Search Results (198)

Chronic arsenic exposure causes neurological damage, but the underlying mechanisms remain incompletely understood. This study investigated whether Saposhnikoviae Radix (SR) aqueous extract protects against arsenic-induced neurotoxicity by modulating pyroptosis. Kunming mice were exposed to NaAsO₂ (10 mg/kg) with or without SR (3, 6, 12 g/kg). NaAsO₂ exposure induced anxiety-like behaviors and spatial memory deficits, accompanied by widespread neuronal damage (hippocampal pyramidal cell disarray, cerebellar Purkinje cell loss, and cortical vacuolation) and upregulation of pyroptosis-related proteins (NLRP3, Cleaved-Caspase-1, GSDMD-N, IL-1β, IL-18) in brain tissues. SR treatment significantly ameliorated these behavioral and pathological changes. In HT22 cells, NaAsO₂ (12.5 μM) reduced cell viability, increased LDH release, induced pyroptotic ultrastructural features (membrane blebbing and pore formation), and upregulated pyroptosis markers; SR (400 μg/mL) effectively reversed these effects. Mechanistically, SR suppressed the NLRP3/Caspase-1/GSDMD axis activation, as confirmed by both protein and mRNA analyses. These findings demonstrate that SR aqueous extract attenuates arsenic-induced central nervous system injury through specific inhibition of the pyroptosis pathway, providing an experimental basis for the potential use of traditional Chinese medicine in preventing environmental metalloid-induced neurotoxicity. 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

Spongiform degeneration, or status spongiosis, is characterized by vacuoles within the central nervous system. It appears in numerous neurological diseases, including transmissible spongiform encephalopathies, mitochondrial disorders, and lysosomal storage diseases. Traditionally considered secondary to neurodegeneration, vacuolar changes frequently involve white matter and form within the myelin sheath. This review examines the evidence from various diseases and genetic models that exhibit this pathology to support the hypothesis that white matter vacuolation represents a myelin defect and explores potential causative mechanisms. Our findings suggest that spongiform change in white matter represents a common endpoint of pathway disruptions that lead to metabolic or ionic dyshomeostasis, causing an osmotic imbalance and vacuole formation within myelin. We advocate for further research into myelin-preserving pathways as potential therapeutic avenues to treat conditions exhibiting this pathology. Full article

Peptides as signaling molecules play an important role in intercellular communication. Exogenous peptides AlaGluAspLeu (AEDL) and AlaGluAsp(OMe)Leu (AED(OMe)L) at a concentration of 10⁻⁷ M stimulate the growth and development of Nicotiana tabacum. A detailed study of Nicotiana tabacum root cells grown in the presence of exogenous peptides AEDL and AED(OMe)L using transmission electron microscopy revealed characteristic differences in the ultrastructure of some cytoplasmic organelles compared to control cells. Importantly, vacuoles and autophagosomes differing in size and content, as well as amyloplasts and proteinoplasts never previously described in the literature, were found in the cells of the outer and inner root cortex. Only lytic vacuoles were detected in the cytoplasm of control cells, whereas in the presence of peptides, predominantly protein-storing vacuoles were found in root cells. In the presence of the exogenous short peptide AEDL, tobacco root cells contained amyloplasts with numerous large starch granules in the stroma, which were not detected in control cells. In the presence of the modified short peptide AED(OMe)L, leukoplasts contained protein bodies. Moreover, in contrast to control cells and cells grown in the presence of the AEDL peptide, a megaphagic (pexophagic) variant of autophagosomes with peroxisomes was detected for the first time in tobacco cells treated with AED(OMe)L. Characteristic types of phagophores were identified, forming numerous small autophagosomes with cytoplasmic regions, multivesicular bodies or concentric membranes, and cytoskeletal elements. Data on the expression of the ATG, TOR, and FREE1 genes confirmed the pattern of the existence of a large number of small autophagosomes. Based on the obtained data, a scheme for the regulation of the formation of root architecture of Nicotiana tabacum in the presence of AEDL and AED(OMe)L was proposed. Full article

