Search Results (1,631)

Halophytes are recognized for their adaptive capacity and potential applications in phytomanagement and ecosystem restoration. This study investigates the comparative physiology and antioxidant responses of two native halophytes, Caroxylon vermiculatum (L.) and Mesembryanthemum nodiflorum L., growing naturally in saline and metal-affected coastal environments. A comprehensive set of physiological and biochemical parameters was assessed, including macro- and microelements (Na, K, Ca, Fe, Zn, Cd), photosynthetic pigments (chlorophyll a, chlorophyll b, and carotenoids), soluble sugars, and proteins. In addition, oxidative stress markers (hydrogen peroxide, H₂O₂, and malondialdehyde, MDA), enzymatic antioxidants (superoxide dismutase, SOD, catalase, CAT, and guaiacol peroxidase, GPX), and non-enzymatic antioxidants (total phenolics, flavonoids, and proanthocyanidins) were evaluated. Antioxidant activities, including DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and reducing power, were also measured. The results revealed clear species-specific adaptive strategies. Mesembryanthemum nodiflorum exhibited higher accumulation of Na and K, together with elevated levels of carotenoids and oxidative stress markers. This species showed translocation factors (TF > 1) for Na (~1.60) and K (~1.90), indicating efficient ion transport to aerial parts, while displaying low bioconcentration (BCF < 0.5 for most trace elements) and biological accumulation factors (BAF < 1), suggesting limited capacity for heavy metal accumulation. In contrast, Caroxylon vermiculatum showed higher concentrations of chlorophylls, carotenoids, phenolic compounds, flavonoids, and proteins, along with stronger superoxide dismutase activity. It also exhibited lower translocation of trace elements (TF < 1) and higher root retention of metals (BCF up to ~0.5), indicating a more effective exclusion and detoxification strategy. Overall, these findings demonstrate that M. nodiflorum relies on ion accumulation and translocation, whereas C. vermiculatum exhibits stronger ion regulation and antioxidant protection. Given the moderate BAF and BCF values observed, both species are more likely to contribute to phytomanagement through ion regulation and phytostabilization rather than efficient phytoextraction. Full article

Methotrexate (MTX) remains central to the treatment of rheumatoid arthritis and several malignancies, yet its use is complicated by dose-dependent toxicity, variable oral exposure, photolability, and pH-dependent solubility. Cyclodextrins (CDs) can alter the molecular environment of MTX, but the literature often conflates true inclusion complexes with formulations in which CD merely forms part of a larger carrier. This review critically distinguishes direct MTX–CD complexes, dosage forms built from a preformed complex, CD-containing carriers without direct evidence of cavity occupancy, and covalent MTX–CD conjugates. Particular attention is given to binding stoichiometry, apparent association constants, guest orientation, preparation methods, and the evidence needed to establish inclusion. Both solution-state host–guest association and isolated solid products are considered; however, solid-state changes are treated as supportive evidence rather than as stand-alone proof of cyclodextrin cavity occupancy. Among the limited head-to-head comparisons of native cyclodextrins, β-CD generally showed more favorable MTX recognition than α- or γ-CD, although the magnitude of this difference is method- and condition-dependent. Complexation can improve dissolution, photostability, and oral or local delivery; however, greater solubilization does not necessarily enhance membrane transport. In carrageenan hydrogels, β-CD increased MTX loading and release while reducing membrane permeation, illustrating the importance of the equilibrium between complexed and freely permeating drug. The most promising systems remain preclinical. Progress toward translation will require clearer nomenclature, orthogonal structural characterization, mechanism-resolving controls, and standardized pharmacokinetic and safety studies. Full article

