Search Results (1,665)

Background/Objectives: Acute generalized exanthematous pustulosis (AGEP) is a severe drug-induced cutaneous reaction characterized by the abrupt onset of sterile pustules, fever, neutrophilia, and a T cell-mediated type IVd hypersensitivity response. This narrative review synthesizes current evidence on pharmacological triggers, immunopathogenic mechanisms, diagnostic criteria, and differential diagnosis to provide a clinically oriented framework. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and SpringerLink for studies published between 2000 and 2025, complemented by selected clinical reference sources. Studies addressing clinical features, immunological pathways, pharmacovigilance signals, and diagnostic tools for AGEP were included. Synthesis of Evidence: β-lactam antibiotics remain the most frequent triggers, while increasing associations have been reported with hydroxychloroquine, targeted therapies, immune checkpoint inhibitors, psychotropic agents, and vaccines. Immunopathogenesis is driven by IL-36 activation, CXCL8/IL-8–mediated neutrophil recruitment, and IL36RN mutations, explaining overlap with pustular psoriasis. Diagnostic accuracy improves through integration of drug latency, clinical morphology, histopathology, biomarkers, and standardized tools such as the EuroSCAR score. Conclusions: AGEP is a complex pustular reaction induced by diverse drugs and amplified by IL-36-mediated inflammation. Accurate diagnosis requires a multidimensional approach supported by structured algorithms and robust pharmacovigilance to identify evolving drug-associated patterns. Full article

Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD), as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Recent phase II/III trials in steroid-refractory (SR)-aGVHD have demonstrated overall response rates ranging from 48 to 71%. Efficacy appears particularly enhanced in pediatric patients and with early MSC administration. Across studies, MSC therapy shows a favorable safety profile; however, heterogeneity in response and inconsistent survival outcomes remain notable limitations. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials. Full article

Segment regeneration in earthworms is a remarkable example of postembryonic morphogenesis, yet its fidelity and cellular mechanisms remain incompletely understood. The present study investigated posterior segment regeneration in adult specimens of the earthworm model Eisenia andrei from wound closure to the 5th postoperative week using anatomical, histological, and ultrastructural approaches. Rapid wound closure occurred through fusion of the cut edges of the body wall and midgut without direct involvement of coelomocytes. The regeneration blastema consisted of dedifferentiated epithelial and muscle cells, innervated by fibers from the last intact ventral nerve cord ganglion. Coelomocytes accumulated in the last intact segments and were primarily involved in debris clearance. Notably, early regenerating tissues lacked collagen fibers, which appeared only after the third postoperative week and remained sparse until the fifth week, whereas original segments exhibited intense, region-specific collagen deposition. Transmission electron microscopy revealed characteristic cytological changes in distinct stages of body wall regeneration, including muscle dedifferentiation and the emergence of collagen-producing fibroblasts. These findings indicate that early cell migration, proliferation, and orientation in the blastema proceed independently of collagen and that collagen functions as a delayed structural scaffold, supporting tissue integrity without impeding regeneration. Importantly, no scar formation was observed between old and new tissues, resembling scarless fetal wound healing. Overall, we clarified previously controversial cellular mechanisms and propose a new, comprehensive model for the early stages of segment regeneration. Our results highlight that coordinated dedifferentiation, spatiotemporal extracellular remodeling, and delayed collagen deposition underlie effective, scar-free regeneration in earthworms, offering insights into conserved mechanisms of regenerative repair across metazoans and potential strategies for enhancing tissue regeneration in mammals. Full article