Glioblastoma (GBM) is a devastating brain tumor heavily reliant on metabolic reprogramming for survival. The DNA aptamer AS1411 specifically targets cell-surface nucleolin (NCL), a protein overexpressed in GBM; however, its precise metabolic consequences remain largely unexplored. This study investigated the direct impact of AS1411-mediated NCL inhibition on the lipidomic profile of U-87 glioblastoma cells. It was demonstrated that AS1411 treatment induced acute cytotoxicity within 24 h. Subsequently, high-resolution mass spectrometry (MS) lipidomics was utilized to identify the lipidomic rewiring triggered by AS1411. Significant changes, such as the upregulation and/or exclusive emergence of specific long-chain and highly polyunsaturated diacylglycerol (DAG), triacylglycerol (TAG), and glycerophospholipid (GP) species, were determined in the species-level analyses. Additionally, our findings revealed that AS1411 treatment induced substantial alterations that profoundly affected membrane biophysics by modifying lipid saturation and acyl chain lengths. An increase in fully saturated sphingomyelin (SM) and cholesteryl ester (CE) levels was observed, leading to the formation of saturated lipid microdomains (lipid rafts) in endosomal and ER membranes, which causes membrane rigidification and decreased fluidity. Our results also demonstrate that PEs containing long-chain polyunsaturated fatty acids (PUFAs)—the primary substrates for ferroptosis—were upregulated. While AS1411 subjects cancer cells to methuotic vacuolization stress, it simultaneously reduces internal structural membrane fluidity and renders the cells metabolically vulnerable to ferroptosis. In conclusion, these detailed lipidomic results indicate that AS1411 treatment proceeds strictly through targeted remodeling and an adaptive scaffolding response. Full article

Autophagy is a crucial mechanism in the host response to intracellular bacterial pathogens during which microorganisms may undergo direct degradation in autophagolysosomes. As a highly virulent intracellular pathogen, Francisella tularensis has developed survival strategies to escape from the phagosome, replicate in the cytosol of mononuclear cells, and avoid degradation within the double-membrane vacuole during the autophagy-mediated response. The aim of this study was to investigate the role of the ATG5 autophagy protein in the host immune response to Francisella tularensis subsp. holarctica, live vaccine strain (LVS), since ATG5 plays an important role in autophagosome formation during canonical autophagy. In vitro experiments were conducted on immortalized bone marrow macrophages subjected to starvation-induced autophagy. Transgenic mice deficient in ATG5 of cells of the myeloid lineage (monocytes/macrophages and granulocytes) were used to analyze the immunological responses after intradermal infection. Cytokine levels were analyzed using Luminex, RT-qPCR, and ELISA, while inflammatory cell infiltration in the lung was analyzed by immunohistochemistry. Our results demonstrate that induced autophagy decreased bacterial replication in vitro. However, ATG5 deficiency in myeloid cells in vivo significantly diminished levels of pro-inflammatory cytokine IFN-γ in the sera, spleen, liver, and lung during Francisella infection. The attenuated pro-inflammatory response also led to significantly reduced macrophage and T cell infiltration in the lung tissue. Our findings also reveal that neutralization of IL-1β in myeloid ATG5ΔMye mice increased susceptibility to tularemia by increasing bacterial burden in organs. Full article

