Search Results (3,522)

Exposure to per- and polyfluoroalkyl substances (PFASs) can cause detrimental health effects. The consumption of contaminated food is viewed as a major exposure pathway for humans, but the relationship between agriculture and PFASs has not been investigated thoroughly, and it is becoming a pressing issue since health advisories are continuously being reassessed. This semi-systematic literature review connects the release, environmental fate, and agriculture uptake of PFASs to enhance comprehension and identify knowledge gaps which limit accurate risk assessment. It focuses on the heavily agricultural state of Minnesota, USA, which is representative of the large Midwestern US Corn Belt in terms of agricultural activities, because PFASs have been monitored in Minnesota since the beginning of the 21st century. PFAS contamination is a complex issue due to the over 14,000 individual PFAS compounds which have unique chemical properties that interact differently with air, water, soil, and biological systems. Moreover, the lack of field studies and monitoring of agricultural sites makes accurate risk assessments challenging. Researchers, policymakers, and farmers must work closely together to reduce the risk of PFAS exposure as the understanding of their potential health effects increases and legacy PFASs are displaced with shorter fluorinated replacements. Full article

Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., commonly known as divaricate siler, is a well-known medicinal plant from the Apiaceae family. Its natural habitat is rapidly declining owing to the harvesting of its roots, used as fángfēng in traditional Oriental medicine. This underutilized herb may serve as a valuable source of bioactive phenolic compounds, which can potentially be influenced by salicylic acid (SA) elicitation—a practical method to increase the concentration of valuable substances in plants. A field study showed that foliar application of SA on one-year-old S. divaricata positively influenced the total phenolic content in the herb, with the highest increase observed at 1.0 mM SA. Liquid chromatography–mass spectrometry (LC–MS) data became increasingly complex with rising SA levels, identifying up to 48 compounds, including cinnamoyl quinic acids (CQAs), dihydrofurochromones (DFCs), and flavonol O-glycosides (FOGs), most reported for the first time in this species. The highest concentrations of CQAs, DFCs, and FOGs in plants treated with 1.0 mM SA were 83.14, 3.75, and 60.53 mg/g, respectively, compared to 42.76, 0.95, and 40.73 mg/g in untreated (0.0 mM SA) plants. Nine in vitro antioxidant assays revealed strong radical-scavenging and nitric oxide (NO)- and Fe²⁺-chelating activities in 1.0 mM SA-treated plants, indicating robust antioxidative properties of the S. divaricata herb. Thus, foliar application of SA considerably enriches the herb with target antioxidants, increasing its medicinal value, which is reflected in the plant’s biological response. This could potentially reduce the overexploitation of natural populations of S. divaricata, helping to preserve this valuable plant. Full article

Anthocyanins, a subclass of flavonoid pigments, impart vivid red, purple, and blue coloration to horticultural plants, playing essential roles in ornamental enhancement, stress resistance, and pollinator attraction. Recent studies have identified B-box (BBX) proteins as a critical class of transcription factors (TFs) involved in anthocyanin biosynthesis. Despite these advances, comprehensive reviews systematically addressing BBX proteins are urgently needed, especially given the complexity and diversity of their roles in regulating anthocyanin production. In this paper, we provide an in-depth overview of the fundamental structures, biological functions, and classification of BBX TFs, along with a detailed description of anthocyanin biosynthetic pathways and bioactivities. Furthermore, we emphasize the diverse molecular mechanisms through which BBX TFs regulate anthocyanin accumulation, including direct activation or repression of target genes, indirect modulation via interacting protein complexes, and co-regulation with other transcriptional regulators. Additionally, we summarize the known upstream regulatory signals and downstream target genes of BBX TFs, highlighting their significance in shaping anthocyanin biosynthesis pathways. Understanding these regulatory networks mediated by BBX proteins will not only advance fundamental horticultural science but also provide valuable insights for enhancing the aesthetic quality, nutritional benefits, and stress adaptability of horticultural crops. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, significantly increases the risk of infection, delayed healing, and adverse outcomes. Traditional wound dressings frequently prove inadequate under such extreme conditions, as they have not been designed to address the specific physiological and logistical constraints present during armed conflicts. This review provides a comprehensive overview of recent progress in the development of advanced wound dressings tailored for use in military scenarios. Special attention has been given to multifunctional dressings that go beyond basic wound coverage by incorporating biologically active macromolecules such as collagen, chitosan, thrombin, alginate, therapeutic peptides, and growth factors. These compounds contribute to properties including moisture balance control, exudate absorption, microbial entrapment, and protection against secondary infection. This review highlights the critical role of advanced wound dressings in improving medical outcomes for injured military personnel. The potential of these technologies to reduce complications, enhance healing rates, and ultimately save lives underscores their growing importance in modern battlefield medicine. Full article

