Search Results (177)

Membrane rupture, induced by lipid peroxidation, is a severe threat to osmotic balance, as membrane pores contribute to ferroptosis, an iron-dependent cell death. To alleviate osmotic stress, membrane constituents dynamically reconstruct the membrane and interact with intracellular molecules. Tumor-derived acidosis shift glycolysis-dependent metabolism toward lipid metabolism, increasing polyunsaturated fatty acids (PUFAs). PUFAs enhance membrane fluidity but make cancer susceptible to lipid peroxidation. Also, the ionization of phospholipids under low pH can accelerate membrane rupture. This stress can be mitigated by the redistribution of cholesterol, which maintains tension–compression balance and acts as antioxidants. When excessive reactive aldehydes—byproducts of lipid peroxidation—overwhelm cholesterol’s protective role, lipid peroxides promote membrane cracks. Moreover, a deficiency in glutathione can alter cholesterol’s function, turning it into a pro-oxidant. In contrast, ceramide, derived from membrane lipids, indirectly prevents ferroptosis by facilitating cytochrome c release. This review integrates recent findings on how membrane components and environmental stressors influence ferroptosis. It also suggests potential therapeutic strategies. This could advance our understanding of ferroptosis in cancer. Full article

Herba Hyssopi is a key remedy in Uighur medicine for asthma and cough, frequently used as the monarch or minister herb in prescriptions. However, the lack of effective quality assessment methods complicates the detection of adulteration with common substitutes. In this study, UPLC-LTQ-Orbitrap-MS, network pharmacology, molecular docking, and cell experiments were employed to establish scientific and effective quality control methods to differentiate Hyssopus cuspidatus Boiss from its common adulterants. The results showed that a total of 41 chemical constituents were identified from Herba Hyssopi. Network pharmacology analysis revealed 133 potential target genes associated with its therapeutic actions, among which EGFR, MMP9, TNF, PTGS2, MAPK3, ESR1, and TP53 emerged as key targets. Cellular experiments further demonstrated that diosmin, linarin, and rosmarinic acid significantly suppressed nitric oxide (NO) generation and the release of pro-inflammatory cytokines. Based on these findings, a validated HPLC method was established for the simultaneous quantification of these three bioactive markers, providing a reliable tool for the quality assessment and authentication of Herba Hyssopi. This study offers a scientific basis for improving the standardization and quality control of Herba Hyssopi in traditional medicine applications. Full article

Cigarette smoking is the leading preventable cause of chronic diseases (e.g., COPD, cardiovascular disease, cancer), largely driven by persistent immune-inflammatory mechanisms. This review synthesizes the molecular and cellular cascades linking cigarette smoke (CS) exposure to chronic pathology. CS constituents, particularly ROS/RNS, induce rapid oxidative stress that overwhelms antioxidant defenses and generates damage-associated molecular patterns (DAMPs). These DAMPs activate pattern recognition receptors (PRRs) and the NLRP3 inflammasome, initiating NF-κB signaling and the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). CS exposure causes profound innate immune dysregulation, including airway epithelial barrier disruption, hyperactivated neutrophils, and dysfunctional alveolar macrophages (AMs) that release destructive proteases (e.g., MMP-12) and acquire foam-cell–like characteristics. Furthermore, CS drives adaptive immunity toward a Th1/Th17-dominant phenotype while suppressing regulatory T-cell (Treg) function, thereby promoting autoimmunity and chronic tissue injury. Critically, CS induces epigenetic reprogramming (e.g., DNA methylation, miRNA dysregulation), locking immune cells into a persistent pro-inflammatory state. This convergence of oxidative stress, innate and adaptive immune dysregulation, and epigenetic alterations underlies the systemic low-grade inflammation that fuels smoking-related chronic diseases, highlighting key targets for novel therapeutic interventions. Full article

