Search Results (3,472)

Acetaminophen (paracetamol, APAP) is a widely used analgesic and antipyretic drug. Under normal physiological conditions, it does not directly interact with or disrupt cellular membranes. However, in cases of acetaminophen overdose or toxicity, severe cellular damage has been described, involving a broad spectrum of effects at different cellular levels. These toxic effects may involve membrane structures, including mitochondrial, plasma, and other intracellular membranes. Antimicrobial peptides (AMPs) are short, usually cationic and amphipathic peptides produced by both microorganisms and multicellular organisms, serving diverse defensive and competitive functions. In many cases, they exert their antimicrobial activity by direct interaction with bacterial or fungal membranes, leading to membrane destabilization and cell death. Owing to this membrane-targeting mechanism, AMPs may also interact with eukaryotic cell membranes, thereby exerting toxic or off-target effects under certain conditions. Here, we review the current knowledge on the membrane-related effects of acetaminophen toxicity and the mechanisms by which AMPs interact with biological membranes. In the event of combined exposure to acetaminophen and AMPs in therapeutic or experimental settings, the biological consequences remain unexplored. Such combined exposure may give rise to toxic effects and membrane-associated alterations. We further discuss potential mechanisms of interference, additive toxicity, and synergistic interactions between acetaminophen and AMPs, highlighting critical knowledge gaps and directions for future research. Full article

Functional imaging has become an important approach for evaluating tumor physiology in vivo beyond morphologic assessment. Radiotracers used for cancer imaging are designed to mimic endogenous substrates or substrate analogues, and their accumulation can depend on membrane transport, intracellular metabolism, and clearance from normal tissues. Specifically, SLC transporters contribute to tracer uptake and signal formation, linking transporter activity with measurable imaging signals in cancer. While [¹⁸F]FDG PET/CT remains the most widely used example of transporter-associated metabolic imaging, SLC transporter-mediated imaging strategies have been developed to assess amino acid transport, sodium-dependent glucose uptake, redox metabolism, lactate exchange, nucleoside metabolism, choline metabolism, and iodide accumulation. Herein, we provide an overview of current applications of SLC transporter-mediated functional imaging in cancer diagnosis, with an emphasis on glucose and amino acid systems. Special attention is given to the relationship between transporter physiology, tracer uptake, tumor type, and diagnostic application. Full article

Background/Objectives: Filipendula ulmaria (L.) Maxim. (meadowsweet) is a medicinal plant traditionally used for its antioxidant and anti-inflammatory effects. There is also some data indicating its anticancer potential; however, its impact on colorectal cancer cells remains poorly understood. Here we investigated the cytotoxic and pro-apoptotic effects of an aqueous F. ulmaria extract on human LoVo colorectal cancer cells and analyzed some of the mechanisms underlying it. Methods: LoVo colorectal cancer cells were treated with the aqueous extract and analyzed for intracellular reactive oxygen species (ROS), mitochondrial membrane potential, DNA damage, lysosomal alterations, apoptosis-related mechanisms, and antioxidant activity. Phytochemical profiling was performed by HPLC-TOF/MS. Results: The extract elevated intracellular ROS levels, disrupted mitochondrial membrane potential, and induced DNA damage in LoVo cells. Activation of crucial caspases, along with increased p53 levels, confirmed engagement of both extrinsic and intrinsic apoptotic pathways. Changes in lysosomal fluorescence were also observed, indicating alterations in lysosomal properties. In chemical assays (FRAP, TAC, DPPH, ABTS, and superoxide scavenging), the extract demonstrated robust antioxidant capacity comparable to or exceeding that of ascorbic acid. Phytochemical profiling by HPLC-TOF/MS revealed a rich presence of bioactive flavonoids, phenolic acids, and coumarins. Altogether, our findings indicate that the extract’s cytotoxicity against colon cancer cells arises from a multifaceted mechanism involving oxidative stress, organelle dysfunction, and apoptosis induction. Conclusions: These results highlight F. ulmaria aqueous extract as a promising candidate for colorectal cancer phytotherapy as a form of supportive treatment and warrant further preclinical validation. Full article

Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can function as authentic immunogenic cell death (ICD) inducers by promoting the release of damage-associated molecular patterns (DAMPs), including calreticulin (CRT), ATP, and HMGB1. These events facilitate dendritic cell activation, antigen presentation, and the generation of long-term antitumor T-cell immunity. In addition to enhancing tumor immunogenicity, nsEPs profoundly remodel the tumor microenvironment (TME), including disruption of tumor vasculature, reduction in immunosuppressive cell populations, and alteration of stromal components. Emerging studies further suggest that nsEPs act as electric metabolic modulators capable of influencing mitochondrial function, calcium signaling, and metabolism-associated signaling pathways. Current evidence indicates that the immunological outcomes induced by nsEPs are highly dependent on pulse parameters, waveform characteristics, and tumor type. Despite its considerable therapeutic promise, the development of nsEP-induced ISV immunotherapy faces several important challenges, including standardization and optimization of pulse protocols, identification of critical molecular and cellular targets, and clarification of tumor- and cell-type-specific responses. Addressing these challenges through multidisciplinary collaboration and advanced technologies, including multi-omics, spatial analysis, and computational modeling, may accelerate the development of next-generation bioelectric immunotherapies for cancer treatment. Full article

Conventional water treatment relies on sequential flocculation and disinfection, which inflates infrastructure costs and heightens the risk of disinfection byproduct formation. Here, we report a magnetic lignin-based flocculant (LS-DMC-AM@Fe₃O₄) that integrates flocculation, sterilization, and rapid magnetic separation within a single material. The composite was synthesized by thermally initiated graft copolymerization of methacryloyloxyethyl trimethylammonium chloride (DMC) and acrylamide (AM) onto sodium lignosulfonate (LS), followed by incorporation of Fe₃O₄ nanoparticles (NPs) at 15 wt% loading; the product exhibited a saturation magnetization of 12.8 emu g⁻¹. LS-DMC-AM@Fe₃O₄ achieved 98.2% kaolin turbidity removal at 1 mg L⁻¹ and 98.6% E. coli removal at 8 mg L⁻¹, and displayed a markedly broader effective dosage window than its non-magnetic analog. We attribute this broadened window to Fe₃O₄-enhanced membrane disruption, which liberates anionic intracellular contents that buffer excess cationic charge and thereby suppress restabilization. The bactericidal efficiency reached 90% at 18 mg L⁻¹, 1.6-fold higher than LS-DMC-AM, governed by a synergistic dual mechanism: quaternary ammonium contact-killing coupled with Fe₃O₄ NP-induced intracellular reactive oxygen species (ROS) accumulation. Under an external magnetic field, flocs underwent rapid phase separation and displayed enhanced shear-regrowth capacity (E. coli floc recovery factor: 53% vs. 26%); Fe₃O₄ NPs were recovered at >95% efficiency over two cycles. Despite higher unit production costs, LS-DMC-AM@Fe₃O₄ delivers competitive per-unit-volume treatment economics through its ultralow effective dosage and magnetic seed recyclability. These results establish a viable strategy for engineering multifunctional, recyclable flocculants from industrial lignin waste. Full article

Tea tree essential oil (TTO), extracted from Melaleuca alternifolia, is a terpene-rich botanical antimicrobial with demonstrated broad-spectrum activity against foodborne pathogens and spoilage microorganisms. Its bioactivity is principally attributed to oxygenated monoterpenes, most notably including terpinen-4-ol, γ-terpinene, and α-terpinene, whose structure–activity relationships govern interactions with microbial membranes and intracellular targets. This review provides a comprehensive, mechanistically grounded analysis of TTO as a sustainable antimicrobial platform for food preservation applications. The physicochemical determinants of TTO performance are critically assessed, encompassing chemotype-dependent compositional variability, hydrophobicity, limited aqueous solubility, and oxidative instability, with emphasis on how these properties constrain efficacy in complex food matrices. Antimicrobial mechanisms are systematically examined, including membrane permeabilization, disruption of cellular homeostasis, oxidative stress induction, and quorum-sensing interference. Focus is placed on nanostructured delivery systems, including nanoemulsions, biopolymer-based encapsulants, and hybrid nanocomposites, that improve physicochemical stability, modulate release kinetics, and potentiate antimicrobial activity. The integration of these engineered formulations into edible coatings, active packaging, and sanitation protocols across fresh produce, meat, and dairy systems is evaluated in the context of practical food safety applications. Translational limitations are addressed, including volatility, sensory incompatibility, regulatory constraints, and concentration-dependent cytotoxicity considerations. Collectively, this review positions TTO-based nanoformulations as a scientifically promising and technologically scalable approach to next-generation food preservation, while identifying critical gaps that must be resolved to support regulatory acceptance and commercial implementation. Full article

