myocardial tissue. These genes were mainly linked to SNARE-dependent vesicle trafficking and lysophagy regulation. A diagnostic model incorporating these hub genes demonstrated good discriminatory performance in both the training dataset and a small independent validation cohort, supporting further evaluation of their potential diagnostic value. Single-cell analysis further indicated that these genes were primarily enriched in cardiac FOLR2⁺ tissue-resident macrophages (TRMs). Pseudotime and cell–cell communication analyses associated this module with FOLR2⁺ TRM cell states and predicted interactions with cardiac stromal cells. In the HF mouse model, the mRNA levels of all five hub genes were decreased, with concurrent reductions in VAMP8, MCOLN1 and DERL1 protein expression. In Ang II/LLOMe-induced H9c2 cells, VAMP8 overexpression was associated with reduced cardiomyocyte injury, attenuation of changes in the abundance of lysosome- and autophagy-related proteins, and fewer ultrastructural abnormalities, suggesting a potential cardioprotective effect. Conclusions: VAMP8, STX2, MCOLN1, DERL1, and PTP4A2 were identified as candidate molecular markers of HF that reflect alterations in a lysophagy- and vesicular-transport-related program associated with FOLR2⁺ tissue-resident macrophages. These findings provide new insights into immune-microenvironment remodeling in HF and suggest potential directions for mechanistic and therapeutic investigations. Full article

Melanoma dissemination depends on tumor cell plasticity, extracellular matrix remodeling, and adaptive signaling pathways that promote survival, migration, invasion, and therapeutic resistance. In this study, we investigated the antitumor effects of the plant-derived Kunitz-type protease inhibitor EcTI using both in vitro B16F10-Nex2 melanoma cells and an in vivo murine melanoma model, focusing on adhesion-dependent signaling, autophagy, mitochondrial dysfunction, and regulated cell death. EcTI was efficiently internalized by melanoma cells and showed partial colocalization with lysosomal and mitochondrial compartments, suggesting intracellular trafficking toward these organelles. Treatment reduced cell adhesion to extracellular matrix proteins, particularly fibronectin and laminin, and inhibited migration, invasion, and angiogenic signaling. These effects were associated with modulation of the adhesion-dependent FAK/Src/ERK signaling axis and decreased MMP-9 activity. EcTI also disrupted autophagy, as indicated by accumulation of acidic vesicular organelles, increased LC3-II levels, and modulation of ULK1, Ambra1, and Beclin-1 signaling. In parallel, EcTI induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, intracellular Ca²⁺ dysregulation, and increased reactive oxygen species production. These alterations triggered regulated cell death involving apoptotic and necroptosis-like mechanisms. Importantly, EcTI significantly suppressed tumor growth in vivo without detectable systemic toxicity and modulated inflammatory mediators associated with tumor progression. Overall, these findings demonstrate that EcTI exerts broad antitumor activity by modulating multiple signaling pathways associated with melanoma progression and represents a promising therapeutic candidate for melanoma treatment. Full article

A 13-year-old German Riding Pony mare was referred for evaluation of progressive respiratory noise and mixed dyspnoea, which rapidly deteriorated to respiratory distress. Clinical examination revealed marked rattling inspiratory and expiratory tracheal sounds and severe, rattling, vesicular lung sounds. Arterial blood gas analysis demonstrated moderate hypoxaemia (partial pressure of arterial oxygen 76 mmHg at rest). Upper airway endoscopy identified a pink, cauliflower-like pedunculated mass originating from the dorsal tracheal wall approximately 15 cm cranial to the tracheal bifurcation, causing an estimated 60% luminal obstruction. The mass was successfully removed via transendoscopic electrosurgical excision. However, complete tumour-free margins were not achieved. Histopathological examination revealed the diagnosis of leiomyosarcoma. Following surgery, the mare exhibited rapid clinical improvement. Peri-operative treatment included antimicrobial, anti-inflammatory, and bronchodilatory therapy. A follow-up endoscopy one month after surgery showed adequate healing of the surgical site. A small, vascularized tissue structure within the scar tissue, considered suspicious for residual tumour growth, was identified. However, no significant progression was observed during a follow-up examination seven months postoperatively. This case highlights tracheal leiomyosarcoma as a rare differential diagnosis in horses with respiratory distress and describes transendoscopic electrosurgical excision as a feasible therapeutic option. Full article