MicroRNA-211 (miR-211) is a versatile regulatory molecule that plays critical roles in cellular homeostasis and disease progression through the post-transcriptional regulation of gene expression. This review comprehensively examines miR-211’s multifaceted functions across various biological systems, highlighting its context-dependent activity as both a tumor suppressor and oncogene. In physiological contexts, miR-211 regulates cell cycle progression, metabolism, and differentiation through the modulation of key signaling pathways, including TGF-β/SMAD and PI3K/AKT. miR-211 participates in retinal development, bone physiology, and protection against renal ischemia–reperfusion injury. In pathological conditions, miR-211 expression is altered in various diseases, particularly cancer, where it may be a useful diagnostic and prognostic biomarker. Its stability in serum and differential expression in various cancer types make it a promising candidate for non-invasive diagnostics. The review also explores miR-211’s therapeutic potential, discussing both challenges and opportunities in developing miRNA-based treatments. Understanding miR-211’s complex regulatory interactions and context-dependent functions is crucial for advancing its clinical applications for diagnosis, prognosis, and targeted therapy in multiple diseases. Full article

Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article

Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon complexation with a DNA-based nanostructure. Upon localized plasma exposure, DNA masking was disrupted, restoring the biological functions of the peptides. Transmission electron microscopy revealed that the synthesized DNA nanoflower structures were approximately 150–250 nm in size. Structural and functional analyses confirmed that the system remained inert under physiological conditions and was rapidly activated by plasma treatment. Fluorescence recovery, cellular uptake assays, and cytotoxicity measurements demonstrated that the peptide activity could be precisely controlled in both monolayer and three-dimensional spheroid models. This externally activatable nanomaterial-based system enables the spatial and temporal regulation of peptide function without requiring biochemical triggers or permanent chemical modifications. This platform provides a modular strategy for the development of potential peptide therapeutics that require precise control of activation in complex biological environments. Full article

Antimicrobial resistance (AMR) poses a critical global health threat by rendering existing antibiotics ineffective against infections, leading to increased mortality, prolonged illnesses, and higher healthcare costs. Developing new antibiotics is essential to combat resistant pathogens, safeguard modern medical procedures, and prevent a return to a pre-antibiotic era where common infections become untreatable. We report a series of chiral tricarbonyl rhenium(I) complexes incorporating enantiopure pinene-substituted bipyridine ligands (L#) of the general formula fac-[Re(CO)₃L#X] and fac-[Re(CO)₃L#Py]⁺ (where X = Cl or Br and Py = pyridine). These complexes were isolated as mixtures of two diastereomers, characterized by standard techniques, and evaluated for cytotoxic activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA). The results revealed notable antibacterial efficacy (MIC = 1.6 μM), reflected in high therapeutic indices (Ti > 10). In contrast, analogous complexes bearing non-chiral 2,2′-bipyridine ligands exhibited no activity, underscoring the critical role of chirality in modulating biological interactions at the molecular level. These findings highlight the potential of chiral Re(I) complexes as promising scaffolds for the development of more potent and selective antibacterial agents. Full article