The intestine, particularly the gut microbiota, and the liver play key roles in digestion, nutrient transformation, and immune regulation in fish. However, limited information is available regarding how different ornamental fish species regulate these systems under identical aquaculture conditions. Therefore, this study systematically compared gut microbiota diversity, structural variation, and predicted ecological functions among eight ornamental fish species reared in the same environment, using 16S rRNA high-throughput sequencing combined with digestive enzyme indices and histological analysis of intestinal and liver tissues. The results showed that goldfish (Carassius auratus) and crucian carp exhibited efficient digestive and absorptive capacities, supported by a thickened muscularis and prominent mucosal layers (p < 0.001). High goblet cell density was observed in red swordtail (Xiphophorus hellerii) and Mickey Mouse platy (Xiphophorus hellerii × X. maculatus) (p < 0.001). Larger hepatocyte perimeter and area were observed in red swordtail (p = 0.022, p = 0.015), whereas platinum mini parrot cichlid and sapphire mini parrot cichlid showed significant hepatocyte vacuolization. Microbial analysis showed that the eight fish species had similar α diversity indices, while the gut microbial profiles of Mickey Mouse platy and golden crucian carp differed the most. At the genus level, beneficial taxa such as Lactococcus, Paracoccus, and Cetobacterium were significantly enriched in red swordtail, sailfin molly, and goldfish, respectively, whereas opportunistic pathogens, including Edwardsiella, Aeromonas, and Acinetobacter, were enriched in Mickey Mouse platy, sapphire mini parrot cichlid, and golden crucian carp, respectively (p < 0.05). Functional prediction based on KEGG pathways indicated that sailfin molly and Mickey Mouse platy exhibited the broadest functional enrichment, primarily involving amino acid metabolism, fatty acid metabolism, and antibiotic biosynthesis. Crucian carp and golden crucian carp showed higher activity in amino acid biosynthesis and glycolysis/gluconeogenesis pathways. The two parrot cichlid species were characterized by enrichment in biofilm formation pathways of pathogenic bacteria and amino sugar and nucleotide sugar metabolism pathways. Goldfish and red swordtail were mainly associated with quorum sensing and ABC transporter pathways. These results provide a theoretical foundation for optimizing aquaculture conditions for ornamental fish and improving fish health and production efficiency. Full article

Post-acute sequelae of SARS-CoV-2 infection (PASC) extend well beyond the acute respiratory phase, with accumulating virological evidence that SARS-CoV-2 RNA, viral antigens, and proteolytic fragments may persist in cardiovascular and other extrapulmonary tissues, although the extent to which such detection represents replication-competent reservoirs versus residual viral material with uncertain pathological relevance remains under active investigation. Sudden cardiac death (SCD) and fatal pulmonary thromboembolism (PTE) have emerged as forensically and epidemiologically significant outcomes in individuals with prior infection, situated at the intersection of microbiology, public health, and forensic medicine. To synthesize current evidence on the virological mechanisms by which SARS-CoV-2 may contribute to post-acute sudden cardiac death (SCD) and pulmonary thromboembolism (PTE), the population-level epidemiology of these outcomes, and their implications for public health surveillance and forensic practice, we conducted a narrative review of PubMed (MEDLINE), Scopus, and Web of Science Core Collection. The search covered publications from January 2020 to December 2025 and focused on SARS-CoV-2 cellular tropism and tissue persistence, immune-mediated and thromboinflammatory mechanisms, excess cardiovascular and thromboembolic mortality, and autopsy-based pathological findings. After de-duplication of 1837 initially identified records (412 duplicates removed) and screening of 1425 unique records, 78 studies were retained for final synthesis based on virological, epidemiological, and forensic relevance. SARS-CoV-2 enters cardiomyocytes, pericytes, and vascular endothelial cells through ACE2-dependent mechanisms, with cathepsin L compensating for the limited cardiac expression of TMPRSS2. Viral RNA and antigen have been detected in cardiovascular and other extrapulmonary tissues months after symptom onset in selected autopsy series, although persistent detection of viral components does not necessarily indicate ongoing productive infection or direct tissue injury. Endothelial dysfunction, neutrophil extracellular trap (NET) formation, complement activation, and persistent thromboinflammation have been proposed as plausible mechanistic substrates for arrhythmogenic remodelling and thromboembolic events, although definitive causal pathways remain incompletely understood. Population-based studies document persistent excess cardiovascular mortality across multiple jurisdictions, with hazard ratios for pulmonary embolism remaining elevated months after acute infection, particularly in unvaccinated individuals. Autopsy series identify mixed pathological patterns including focal lymphocytic infiltrates, microvascular thrombosis, contraction-band necrosis, and cardiomyocyte vacuolation, although fulminant lymphocytic myocarditis fulfilling Dallas criteria remains uncommon. A microbiology-informed framework uniting tissue-based viral detection, standardized cardiac and pulmonary sampling protocols, and prospective post-mortem registries is needed to better characterize the potential contribution of SARS-CoV-2 to post-acute cardiovascular mortality and to support cause-of-death certification, public health surveillance, and medicolegal practice in the post-pandemic era. Many of the proposed mechanisms remain under active investigation, and definitive causal relationships between viral persistence and adverse cardiovascular outcomes have not yet been conclusively established. Full article