Background/Objectives: Wound healing is a complex biological process influenced by inflammation, oxidative stress, and cellular regeneration. Plant-derived bioactive compounds have shown potential to accelerate tissue repair through antioxidant and anti-inflammatory mechanisms. This study aimed to develop and evaluate a Platanus orientalis extract-loaded liposomal formulation for potential wound-healing applications. Methods: Four polar extracts (P1–P4) were prepared using different solvent systems and extraction techniques and were characterized by LC-HRMS to determine their phytochemical profiles. Among the identified constituents, quercetin was consistently detected across all extracts and selected as the reference compound due to its well-known wound-healing activity. Liposomes were prepared via thin-film hydration followed by probe sonication and characterized for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and total drug content. In vitro release, cytotoxicity, and wound-healing assays were subsequently conducted to assess performance. Results: The optimized liposome formulation had a mean particle size of 106.6 ± 5.4 nm, a PDI of 0.11 ± 0.04, and a zeta potential of −14.1 ± 0.5 mV. Environmental scanning electron microscopy (ESEM) confirmed the nanosized spherical morphology and homogeneous vesicle distribution, supporting the successful development of the liposomal delivery system. Encapsulation efficiency and total drug content were determined as 72.25 ± 1.05% and 96.15 ± 0.14%, respectively. In vitro release studies demonstrated a biphasic pattern with an initial burst followed by a sustained release, reaching approximately 75% cumulative quercetin release within 24 h. Physical stability testing confirmed that the optimized liposomal formulation remained physically stable at 5 ± 3 °C for at least 60 days. The optimized formulation showed no cytotoxic effects on CDD-1079Sk fibroblast cells and exhibited significantly enhanced wound closure in vitro. Conclusions: These findings indicate that the liposomal delivery of Platanus orientalis extract provides a biocompatible and sustained-release system that enhances wound-healing efficacy, supporting its potential use in advanced topical therapeutic applications. Full article

Calcium (Ca²⁺) is a signal messenger for ion flow in and out of microbial, parasitic, and host defense cells. Manipulation of calcium ion signaling with ion blockers and calcineurin inhibitors may improve host defense while decreasing microbial/parasitic resistance to therapy. Ca²⁺ release from intracellular storage sites controls many host defense functions (cell integrity, movement, and growth). The transformation of phospholipids in the erythrocyte membrane is associated with changes in deformability. This type of lipid bilayer defense mechanism helps to prevent attack by Plasmodium. Patients with sickle cell disease (SS hemoglobin) do not have this protection and are extremely vulnerable to massive hemolysis from parasitic infestation. Patients with thalassemia major also lack parasite protection. Alteration of Ca²⁺ ion channels responsive to environmental stimuli (transient receptor potential) results in erythrocyte protection from Plasmodium. Similarly, calcineurin inhibitors (cyclosporine) reduce heart and brain inflammation injury with Trypanosoma and Taenia. Ca²⁺ channel blockers interfere with malarial life cycles. Several species of parasites are known to invade hepatocytes: Plasmodium, Echinococcus, Schistosoma, Taenia, and Toxoplasma. Ligand-specific membrane channel constituents (inositol triphosphate and sphingosine phospholipid) constitute membrane surface signal messengers. Plasmodium requires Ca²⁺ for energy to grow and to occupy red blood cells. A cascade of signals proceeds from Ca²⁺ to two proteins: calmodulin and calcineurin. Inhibitors of calmodulin were found to blunt the population growth of Plasmodium. An inhibitor of calcineurin (cyclosporine) was found to retard population growth of both Plasmodium and Schistosoma. Calcineurin also controls sensitivity and resistance to antibiotics. After exposure to cyclosporine, the liver directs Ca²⁺ ions into storage sites in the endoplasmic reticulum and mitochondria. Storage of large amounts of Ca²⁺ would be useful if pathogens began to occupy both red blood cells and liver cells. We present scientific evidence supporting the benefits of calcium channel blockers and calcineurin inhibitors to potentiate current antiparasitic therapies. Full article

Objective: Ischemic stroke (IS) is an acute neurologic injury in which inflammatory responses play a key role. Yinchen, a common medicinal plant used in Traditional Chinese Medicine (TCM), has been proven to possess strong anti-inflammatory effects. However, its efficacy in treating IS remains unclear. In this study, we aimed to investigate the therapeutic potential of Yinchen for IS and the material basis of this potential. Methods: The main active components in Artemisia scoparia extract (ASE, the extract of Yinchen), were identified by HPLC and MS. The targets of Yinchen and IS were obtained from public databases. Network pharmacology, molecular docking, and experimental investigation were further applied to acquire the core constituents in Yinchen that work against the neuroinflammation that occuring during IS. The neurological outcomes were evaluated in a transient Middle Cerebral Artery Occlusion (tMCAO) rat model. Additionally, the changes in the inflammatory responses in both the ischemic brain and in lipopolysaccharide (LPS)-treated microglial cells were examined using real-time qPCR. Results: Four active compounds of ASE, including isochlorogenic acid C (ICGA-C), isochlorogenic acid B (ICGA-B), isochlorogenic acid A (ICGA-A), and chlorogenic acid (CGA), were identified by HPLC and MS. Network pharmacology predicted that 103 compounds of Yinchen had 198 intersection targets with IS. The top five of these targets were TNF, STAT3, IL1B, AKT1, and SRC. Molecular docking results demonstrated that the abovementioned four compounds detected in ASE showed good interaction with all of the above five core targets. Moreover, both the four compounds and ASE were observed to attenuate NO release and suppress the release of various inflammatory factors (TNF-α, IL-1β, IL-6, and MCP-1) in a dose-dependent manner in LPS-induced BV2 microglial cells. ASE was further found to exert neuroprotective effects against ischemia–reperfusion (I/R) injury and inhibit the production of inflammatory factors in tMCAO rats. Conclusions: Yinchen exerts an anti-neuroinflammatory effect on IS, and its constituents with high scores binding to five core targets contribute to this effect. This supports its potential as an anti-inflammatory agent for the treatment of IS. Full article