Early detection of acute lung injury (ALI) remains challenging, as conventional diagnostics rarely capture initial molecular changes. We therefore examined whether extracellular vesicles (EVs) in bronchoalveolar lavage fluid (BALF) can detect early regional injury and distinguish initial stress mechanisms in a porcine ALI model. Unilateral ALI was induced using Triton X-100, followed by six hours of mechanical ventilation with either fixed positive end-expiratory pressure (PEEP) at 5 cmH₂O or transpulmonary-pressure (TPP)-guided PEEP. Spatially separated BALF sampling allowed direct comparison between injured and contralateral mechanically stressed lungs. EV concentration and size distribution were quantified by nano-flow cytometry, while vesicular identity was confirmed by transmission electron microscopy and tetraspanin dot blot analyses. Furthermore, EV metrics were related to corresponding histologic injury scores. Across both PEEP strategies, EV concentration was markedly higher in both directly injured and contralateral mechanically stressed lungs compared with sham controls, indicating alveolar stress beyond the primary injury site. Median EV size differed significantly by injury type and correlated inversely with histologic injury, particularly with alveolar neutrophil infiltration. BALF-derived EV concentration and size may therefore provide complementary, spatially resolved molecular readouts of early ALI. Full article

The renin–angiotensin–aldosterone system (RAAS) is a fundamental regulator of blood pressure, electrolyte balance, fluid homeostasis, and tissue remodeling. The discovery of the prorenin receptor (PRR), the protein encoded by the ATP6AP2 gene, has substantially expanded the classical RAAS paradigm by demonstrating that prorenin possesses biological activity beyond its proteolytic conversion to renin. Binding of renin or prorenin to PRR enhances local angiotensin II (Ang II) generation while simultaneously initiating Ang II-independent intracellular signaling pathways, including ERK1/2, mitogen-activated protein kinases, PI3K/Akt, transforming growth factor-β, and nuclear factor-κB, thereby promoting inflammation, oxidative stress, fibrosis, cellular proliferation, and extracellular matrix accumulation. Beyond its receptor function, PRR serves as an essential accessory component of the vacuolar H+-ATPase (V-ATPase) complex, regulating vesicular acidification, lysosomal function, autophagy, protein trafficking, cellular metabolism, and Wnt/β-catenin signaling. These diverse functions explain its indispensable role in embryonic development, cell differentiation, and tissue homeostasis, as evidenced by the embryonic lethality associated with ATP6AP2 gene deficiency. PRR is predominantly localized to intracellular organelles, including the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, and autophagic vesicles, although membrane-bound and soluble forms also contribute to physiological and pathological processes. Increasing evidence implies dysregulated PRR signaling in the development and progression of hypertension, cardiovascular disease, chronic kidney disease, diabetes, obesity, and other metabolic disorders. This review summarizes current advances in PRR and soluble PRR biology, discusses unresolved mechanistic and translational questions, and evaluates the potential of PRR as a biomarker and therapeutic target for cardiovascular, renal, and metabolic diseases. Full article