Atmospheric particulate matter (PM) is a heterogeneous carrier of toxic metals whose environmental fate and biological effects depend on particle size, source-related composition, chemical form, solubility, and bioaccessibility. Lead (Pb), cadmium (Cd), and nickel (Ni) are of particular concern because atmospheric transport and deposition connect air pollution with persistent contamination of soils, vegetation, waters, sediments, food, and feed, followed by human and animal exposure. This review integrates evidence across a source-to-effect continuum encompassing emission, atmospheric transport, deposition, post-depositional redistribution, food-chain transfer, bioaccessibility, toxicokinetics, molecular toxicity, biomonitoring, remediation, and predictive assessment. Total PM mass and total metal concentration do not adequately represent biologically effective exposure, which is additionally determined by respiratory deposition, gastrointestinal release, dissolution kinetics, absorption, tissue distribution, intracellular retention, and interactions with co-associated constituents. Pb, Cd, and Ni share downstream effects including oxidative imbalance, inflammation, mitochondrial dysfunction, DNA damage, impaired genome maintenance, epigenetic remodeling, and cytogenetic abnormalities, but differ in environmental mobility, persistence, target-organ distribution, and molecular mechanisms. Effective risk assessment therefore requires coordinated multi-matrix monitoring, distinction between total and biologically accessible fractions, pathway-specific remediation, and appropriately validated predictive models. An integrated One Health framework can improve identification of priority matrices, exposure pathways, and risk-reduction measures. Full article

Background: Members of the tumor necrosis factor receptor superfamily (TNFRSF), including 4-1BB (CD137) and OX-40 (CD134), play central roles in regulating cytotoxic lymphocyte activation and anti-tumor immunity. In addition to their membrane-bound forms, soluble receptor isoforms may modulate signaling by influencing ligand availability and receptor engagement. However, the peripheral regulation of soluble and membrane 4-1BB and OX-40 in cervical cancer remains incompletely defined. Methods: Plasma concentrations of soluble 4-1BB (s4-1BB) and soluble OX-40 (sOX-40) were quantified by ELISA in 20 treatment-naïve cervical cancer (CC) patients and 20 healthy controls (HCs). Membrane expression (m4-1BB and mOX-40) on circulating T cells and NK cells was evaluated by flow cytometry. Correlation and stage-stratified analyses were performed. Results: Plasma levels of s4-1BB and sOX-40 were significantly elevated in CC patients compared with HCs. Membrane 4-1BB expression was increased on both T cells and NK cells, while OX-40 expression was selectively elevated in NK cells, with no difference observed in T cells. A moderate positive correlation was identified between s4-1BB and T-cell membrane 4-1BB expression. Notably, membrane 4-1BB expression decreased in advanced-stage disease, whereas soluble concentrations remained unchanged. Conclusions: These findings demonstrate differential regulation of soluble and membrane 4-1BB and OX-40 in the peripheral compartment in cervical cancer, highlighting distinct regulatory layers within the TNFRSF axis. Full article

While carbon dots (CDs) are promising green nanomaterials for sustainable agriculture, how they regulate cotton growth via physiological and metabolic reprogramming remains poorly understood. This study evaluated foliar CD application (0–200 mg·L⁻¹) to uncover dose–response patterns and metabolic drivers. CDs exerted a concentration-dependent impact, with 100 mg·L⁻¹ yielding optimal results. This application markedly boosted shoot and root biomass (fresh weight: 103.43% and 44.28%; dry weight: 56.03% and 40.39%) and enhanced specific leaf area by 52.51% over the control. CDs improved photosynthetic efficiency (elevated Pn, Gs, and E values, alongside increased chlorophyll a and carotenoids) and strengthened antioxidant defenses (enhanced leaf POD/SOD and root POD/CAT activities). Despite mild MDA increases indicating oxidative stress, accumulated proline and soluble sugars in roots suggested adaptive osmotic adjustment. These findings suggest that CDs maintain physiological homeostasis by modulating antioxidant defense and osmotic adjustment. Untargeted metabolomics identified 2440 metabolites. Phenylpropanoid biosynthesis and flavonoid biosynthesis were the most prominently enriched pathways based on KEGG enrichment results. K-means and correlation analyses revealed key metabolites linked to cotton biomass. Overall, CDs facilitate cotton development through synergistic physiological and metabolic reprogramming, underscoring their potential as innovative agricultural growth regulators. Full article