White-nose syndrome (WNS), caused by the psychrophilic fungus Pseudogymnoascus destructans, poses a severe threat to wild bat populations. Caves serve as unique microecosystems. Exploring antagonistic microorganisms and their volatile antifungal compounds within these native environments has emerged as a promising ecological control strategy. In this study, we isolated four antagonistic bacterial strains from bat cave soil that completely inhibit P. destructans. Additionally, we identified benzaldehyde (BzH) and 2,5-dimethylpyrazine (2,5-DMP) as their primary antifungal volatile organic compounds (VOCs). Combined physiological, biochemical, and multi-omics analyses revealed that these two VOCs disrupt the structural integrity of the fungal cell wall and membrane. This disruption triggers abnormal energy metabolism and compensatory ATP accumulation, leading to a significant intracellular burst of reactive oxygen species and the impairment of primary antioxidant defenses. This sustained oxidative stress causes irreversible DNA damage, endoplasmic reticulum stress, and basal metabolic dysfunction. Consequently, this cascade induces apoptosis and significantly downregulates the expression of essential virulence genes. In conclusion, this study systematically elucidates the molecular network through which VOCs released by cave soil microorganisms antagonize P. destructans. These findings provide a theoretical foundation and candidate intervention molecules for the contactless biocontrol of WNS. Full article

Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation and membrane damage, with broad relevance to human disease. Accumulating evidence suggests that ferroptosis is governed by coordinated organelle-level regulation, among which lysosomes have emerged as central hubs. By controlling endolysosomal iron processing, transport, and degradation pathways, lysosomes shape the intracellular distribution and reactivity of iron, thereby modulating iron-driven lipid peroxidation. The acidic, iron-rich microenvironment and limited local antioxidant capacity render lysosomal membranes highly susceptible to oxidative injury, positioning lysosomes as initiation and amplification sites of lipid peroxidation. Meanwhile, lysosome-dependent selective autophagy pathways actively remodel iron homeostasis, lipid metabolism, and cellular antioxidant defenses, thereby dynamically modulating ferroptotic sensitivity. Mitochondria–lysosome crosstalk further redistributes iron, reactive oxygen species, and lipid substrates, linking lysosomal activity to interorganelle control of ferroptosis. Lysosomal stress-responsive signaling also coordinates metabolic adaptation and redox control. This review summarizes and integrates current evidence on lysosome-centered mechanisms that organize iron metabolism, lipid peroxidation, selective autophagy, organelle crosstalk, and stress-responsive signaling during ferroptosis, and further discusses their disease-specific roles, therapeutic potential, and translational challenges. Full article

Eosinophils are highly granulated white blood and tissue cells that play complex roles in the immune system including host protection against helminthic parasites, viruses, fungi, and bacteria. These bone marrow-derived cells cause tissue damage in a range of diseases and disorders, particularly in allergy, asthma, and chronic rhinosinusitis with nasal polyps. Eosinophils are recruited to tissues in response to chemotactic signals, and during inflammation, they release a plethora of mediators, including immunoregulatory cytokines, through multiple pathways involving degranulation, respiratory burst, lipid mediator release, exosome release, and extracellular trap formation. Degranulation from eosinophils has been implicated as a major effector mechanism in airway diseases, particularly late phase asthma responses and in nasal polyps from patients with chronic rhinosinusitis. In degranulation responses, eosinophils release numerous granule proteins by classical exocytosis, compound exocytosis, piecemeal degranulation, and cytolysis, which refers to cell lysis through membrane rupture and cell destruction. Cytolysis can lead to suicidal extracellular trap formation, which is a regulated form of cell death involving the release of extracellular DNA traps and granule proteins. Granule release from eosinophils is dependent on activation of specific and tightly regulated intracellular signaling pathways, including Rac and Rab guanosine triphosphatases, soluble NSF attachment protein (SNAP) receptors (SNAREs), Cdk5 kinase, and actin dynamics. These observations have shown selective and nonredundant roles for signaling in degranulation responses. In this review, we explore findings from the literature on the mechanisms controlling granule-derived mediator release from eosinophils. Full article