Filoviruses cause highly lethal infectious diseases with hemorrhagic symptoms and extremely high fatality rate (up to 90%). Although two vaccines against Ebola virus (EBOV) are licensed for application in endemic areas, vaccines against other filoviruses (SUDV, BDBV, MARV) are still at pre-clinical or clinical stages. The development of vaccines requires protective efficacy studies using animal models of infection. However, animal studies using wild-type filoviruses require maximum biosafety level (BSL-4), which hinders filoviral vaccine advancement. In this study, we developed a surrogate animal model of EBOV-, SUDV-, BDBV- and MARV- GP-mediated entry using Ifnar1-knockout (-/-) mice and recombinant vesicular stomatitis viruses (rVSVs), carrying a genetic sequence of filoviral glycoprotein (GP) and pseudotyped with correspondent GP. We showed that rVSV-EBOV-GP was 100% lethal for Ifnar1(-/-) mice after inoculation by multiple routes, and its active propagation was within 24 h post-infection. We performed dose-dependent lethality assessment in small groups to estimate median lethal doses for rVSV-EBOV-GP, rVSV-SUDV-GP, rVSV-BDBV-GP, rVSV-MARV-GP in Ifnar1-knockout mice and showed high viral load in liver and immune cell reservoirs. The developed models contribute to safe and effective research of filoviral vaccines and therapeutic antibodies under BSL-2 conditions. Full article

Papua New Guinea (PNG) remains one of the least studied regions in the Southwest Pacific, and the tectono-magmatic evolution of extensive areas such as the Fly Platform remains poorly constrained. This study presents the first investigation of basaltic volcanism on the Fly Platform based on the discovery of two previously unrecognized volcanic centres, Meahill and Yemsigi, located approximately 13 km apart along a northeast–southwest alignment. Integrated field observations and petrographic studies reveal contrasting eruptive and emplacement histories. Yemsigi is characterized by coherent porphyritic basalts, whereas Meahill comprises highly vesicular porphyritic to micro-porphyritic basalts indicative of explosive volcanism. Mineral chemistry and whole-rock geochemistry indicate that both basalt suites were derived from a common magma source. The K–Ar age of 0.57 ± 0.09 Ma for the Meahill basalts suggests that volcanism on the Fly Platform represents a late-stage magmatic event that post-dates the Maramuni Arc and Central Highlands magmatism on the PNG mainland. These findings provide the first evidence for Middle Pleistocene volcanism on the Fly Platform and place new constraints on the tectono-magmatic evolution of southern PNG. Full article

Background/Objectives: Time-varying low-frequency electromagnetic fields (LF-EMFs), including pulsed electromagnetic fields (PEMFs) and sinusoidal low-frequency electromagnetic fields, have been investigated as modulators of tissue repair and vascular remodeling. Although numerous studies report pro-angiogenic effects in endothelial systems, the underlying mechanisms remain incompletely understood. This review synthesizes evidence for LF-EMF-induced endothelial angiogenesis and evaluates emerging mechanistic explanations. Methods: Literature was identified through searches of PubMed, Web of Science, and Google Scholar through March 2026. Peer-reviewed studies emphasizing in vitro endothelial angiogenesis models were prioritized, with selected in vivo studies included when relevant to mechanistic interpretation. The review was conducted as a narrative synthesis rather than a systematic review or meta-analysis. Results: Experimental evidence indicates that LF-EMF exposure can enhance endothelial proliferation, migration, sprouting, tube formation, and survival across diverse model systems. Reported mechanisms include modulation of growth factor signaling, calcium-dependent pathways, nitric oxide production, cytoskeletal remodeling, and mechanotransduction. Reexamination of early ultrastructural studies suggests that membrane ruffling, vacuole formation, and vesicular structures observed following LF-EMF exposure may be interpreted within the framework of macropinocytosis and vesicular trafficking, providing a potential mechanistic link between electromagnetic stimulation and endothelial morphogenesis. Conclusions: Current evidence supports the conclusion that LF-EMFs can modulate key endothelial processes involved in angiogenesis and vascular remodeling. Membrane trafficking and macropinocytosis provide a biologically plausible framework linking historical observations with contemporary endothelial cell biology, although direct experimental validation is needed. Future progress will require standardized exposure paradigms and mechanistic studies using physiologically relevant angiogenesis models. Full article