Platelet activation plays a central role in arterial thrombosis, thromboinflammation, and microvascular injury. Conventional platelet function tests evaluate platelet responsiveness to exogenous agonists ex vivo but do not directly reflect in vivo platelet activation. Although several soluble platelet-derived molecules, including platelet factor 4 (PF4), β-thromboglobulin (β-TG), soluble P-selectin, soluble CD40 ligand, glycocalicin, and soluble glycoprotein (GP) VI, have been investigated as in vivo platelet activation markers, their clinical use is limited by preanalytical instability, lack of platelet specificity, constitutive shedding, or uncertain disease specificity. Soluble C-type lectin-like receptor 2 (sCLEC-2) has recently emerged as a promising biomarker of in vivo platelet activation. CLEC-2 is expressed predominantly in platelets and megakaryocytes, and its soluble form is released from activated platelets as both a shed molecule and a microparticle-associated form. Compared with PF4 and β-TG, sCLEC-2 is less susceptible to artifactual release during routine blood collection, making it more suitable for clinical laboratory testing. Elevated sCLEC-2 levels have been reported in acute coronary syndrome, acute ischemic stroke, disseminated intravascular coagulation, thrombotic microangiopathy, antiphospholipid antibody syndrome, and coronavirus disease 2019 (COVID-19). In thrombocytopenic disorders, indices incorporating platelet count, such as the C2PAC index, sCLEC-2/D-dimer ratio, and sCLEC-2 × D-dimer/platelet count, may better reflect platelet activation and disease status than sCLEC-2 concentration alone. However, preanalytical standardization, assay harmonization, reference interval validation, and disease-specific cutoff values remain essential. This review summarizes the biological basis, assay systems, clinical evidence, and future perspectives of sCLEC-2 as an emerging laboratory marker of in vivo platelet activation. Full article

Soluble variants of recombinant T cell receptors (TCRs) have become attractive tools for the retargeting of cytotoxic T cells toward intracellular tumor or viral antigens by combining them with CD3-binding antibodies in bispecific T cell engagers; however, TCR-based NK cell engagers have not been studied so far. Here, we developed TCR-based bispecific agents for the redirection of NK cells utilizing a bivalent IgG1-like format. Trifunctional NK engagers included an Fc part with enhanced binding to FcγRIII/CD16A and single-chain (scFv) antibodies recognizing either NKp46 or CD16A, activating NK cell receptors. HCMV pp65/HLA-A2 reactive TCR-scFv-Fc fusion proteins incorporating an affinity-matured TCR and anti-NKp46 scFv activated peripheral blood NK cells and induced cytotoxicity in an antigen-specific manner. For T cell redirection, TCR-scFv-Fc fusion proteins included an scFv antibody recognizing CD3ε. Compared with NK cell engagers, T cell engagers showed similar sensitivity but lower peptide selectivity. For two TCRs recognizing melanoma-associated peptides, affinity-matured TCR-scFv-Fc fusion proteins enabled NK and T cell redirection and activation, and killing of tumor target cells loaded with exogenous peptides. Our results expand the versatility of the soluble TCR technology to NK cell engagers; however, they still require improvement in sensitivity to target tumor cells with low peptide/MHC-I complex densities. Full article