G protein-coupled receptors (GPCRs) are key regulators of cerebrovascular function, integrating vascular, inflammatory, and neuronal signaling within the neurovascular unit (NVU). Increasing evidence suggests that GPCR actions are highly dependent on cell type, signaling pathway, and disease stage, leading to distinct, and sometimes opposing, effects during acute ischemic injury and post-stroke recovery. In this review, we reorganize GPCR signaling mechanisms using a disease-stage-oriented and NVU-centered framework. We synthesize how GPCR-mediated intercellular communication among neurons, glial cells, and vascular elements dynamically regulates cerebral blood flow, neuroinflammation, blood–brain barrier (BBB) integrity, and neuronal circuit remodeling. Particular emphasis is placed on phase-dependent GPCR signaling, highlighting receptors whose functions shift across acute injury, secondary damage, and recovery phases. We further critically evaluated the translational implications of GPCR-targeted therapies, discussing why promising preclinical neuroprotection has frequently failed to translate into clinical benefit. By integrating molecular mechanisms with temporal dynamics and translational constraints, this review provides a framework for the rational development of cell-type and stage-specific GPCR-based therapeutic strategies in cerebrovascular disease. Full article

Background/Objectives: Cigarette smoke (CS) drives pathogenesis across the spectrum of chronic respiratory disorders, exerting its detrimental effects primarily through oxidative stress and programmed cell death. Scutellarein (Scu), a botanical-origin flavonoid enriched in respiratory therapeutics-oriented Chinese medicinal herbs, demonstrates established anti-inflammatory applications. This study systematically evaluated the protective roles of Scu against CS-induced lung injury and explored the underlying mechanisms. Methods: Subacute CS-exposed mice were used to evaluate the therapeutic effects of Scu on lung injury. Immunofluorescence and quantitative PCR were used to examine the expression levels of junctional proteins and proinflammatory mediators. Apoptotic cell death was quantified using Annexin V-FITC/7-AAD staining. Transepithelial electrical resistance and dextran permeability assay were used to access the barrier integrity in alveolar epithelial MLE-12 cells. Western blotting was used to detect the changes in the signal pathway. Results: In CS-exposed mice, Scu administration dose-dependently reduced histopathological scores, pulmonary edema, changes in the alveolar structure, and inflammatory cell infiltration. In MLE-12 cells, Scu significantly suppressed cigarette smoke condensate (CSC)-induced inflammatory mediators, oxidative stress, caspase-3 activation, and apoptosis and preserved CSC-suppressed tight junction protein expression and barrier disruption. Scu also rescued CSC-altered expression levels of Hrk, Ecscr, and Myo5b and mitigated the CSC-suppressed PI3K/AKT/mTOR pathway. Conclusions: Scu alleviates CS-induced subacute lung injury through its antioxidant, anti-apoptotic effects to maintain epithelial barrier integrity likely via the mitigation of the CSC-suppressed PI3K/AKT/mTOR pathway. Full article

Background: The anterior cruciate ligament (ACL) and medial collateral ligament (MCL) display strikingly different healing behaviors, despite their similar structural roles within the knee. The epiligament (EL)—a vascular and cellular envelope surrounding each ligament—has emerged as a critical determinant of repair capacity. The aim of this study was to perform a region-specific, comparative analysis of EL molecular profiles in the ACL and MCL to elucidate the mechanisms underlying their contrasting reparative outcomes. Methods: Human ACL and MCL specimens were obtained from 12 fresh knee joints. Immunohistochemical labeling for CD34, α-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF) was performed across proximal, mid-substance, and distal EL regions. Quantitative image analysis using IHC Profiler for ImageJ generated semiquantitative (negative, low-positive, positive) distributions, and inter-ligament comparisons were quantified using t-tests (p  <  0.05). Results: Distinct, region-specific EL signatures were identified. The ACL EL exhibited strong proximal α-SMA expression (0% neg/66.8% low+/33.2%+) and notable distal CD34 positivity (0% neg/83.3% low+/16.7%+), while VEGF expression was confined to the mid-substance (≈55% low+/26%+). In contrast, the MCL EL was largely negative for CD34 and VEGF across all regions, showing a homogeneous but functionally oriented α-SMA profile: proximally negative, sparse mid positivity, and high distal low-positive staining (93.4% low+). Differences in proximal and distal CD34 and α-SMA expression between the ACL and MCL were highly significant (p  <  0.0001–0.001), confirming a mechanistic divergence in EL organization. Conclusions: The ACL EL is regionally heterogeneous, vascularly biased, and enriched in contractile α-SMA+ cells, suggesting localized but poorly coordinated reparative potential. In contrast, the MCL EL is structurally uniform, with distributed α-SMA activity supporting stable wound contraction and tissue continuity, despite limited angiogenic signaling. These findings indicate that the ACL’s failure to heal is not attributable to the absence of progenitor or angiogenic factors, but rather to its fragmented spatial organization and dominant contractile phenotype. Therapeutically, preserving and modulating the EL, particularly its CD34+ and α-SMA+ compartments, could be key to enhancing intrinsic ACL repair and improving outcomes in ligament reconstruction and regeneration. Full article