Background: Niosomes are spherical, non-ionic surfactant-based vesicular carriers structured as lipid bilayers that are widely utilised in pharmaceutical and cosmetic research for integration into topical formulations like gels and creams. Objective: This study presents a novel contribution concerning the preparation of niosomes using a mixture of distinct Span and Tween non-ionic surfactants and diverse biomolecules. Methods: In this context, novel formulations of niosomes have been prepared by including into their composition a mixture of Span 80 and Tween 20 (in order that HLB = 8.42) non-ionic surfactants with cholesterol (Chol) in a Span 80:Tween 20:Chol = 2:1:1 molar ratio, which is meant to optimise their rigidity and stability, respectively. Their preparation was achieved through three methods: probe sonication, bath sonication and thin-film hydration (TFH). Additionally, the samples were analysed by means of Fourier-Transform Infrared Spectrometry (FT-IR). On the other hand, the antioxidant capacity profile of the formulas of interest was assessed by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical reduction method. The investigated bioactive molecules were ascorbic acid (AA) and a yellow dye of fungal origin, previously extracted from an Epicoccum nigrum strain. Results: The average particle size of the niosomes ranged from 2.771 ± 0.808 to 3.397 ± 0.917 μm. Furthermore, high entrapment efficiency was observed for both AA (92.71 ± 0.01%) and the fungal dye (83.54 ± 0.08%), particularly in the formulations prepared through an optimised procedure. The gathered results illustrated that the highest DPPH radical scavenging percentage (48.71 ± 0.05%) occurred when the bath sonication technique was applied. Conclusions: These findings demonstrate that the entrapment of active biomolecules depends on the preparation methods utilised. Furthermore, employing fungal dyes represents a promising strategy to simultaneously enhance both the antioxidant and dyeing capacities exhibited by the formulated niosomal colloidal systems. Full article

Extracellular vesicles (EVs) have emerged as fundamental pillars of intercellular communication, acting as primary mediators of the bidirectional biochemical crosstalk within the integrated bone–muscle unit. This review provides a comprehensive synthesis of EV-mediated signaling across the bone–muscle axis, offering a side-by-side mapping of vesicular biogenesis, cargo composition, and functional roles in both tissues. Under physiological conditions, skeletal muscle- and bone-derived EVs orchestrate tissue homeostasis, adaptations to physical exercise, myogenesis, and bone remodeling by transferring unique molecular cargos of proteins and specific microRNAs. However, aging induces a profound remodeling of the EV secretome toward a senescent profile characterized by harmful vesicular factors. This dysfunctional vesicular signaling impairs both muscle regeneration and osteogenesis, directly contributing to the pathogenesis of interconnected age-related disorders like sarcopenia, osteoporosis, and osteosarcopenia. Concurrently, circulating EVs represent valuable, minimally invasive biomarkers for early diagnosis. On the therapeutic front, this review critically evaluates emerging EV-based approaches, utilizing mesenchymal stem cell-derived, bioengineered, or biomaterial-incorporated EVs, offering promising, low-immunogenic alternatives to cell transplantation to enhance musculoskeletal tissue repair and restore bone–muscle homeostasis. Despite persisting technical challenges regarding large-scale production and standardization, targeting or leveraging EV-mediated communication represents one of the most innovative and revolutionary strategies to counteract age-related musculoskeletal decline. By unifying physiological mechanisms, age-related molecular reprogramming, and therapeutic engineering across both muscle and bone into a single narrative, this review provides a comprehensive framework to guide future research and clinical translation in musculoskeletal health. Full article