Background/Objectives: The aim of this study was to develop and validate a simple, accurate, reproducible, and sensitive reverse-phase high-performance liquid chromatography method for the quantification of reproxalap (RP) in cyclodextrin (CD) inclusion complexes and poloxamer 407 hydrogel formulations. Methods: Chromatographic separation was achieved using a mobile phase of deionized water and an organic phase (methanol:acetonitrile, 55:45 v/v) in a 40:60 (v/v) ratio, at a flow rate of 0.9 mL/min and a run time of 10 min. Validation assessed linearity, specificity, accuracy, and sensitivity over a concentration range of 1–60 μg/mL. Phase-solubility studies were conducted to determine the apparent stability constant (K_1:1), and inclusion complexes were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The method demonstrated specificity, linearity, sensitivity, and accuracy within the tested concentration range of 1–60 μg/mL. The apparent stability constants (K_1:1), calculated from the phase-solubility plot slopes, were 2666.66 M⁻¹ for Sulfobutyl Ether β-Cyclodextrin (SBE-β-CD) and 526.3 M⁻¹ for Hydroxypropyl-β-Cyclodextrin (HP-β-CD). The solubility of RP in deionized water (0.25 mM) increased 8.6-fold to 2.15 mM with the HP-β-CD inclusion complex and 22.4-fold to 5.6 mM with the SBE-β-CD inclusion complex. The method was successfully applied to determine RP in inclusion complexes and poloxamer 407 hydrogel formulations, with no interference from formulation excipients. Conclusions: The validated RP-HPLC method is suitable for quality control analysis of RP in CD inclusion complexes and poloxamer 407 hydrogel formulations, supporting its application in the future development of these drug delivery systems. Full article

Objective: Conventional progesterone (P4) formulations suffer from low bioavailability, severe local irritation, and poor patient adherence due to P4’s poor aqueous solubility. This work aimed to develop and screen a biodegradable PLGA/NMP (Poly(lactic-co-glycolic acid)/N-methyl-2-pyrrolidone) injectable in situ gel for sustained P4 delivery to overcome these clinical limitations. Significance: Commercial oral, vaginal, and oil-based intramuscular P4 preparations cannot maintain stable long-term drug exposure, and they cause injection-site pain/inflammation. The screened in situ depot system reduces administration frequency and local tissue irritation, supporting convenient luteal phase support and pregnancy maintenance. Methods: Nine formulations with variable P4 loading (10–50% w/w) and PLGA concentration (15–55% w/w) were fabricated. Formulations were screened via three core endpoints: injectability (injection force and discharge rate), in vitro sustained release in 10% Hydroxypropyl-β-cyclodextrin (HP-β-CD)-Phosphate-buffered saline (PBS) sink medium, and 7-day subcutaneous histocompatibility in rats. high-performance liquid chromatography (HPLC) was validated for progesterone quantification; Hematoxylin and eosin (H&E) staining assessed local inflammatory responses. Results: Formulations with progesterone ≤ 30% w/w and PLGA ≤ 35% w/w exhibited acceptable injectability (injection force < 50 N; discharge rate > 79%). Higher PLGA concentrations suppressed initial burst release (16.74% at 8 h for 35% PLGA vs. 29.8% for 20% PLGA). All formulations formed stable ellipsoidal subcutaneous depots and completed progesterone release within 4 days. Histopathology revealed only mild local inflammation (histological score = 1) without severe necrosis, superior to highly irritating oil injections in formulation control groups. Conclusions: The screened PLGA-based progesterone in situ gel resolves critical drawbacks of traditional progesterone dosage forms. This low-irritation, sustained-release injectable platform provides a scalable industrial formulation candidate for long-acting hormone therapy. Full article

