Search Results (8,773)

Surface modification of zinc oxide nanoparticles (ZnO NPs) with organosilane capping agents represents an effective strategy to control their physicochemical and biological properties. In this work, we report for the first time the use of halogenosilanes, namely (3-chloropropyl)trimethoxysilane (CPTMS), (3-bromopropyl)trimethoxysilane (BPTMS) and (3-iodopropyl)trimethoxysilane (IPTMS), for the surface functionalization of ZnO NPs obtained by chemical precipitation. Structural and morphological characterization (PXRD, TEM, SEM-EDX and FTIR) confirmed successful surface modification and revealed a significant particle size reduction from ~31 nm for unmodified ZnO to ~8 nm for BPTMS-modified ZnO (ZnO_b). The biological evaluation showed that halogenosilane-modified ZnO NPs exhibit enhanced cytotoxic activity against prostate cancer cell lines (PC3 and 22Rv1), with ZnO_b displaying the highest activity, likely associated with improved cellular uptake and increased reactive oxygen species (ROS) generation. In contrast, antimicrobial assays revealed only moderate bactericidal effects against Escherichia coli and Staphylococcus aureus at relatively high concentrations (≥1250 µg mL⁻¹), while no significant activity was observed against Pseudomonas aeruginosa, Burkholderia contaminans or Candida spp, within the tested range. These findings suggest that halogenosilane functionalization modulates the biological profile of ZnO nanoparticles by enhancing anticancer effects while also influencing microbiocidal activity, highlighting the role of surface chemistry in tuning biological selectivity. The present study supports the concept that rational surface engineering of ZnO-based nanoplatforms can be exploited to favor tumor-targeted activity over broad-spectrum antimicrobial effects, providing new perspectives for the design of application-oriented nanomaterials. Full article

Background: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. EJPs (Erjing Pills) are believed in Traditional Chinese Medicine to have the effects of a nourishing essence and a brightening of the eyes, but the specific effect on DR remains unclear. This study aims to investigate the therapeutic effects and underlying mechanisms of EJPs on DR. Methods: The chemical profile of EJPs was characterized by UHPLC-MS. Network pharmacology and molecular docking were employed to predict its active ingredients and potential targets. A DR rat model was induced by streptozotocin. Retinal morphology and function were assessed by OCT, FFA, and H&E staining. The expressions of proteins and mRNAs related to the AGE-RAGE pathway, oxidative stress, inflammation, and tight junctions were detected by Western blot, qPCR, and ELISA. Results: LC-MS and network pharmacology analysis identified 638 common targets between EJPs and DR, with core targets including SRC, AKT1, and MAPK1, primarily enriched in the AGE-RAGE signaling pathway. Molecular docking confirmed strong binding (binding energy < −5.0 kcal/mol) between key EJP constituents and core targets. In vivo, EJP treatment significantly alleviated retinal vascular leakage, improved retinal thickness, and alleviated histopathological damage. In addition, EJPs downregulated the AGEs-RAGE/NF-κB axis and pro-inflammatory cytokines while enhancing antioxidant defenses and tight junction proteins in the retinas of DR rats. Conclusions: EJPs ameliorate DR by protecting the blood–retinal barrier and modulating the AGE-RAGE/oxidative stress/inflammation network, demonstrating a multi-component, multi-target, and multi-pathway mechanism. This study provides a mechanistic basis for the potential application of EJPs in DR management. Full article

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents against H. pylori infection, molecular hybridization has now been applied to the synthesis of the new compound 3. Its structure connects the metronidazole moiety to pectolinarigenin, the latter obtained by acid hydrolysis of glycosylated flavonoids isolated from the plant Linaria reflexa Desf. The NOE effect supported the C-7 functionalization of 3, as evidenced by the energy-minimized DFT-calculated structure. The new molecule enriches the chemical space of known metronidazole–flavonoid analogs, among which the genistein derivative 2 was reported as the most active in inhibiting bacterial strains. The computational analysis of 2 and 3 compared with metronidazole as the reference has provided favorable data for both Absorption, Distribution, Metabolism, and Excretion (ADME) predictions and the probability of anti-H. pylori activity, besides rising docking evaluation on three specific targets and dynamics simulation as inhibitors of the flavodoxin enzyme. The results are promising for further in-depth biological investigation. Full article