This manuscript presents the development of an electrochemical biosensor designed to detect K-562 chronic myeloid leukemia (CML) cells. The biosensor was made of highly oriented pyrolytic graphite (HOPG), functionalized with -OH and -COOH groups by surface etching with strong acids, and subsequently coated with modified titanium dioxide (TiO₂-m). TiO₂-m is TiO₂ modified during its synthesis process using carbon nanotubes functionalized with -OH and -COOH groups. These changes improve the electron transfer kinetics and physicochemical properties of the electrode surface. TiO₂-m improves the sensitivity and selectivity towards leukemic cells. The detection process involved three stages: cell culture, cell adhesion onto the TiO₂–m electrode, and measurement of the electrochemical signal. Fluorescence microscopy and SEM-EDS confirmed cell adhesion and pseudopod formation on the TiO₂-m surface, which is an important finding because K-562 cells are typically nonadherent. Cyclic voltammetry (VC) and differential pulse voltammetry (VDP) demonstrated rapid and sensitive detection of leukemic cells within the concentration range of 6250 to 1,000,000 cells/mL, achieving high reproducibility and strong linearity (R² = 98%) with a detection time of 25 s. The VC and VDP demonstrated rapid and sensitive detection of leukemic cells over a concentration range of 6250 to 1,000,000 cells/mL, achieving adequate reproducibility and stable linearity (R² = 98%), with a detection time of 25 s. These results indicate that the TiO₂-m biosensor is a promising platform for the rapid and efficient electrochemical detection of leukemia cells. Full article

This study reports the development of paclitaxel (PTX)-loaded human serum albumin (HSA) nanoparticles (NPs), surface-decorated with trastuzumab (TMAB), with potential applicability in HER2-oriented delivery. The NPs were obtained via thermally driven self-assembly followed by non-covalent antibody adsorption and they were characterized using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and ζ-potential analysis. The drug association efficiency (%DAE), defined exclusively for PTX, was high for both HSA-PTX and HSA-PTX-TMAB NPs (96.4% and 98.2% w/w, respectively), with loading capacities (%LC) of 8.9% and 7.4%, respectively. TMAB decoration led to a modest increase in mean diameter and a reduction in surface charge, consistent with successful surface modification. Both formulations exhibited rapid early-phase PTX release followed by an apparent stabilization phase, with distinct kinetic behavior between HSA–PTX and HSA–PTX–TMAB NPs. Cytotoxicity in A549 cells after 18 h of exposure showed modest, non-differential effects consistent with controlled release and short-term assessment of non-specific toxicity. Overall, this thermally assembled albumin-based system provides a promising foundation for further evaluation of HER2-oriented PTX delivery. Full article