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an overview of structural variations, their mutagenesis mechanisms, and their detection in the genomics era, focusing on the biological significance, methodologies, and future directions in the field. Full article

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field. Full article

Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within the complex ecosystem of TME, with significant heterogeneity and plasticity in origin and functional phenotypes. Very enigmatic cells, CAFs determine the progress and outcomes of tumors through extensive reciprocal signaling with different tumors infiltrating immune cells in the TME. In their biological drive, CAFs release numerous chemical mediators and utilize various signaling pathways to recruit and modulate tumor-infiltrating immune cells. The CAF-induced secretome and exosomes render immune cells ineffective for their antitumor activities. Moreover, by upregulating immune inhibitory checkpoints, CAFs create an immunosuppressive TME that impedes the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs). Further, by depositing and remodeling extracellular matrix (ECM), CAFs reshape the TME, which enhances tumor growth, invasion, metastasis, and chemoresistance. Understanding of CAF biology and its crosstalk with tumor-infiltrating immune cells is crucial not only to gain insight in tumorigenesis but to optimize the potential of novel targeted immunotherapies for cancers. The complex relationships between CAFs and tumor-infiltrating immune cells remain unclear and need further study. Herein, in this narrative review we have focused on updates of CAF biology and its interactions with tumor-infiltrating immune cells in generating immunosuppressive TME and resistance to cell death. Full article

The development of novel platinum-based anticancer agents remains a critical objective in medicinal inorganic chemistry, particularly in light of resistance and toxicity limitations associated with cisplatin. In this study, the synthesis, structural characterization, quantum chemical analysis, and cytotoxic evaluation of four new acetylplatinum(II) complexes (cis-[Pt(COMe)₂(PASO₂)₂], cis-[Pt(COMe)₂(DAPTA)₂], trans-[Pt(COMe)Cl(DAPTA)₂], and trans-[Pt(COMe)Cl(PASO₂)]: 1–4, respectively) bearing cage phosphine ligands PASO₂ (2-thia-1,3,5-triaza-phosphaadamantane 2,2-dioxide) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) are presented. The coordination geometries and NMR spectral features of the cis/trans isomers were elucidated through multinuclear NMR and DFT calculations at the B3LYP/6-311++G(d,p)/LanL2DZ level, with strong agreement between experimental and theoretical data. Quantum Theory of Atoms in Molecules (QTAIM) analysis was applied to investigate bonding interactions and assess the covalent character of Pt–ligand bonds. Cytotoxicity was evaluated against five human cancer cell lines. The PASO₂-containing complex in cis-configuration, 1, demonstrated superior activity against thyroid (8505C) and head and neck (A253) cancer cells, with potency surpassing that of cisplatin. The DAPTA complex 2 showed enhanced activity toward ovarian (A2780) cancer cells. These findings highlight the influence of ligand structure and isomerism on biological activity, supporting the rational design of phosphine-based Pt(II) anticancer drugs. Full article

Codonopsis pilosula polysaccharides have demonstrated multiple biological activities including immune regulation, antitumor, and antioxidant properties. The rapid development and integrated application of multi-omics can facilitate the unraveling of the complex network of immune system regulation. In this study, C. pilosula alkali-extracted polysaccharide (CPAP) were prepared, and their effects on gut microbiota compositions, metabolic pathways, and protein expressions in peripheral blood and solid tumors in mice were further evaluated. The 16S rDNA sequencing results showed that CPAP could effectively promote the enrichment of intestinal Lactobacillus in tumor-bearing mice. In addition, it could be inferred from peripheral blood and solid tumor proteomics results that CPAP might activate T cell-mediated antitumor immune functions by regulating purine metabolism and alleviate tumor-caused inflammation by promoting neutrophil degranulation, finally inducing apoptosis in tumor cells by increasing oxidative stress. These results will provide a theoretical foundation and data support for the further development of CPAP as dietary adjuvants targeting immune deficiency-related diseases. Full article