Pseudomonas aeruginosa, an opportunistic pathogen, is a major threat to hospital infection control and global public health due to its strong environmental adaptability, complex virulence systems, efficient biofilm formation capability, and widespread multidrug resistance. Traditional single-target antibiotics are often inadequate for clinical treatment. The research into Plant-Derived Bioactive Compounds for combating P. aeruginosa infections is reviewed, highlighting their advantages (many of which are extensively studied in Traditional Chinese Medicine) over conventional antibiotics. The antimicrobial mechanisms of these compounds include the inhibition of bacterial quorum sensing (QS) systems to suppress virulence factor expression rather than direct anti-bactericidal effects, delaying the development of resistance. The abundant natural medicinal plants and their diverse chemical structures provide ample material for active compound screening to identify unique chemical compositions with specific binding to pathogen targets. Plant-Derived Bioactive Compounds exhibit excellent safety profiles, targeting bacterial-specific pathways or host immune regulation, resulting in minimal off-target toxicity. Plant-Derived Bioactive Compounds exert anti-P. aeruginosa effects via inhibition of QS systems to reduce pathogenicity by disrupting intercellular signaling, suppressing biofilm formation/maturity to overcome biofilm-associated resistance, directly interacting with bacterial structure. Plant-Derived Bioactive Compounds are promising treatments for drug-resistant P. aeruginosa infections, providing lead compounds for novel anti-infective drug development. Full article

Gao-shan-hong-jing-tian (GSHJT) Oral Liquid is a phytochemical-rich preparation derived from Rhodiola, yet its anti-hypoxic active constituents and molecular mechanisms remain poorly understood. This study aimed to identify the key anti-hypoxic phytochemicals in GSHJT Oral Liquid and clarify their mechanisms of action to support its potential use in managing acute mountain sickness (AMS). We first established and validated an HPLC method for quality control, then comprehensively profiled the chemical composition using LC-MS. Network pharmacology and molecular docking were applied to predict the core anti-hypoxic components, candidate targets and signaling pathways. The primary bioactivity was further verified through an in vitro carbonic anhydrase (CA) inhibition assay. A total of 71 constituents were identified, with kaempferol and ellagic acid emerging as the primary anti-hypoxic phytochemicals. These compounds target seven core proteins (SRC, PIK3R1, ESR1, EGFR, PTK2, IGF1R, and LYN) to regulate vascular tone, inflammation, oxidative stress, blood–brain barrier integrity, and cell survival under hypoxic conditions. By modulating pathways such as HIF-1α, PI3K/AKT, FAK/PTK2, SRC, and IGF1R, these phytochemicals ultimately influence the onset and alleviation of AMS. Enzyme inhibition assays demonstrated that kaempferol and ellagic acid inhibited CA with IC₅₀ values of 34.05 μM and 119.1 μM, respectively. Molecular docking further revealed that both compounds suppressed CA activity through a combination of hydrogen bonding and hydrophobic interactions, consistent with a zinc-bound water-anchoring mechanism. This study elucidates the phytochemical basis and molecular mechanism responsible for the anti-hypoxic effects of GSHJT Oral Liquid, providing scientific support for its potential application as a natural, plant-derived intervention for preventing and alleviating acute mountain sickness, providing scientific support for its potential application and offering a reproducible paradigm for the rational development of other Rhodiola-based phytomedicines, though further in vivo validation is required to confirm the anti-hypoxic efficacy. Full article