Background/Objectives: Phytochemicals from Chaenomeles japonica (CJ) (Thunb.) Lindl. ex Spach, a plant belonging to the Rosaceae family, are recognized for their potential to inhibit enzymes associated with diabetes, obesity, neurodegeneration, and inflammation. However, the influence of constituents from different plant parts on cytokine secretion has not yet been explored or comparatively analyzed. Methods: This study aimed to evaluate the anti-inflammatory potential of CJ by assessing its effects on chemokine and cytokine secretion, including interleukin (IL)-8, IL-1β, TNF-α, IL-6, and IL-10. Extracts from various plant parts (fruit, seed, flower, and leaf) were examined for their ability to modulate cytokine production in human neutrophils (PMNs). Among them, the aqueous fruit extract exhibited the strongest activity and was subsequently tested on peripheral blood mononuclear cells (PBMCs) and the human intestinal epithelial cell line Caco-2. The extract was also subjected to in vitro gastrointestinal digestion to assess the stability and bioactivity of its metabolites. The phytochemical composition of CJ preparations was characterized by ultra-high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (UHPLC-DAD-MS/MS). Results: The aqueous fruit extract significantly reduced the secretion of pro-inflammatory cytokines across all tested models. Fractions obtained after in vitro digestion also inhibited IL-8 release in Caco-2 cells. Conclusions: The most active fractions were rich in flavan-3-ols and proanthocyanidins. These findings indicate that CJ fruit possesses notable anti-cytokine properties and may serve as a promising natural source for developing functional food. Full article

Garlic (Allium sativum L.) has served as a food source and medicinal agent for over thousands of years. Bioactive constituents, including allicin, diallyl sulfide/disulfide/trisulfide, ajoene, and S-allyl-cysteine, demonstrate antioxidant, anti-inflammatory, antithrombotic, antineoplastic, antimicrobial and neuroprotective properties. Convergent mechanistic evidence suggests the modulation of redox homeostasis, attenuation of pro-inflammatory signaling, regulation of platelet activation, and induction of apoptosis and cell-cycle arrest in tumor models. Computational studies, in conjunction with wet-lab data, offer molecular-level insights and guide candidate prioritization. Density functional theory elucidates radical-scavenging pathways and electronic descriptors that account for redox activity. Structure-based methods, including docking, molecular dynamics, and MM-GBSA, elucidate potential interactions between organosulfur scaffolds and enzymes or receptors pertinent to pharmacological effects. In silico ADME/Tox platforms predict generally favorable oral absorption for hydrophobic allyl sulfides, while polar derivatives exhibit more limited brain penetration. Emerging AI/ML pipelines combine network pharmacology with QSAR to focus on important targets and chemical types, while also spotting potential development. Formulation strategies, including nanoencapsulation and controlled-release systems, are utilized to stabilize labile thiosulfinates and modulate hydrogen-sulfide-releasing profiles, with potential applications in various disease conditions. Significant challenges encompass the standardization of preparations, variability in pharmacokinetics, heterogeneity in dose–response relationships, and interactions between drugs and nutrients or other drugs. The integration of mechanistic, computational, and formulation insights delineates a systematic approach to progress garlic-derived agents from diverse natural products to reproducible, mechanism-guided pharmaceuticals. Full article

