Search Results (15,532)

The development of non-toxic silver nanoparticles (AgNPs) for medical and other diverse applications is steadily increasing. However, this study specifically aims to determine the cytotoxic effects of AgNPs synthesized via a green chemistry approach using aqueous-ethanol and ethyl acetate extracts of Artemisia terrae-albae. The photophysical, morphological, and size distribution characteristics of the synthesized AgNPs are analyzed using UV-Vis spectroscopy and transmission electron microscopy (TEM). A modified Allium cepa assay is employed to evaluate biological responses, including root growth, root number, and mitotic index. In this assay, the cell cycles of onion bulbs are synchronized and pre-incubated at 4 °C for 72 h prior to treatment. This study reveals that the AgNPs synthesized from the ethanol extract exhibit notable stability and higher cytotoxicity activity, with a root length of 0.6 ± 0.13 cm, root number of 16 ± 6.88, and mitotic index of 25.0 ± 2.6. These values are significantly more cytogenotoxic than those observed for the ethyl-acetate-derived nanoparticles, which show a root length of 0.8 ± 0.17 cm, root number of 18 ± 6.27, and mitotic index of 36 ± 3.6. These findings highlight the potential of green-synthesized AgNPs as effective cytotoxic agents, especially those obtained from ethanol extract, possibly due to a greater influence of the quantity of diverse phenolic compounds present in the complex mixtures than in the ethyl acetate extract, which otherwise enhanced their morphology, shape, and size. These, overall, contributed to the biological activity. Full article

Background: Avian pathogenic Escherichia coli (APEC) is a leading cause of colibacillosis in poultry. Piper betle L. is a medicinal plant rich in bioactive compounds including hydroxychavicol that possess potent antibacterial activity. This study aimed to investigate the efficacy of a P. betle L. leaf nanoemulsion (NEPE) and hydroxychavicol against multidrug-resistant APEC isolates. Methods: In vitro and in silico analysis of NEPE and hydroxychavicol against APEC were determined. Results: The nanoemulsion exhibited potent antibacterial activity, with MIC and MBC values of 0.06–0.25% v/v and 0.125–0.25% v/v, respectively. The MIC and MBC values of hydroxychavicol against isolates ranged from 0.25 to 1.0 mg/mL. A time–kill assays revealed rapid bactericidal effects of both compounds, achieving a ≥3-log reduction within 4 h at 4 × MIC. Scanning electron microscopy demonstrated that APEC cells treated with hydroxychavicol exhibited filamentous cells with incomplete septa. Molecular docking and dynamics simulations of hydroxychavicol against APEC cell division proteins were investigated. According to the binding energy, hydroxychavicol exhibited the highest affinity with ZapE, FtsW, FtsX, FtsZ, and FtsA, respectively. However, the FtsA protein showed the least protein conformational change throughout the 5000 ns simulation, reflecting a highly stable conformation. Conclusions: These confirm the potential stability of protein and ligand, as supported by molecular dynamics simulation. The results suggested the potential of NEPE and hydroxychavicol, which may have promising antibacterial potential that can be used to inhibit APEC growth. Full article

Annona amazonica R.E. Fries (synonyms Annona amazonica var. lancifolia R.E. Fries), popularly known in Brazil as “envireira”, is a tropical tree belonging to the Annonaceae family and is traditionally used as a food source. In this work, the in vitro and in vivo anti-liver cancer effects of essential oil (EO) from A. amazonica leaves were investigated for the first time. The chemical composition of the EO was evaluated via GC–MS and GC–FID. The alamar blue assay was used to evaluate the cytotoxicity of EOs against different cancerous and noncancerous cell lines. Cell cycle analyses, YO-PRO-1/PI staining, and rhodamine 123 staining were performed via flow cytometry in HepG2 cells treated with EO. The in vivo antitumor activity of EO was evaluated in NSG mice that were xenografted with HepG2 cells and treated with EO at a dose of 60 mg/kg. The major constituents (>5%) of the EO were (E)-caryophyllene (32.01%), 1,8-cineole (13.93%), α-copaene (7.77%), α-humulene (7.15%), and α-pinene (5.13%). EO increased apoptosis and proportionally decreased the number of viable HepG2 cells. The induction of DNA fragmentation and cell shrinkage together with a significant reduction in the ΔΨm in EO-treated HepG2 cells confirmed that EO can induce apoptosis. A significant 39.2% inhibition of tumor growth in vivo was detected in EO-treated animals. These data indicate the anti-liver cancer potential of EO from A. amazonica leaves. Full article