Volcanic super-eruptions can perturb atmospheric composition and climate-relevant radiative properties in ways that are not captured by simple scaling from Pinatubo-like events. This study presents a reduced-order regime theory for the coupled evolution of stratospheric sulfur, sulfate aerosol burden, reactive halogens, ozone loss, stratospheric thermal adjustment, and aerosol residence time. The analysis is intended as an interpretive tool for organizing sulfur-rich volcanic scenarios, comparing literature-based benchmark classes, and designing chemistry–climate model experiments, rather than as an event-specific calibration or a substitute for three-dimensional models. Four control parameters structure the response: sulfur loading relative to microphysical saturation, effective halogen strength, ash-uptake efficiency, and dynamical lifetime sensitivity, with hemispheric asymmetry treated diagnostically. An external consistency check against published Pinatubo-like, idealized 10–40 teragrams of sulfur (Tg S), Toba-like, and Los Chocoyos-like responses is used to evaluate whether the reduced theory reproduces the expected rank ordering of aerosol saturation, forcing-efficiency decline, ozone-loss amplification, ash-driven sulfur suppression, and residence-time sensitivity. This comparison does not assign pointwise error margins against three-dimensional model output; it evaluates regime membership, sign of response, rank ordering, and broad magnitude behavior. The main conclusion is that volcanic super-eruption impacts are governed by interacting regime transitions rather than by sulfur mass alone. Microphysical saturation can limit forcing efficiency, halogens can shift the system toward chemically amplified ozone depletion, ash uptake can reduce the effective sulfur burden during the early phase, and dynamical state can control persistence and hemispheric expression. By separating these mechanisms, the study provides a compact basis for interpreting large volcanic perturbations to atmospheric chemistry and for designing targeted model experiments on extreme eruption scenarios. Full article

Chemical agents have long been used to control plant diseases, but their effects on the environment and lack of alignment with sustainable development goals are making them gradually unsuitable. One trend in green agriculture is the use of Bacillus species for the biocontrol of plant diseases. Due to their vast metabolic and genetic diversity, Bacillus spp. can contribute significantly to the soil ecosystem, while also enhancing plant resilience to biotic and abiotic stresses. Bacillus spp. are widely used in the agrobiotech industry due to their multi-functional versatility and are well-known for protecting plants from numerous plant diseases. In this review, we discussed the diversity and functions of antimicrobial compounds (AMCs) produced by Bacillus spp., along with their roles in plant growth promotion (PGP), and immunity. Furthermore, we highlighted the potential of Bacillus spp. as biopesticides in host plants, ways to enhance their biocontrol efficacy, and also addressed their possibility to cause disease in host plants. Considering the beneficial impacts of Bacillus spp. on PGP and pathogen biocontrol and their disease-causing capability, we discussed the possible solutions for a safe development of Bacillus-based biocontrol agent (BCA). Collectively, these insights can guide the selection of Bacillus strains with broad-spectrum or target-specific activity against pathogens, ensuring minimal adverse effects on the host. Full article

Mitochondrial reactive oxygen species (mtROS) are central regulators of cellular function, yet their biological roles are often reduced to an oxidative-stress/antioxidant dichotomy. This review reframes mtROS through the concept of mitohormesis, in which outcomes are neither inherently harmful nor beneficial but are determined by a defined set of contextual variables. We present a mechanistic framework in which mtROS effects depend on chemical species identity, sub-mitochondrial site of production, temporal dynamics, redox-buffering capacity, and metabolic state; together, these variables determine whether mtROS promote adaptive eustress or pathological distress. We then show that, across polyphenols, isothiocyanates, terpenoids, alkaloids, and quinones, the biologically relevant effects of natural redox-modulating compounds are mediated less by direct radical scavenging than by pro-hormetic mechanisms, including mild electron transport chain perturbation, nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) activation, modulation of mitochondrial membrane potential, mitochondrial quality control, and NAD⁺/NADPH regulation. Applying this framework to disease reveals strong tissue and state dependence: neurodegeneration favors buffering expansion and mitophagy; metabolic disease may benefit from exercise-mimetic and NRF2-activating strategies; cardiovascular disease illustrates mitohormesis through ischemic preconditioning and CoQ10 supplementation; and cancer requires distinction between prevention and therapy because redox buffering can either protect normal tissue or support tumor survival. Finally, we argue that the failure of non-specific antioxidant supplementation is mechanistically predictable and propose context-aware, biomarker-guided, temporally optimized, and compartment-targeted redox interventions as a more rational translational path. Full article