Although evolutionarily distant, the bacteria Listeria monocytogenes, Shigella flexneri, and Burkholderia thailandensis each undergo a “cell-to-cell” spreading process that allows these pathogens to disseminate within human tissues. Spread initiates when bacteria polymerize actin filaments that propel them through the host cell cytosol. The pathogens then remodel the plasma membrane into protrusions that are internalized by adjacent cells and resolved into double membranous vacuoles (DMVs) which lyse to liberate bacteria. In this review, we discuss recent publications indicating that L. monocytogenes, S. flexneri, and B. thailandensis each enhance their spread by altering the subcellular localization of human Dynamin 2—a GTPase that regulates endocytosis and other trafficking pathways. Interestingly, Dynamin 2 controls distinct steps in spread of L. monocytogenes, S. flexneri, and B. thailandensis. In the case of L. monocytogenes, the GTPase has the potential to restrict protrusion formation by generating tension at tight junctions. However, L. monocytogenes secretes a protein that relieves this restriction of protrusions, allowing efficient spread. During dissemination of S. flexneri and B. thailandensis, Dynamin 2 is co-opted to resolve protrusions into DMVs. B. thailandensis also mobilizes Dynamin 2 to lyse DMVs. These findings highlight diverse ways in which bacteria control Dynamin 2 to augment spread. Full article

The co-occurrence of mucilage and phenolic compounds within the same secretory cell is rarely documented in plants. Recently, such cells were reported in vegetative and floral organs of sensitive legumes (Mimosa), but without detailed subcellular analysis. To address this gap, we used transmission electron microscopy to examine the organelles involved in biosynthesis, the intracellular sites of metabolite storage, and the secretion processes across floral and foliar organs in five Mimosa species. Secretory epidermal cells of sepals, petals, and leaf blades produce both mucilage and phenolics, with no significant differences between organ types. Dictyosomes, rough endoplasmic reticulum, and plastids predominated in the cytoplasm of the secretory cell during biosynthesis. Dictyosomes may mediate mucilage production, the rough endoplasmic reticulum may be involved in phenolic synthesis, and plastids may contribute to the biosynthesis of both compounds. These metabolites are stored in distinct cellular domains: phenolics accumulate in a large vacuole near the outer periclinal wall, while mucilage is deposited between the microfibrils of the inner periclinal wall. This spatial separation is evident by the distention of the inner periclinal wall due to mucilage accumulation. The absence of karyokinesis and phragmoplast formation during metabolite segregation confirms that these secretory cells have two different functional domains, forming a uniseriate rather than biseriate epidermis. Notably, the inclusion of several species in the ultrastructural analyses enhances the significance of these findings. Full article

