Search Results (455)

Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Existing research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells, and bone resorption in an ovariectomized rat model. The results revealed that L-quebrachitol suppressed RANK-mediated signaling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both the gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. In addition, proteasome subunit alpha type-5 (PSMA5), which is involved in the degradation of the NF-κB inhibitor, was also suppressed. In particular, the animal study clearly supported the bone homeostasis property of the agent by increasing the BV/TV (bone volume/total volume) and Tb.Th (trabecular thickness) in ovariectomized rats. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of RANK-mediated signaling pathways and prevention of bone loss in an animal model. However, further exploration of the potential of L-quebrachitol as an effective approach for osteoporosis is required. Full article

Microparticle detection technology uses materials that can specifically recognize complex biostructures, such as antibodies and aptamers, as trapping agents. The development of antibody production technology and simplification of sensing signal output methods have facilitated commercialization of disposable biosensors, making rapid diagnosis possible. Although this contributed to the early resolution of pandemics, traditional biosensors face issues with sensitivity, durability, and rapid response times. We aimed to fabricate microspaces using metallic materials to further enhance durability of mold fabrication technologies, such as molecular imprinting. Low-damage metal deposition was performed on target protozoa and Norovirus-like particles (NoV-LPs) to produce thin metallic films that adhere to the material. The procedure for fitting the object into the bio structured space formed on the thin metal film took less than a minute, and sensitivity was 10 fg/mL for NoV-LPs. Furthermore, because it was a metal film, no decrease in reactivity was observed even when the same substrate was stored at room temperature and reused repeatedly after fabrication. These findings underscore the potential of integrating stable metallic structures with bio-recognition elements to significantly enhance robustness and reliability of environmental monitoring. This contributes to public health strategies aimed at early detection and containment of infectious diseases. Full article

Acute pancreatitis (AP) is a severe inflammatory disorder characterized by a complex molecular pathophysiology involving premature zymogen activation, organelle dysfunction, and systemic immune dysregulation. Current therapeutic strategies remain largely supportive, underscoring the critical need for specific molecular-targeted interventions. Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis Georgi, has emerged as a potent pleiotropic agent. This review comprehensively synthesizes the molecular mechanisms underlying baicalein’s therapeutic efficacy in AP. Its capacity to intercept the pathological cascade at multiple checkpoints is elucidated, from mitigating the initiating cytosolic calcium overload and preserving mitochondrial integrity to suppressing the cytokine storm via the TLR4/NF-κB/MAPK signaling axis. Crucially, baicalein modulates the pancreatic immune microenvironment by driving the phenotypic polarization of macrophages from pro-inflammatory M1 to reparative M2 states and regulating neutrophil dynamics, specifically by inhibiting infiltration and neutrophil extracellular trap formation. Furthermore, its role in orchestrating regulated cell death pathways is highlighted, specifically by blocking pyroptosis and ferroptosis while modulating apoptosis, and its function as a biophysical scavenger of circulating histones and pancreatic lipase to neutralize systemic toxins. Consequently, this review emphasizes the multi-target biological activities of baicalein, providing a mechanistic rationale for its development as a precision therapeutic candidate for AP. Full article

Pulmonary arterial hypertension (PAH) is a severe, progressive vasculopathy characterized by endothelial dysfunction, medial hypertrophy, and maladaptive vascular and cardiac remodelling that ultimately leads to right-heart failure and premature death. Despite advances in vasodilator therapies targeting endothelin, nitric oxide, and prostacyclin pathways, a substantial proportion of patients fail to achieve or maintain a low-risk profile, highlighting the need for disease-modifying strategies. Dysregulation of transforming growth factor-β (TGF-β) superfamily signalling, with excessive activin and growth differentiation factor activity and impaired bone morphogenetic protein signalling, plays a central role in PAH pathobiology. Sotatercept, a first-in-class activin signalling inhibitor, restores this imbalance by selectively trapping pro-proliferative ligands, thereby addressing a key molecular driver of pulmonary vascular remodelling. Evidence from pivotal phase II and III trials—PULSAR, STELLAR, ZENITH, and HYPERION—demonstrates that sotatercept significantly improves exercise capacity, haemodynamics, and risk status when added to background therapy. This review summarises the molecular mechanisms underlying sotatercept’s therapeutic effects, synthesises the current clinical evidence, and discusses its emerging role as a disease-modifying agent capable of promoting reverse pulmonary vascular remodelling within contemporary PAH management. Full article