Persistent organic contaminants and complex wastewater matrices challenge conventional treatment because parent-compound removal does not necessarily imply mineralization, detoxification, or improved environmental safety. Advanced oxidation processes can address these limitations, but practical effectiveness is often constrained by oxidant activation, gas–liquid mass transfer, reagent distribution, light penetration, catalyst contact, energy demand, and matrix scavenging. This work critically examines hydrodynamic cavitation-assisted advanced oxidation processes for water and wastewater treatment, including systems based on hydrogen peroxide, ozone, Fenton and Fenton-like reactions, persulfate, peroxydisulfate, peroxymonosulfate, UV irradiation, photocatalysis, cold plasma, multi-hybrid configurations, and emerging reduction-oriented approaches. The discussion covers reactor configurations, target contaminants, real matrices, and sustainability-related performance metrics. The central argument is that hydrodynamic cavitation is not automatically sustainable as a stand-alone treatment. It becomes relevant as a sustainable intensification module only when measurable improvements are demonstrated in oxidant activation, mass transfer, treatment depth, biodegradability, toxicity reduction, process integration, or scale-up at acceptable energy and chemical cost. A reporting framework is proposed based on mineralization, COD/TOC reduction, by-products, toxicity, biodegradability, normalized energy consumption, chemical efficiency, real-matrix validation, reproducibility, and cost-relevant indicators. Future progress should move from isolated degradation tests to integrated, controllable, and scalable treatment frameworks. Full article

Azole resistance in Candida albicans is an increasing clinical challenge. Upc2 is a key transcription factor regulating ergosterol biosynthesis, but its additional roles in azole tolerance remain unclear. This study investigated whether Upc2 contributes to azole resistance through pathways beyond ergosterol synthesis. Chemical sensitivity screening, RNA sequencing, flow cytometry, and molecular assays were performed to compare wild-type C. albicans and the upc2Δ/upc2Δ mutant under fluconazole (FLC) treatment. The UPC2 gene deletion affected physiological processes that are dependent on the calcineurin signaling pathway and led to an overall negative enrichment trend in the unfolded protein response (UPR) pathway gene set. Mechanistically, the UPC2 gene deletion impaired unconventional splicing of HAC1 mRNA, leading to accumulation of unfolded proteins and phenotypically its deletion enhanced sensitivity of C. albicans to FLC in planktonic growth, hyphal development, and biofilm formation. Our findings reveal that Upc2 regulates proteostasis in C. albicans, and its absence enhances FLC efficacy by disrupting the UPR pathway. Targeting Upc2-mediated UPR signaling may represent a promising strategy to combat azole resistance. Full article

Marburg virus (MARV), a highly pathogenic member of the Filoviridae family, causes severe hemorrhagic fever with a high case fatality rate and currently lacks effective therapeutics. The viral entry process, mediated by the interaction between the MARV glycoprotein (GP) and host receptor C-type lectin domain family 4 member M (CLEC4M) (L-SIGN), represents a critical target for early-stage intervention. The active compounds from BindingDB and the decoy from DUDE were used. The RDKit was used for feature engineering. Machine learning models were trained on an initial dataset consisting of 56 active chemicals and 1232 decoys. Among the tested algorithms, the Random Forest model demonstrated superior performance, achieving the highest discriminative ability (AUC = 0.93, MCC = 0.88) on the test set. Virtual screening of 11,032 phytochemicals resulted in 120 predicted actives, of which 42 compounds satisfied drug-likeness criteria. Subsequent molecular docking identified three lead compounds (PubChem IDs: 42608095, 5281601, and 11243993) with moderate-to-promising binding affinities (−6.3 to −6.5 kcal/mol) toward the CLEC4M binding site. ADMET analysis revealed favorable pharmacokinetic and toxicity profiles for the selected lead compounds. DFT calculations of the three compounds highlighted their electronic stability and reactive nature, indicating that PubChem IDs 42608095 and 5281601 possess particularly stable electronic properties conducive to favorable target interactions. Combining machine learning models with molecular docking and Molecular Dynamics (MD) simulations worked well in finding promising phytochemical inhibitors. The MM/GBSA binding free energy calculations further confirmed binding affinities, with values of −10.83 and −11.08 kcal/mol, respectively, suggesting favorable complex stability. These findings provide a pathway for developing new antiviral agents against MARV, pending further experimental validation and optimization. Full article