Rab proteins are key members of the Ras superfamily that regulate vesicular trafficking in eukaryotic cells, ensuring accurate cargo transport and cellular homeostasis. To investigate the functional role of Rab proteins, RNA interference (RNAi) was employed to silence LmRab11A in Locusta migratoria, followed by integrated transcriptomic and metabolomic analyses. Transcriptomic profiling identified 54 downregulated and 71 upregulated genes upon LmRab11A knockdown. Based on Log2 fold change values and statistical significance, 15 downregulated genes were selected for further analysis. RT-qPCR validation confirmed that 9 of these genes were significantly downregulated following LmRab11A silencing. Subsequent RNAi-mediated knockdown of these 9 genes revealed that silencing of only LOCMI11062 (β-tubulin) resulted in 100% mortality and severe morphological defects in locust nymphs, indicating its critical role in development. Metabolomic analysis identified 11 significantly altered metabolites, including 8 exhibiting increased abundance and 3 exhibiting decreased abundance. Spearman correlation analysis between the 9 downregulated genes and the altered metabolites suggested potential associations between 6 metabolites and specific genes. Collectively, these findings demonstrate that suppression of LmRab11A disrupts downstream gene expression and alters the metabolite network, thereby impairing growth and development. Full article

Essential oils are widely recognised for their bioactive properties and therapeutic effects. Despite their potential, their practical application is often limited by intrinsic physicochemical constraints, including volatility, chemical instability, hydrophobicity and, most of all, compositional complexity. The development of effective delivery systems is therefore key to stabilise essential oil constituents, improve bioavailability and enable controlled release. Here we provide a comprehensive analysis of formulation strategies for essential oils, focusing on emulsification and encapsulation techniques. Emulsion-based delivery systems, including nanoemulsions and microemulsions, are discussed in relation to their interfacial behaviour, surfactant interactions and preparation methods. In parallel, encapsulation systems, such as vesicular systems, lipid-based carriers, polymeric nanoparticles and inclusion complexes, are evaluated according to their structural characteristics, protective capabilities, encapsulation efficiencies and release profiles. Collectively, these approaches are examined in the context of their influence on the stability, functionality, and overall performance of essential oil formulations. Emphasis is placed on essential oil-specific challenges that arise when preparing a formulation, especially the heterogenous nature of their chemical composition and its impact on physicochemical properties, partitioning, loading capacity, stability and safety. To contextualise these principles, representative examples of essential oil-based formulations (e.g., thyme, clove, rosemary and mint), formulated singular metabolites (e.g., carvacrol, eucalyptol, limonene and eugenol) and essential oil patent applications (>20,000) and products are outlined to illustrate behaviour and performance within the respective delivery system. Overall, the fundamental design considerations that guide the rational selection, preparation and evaluation of formulations for essential oil-based applications are discussed. Considerations for future directions are also outlined. Full article

Most patients with solid tumors do not respond to immune checkpoint blockade, and inadequate T cell infiltration of the tumor parenchyma is the dominant mechanism of primary resistance. Oncolytic viruses address this problem by a distinct route: they replicate selectively within tumor cells, produce immunogenic cell death, and convert infected cells into local sources of any encoded transgene. Most armed designs to date have carried cytokine or checkpoint-antibody payloads, and chemokines have attracted comparatively little attention despite bearing directly on the trafficking bottleneck. This review synthesizes the preclinical literature on chemokine-armed oncolytic viruses across three receptor axes: CXCR3 (CXCL9, CXCL10, CXCL11), CCR5 (CCL5/RANTES), and CCR7 (CCL19). The accumulated evidence indicates that therapeutic outcome depends less on the chemokine payload itself than on the interaction between payload and viral backbone. CXCL11 outperforms its sister CXCR3 ligands not through intrinsic potency but because it is non-redundant with the endogenous chemokines induced by vesicular stomatitis virus and vaccinia, and because it largely escapes proteolytic cleavage by dipeptidyl peptidase 4 (DPP4). CCL5 has shown the most consistent activity in dual-payload designs that pair chemotaxis with a T cell survival cytokine such as IL-15. CCL19, which addresses lymphoid organization rather than effector recruitment, rests on a single published construct. One evidence gap is central: no head-to-head comparison of chemokine payloads within a single viral platform has been published. We therefore propose a translational decision framework that aligns chemokine selection with the immune contexture of the target tumor. Full article