Mushrooms like Inonotus obliquus and Ganoderma lucidum show significant pharmacological promise. This review analyzes fungi as sources of natural inhibitors against Advanced Glycation End-products (AGEs)—key drivers of diabetes and neurodegeneration. We highlight that extracts from Lignosus rhinocerus and Auricularia auricula exhibit antiglycation potency (IC₅₀ as low as 0.001 mg/mL) superior to aminoguanidine. Inhibitory effects are attributed to bioactive fractions including FYGL proteoglycans, uronic acid-rich polysaccharides, and fungal-specific metabolites like ergothioneine. These compounds act through multi-target mechanisms across the glycation cascade: competitive inhibition of Schiff base formation, trapping reactive dicarbonyls (e.g., methylglyoxal), transition metal chelation, and direct scavenging of reactive oxygen species (ROS). Furthermore, the review addresses the transition from in vitro potency to in vivo efficacy (RAGE pathway modulation), stability during food processing (UV-B irradiation), and critical safety issues regarding heavy metal bioaccumulation. Mushroom-derived inhibitors represent a sustainable therapeutic alternative to synthetic agents, offering broader protection against glycative stress. This synthesis provides a foundation for developing standardized mushroom-based nutraceuticals for managing AGE-related chronic disorders. Full article

Background: The in vivo accumulation of Advanced Glycation End products (AGEs) is associated with the development of several chronic aging-related and degenerative diseases, as they alter protein structures and activate oxidative and inflammatory processes through interactions with the receptor for AGEs (RAGE). Plant secondary metabolites play a key role in counteracting the glycation process through various mechanisms of action. Therefore, Aloysia citrodora leaf polyphenolic extract could represent a source of anti-glycative compounds. Methods: The methanolic extract was characterized by RP-HPLC-DAD-MSⁿ, and its anti-glycative properties were investigated using several in vitro assays mimicking the different steps of the glycation reaction. In parallel, molecular docking studies were carried out to evaluate potential interactions between the identified metabolites and RAGE. Furthermore, A. citrodora metabolites’ stability under simulated in vitro digestion was assessed, and the anti-glycative activity of the bioaccessible fraction was investigated. Results:A. citrodora extract, rich in iridoid glycosides, phenylethanoid glycosides, and flavones, strongly inhibited AGE formation (from 10% to 100%) in both the middle and end step of the reaction and had high methylglyoxal and glyoxal trapping capacity. However, the digestion process affected extract stability, particularly under intestinal conditions, yielding an overall bioaccessibility of about 40% and leading to a subsequent reduction in anti-glycative properties. Finally, molecular modeling analysis highlighted the ability of the studied metabolites to bind RAGE. Conclusions:A. citrodora represents a promising source of natural anti-glycative agents with potential applications as food ingredients. However, it is essential to improve the extract bioaccessibility and to preserve its anti-glycative properties by developing a suitable formulation. Full article