First-principles calculations of the structural and magnetic properties of kotoite Ni₂Co(BO₃)₂ are carried out. The minimization of the lattice parameters shows the values to be in good agreement with the experimental data (the difference is less than 1%). The atomic coordinates are calculated. Cobaltions are found tending to occupy position 2a and nickel ions tending to occupy position 4f. The same magnetic cell as in Ni₃(BO₃)₂, but quadrupled in size (2a × b × 2c), found having the minimum exchange energy for Ni₂Co(BO₃)₂. In Ni₂Co(BO₃)₂, the magnetic moments are obtained oriented along the baxis, similar to that in Co₃(BO₃)₂. Full article

Urethral stricture is a disease of fibrotic narrowing that compromises the urethral mucosa and spongiosum. Oral mucosal graft urethroplasty delivers excellent outcomes in complex cases, yet its procedural demands restrict availability beyond specialized centers. Endoscopic transplantation of oral mucosa has been proposed; while feasibility is shown, clinical efficacy remains suboptimal. We asked whether extracellular vesicles from stem cells of human exfoliated deciduous teeth (SHED-EVs) promote oral mucosa fibroblast (OMF) growth under urethra-mimetic paracrine conditions and whether culture growth phase tunes EV function. SHED-EVs were collected during logarithmic (SHED-EV-L) or stationary (SHED-EV-S) phases under xeno-free conditions, isolated by a standardized workflow, and characterized by nanoparticle tracking analysis. miRNA cargo was profiled with a human miRNA microarray platform and normalized for comparative analyses. OMF proliferation was quantified in a horizontal indirect co-culture with urethral epithelial cells using incubator-based time-lapse imaging. SHED-EV-L produced a sustained pro-proliferative effect across 24–96 h, whereas SHED-EV-S showed a weaker early effect with a late catch-up; both exceeded vehicle at 96 h. Fibrosis-related miRNA heat maps showed culture growth phase-dependent patterns: SHED-EV-L displayed relatively higher signals for miR-31-3p, miR-146b-3p, several let-7 members, and selected miR-181 isoforms, whereas SHED-EV-S showed a marked relative increase of miR-486-3p; miR-21, miR-99/100, and miR-205 were broadly comparable between phases. These findings indicate that culture growth phase is a practical design lever that orients SHED-EV cargo and function, supporting phase-matched formulations for adjunctive transurethral applications and motivating in vivo validation and manufacturing-oriented quality controls. Full article

Collaborative multi-UAV swarms are central to many missions. This review covers the most recent two years. It organizes the literature with a scenario-aligned taxonomy. The taxonomy has 12 cells (Path/Distribution/Coverage × offline/online × static/dynamic). Nine cells are well populated and analyzed. For each, representative techniques, reported limitations, and scenario-appropriate use are summarized. Cross-scenario trade-offs are made explicit. Key examples include scalability vs. energy efficiency and centralized vs. decentralized (hybrid) architectures. The review also links offline pre-planning to online execution through architecture choices, digital-twin validation, and safety-aware collision avoidance in cluttered airspace. Unlike prior algorithm-centric or bibliometric surveys, this work applies a scenario-conditioned taxonomy, ties best-suited method families to each populated cell, and surfaces reported limitations alongside trade-offs. The result is deployment-oriented guidance that maps methods to mission context. Finally, five near-term priorities are highlighted: (i) compute-aware real-time adaptivity on resource-constrained platforms; (ii) scalable multi-objective scheduling with coupled motion and cooperative control; (iii) bandwidth-aware, conflict-resilient intra-swarm communication with reliability guarantees; (iv) certifiable planning for dense urban low-altitude corridors; and (v) energy-aware, hierarchical planners that couple offline pre-planning with online replanning. Full article