Background: Membrane potential represents one of the fundamental physiological characteristics of cells, playing a critical role in cellular function. Studies have shown that membrane hyperpolarization positively regulates the osteogenic differentiation of mesenchymal stem cells. Optogenetic technology based on the Natronomonas pharaonis halorhodopsin (NpHR) light-activated channel can induce membrane hyperpolarization through optical methods. Given the working principle of optogenetic technology, this study aimed to investigate whether optogenetic activation of NpHR channels could induce membrane hyperpolarization in human dental follicle stem cells (hDFCs)—mesenchymal stem cells derived from dental follicle tissue—to regulate their osteogenic differentiation. Methods: hDFCs were isolated and cultured. Engineered hDFCs expressing the NpHR channels were constructed through lentiviral transduction. Patch clamps were performed to observe the effects of optogenetic activation of NpHR channels on membrane potentials of hDFCs. Single-cell Ca²⁺ imaging were performed to observe the effects of membrane hyperpolarization via modulation of extracellular K⁺ concentration ([K⁺]_e) on the intracellular Ca²⁺ levels of hDFCs. Cell viability assay, transwell chamber assay, wound healing assay, osteogenic differentiation induction, alizarin red staining, alkaline phosphatase (ALP) staining, real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and Western blot (WB) were performed to observe the effects of optogenetic activation of NpHR channels on proliferation, migration, and osteogenic differentiation of NpHR-hDFCs. Results: Reversing membrane hyperpolarization via modulation of extracellular K⁺ concentration ([K⁺]_e) was shown to suppress osteogenic differentiation of hDFCs, whereas promoting membrane hyperpolarization via opening ATP-sensitive K⁺ channels was shown to enhance osteogenic differentiation of hDFCs. Hyperpolarizing cells by decreasing [K⁺]_e increased intracellular Ca²⁺ levels of hDFCs. Optogenetic activation of NpHR channels by an optogenetic system induced membrane hyperpolarization and significantly enhanced the proliferation, migration, and osteogenic differentiation abilities of NpHR-hDFCs. Conclusions: Hyperpolarization by optogenetic activation of NpHR channels can promote hDFCs’ proliferation, migration, and osteogenic differentiation abilities. Full article

Carbohydrate-active enzymes (CAZymes) encoded by the human gut microbiome are central mediators of dietary glycan metabolism and host–microbe biochemical homeostasis. Among these, β-glucuronidases represent functionally pivotal hydrolases implicated in metabolism, intestinal physiology, and therapeutic modulation. The present study performs an integrative in silico structural and functional interrogation of β-glucuronidases derived from Acidobacterium capsulatum (3VNY), Bacteroides ovatus (6D8K), and Faecalibacterium prausnitzii (6ED2). An integrated computational framework encompassing physicochemical parameters profiling, hierarchical structural prediction, tertiary-structure validation, salt-bridge energetics, functional domain and motif annotation, protein–protein interaction reconstruction, ligand-binding thermodynamics via molecular docking, and residue-resolved non-covalent interaction network mapping using the Protein Contacts Atlas (PCA) was employed. Physicochemical analyses indicated that all enzymes are thermostable, intracellular, and hydrophilic, while secondary-structure organization revealed a functional balance between helix-mediated rigidity and coil-driven flexibility. Structural validation metrics identified 6ED2 as the most conformationally stable architecture, whereas 6D8K displayed enhanced functional complexity, including enriched motif composition, membrane-associated features, and superior ligand-binding affinity. Docking simulations highlighted castanospermine and calcium saccharate as the most favorable interacting ligands across enzyme variants. Importantly, PCA-based interaction analysis revealed distinct ligand-centered atomic contact networks, with immediate contact counts of 57 (3VNY), 32 (6D8K), and 41 (6ED2), providing residue-level insight into stabilization mechanisms and interaction topology beyond conventional docking metrics. Collectively, these findings establish a multidimensional computational framework linking structural stability, functional diversification, ligand recognition, and atomic interaction networks in gut microbial β-glucuronidases, thereby supporting future biochemical validation, microbiome-targeted therapeutics, and biotechnological or cosmeceutical applications. Full article

Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase activity assays. Combined nsPEF–CAP treatment significantly outperformed either modality alone in inducing cell death. Mechanistically, dual treatment triggered a surge in intracellular ROS, particularly mitochondrial superoxide, indicating severe oxidative stress. Distinct mitochondrial responses were observed: nsPEF reduced mitochondrial membrane potential, whereas CAP alone caused a slight elevation. Notably, while CAP induced apoptosis (evidenced by increased cleaved caspase-3 and caspase-3/7 activity), lethal nsPEF (100 pulses) caused cell death without triggering apoptotic signaling. However, mild nsPEF (20 pulses) significantly potentiated CAP-induced apoptosis. These findings suggest that nsPEF sensitizes cells to CAP treatment by amplifying oxidative stress and mitochondrial dysfunction. This synergistic combination represents a promising therapeutic approach for managing pancreatic cancer cells resistant to conventional therapies. Full article

The non-specific lipid transfer proteins (nsLTPs) are able to bind various hydrophobic compounds and facilitate the transport of fatty acids between intracellular membranes, and nsLTPs are found in rice endosperm and embryo during seed development. However, whether nsLTPs function as lipid carriers and thereby affect lipid metabolism in rice grains remains unclear. To elucidate whether nsLTPs influence fatty acid distribution in rice, we generated OsLTP10-OE (OsLTP10 overexpression) and OsLTP10-CR (OsLTP10 CRISPR/Cas9) lines. Phenotypic and metabolic analyses indicated that OsLTP10 expression is closely associated with fatty acid (FA) profiles and grain appearance. In general, total fatty acid content in the brown rice of OsLTP10-OE was higher than that in wildtype, but OsLTP10-CR was lower than wildtype. While FA accumulation was altered in both tissues, the endosperm (milled grain) was more severely affected than the bran, with individual FAs in the milled grains of OsLTP10-OE expanding by 31.87–52.00%. Additionally, key grain quality traits were substantially altered; OsLTP10-CR lines displayed a significantly enlarged white-belly chalkiness area alongside a 19.50% reduction in amylose content, whereas OsLTP10-OE lines showed decreased chalkiness and a 7.80% increase in amylose. Overall, the fatty acid content and composition, chalkiness, brown rice size, and amylose were influenced by OsLTP10. Full article

Chlamydia trachomatis is an obligate intracellular prokaryote. During the process of infecting host cells, C. trachomatis forms a unique inclusion structure, which serves as a critical niche for the survival and replication of C. trachomatis within host cells. The inclusion membrane is composed of various inclusion membrane proteins (Inc proteins), which play a pivotal role in the interaction between C. trachomatis and host cells. This review illustrates functional research progress of C. trachomatis Inc proteins and their molecular interactions with host cells, facilitating deeper understanding of chlamydial pathogenic mechanisms. Full article

Carnosine is a naturally occurring endogenous dipeptide with great potential to improve reproductive function and fertility. In this study, supplementation of 1 μg/mL carnosine during in vitro maturation (IVM) significantly enhanced the developmental competence and quality of the resulting bovine embryos. Carnosine treatment effectively elevated mitochondrial membrane potential, mitochondrial activity, and ATP content in oocytes. Moreover, it strengthened the antioxidant and anti-apoptotic capacities of oocytes, as evidenced by reduced intracellular reactive oxygen species (ROS) levels, lowered DNA damage and an early apoptosis rate, alongside increased glutathione (GSH) content, an elevated BCL2/BAX mRNA ratio, and upregulation of antioxidant genes SOD1, CAT, GPx1, and GPx4. Notably, combined application of 1 μg/mL carnosine during IVM and 10⁻⁷ M melatonin during in vitro culture (IVC) synergistically improved both blastocyst development and quality. Collectively, these findings provide novel evidence supporting the therapeutic potential of carnosine in optimizing in vitro embryo production in bovine, and highlight the value of stage-specific supplementation strategies to further improve embryonic development efficiency. Full article