The vegetative mycelium of Pleurotus ostreatus (oyster mushroom) exhibits the ability to reduce nematode populations. This property may be utilized in integrated management programs targeting harmful nematodes such as Heterodera schachtii, a major pest of sugar beet crops. In addition to sugar beet, many other plant species serve as hosts for this nematode; susceptible plants promote H. schachtii development and population growth. Current control strategies rely on integrated plant protection methods, including the use of tolerant cultivars, fallowing, and trap crops such as oilseed radish and white mustard. This study aimed to determine whether sugar beet cv. Janetka or nematocidal plants—oilseed radish cv. Romesa and white mustard cv. Bardena—affect the nematocidal activity of P. ostreatus mycelium when applied together. Specifically, the influence of root or seed secretions from these plants on the activity of ten P. ostreatus mycelial strains was assessed using the model nematode Caenorhabditis elegans and the target pest H. schachtii. Experiments were conducted under laboratory conditions on water agar media colonized by P. ostreatus mycelium. Seeds or root exudates of the tested plants were applied to the mycelial surface. Following incubation, nematode mobility (C. elegans) and cyst entwining by the mycelium (H. schachtii) were evaluated, along with the ability of the mycelium to produce toxocysts. The results indicate that trap plants did not significantly alter the nematocidal activity of the mycelium. However, certain mycelial strains were slightly stimulated by seed diffusates or root exudates. Oilseed radish moderately influenced the nematocidal activity of four mycelial strains against C. elegans, whereas in the case of H. schachtii, similar effects were observed with white mustard. The mycelial elimination of H. schachtii occurred through cyst entwining, which was generally more effective in the presence of plant exudates. Overall, the findings demonstrate that incorporating trap crops such as oilseed radish cv. Romesa or white mustard cv. Bardena, as green manure in crop rotation systems, does not interfere with the nematocidal activity of P. ostreatus mycelium and simultaneously may enrich the soil with nutrients. The study further confirms that P. ostreatus maintains its ability to effectively entwine and eliminate H. schachtii cysts even in the presence of sugar beet, supporting its potential role as a biological control agent. To our knowledge, this is the first experiment that integrates the activities of trap plants and sugar beet with the nematocidal effects of P. ostreatus mycelium. Full article

The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article

In capital-intensive industries, operational knowledge is often trapped in unstructured technical manuals, creating a barrier to efficient and reliable maintenance planning. This work addresses the need for an integrated system that can automate knowledge extraction and generate optimized, resilient, operational plans. A synergistic multi-agent framework is introduced that transforms unstructured documents into a structured knowledge base using a self-validating pipeline. This validated knowledge feeds a scheduling engine that combines multi-objective optimization with discrete-event simulation to generate robust, capacity-aware plans. The framework was validated on a complex maritime case study. The system successfully constructed a high-fidelity knowledge base from unstructured manuals and the scheduling engine produced a viable, capacity-aware operational plan for 118 interventions. The optimized plan respected all daily (6) and weekly (28) task limits, executing 64 tasks on their nominal date, bringing 8 forward, and deferring 46 by an average of only 2.0 days (95th percentile 4.8 days) to smooth the workload and avoid bottlenecks. An interactive user interface with a chatbot and planning calendar provides verifiable “plan-to-page” traceability, demonstrating a novel, end-to-end synthesis of document intelligence, agentic AI, and simulation to unlock strategic value from legacy documentation in high-stakes environments. Full article

Soil-dwelling beetles, including native and invasive species such as Popilia japonica Newman (Coleoptera: Scarabaeidae), are persistent and damaging agricultural pests worldwide. Mass trapping, using pheromone-, light-, or food-based lures to attract and remove adults, is being developed as an environmentally sustainable alternative within integrated pest management (IPM). Scarab beetles respond positively to attractant-based traps, and large-scale programs against P. japonica in North America provide valuable insights for global applications. The efficacy of mass trapping depends on species biology, trap density, environmental conditions and landscape structure. Capturing adults does not always immediately reduce larval populations, as underground stages persist in soil for multiple years. Light traps are effective but often attract many non-target insects, whereas pheromone traps are more selective but require careful optimization of lure composition, release rate and placement. To achieve reliable suppression, mass trapping should be integrated with complementary strategies such as biological control agents (Beauveria spp., Metarhizium spp.), crop rotation, tolerant crop varieties and soil management. Future research should focus on refining lure design, optimizing deployment, testing predictive models and evaluating multi-bait systems. Overall, mass trapping represents a promising and environmentally sustainable tool that, when incorporated into integrated approaches, can enhance the management of soil-dwelling scarab beetles across diverse agroecosystems worldwide. Full article