To explore the emerging role of natural ligands, specifically coumarin and curcumin, and their coordination with the transition metals ruthenium (Ru) and iridium (Ir) as photosensitizers (PSs) in photodynamic therapy (PDT) for cancer. This highlights the integration of natural compounds and transition metals to overcome limitations in photophysical properties, hypoxia tolerance, and clinical translation. Regarding PDT oncology, this examines an immunological effect on Ru/Ir complexes and natural ligand-metal hybrids. They induce immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, calreticulin exposure, extracellular ATP release, and HMGB1 secretion. These damage-associated molecular patterns act as “danger signals” to recruit dendritic cells, prime CD8⁺ cytotoxic T-cells, and establish systemic antitumor immunity. This study compares natural ligand-metal complexes with conventional Ru(II)/Ir(III) complexes and clinical PSs to assess their translational potential as immune-activating agents in PDT oncology, as well as focusing on the integration of nanotechnology with natural ligand-metal complexes to enhance delivery, biocompatibility, and clinical translation. A narrative review was conducted of the literature published between 2010 and 2025 across multiple electronic databases, including WanFang Data, PubMed, ScienceDirect, Scopus, Web of Science, Springer Link, SciFinder, and CNKI, without language restrictions. Studies focusing on coumarin, curcumin, Ru(II), Ir(III), and PDT were analyzed. Extracted data included chemical structures, absorption and emission spectra, singlet oxygen yields, biological activities, and therapeutic outcomes. Comparative evaluation was performed between free natural ligands, their Ru(II)/Ir(III) complexes, and nanodelivery systems to assess efficacy, biocompatibility, and translational potential. Coumarin and curcumin exhibited intrinsic antioxidant, anti-inflammatory, and anticancer properties but were limited by short absorption/emission ranges, poor photostability, and low singlet oxygen yields, restricting preclinical application. Coordination with Ru(II) and Ir(III) significantly enhanced intersystem crossing, extended absorption into the near-infrared region, and improved singlet oxygen quantum yields (Φ_Δ up to ~0.78). These complexes demonstrated potent photocytotoxicity under normoxia and hypoxia, achieving IC₅₀ values in the nanomolar range, which indicated organelle-specific targeting (mitochondria, lysosomes, ER), induced ICD, and synergized with checkpoint blockade. Nanocarrier encapsulation further improved solubility and tumor selectivity, and reduced systemic toxicity. Coumarin- and curcumin-based Ru/Ir complexes represent promising next-generation or immune activating PDT agents by combining natural pharmacological activity with superior photophysical performance. The ability to generate reactive oxygen species under hypoxia and achieve multimodal therapeutic effects positions them as strong candidates for clinical translation. Clinical approval of natural ligand-Ru/Ir complexes depends on rigorous safety, pharmacokinetic, and nanodelivery validation, but these complexes clearly extend PDT beyond local cytotoxicity toward durable immune protection. Future research should prioritize ligand engineering, nanotechnology integration, and translational models to bridge preclinical promise with safe and effective clinical applications. Full article

Periodontal and alveolar bone regeneration requires coordinated angiogenic and osteogenic responses supported by biomimetic scaffolds. This study compared three-dimensional bioprinted hydroxyapatite–acrylated palm olein (3D-HA–APO) scaffold formulations containing 5%, 7% and 10% (w/v) hydroxyapatite (HA), designated F1, F2 and F3, respectively. Human umbilical vein endothelial cells were cultured on the scaffolds, and background-corrected soluble vascular endothelial growth factor (VEGF) concentrations in culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). Angiogenic-related responses of human periodontal ligament stem cells were assessed by VEGF and cluster of differentiation 31 (CD31) immunofluorescence after endothelial induction, while alkaline phosphatase (ALP) activity in construct lysates was used as an indicator of early osteogenic activity. Soluble VEGF concentrations increased from F1 to F3, with significant differences between all formulations. VEGF-associated signal proportions differed among formulations, with F3 significantly higher than F1. CD31-associated signal proportions increased progressively from F1 to F3, with significant differences between all formulation pairs. ALP activity increased over time in all scaffold groups, and F3 generally showed the highest activity from Day 4 onwards. Overall, F3 showed the most favourable formulation-level profile across the selected angiogenic-related and early osteogenic outcomes. Full article