Synapses, abundant in the brain, are structures needed for life. Our Introduction, based on the forms of such structures published few decades ago, helped in developing recent concepts of health and diseases. Growing axons govern their growth by cell-to-cell communication, axon guidance, and synapse orientations. The assembly of synapses requires the organization and function of pre-synaptic and post-synaptic neuronal terminals with a liquid–liquid phase, governed by Ca²⁺ responses of thin astrocyte domains. Upon synapse stimulation, the clefts expand up to several folds while pre- and post-synaptic thickness remains unchanged. In additional responses, neurons co-operate with astrocytes and extracellular vesicles (EVs), the latter dependent on extracellular and intracellular spaces. Astrocyte and microglia cells and/or EV secretions induce neurons by various effects including traveling changes. Pre-synaptic responses are defined as canonical if based on neurotransmitter release; non-canonical if they are without release and are discharged by EVs, not neurotransmitters. Health and diseases depend on other general properties, such as those defined molecularly. Among neurodegenerative diseases, attention is specified by various properties of Alzheimer’s and other diagnoses. Critical identifications can be due to astrocyte and microglia cells or multiple effects induced by EVs. At present, the complexity of therapies, although of limited success, is developing innovative initiatives. Full article

Background/Objectives: Facial nerve injury from conditions such as Bell’s palsy, trauma, surgery, and infection leads to facial asymmetry and motor deficits. Axotomy models reproduce peripheral nerve disruption and consequent motor impairment. To compare the effects of forward versus reverse autologous nerve suturing on neural regeneration and motor recovery within the facial nucleus after axotomy. Methods: In rats subjected to facial nerve axotomy, motor recovery was assessed at 8 weeks using whisker movement and blink reflex tests. Immunohistochemistry quantified choline acetyltransferase (ChAT), sirtuin 1 (SIRT1), and Iba-1 as indices of cholinergic function, cellular stress/inflammation modulation, and microglial activation in the facial nucleus. Results: Axotomy significantly reduced whisker and blink scores compared with sham. Both forward and reverse suturing significantly improved these behavioral outcomes versus axotomy. Within the facial nucleus, axotomy decreased ChAT- and SIRT1-positive cells and increased Iba-1 expression, while both suturing techniques increased ChAT and SIRT1 and reduced Iba-1. These changes suggest enhanced cholinergic function, mitigation of stress/inflammatory responses, and attenuation of microglial activation following repair. Conclusions: Forward and reverse suturing were each associated with improved motor function and favorable molecular and cellular changes in the facial nucleus after facial nerve axotomy. These findings support the utility of surgical repair irrespective of graft orientation and highlight involvement of key pathways—cholinergic signaling, SIRT1-related regulation, and microglial activity—in nerve restoration. This work extends our previous study, which focused on peripheral nerve regeneration after forward and reverse suturing, by elucidating how graft orientation affects central facial nucleus responses. By integrating behavioral outcomes with ChAT, Iba-1, and SIRT1 expression, the present study provides novel insight into the central mechanisms underlying motor recovery after facial nerve repair and helps explain why comparable functional outcomes are achieved regardless of graft polarity. Full article

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in medicine, cosmetics, and environmental technologies, yet their interactions with blood cells remain poorly understood, raising cross-species safety concerns. Using frog (nucleated) and human (anucleate) erythrocytes as comparative models, we show that cellular architecture fundamentally shapes responses to ZnO NPs exposure. Human erythrocytes exhibited a dose-dependent progression from membrane deformation to eryptosis and hemolysis, reflecting the pronounced vulnerability of anucleate cells. In contrast, frog erythrocytes sustained nuclear DNA damage while largely preserving membrane integrity, highlighting the protective or reparative role of the nucleus. Molecular docking revealed energetically favorable interactions of ZnO NPs with ERα-LBD and DNA (ΔG = −4.28 and −5.68 kcal/mol, respectively), while quantum chemical analyses indicated electron-accepting properties and a narrow HOMO–LUMO gap, suggesting efficient macromolecular interactions and intracellular ROS generation. Together, these findings demonstrate that the presence of a nucleus shifts the primary target of nanoparticle toxicity from membrane to genome, providing novel mechanistic insights. This comparative study offers a robust framework for understanding nanomaterial reactivity across taxa and informs One Health-oriented risk assessments. Full article

Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings. Full article