Autophagy, also referred to as the “self-eating machinery”, is a crucial process where organisms maintain intracellular homeostasis through recycling or degrading non-essential and damaged cellular components. It is important in numerous biological functions such as cellular differentiation, aging, nutrient sensing, stress response, tissue homeostasis, immunity, and programmed cell death. Autophagy induction occurs with the formation of a double-layered membrane structure called “autophagosome”. The autophagosome wraps damaged organelles or proteins and transports them to the vacuole or lysosome for degradation. Autophagy is beneficial to organisms, and it should be optimally regulated because elevated or decreased levels are detrimental for survival. To date, more than 40 autophagy-related genes (ATGs) have been identified in the budding yeast Saccharomyces cerevisiae, with most having homologs in fungi and higher eukaryotes. Majority of the ATGs in industrial and pathogenic fungal species have been characterized and known to play vital roles in growth, development, and virulence. In this review we provide a comprehensive overview of ATGs in various fungal species and highlight how autophagy is regulated and controls various functions in plant, human, and industrial fungal species. Full article

Colletotrichum species are among the most destructive phytopathogens worldwide, with appressorium-mediated penetration representing a critical stage in host infection. Targeting this morphogenetic transition offers a promising strategy for sustainable disease control by interfering with the infection process rather than solely inhibiting fungal growth. In this study, chitosan–κ-carrageenan nanoparticles (CS–κ-CRG) without and with lysozyme (CS–κ-CRG/Lz) were synthesized, characterized, and evaluated for their ability to inhibit appressorium formation in Colletotrichum siamense, a strain exhibiting low sensitivity to chitosan. The nanoparticles showed monodisperse size distributions, with hydrodynamic diameters of 503 and 333 nm for CS–κ-CRG and CS–κ-CRG/Lz, respectively, positive surface charges of approximately +26 mV, spherical morphology, and a lysozyme encapsulation efficiency of 63%. Both formulations significantly reduced conidial viability and delayed germination, inducing morphological alterations such as conidial swelling, hyphal deformation, and vacuolization. Fluorescence microscopy using calcofluor white and propidium iodide revealed disturbances in cell wall organization and loss of membrane integrity. Both nanomaterials markedly affected appressorium development in a concentration- and formulation-dependent manner. Notably, CS–κ-CRG/Lz showed stronger suppression of appressorium formation, whereas at 200 µg·mL⁻¹, CS–κ-CRG nanoparticles stimulated appressorium formation, suggesting that sublethal nanoparticle stress may trigger compensatory or hyper-pathogenic responses. These findings highlight the potential and complexity of utilizing chitosan-based nanomaterials for phytopathogen management and emphasize the importance of mechanistic and dose–response evaluations before field application. Full article

Natural products from plants have played an important role in cancer and neurodegenerative diseases. In this context, the root bark of Maytenus chiapensis (Celastraceae) was investigated to examine its chemical constituents and potential biological activities. Chromatographic separation of the root bark extract yielded a new Diels–Alder adduct (morenine) formed by a triterpenophenolic moiety derived from tingenone and a bicyclic guaiane-type sesquiterpene linked through a 1,4-dioxane bridge. In addition, eight previously reported Diels–Alder adducts—retusonine and cheiloclines A–D and F–H—were isolated, together with their biosynthetic precursors, the quinone-methide triterpenoids (QMTs) pristimerin and tingenone. Structural elucidation was achieved through detailed 1D and 2D NMR spectroscopic analyses. The adducts were tested for cytotoxicity against six cancer cell lines (A549, SW1573, MIA PaCa-2, T-47D, HeLa, and WiDr cell lines), showing moderate-to-low activity compared with their precursors. Continuous live cell imaging identified apoptosis and vacuole formation as the main modes of action of pristimerin in SW1573 cells. Moreover, acetylcholinesterase inhibition assays revealed that cheiloclines B–D, F, and H exhibited up to 50% inhibition. These findings reinforce the potential of Celastraceae species as a source of unique and complex compounds and enhance our understanding of their therapeutic potential. Full article