Background/Objectives: Cutaneous lupus erythematosus (CLE) is a complex autoimmune skin disease driven by genetic predisposition, environmental triggers, and immune dysregulation. Environmental factors such as ultraviolet radiation, smoking, and certain drugs can initiate disease onset by inducing keratinocyte apoptosis. The subsequent release of nucleic acids and danger-associated molecular patterns activates pattern recognition receptors (PRRs) on keratinocytes and immune cells, leading to the production of type I and type III interferons (IFNs) and pro-inflammatory cytokines. The objective of this review is to summarize recent advances in understanding the immunopathogenesis of CLE, with particular attention to emerging cellular players and their therapeutic implications. Methods: A narrative review of the recent literature was performed, including experimental, translational, and clinical studies investigating the cellular and molecular mechanisms underlying CLE and novel targeted treatments derived from these findings. Results: Although plasmacytoid dendritic cells (pDCs) have traditionally been considered the major producers of IFN-I, recent data indicate that pDCs in CLE are functionally impaired and are not the primary source. Other cells, such as keratinocytes have emerged as key producers of IFN-I, contributing to a prelesional, IFN-rich microenvironment. This promotes the recruitment and activation of dendritic cells and other inflammatory myeloid subsets, which are now recognized as central players in amplifying local inflammation. Concurrently, T cells infiltrate the skin, where cytotoxic CD8⁺ T cells attack keratinocytes and CD4⁺ T cells further propagate inflammation via cytokine production. B cells and plasma cells produce autoantibodies, forming immune complexes that perpetuate inflammation. Neutrophils release neutrophil extracellular traps (NETs), exposing autoantigens and further stimulating IFN pathways. Macrophages contribute by presenting autoantigens, producing pro-inflammatory mediators, and failing to effectively clear apoptotic cells and immune complexes. Conclusions: The dynamic interplay between the innate and adaptive immune systems sustains the chronic inflammatory state characteristic of CLE. Based on the pathogenetic novelties, new therapeutic agents targeting specific molecules have been developed, which may improve the treatment of this complex disease in the future. Full article

Thymoquinone (TQ), the main bioactive ingredient of Nigella sativa, exhibits numerous pharmacological activities and is used for the prevention of many diseases including hypertension and cancer. However, information concerning the effects of TQ on platelets is limited. In this study, we used the upgraded laser microparticle analyzer LaSca-TMF for simultaneous analysis of platelet shape change, aggregation, and changes in [Ca²⁺]_i. We showed that TQ acutely inhibited platelet aggregation induced by ADP, Trap-6, and CRP; however, the rise of [Ca²⁺]_i was inhibited only in CRP-stimulated platelets, but not in ADP- or Trap-6-stimulated ones. DTT, a thiol-reducing agent, prevented TQ-induced effects in platelets, indicating that protein disulfide isomerases could be involved in the regulation of TQ effects on platelets. Our results, for the first time, demonstrated acute inhibitory effects of TQ on platelet activation induced by GPCRs and ITAM-containing receptors, which were independent of PKA and caspase-3 activation. To the best of our knowledge, this is the first example in which complete inhibition of ADP- and Trap-6-, but not CRP-induced, aggregation is accompanied by high [Ca²⁺]_i levels. Additional experimental approaches are required to explain some effects of TQ on calcium homeostasis and TQ could be a valuable molecule for the analysis of calcium homeostasis in platelets and other cells. Full article

In response to the urgent need for sustainable antibacterial solutions against antibiotic-resistant pathogens, this study presents a facile dendritic polymer-assisted approach for synthesizing highly active ZnO/mesoporous silica nanocomposites (SBA-15, SBA-16, KIT-6, MSU-X). Two hyperbranched polymers—polyethyleneimine (PEI) and carboxy-methylated polyethyleneimine (Trilon-P, TrP)—were employed as templating and metal-trapping agents. The influence of pore geometry, polymer functionality, and polymer-loading method (wet or dry impregnation) on ZnO nanoparticle (NP) formation was systematically examined. All nanocomposites exhibited high structural homogeneity, incorporating ultrasmall or amorphous ZnO NPs (1–10 nm) even at 8 wt.% Zn loading. Zn uptake was strongly dependent on polymer end groups, while the spatial distribution of ZnO NPs was dictated by the silica host structure. Antibacterial assays against Staphylococcus aureus revealed remarkable activity, particularly for ZnO/SBA-15_PEI, ZnO/SBA-16_PEI, and ZnO/MSU-X_TrP nanocomposites, with minimum inhibitory concentrations of 1–2.5 μg mL⁻¹ Zn and over 90% mammalian cell viability. Life Cycle Assessment identified energy use as the main environmental factor, with ZnO/SBA-15_PEI_WI displaying the lowest impact. Overall, the interplay between silica pore architecture, polymer type, and impregnation method governs ZnO accessibility and bioactivity, establishing a versatile strategy for designing next-generation ZnO/SiO₂ nanocomposites with tunable antibacterial efficacy and minimal cytotoxic and environmental footprint. Full article