Toothpaste is an essential oral hygiene product commonly used to sustain oral health due to its incorporation of antimicrobial agents. Numerous functional toothpastes enriched with antimicrobial agents have been developed and are available to consumers. This study evaluates the antimicrobial and antibiofilm efficacy of 12 commercially available toothpaste products, including those with specialized functions. Statistical significance was assessed to validate the differences observed among the toothpaste samples. Their effects on Streptococcus mutans, the primary pathogen responsible for dental caries, were evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and bacterial growth was measured to compare antimicrobial activities. Toothpaste containing 1000 μg/mL fluoride and whitening toothpaste exhibited the strongest antimicrobial effects, effectively inhibiting S. mutans growth. Additionally, bamboo salt-enriched and tartar-control toothpaste demonstrated inhibitory effects on bacterial growth. Assays to evaluate the ability of cells to form biofilms and the expression of genes involved in biofilm formation revealed a partial correlation between biofilm formation and spaP, gtfB, gtfC, and gtfD expression, although some showed opposite trends. Collectively, this study provides valuable insights into the antimicrobial and biofilm inhibition capabilities of commercial toothpastes against S. mutans, offering a foundation for evaluating the efficacy of functional toothpaste products. Full article

Oxybenzone (OBZ), an organic ultraviolet filter, is an emerging contaminant posing severe threats to ecosystem health. Using tobacco (Nicotiana tabacum) as a model plant, this study investigated the alleviation mechanisms of exogenous silicon (Na₂SiO₃, Si) and bamboo-based biochar (Bc) under OBZ stress. We systematically analyzed physiological and biochemical responses, including phenotypic parameters, reactive oxygen species metabolism, photosynthetic function, chlorophyll synthesis, and endogenous hormone levels. Results reveal that OBZ significantly inhibited tobacco growth and triggered a reactive oxygen species (ROS) burst. Additionally, OBZ disrupted antioxidant enzyme activities and hormonal balance. Exogenous Bc mitigated OBZ toxicity by adsorbing OBZ, directly scavenging ROS, and restoring the ascorbate-glutathione (AsA-GSH) cycle, thereby enhancing photosynthetic efficiency, while Si alleviated stress via cell wall silicification, preferential regulation of root development and hormonal signaling, and repair of chlorophyll biosynthesis precursor metabolism and PSII function. The mechanisms of the two stress mitigators were complementary, Bc primarily relied on physical adsorption and ROS scavenging, whereas Si emphasized metabolic regulation and structural reinforcement. These findings provide practical strategies for simultaneously mitigating organic UV filter pollution and enhancing plant resilience in contaminated soils. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Background: DEAD/H box 5 (DDX5) serves as a transcriptional coactivator for several transcription factors including E2F1, the primary target of the tumor suppressor pRB. E2F1 physiologically activated by growth stimulation activates growth-related genes and promotes cell proliferation. In contrast, upon loss of pRB function due to oncogenic changes, E2F1 is activated out of restraint by pRB (deregulated E2F1) and stimulates tumor suppressor genes such as ARF, which activates the tumor suppressor p53, to suppress tumorigenesis. We have recently reported that DDX5 augments deregulated E2F1 activity to induce tumor suppressor gene expression and apoptosis. During the analyses, we noted that over-expression of E2F1 increased DDX5 expression, suggesting a feed forward loop in E2F1 activation through DDX5. Objective: We thus examined whether the DDX5 gene is a target of deregulated E2F1. Method: For this purpose, we performed promoter analysis and ChIP assay. Result: The DDX5 promoter did not possess typical E2F binding consensus but contained several GC repeats observed in deregulated E2F1 targets. Insertion of point mutations in these GC repeats decreased responsiveness to deregulated E2F1 induced by over-expression of E2F1, but scarcely affected responsiveness to growth stimulation. ChIP assays showed that deregulated E2F1 induced by over-expression of E2F1 or expression of E1a, which binds pRB and releases E2F1, bound to the DDX5 gene, while physiological E2F1 induced by growth stimulation did not. Conclusions: These results suggest that the DDX5 gene is a target of deregulated E2F1, generating a feed forward loop mediating tumor suppressive E2F1 activity. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions. Full article

Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the whole genome, and these were further divided into three subgroups (Group I/II, Group III, and the Ancestral Group) through evolutionary analysis. Gene structure and protein motif analyses indicate that closely clustered BdXTH genes are relatively conserved within each group. A highly conserved amino acid domain (DEIDFEFLG) responsible for catalytic activity was identified in all BdXTH proteins. We detected three pairs of segmentally duplicated BdXTH genes and five groups of tandemly duplicated BdXTH genes, which played vital roles in the expansion of the BdXTH gene family. Cis-elements related to hormones, growth, and abiotic stress responses were identified in the promoters of each BdXTH gene, and when roots were treated with two abiotic stresses (salinity and drought) and four plant hormones (IAA, auxin; GA3, gibberellin; ABA, abscisic acid; and BR, brassinolide), the expression levels of many BdXTH genes changed significantly. Transcriptional analyses of the BdXTH genes in 38 tissue samples from the publicly available RNA-seq data indicated that most BdXTH genes have distinct expression patterns in different tissues and at different growth stages. Overexpressing the BdXTH27 gene in Brachypodium led to reduced root length in transgenic plants, which exhibited higher cellulose levels but lower hemicellulose levels compared to wild-type plants. Our results provide valuable information for further elucidation of the biological functions of BdXTH genes in the model grass B. distachyon. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the field of antimicrobial photodynamic therapy. The photodynamic and sonodynamic activity of 3-(3-(diethylamino)phenoxy)propanoxy substituted silicon(IV) Pc were evaluated against bacteria and cancer cells. Stability and singlet oxygen generation upon light irradiation and ultrasound (1 MHz, 3 W) were assessed with 1,3-diphenylisobenzofuran. The phthalocyanine revealed high photostability in DMF and DMSO, although the singlet oxygen yields under light irradiation were low. On the other hand, the phthalocyanine revealed excellent sonostability and caused a high rate of DPBF degradation upon excitation by ultrasounds at 1 MHz. The silicon phthalocyanine presented significant bacterial reduction growth, up to 5 log against MRSA and S. epidermidis upon light excitation, whereas the sonodynamic effect was negligible. The phthalocyanine revealed high activity in both photodynamic and sonodynamic manner toward hypopharyngeal tumor (FaDu, 95% and 42% reduction, respectively) and squamous cell carcinoma (SCC-25, 96% and 62% reduction, respectively). The sensitizer showed ca. 30% aldehyde dehydrogenase inhibition in various concentrations and up to 85% platelet-activating factor acetylhydrolase for 0.25 μM, while protease-activated protein C was stimulated up to 66% for 0.75 μM. Full article