Mucoadhesive drug delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of pharmaceuticals by improving drug residence time, bioavailability, and site-specific targeting. Among various materials investigated, biopolysaccharides have gained significant attention due to their biocompatibility, biodegradability, non-toxicity, and inherent mucoadhesive properties. Natural polymers such as chitosan, alginate, pectin, hyaluronic acid, and cellulose derivatives exhibit strong interactions with mucosal surfaces through hydrogen bonding, electrostatic interactions, and polymer chain entanglement. These properties enable prolonged drug retention at mucosal sites, controlled drug release, and enhanced permeation across biological barriers. Mucoadhesive biopolysaccharides have been explored for diverse routes of administration, including oral, buccal, nasal, ocular, vaginal, and pulmonary delivery. Furthermore, chemical modification and nanostructuring of these polymers have expanded their functionality, enabling targeted delivery of small molecules, proteins, peptides, and nucleic acids. This review highlights the mechanisms of mucoadhesion, key biopolysaccharides used in drug delivery, formulation approaches, and recent advances in their application as versatile platforms for novel therapeutic delivery systems. The continued development of mucoadhesive biopolysaccharide-based carriers holds substantial potential for improving treatment outcomes and patient compliance. Full article

Identification of ligands targeting essential enzymes in Mycobacterium species remains an important strategy for anti-tuberculosis drug discovery. Here, a native mass spectrometry approach was employed using pooled 100-compound mixtures, enabling the direct detection of intact HPPK–ligand complexes in solution. Dual-mode MS acquisitions (low collision energy for complex detection and high collision energy for ligand confirmation), combined with an automated data analysis workflow, ensured robust identification of binding events from these complex samples. This strategy led to the identification of several HPPK-binding small molecules, all belonging to the dammarane triterpene glycoside (ginsenoside) class. Subsequent analysis of the hits revealed clear structure–affinity relationships, highlighting how specific aglycone modifications and glycosylation patterns influence binding to HPPK. Our findings expand the known chemical space of HPPK ligands and demonstrate the utility of native MS-based screening coupled with automated data analysis to uncover new ligand scaffolds for challenging enzyme targets. Full article

Background: Acute myocardial infarction (AMI) remains the most lethal critical emergency worldwide. Although Angong Niuhuang Pill (ANP) is an established rescue medicine that has demonstrated outstanding therapeutic potential for cardiovascular diseases, its modern molecular mechanism has never been systematically elucidated because of its chemical complexity and unidentified targets. Methods: This study utilizes a multi-layer analytical pipeline of AI mining, network pharmacology, transcriptomics, and experimental confirmation. The components of ANP were comprehensively identified by UHPLC-Q Exactive Orbitrap HRMS. The TranSiGen algorithm was utilized to deeply mine the data and rank the components according to their relevance to AMI. The top 20 components were selected as prior weights and introduced into network pharmacology for analysis. Subsequently, a mouse model of AMI was established by ligating the left coronary artery. Cardiac function in the mice was evaluated by echocardiography and serum biochemical indicators. The pathological changes in the heart tissue were assessed by hematoxylin-eosin (H&E) and Masson staining. Cardiac transcriptome sequencing was performed, and pathway enrichment was analyzed by KEGG. The key pathways were verified by qPCR and immunofluorescence, achieving cross-validation between AI prediction and experimental findings. Results: The identification of ANP resulted in the detection of a total of 73 compounds, and the TranSiGen algorithm was employed to prioritize these compounds, yielding a ranked list of the top 20 candidates. Functional evaluation using echocardiography, serum biochemical markers, and histopathological examination demonstrated that ANP significantly ameliorated cardiac function in mice following myocardial infarction. Integration of network pharmacology and transcriptomic enrichment identified convergent axes of IL-17 signaling and mitochondrial quality control, which were subsequently experimentally validated as mechanisms by which ANP ameliorated cardiac injury. Experimental validation confirmed that ANP downregulated protein expression of IL-17A and TNF-α, normalized PINK1 and LC3-II/LC3-I marker profiles, with concomitant p62 reduction, thereby providing comprehensive molecular evidence at both transcriptional and translational levels to support the AI-driven predictions. Conclusions: This study identified IL-17 signaling and mitochondrial quality control as pathway axes associated with ANP-mediated cardioprotection against AMI, supported by AI-driven compound screening, transcriptome-network cross-validation, and experimental confirmation. This analytical framework may be adaptable to other complex TCM formulas for mechanism exploration and clinical translation. Full article