The tormentil rhizome (Potentilla erecta L.) is traditionally used to treat gastrointestinal and inflammatory disorders, yet the mechanisms underlying its immunomodulatory activity remain unclear. No studies have examined the metabolism of tormentil constituents by the human gut microbiota and their effects on innate immune cells. This study evaluated the effects of the ethanolic extract of tormentil rhizome (EtTR) and its gut microbiota-derived metabolites (TRGMs) on innate immune function using human neutrophils and THP-1-derived macrophages. The chemical composition of EtTR and TRGMs was characterized by LC-MS, revealing fractions enriched in catechins and procyanidins (30% MeOH) or ellagic acid derivatives and triterpenes (100% MeOH). EtTR and all TRGM fractions significantly reduced ROS production, while the extract and selected metabolites decreased IL-1β and TNF-α secretion in neutrophils, whereas IL-8 showed marked induction. In macrophages, EtTR and selected fractions suppressed TNF-α and MCP-1 release but variably affected IL-6, reflecting donor-dependent modulation. The strongest inhibition was observed for fractions rich in catechins and triterpenoid conjugates, indicating synergistic activity between these compound classes. Overall, EtTR and its microbiota-derived metabolites exerted complementary antioxidant and immunomodulatory effects, providing mechanistic evidence that microbial transformation of tormentil polyphenols yields bioactive postbiotic metabolites capable of modulating inflammatory signaling. Full article

Paulownia tomentosa flowers are rich in flavonoids with promising biological activities. However, few studies have investigated their potential for α-glucosidase inhibition. This study compared ultrasound-assisted cellulase extraction and ultrasound-assisted aqueous two-phase extraction for the recovery of flavonoids from Paulownia tomentosa flowers. The aqueous two-phase extraction method demonstrated superior performance, with optimal conditions determined as 17.80% (NH₄)₂SO₄, 12 min ultrasonication, and 44 °C. Purification was efficiently achieved using NKA-9 macroporous resin. Scanning electron microscopy revealed that ultrasonic treatment disrupted the cell walls, facilitating flavonoid release. Ultra-performance liquid chromatography–tandem mass spectrometry identified apigenin-7-glucuronide and scutellarin as the predominant flavonoids. Notably, several compounds—including scutellarin, ombuin, robinetin, and astragalin—were reported for the first time in this plant. The extracted flavonoids exhibited significant α-glucosidase inhibitory activity, with an IC₅₀ value of 0.412 mg/mL, and showed mixed-competitive inhibition. Luteolin 7-O-glucuronide was identified as a major active constituent, exhibiting stronger inhibition than the total flavonoids while sharing the same mechanism. These findings establish a theoretical foundation for the efficient and sustainable extraction of P. tomentosa flavonoids and support their further development for pharmaceutical applications. Full article

Aromatic plants are rich sources of bioactive compounds with recognized therapeutic potential. This study investigated the phytochemical composition and biological activities of ethanolic extracts from four aromatic species—Thymus vulgaris L. (thyme), Rosmarinus officinalis L. (rosemary), Aloysia citrodora (lemon verbena), and Tanacetum balsamita L. (costmary)—using HeLa human cancer cells as a model. LC–MS analysis identified 28–44 metabolites per species, with phenolic compounds and terpenoids comprising 58–67% of total metabolites. Biological assays demonstrated concentration-dependent inhibition of HeLa cell metabolism down to 150 µg/mL, with rosemary displaying the strongest effects. LDH assays confirmed membrane disruption, most notably for lemon verbena (ca. 80% of release), and cellular proliferation was significantly disrupted by all extracts, most notably for thyme (70% reduction). Under oxidative conditions, costmary, thyme, and lemon verbena reduced intracellular ROS by up to 35% and all extracts suppressed IL-6 secretion, with rosemary showing the strongest anti-inflammatory response, lowering IL-6 levels to near or below the assay’s detection limit. Out of all the extracts, rosemary exhibited the most pronounced effects across cytotoxic, antioxidant, and cytokine assays, suggesting synergistic activity of its phenolic and terpenoid constituents. Multivariate analyses (correlation and PCA) linked specific metabolite classes to bioactivity patterns, providing insight into the mechanistic diversity underlying plant-specific effects. Overall, the results support the potential of these aromatic plants as sources of multifunctional bioactive compounds with anticancer and anti-inflammatory properties. Full article