Postharvest spoilage of fresh fruits demands efficient bio-based packaging films. Here, chitosan/gelatin (CG) films were incorporated with β-cyclodextrin-encapsulated clove essential oil microcapsules (β-CD@CEO MCs) at varying loadings. The results suggested that CEO encapsulation occurred within β-CD cavities and hydrogen-bond binding of MCs to the CG matrix. At 0.4% MCs, the composite film showed 60.11% higher tensile strength, excellent UV shielding, lower water vapor transmission rate, and strong antioxidant activity (DPPH 89.6%, ABTS 97.1), along with 58.21% biodegradation after 16 days of soil burial. In vitro release studies revealed a pH-responsive sustained release profile of CEO from the composite films, with faster release under acidic conditions (98.5% at pH 3.5 after 72 h) compared to neutral conditions (87.2% at pH 7.0), indicating the potential for targeted release on the weakly acidic grape surface. The film also exhibited significant antimicrobial effects against Botrytis cinerea, Penicillium gladioli, Staphylococcus aureus, and Escherichia coli. In table grape preservation, CG/MCs-0.4 film effectively delayed decay, reduced weight loss by 38.79%, maintained firmness and color, and preserved higher levels of soluble solids, titratable acidity, reducing sugars, and vitamin C compared to polyethylene packaging and untreated controls. Full article

Chiral supramolecular polymers offer a versatile platform for constructing dynamic functional materials, yet their development in aqueous media remains challenging due to weak host–guest interactions and limited chiral macrocyclic systems. Herein, we report a water-soluble chiral luminescent supramolecular polymer assembled from a pair of chiral macrocycle ((R)-/(S)-C[4]B) and an achiral bis-thiazole orange guest. The ultrahigh binding affinity between the host and guest enables stable one-dimensional polymerization in water. Efficient chirality transfer from the macrocyclic host to the achiral luminophore gives rise to pronounced circular dichroism (CD) and circularly polarized luminescence (CPL). The resulting polymer exhibits red emission (625 nm) with a luminescence dissymmetry factor of 8.5 × 10⁻³. This work provides an effective strategy for the development of aqueous CPL-active supramolecular polymers through ultrastrong host–guest recognition. Full article

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder frequently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers reflecting immune activation and endothelial dysfunction, respectively. However, their differential associations with IR in PCOS, particularly in the context of central obesity, remain incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, systolic blood pressure (SBP), and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), or sCD40L. In adjusted regression models, fasting glucose independently predicted sCD40L (β = −0.27, 95% confidence interval (CI): −0.50 to −0.04, p = 0.020), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, 95% CI: 0.17 to 0.65, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. Assessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women. Full article

Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based on a carboxymethyl chitosan (CMCS)/Carbomer 940 (Carb940) composite gel loaded with hydroxypropyl-β-cyclodextrin inclusion complexes of paeonol (Pae-CD) was developed. Pae-CD was prepared using an ultrasound-assisted saturated aqueous solution method, and the physicochemical properties, sustained-release behavior, transdermal permeation, antioxidant activity, and safety of Pae-CD/gel were evaluated. Furthermore, a mouse model of skin photoaging induced by combined ultraviolet A (UVA)/ultraviolet B (UVB) irradiation was established to investigate its reparative effects in vivo. The results showed that Pae-CD/gel exhibited a homogeneous three-dimensional porous structure, favorable sustained-release characteristics, enhanced skin retention capacity, and good cellular compatibility. In vivo experiments demonstrated that Pae-CD/gel markedly ameliorated ultraviolet-induced skin dryness, abnormal epidermal thickening, and dermal collagen loss. It also reduced oxidative stress and inflammatory factor levels, down-regulated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) expression, and promoted the restoration of collagen type I (COL-1) and hydroxyproline (HYP) levels. Systemic safety evaluation revealed no obvious toxicity. In summary, Pae-CD/gel exerts antioxidant and anti-inflammatory effects and regulates collagen metabolism by enhancing transdermal delivery and local retention, thereby providing a safe and effective topical delivery strategy for the repair of skin photoaging. Full article