Background: Acquired epidermodysplasia verruciformis (AEV) is a rare cutaneous disorder arising in immunocompromised individuals. AEV is characterized by flat-topped, wart-like, or hypopigmented lesions predominantly on sun-exposed areas. Unlike classic genetic EV, AEV develops in the absence of germline mutations or family history. AEV most commonly arises in patients receiving iatrogenic immunosuppressive therapy for organ transplantation, autoimmune disease, or hematologic disorders. Methods: A comprehensive literature review was conducted via the PubMed database. Case reports and case series studies describing AEV in transplant and non-transplant iatrogenic immunosuppression were identified through a literature search. There were no restrictions on language or publication year. The last search was conducted in July 2025. Reports were analyzed for patient demographics, immunosuppressive agents, HPV subtypes, clinical and histopathologic features, and treatment outcomes. Results: AEV occurs across a broad spectrum of immunosuppressive therapies, including calcineurin inhibitors, antimetabolites, biologics, tyrosine kinase inhibitors, and cytotoxic chemotherapy. β-HPV subtypes, most commonly HPV 5 and 8, drive lesion formation in the context of impaired cell-mediated immunity. Histopathology demonstrates keratinocyte vacuolization, acanthosis, and perinuclear halos. Lesions may persist despite immunosuppressive adjustment, due to viral latency and incomplete immune reconstitution. Treatment strategies are varied and include topical retinoids, immune response modifiers, systemic retinoids, and HPV vaccination, and have variable efficacy. AEV carries an elevated risk of cutaneous squamous cell carcinoma, particularly in transplant recipients, and highlights the need for proactive dermatologic management. Conclusions: AEV represents a clinically significant consequence of immunosuppression mediated by β-HPV. Early recognition, monitoring for malignant transformation, and individualized multimodal therapy are critical. Future studies should evaluate targeted interventions to enhance antiviral immunity and establish standardized treatment guidelines. Full article

Background/Objectives: Cerebral angiography is a cornerstone diagnostic and therapeutic procedure for cerebrovascular diseases; however, its potential effects on vascular integrity and cellular homeostasis remain incompletely elucidated. This systematic review aims to comprehensively evaluate endothelial and histopathological alterations induced by cerebral angiographic procedures, with particular emphasis on oxidative stress, inflammation, endothelial dysfunction, and blood–brain barrier disruption. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science databases were systematically searched for studies published between 1981 and 2025 using predefined keywords related to cerebral angiography, endothelial injury, oxidative stress, inflammation, and histopathological changes. A total of 1142 records were identified, and 216 duplicates were removed. Following title and abstract screening, 312 full-text articles were assessed for eligibility, of which 112 were excluded due to irrelevance or insufficient endothelial or histopathological data. Ultimately, 200 studies were included in the qualitative synthesis. The literature identification, screening, and selection process are summarized in the manuscript. The review protocol was not prospectively registered. Results: The included studies demonstrated that cerebral angiographic procedures induce endothelial and microvascular alterations through both mechanical and contrast-mediated mechanisms. Iodinated contrast agents were consistently associated with increased reactive oxygen species production, reduced endothelial nitric oxide bioavailability, mitochondrial dysfunction, and activation of pro-inflammatory signaling pathways, including nuclear factor kappa B (NF-κB). Histopathological findings revealed endothelial swelling, vacuolization, apoptosis, microthrombus formation, inflammatory cell infiltration, and disruption of endothelial junctions, leading to increased vascular permeability and blood–brain barrier impairment. Mechanical factors related to catheter manipulation and high-pressure contrast injection further exacerbated endothelial injury by altering shear stress and promoting leukocyte adhesion. The severity of endothelial damage and inflammatory responses was consistently greater in patients with comorbid conditions such as diabetes mellitus, hypertension, and atherosclerotic disease. Conclusions: Cerebral angiography may induce endothelial dysfunction and histopathological vascular injury predominantly through oxidative and inflammatory mechanisms. Optimization of contrast agent selection, refinement of procedural techniques, and implementation of endothelial-protective strategies may mitigate vascular injury and improve procedural safety. Further translational and clinical studies are warranted to identify biomarkers and protective interventions targeting angiography-induced endothelial damage. Full article