Heparan sulfate proteoglycans (HSPGs) are essential constituents of the extracellular matrix (ECM) and cell surface, orchestrating a wide range of biological processes, such as cell adhesion, migration, proliferation, and intercellular communication. Through their highly sulfated glycosaminoglycan chains, HSPGs serve as crucial modulators of bioavailability and signaling of growth factors, cytokines, and chemokines, thereby influencing tissue homeostasis. Their dynamic remodeling is mediated by numerous enzymes, with heparanase (HPSE) playing a predominant role as the only known human endo-β-D-glucuronidase that specifically cleaves heparan sulfate chains. Beyond its well-documented enzymatic activity in ECM degradation and the release of HS-bound molecules, HPSE also exerts non-enzymatic functions that regulate intracellular signaling cascades, transcriptional programs, and immune cell behavior. Dysregulated HPSE expression or activity has been implicated in various pathological conditions, including fibrosis, chronic inflammation, cancer progression, angiogenesis, metastasis, and immune evasion, positioning this enzyme as a pivotal driver of ECM plasticity in both health and disease. This review provides an updated overview of HSPG biosynthesis, structure, localization, and functional roles, emphasizing the activity of HPSE and its impact on tissue remodeling and disease pathogenesis. We further explored its involvement in the hallmark processes of cancer, the inflammatory tumor microenvironment, and its contribution to fibrosis. Finally, we summarize current therapeutic strategies targeting HPSE, outlining their potential to restore ECM homeostasis and counteract HPSE-driven pathological mechanisms. A deeper understanding of the HSPG/HPSE axis may pave the way for innovative therapeutic interventions in cancer, inflammatory disorders, and fibrotic diseases. Full article

The effect of KOH concentration as a boron-free coolant for prospective use in Small Modular Reactors (SMRs) on the corrosion of Alloy 690 is studied by in situ impedance spectroscopy at 280 °C/9 MPa during 168 h exposure in a flow-through cell connected to a high-temperature/high-pressure loop. To follow further oxidation of the passive film, the samples were subsequently polarized up to potentials 0.5 V more positive than the corrosion potential. The formed oxides were analyzed ex situ by measuring the atomic concentration of the constituent elements via glow discharge optical emission spectroscopy (GDOES) depth profiling. The Mixed-Conduction Model for Oxide Films (MCM) was employed to quantitatively interpret the impedance results. The estimated parameters are used to quantify the influence of KOH concentration and anodic polarization on oxide formation and soluble product release rates. Results are compared to those obtained in the nominal primary chemistry of pressurized water reactors and indicate that Alloy 690 can also be successfully used as a steam generator tube material in SMRs. Full article

Background/Objectives: This study aimed to develop an advanced oral delivery platform for Salvia officinalis (S. officinalis) extract by co-encapsulating it with inulin and pectin in alginate-based microbeads, formulated via ionic gelation. Methods: The microbeads were comprehensively characterized, including the assessment of morphology, particle size, encapsulation efficiency, swelling behavior, in vitro dissolution, and enzymatic stability, and Caco-2 cell-based assays for cytocompatibility, permeability, and transepithelial electrical resistance. Antioxidant capacity and anti-inflammatory effects were also evaluated. Results: The resulting microbeads (~275 µm) achieved > 90% encapsulation efficiency and exhibited pronounced swelling (~90%). The release of S. officinalis constituents displayed pH sensitivity, with sustained release in simulated intestinal fluid, alongside significant enhancement of enzymatic stability. Encapsulation led to markedly improved permeability of bioactive compounds across Caco-2 monolayers, attributable to reversible modulation of tight junctions. Encapsulated extract retained potent antioxidant activity and significantly reduced pro-inflammatory cytokines. The formulation, across various concentrations, further promoted the growth and viability of Lactobacillus strains. Conclusions: Collectively, these findings demonstrate that alginate–inulin–pectin microbeads provide a multifunctional system for stabilizing S. officinalis extract, enabling controlled release, enhanced intestinal absorption, and maintained bioefficacy. Importantly, the formulation also promoted Lactobacillus viability, indicating a prebiotic effect and offering considerable potential for improved oral therapeutic applications. Full article

Lithium iron phosphate (LFP) batteries have become a popular choice for energy storage, electrified mobility, and plants. All lithium-based batteries produce flammable vent gas as a result of failure through thermal runaway. LFP cells produce less gas by volume than nickel-based cells, but the composition of this gas most often contains less carbon dioxide and more hydrogen. However, when LFP cells fail, they generate lower temperatures, so the vent gas is rarely ignited. Therefore, the hazard presented by a LFP cell in thermal runaway is less of a direct battery fire hazard but more of a flammable gas source hazard. This research identified the constituents and components of the vent gas for different sized LFP prismatic cells when overcharged to failure. This data was used to calculate the maximum homogenous concentration of gas that would be released into a 1.73 m³ test rig and the percentage of the lower explosive limit (LEL). Overcharge experiments were conducted using the same type of cells in the test rig in the presence of remote ignition sources. Ignition and deflagration of the vent gas were possible at concentrations below the theoretical LEL of the vent gas if it was homogeneously mixed. Full article