We studied differences in the decomposition rate between Pinus merkusii Jungh. et de Vriese (tusam) leaves, a representative of needle leaf litter, and Diospyros celebica Bakh. (ebony) leaves, a representative of broadleaf litter, in three forest communities (Karst, Lowland, Pine) on the island of Sulawesi, Indonesia, and identified their determinants. Twenty-four 1 m × 1 m quadrats were set up in each forest community to observe the in situ decomposition process. Near each quadrat, 1 m² litter traps were set to monitor litter production. In addition, 30 litter bags containing tusam leaves and 30 litter bags containing ebony leaves were spread in the three forest communities, in both the dry and wet seasons, to observe their decomposition rate during each season. The ANOVA test showed that the one-year in situ Decomposition Rate Constant (k) was significantly highest in the Karst forest (0.0921/year), followed by the Lowland forest (0.0700/year), and the lowest in the Pine forest (0.0277/year). During the dry season, the mean k-value of tusam leaves was significantly faster than ebony leaves in Karst (0.7162/6 months for tusam, 0.3840/6 months for ebony) and Lowland forests (0.3472/6 months for tusam, 0.1017/6 months for ebony), but on the contrary, it is slower in the Pine forest (0.0498/6 months for tusam, 0.0745/6 months for ebony). During the wet season, there was no significant difference between the mean k-value of tusam leaves compared to ebony leaves in the Karst (0.5217/4 months for tusam, 0.4859/4 months for ebony) and Lowland (0.2397/4 months for tusam, 0.2098/4 months for ebony) forests, but in the Pine forest, the mean k-value of ebony leaves was significantly higher than that of tusam leaves (0.0942/4 months for tusam, 0.1650/4 months for ebony). This study explains that the decomposition process of leaf litter is complex, species-specific, and is controlled by a combination of factors. Extrinsic factors play a more critical role than intrinsic factors in determining the k-value. The low rate of decomposition of tusam leaves under its mother tree stands is not caused by intrinsic factors, but rather by extrinsic factors that inhibit the growth of decomposing agents. Full article

In the nuclear industry, the decontamination of nuclear metallic structures is an essential process to reduce radiation exposure during maintenance or dismantling. The oxide layer, such as chromium (III) oxide (Cr₂O₃), formed on stainless steel and nickel-based alloys, contributes significantly to surface radioactivity by trapping radioactive contaminants. To address this, permanganic acid (HMnO₄) has proven to be a promising oxidizing agent for dissolving these oxide layers—particularly chromium oxide—on stainless steel and nickel-based alloys. In this study, HMnO₄ was synthesized via ion exchange using AmberLite IRN97 H resin and potassium permanganate (KMnO₄). The optimized process yielded a highly acidic solution (pH~1.6) with potassium concentrations below 0.1 ppm, indicating near-complete exchange efficiency. Dissolution kinetics were investigated at HMnO₄ concentrations ranging from 240 to 1920 ppm and temperatures from 30 °C to 80 °C. At a constant temperature, increasing HMnO₄ concentration significantly improved Cr dissolution, with up to 31% of total chromium solubilized after 33 h. Lower temperatures favored higher dissolution efficiency, likely due to improved thermal stability of HMnO₄. For durations shorter than 4 h, the influence of temperature was limited compared to the effect of acid concentration. To assess post-treatment options, HMnO₄ decomposition was studied using oxalic acid (H₂C₂O₄) at 80 °C. Results showed that a minimum H₂C₂O₄/HMnO₄ molar ratio above 2.75 was necessary to achieve effective reduction while preventing MnO₂ precipitation. However, even under strongly acidic conditions and with a large excess of reductant, Mn²⁺ yields remained below 55%, suggesting that thermal degradation of oxalic acid and possible formation of undetected manganese species limited the reduction process. Full article