The most prevalent growth of Candida cells is based on biofilm development, which causes the intensification of antifungal resistance against a large range of chemicals. Nanoparticles can be synthesized using green methods via various biological extracts and reducing agents to control Candida biofilms. This study aims to compare copper oxide nanoparticles (CuONPs) synthesized through chemical methods and those synthesized using Cinnamomum verum-based green methods against Candida infections and their biofilms isolated from Iraqi patients, with the potential to improve treatment outcomes. The physical and chemical properties of these nanoparticles were characterized using Fourier-transform infrared spectroscopy (FT-IR,) scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Four strains of Candida were isolated and characterized from Iraqi patients in Tikrit Hospital and selected based on their ability to form biofilm on polystyrene microplates. The activity of green-synthesized CuONPs using cinnamon extract was compared with both undoped and doped (Fe, Sn) chemically synthesized CuONPs. Four pathogenic Candida strains (Candida glabrata, Candida lusitaniae, Candida albicans, and Candida tropicalis) were isolated from Iraqi patients, demonstrating high biofilm formation capabilities. Chemically and green-synthesized CuONPs from Cinnamomum verum showed comparable significant antiplanktonic and antibiofilm activities against all strains. Doped CuONPs with iron or tin demonstrated lower minimum inhibitory concentration (MIC) values, indicating stronger antibacterial activity, but exhibited weaker anti-adhesive properties compared to other nanoparticles. The antiadhesive activity revealed that C. albicans strain seems to produce the most resistant biofilms while C. glabrata strain seems to be more resistant towards the doped CuONPs. Moreover, C. tropicalis was the most sensitive to all the CuONPs. Remarkably, at a concentration of 100 µg/mL, all CuONPs were effective in eradicating preformed biofilms by 47–66%. The findings suggest that CuONPs could be effective in controlling biofilm formation by Candida species resistant to treatment in healthcare settings. Full article

Aluminum (Al) stress is an important factor that inhibits crop growth in acidic soils and poses a threat to pumpkin (Cucurbita moschata) production. In this study, we investigated the effect of endophyte (endophyte) strain J01 of blueberry (Vaccinium uliginosum) on the growth, development, and transcriptional regulatory mechanisms of pumpkin under aluminum stress. The results showed that the blueberry endophyte strain J01 significantly increased the root length of pumpkin under aluminum stress, promoted the growth of lateral roots, and increased root vigor; strain J01 reduced the content of MDA and the relative conductivity in the root system; strain J01 enhanced the activities of superoxide dismutase and catalase in the root system but inhibited ascorbate peroxidase activity. Transcriptome analysis further revealed that strain J01 significantly regulated the expression of key genes associated with aluminum tolerance, including the upregulation of transporter protein genes (aluminum-activated malate transporter and aquaporin), affecting the gene expression levels of genes encoding antioxidant enzymes (ascorbate peroxidase and glutathione S-transferase) and cell wall modification genes (xyloglucan endotransglucosylase/hydrolase and pectin methylesterase). This study provides a theoretical basis and practical guidance for using microbial resources to improve aluminum tolerance in cucurbit crops. Full article

The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits. AKT and JNK did not show treatment-dependent activation and lacked a correlation with functional traits, as shown by ERK1/2. These findings suggest that rrβNGFch may promote the functional activation of sperm cells, particularly during early incubation. The increase in capacitation and AR was not linked to significant changes in pathways related to cell survival or death, indicating a specific action of the treatment. In contrast, prolonged storage negatively affected all sperm parameters. ERK1/2 activation correlated with capacitation, AR, and apoptosis, supporting its role as an NGF downstream mediator. Further studies should analyze other molecular mechanisms of sperm and the potential applications of NGF in assisted reproduction. Full article