Dodonaea viscosa is one of the widely distributed ornamental plants. It is rich in many phytoconstituents. The present study aims to examine the activity of spanlastics formulations loaded with compounds isolated from Dodonaea viscosa leaves extract. The isolated compounds were identified and loaded into nanovesicles. The anti-SARS-CoV-2 activity of selected drug-loaded spanlastics was evaluated using MTT assay and the underlying mechanism of action was determined. The formulations showed high encapsulation efficiency with vesicle diameters in the nanometre range. The vesicles were spherical and exhibited large negative values of zeta potential, indicating good stability. Selected formulations of V and S (V1 and S1) exhibited high antiviral activity against SARS-CoV-2 with IC50 of 4.483 and 9.795 µg/ml for V1 and S1, respectively, through inhibition of virus adsorption for V1 and virucidal activity by 55.7 % for S1. The network pharmacology defined the EGFR as the top annotated gene with 7 edges, followed by PIK3CG, VEGFA, and MMP9 genes with 4 edges for each. Molecular docking simulations reveal favourable binding affinities and diverse interactions with critical amino acid residues. In silico ADMET profiling further indicated that both compounds are drug-like, with favourable absorption and core-safety signatures (non-mutagenic, non-carcinogenic, and non-cardiotoxic). Santin and viscosine formulated nanovesicles represent promising formulations with therapeutic potential against SARS-CoV-2.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited therapies. We explored the anti-HCC mechanisms of Zanthoxylum nitidum (Roxb.) DC. via network pharmacology, bioinformatics and molecular docking. We identified its active components, targets and HCC-related key genes by differential expression analysis. Enrichment analysis showed these targets act in HCC-related pathways like alcoholic liver disease and the PPAR signalling pathway. Machine learning screened 5 characteristic genes (ESR1, CCNA2, CYP2B6, CHRM2, IL10), among which ESR1 and CCNA2 correlate with patient prognosis. These genes regulate tumour microenvironment and show epigenetic variations in methylation and copy number. Molecular docking confirmed stable binding between plant components and core targets. This study first reveals the multi-target anti-HCC mechanisms of Z. nitidum, offering evidence for its clinical use. Follow-up experiments are needed to validate our findings.
Background The aim of this study was to investigate key target(s), mechanism(s) from hepatoma cells in harsh doxorubicin-resistant conditions (DRCs) from GSE125180 datasets in GEO (Gene Expression Omnibus).Methods The identified components can be denoted as a brightness (therapeutic mark) or darkness (resistant mark) in DRCs. The protein-protein interaction (PPI) networks were assembled to identify the relationships between upregulated and downregulated genes via STRING, and R program.Results In the |log2 FC| > 1, and |log2 FC| > 2 subgroups, the uppermost target was a non-receptor tyrosine kinase (SRC) downregulated in DRCs, indicating that the dampened SRC is a therapeutic mark by doxorubicin (DOX). In contrast, in the |log2 FC| > 3 subgroup, the most significant target was Cluster of Differentiation 93 (CD93) upregulated in DRCs, suggesting that the overexpressed CD93 is a resistant mark in DRCs. Metoclopramide (MET) @ CD93 + DOX conformer is a highlighted capture to illuminate as combination therapy to overcome DRCs because MET is an inhibitor against CD93 as well as a non-competitive inhibitor on (MET @ CD93 + DOX) conformer.Conclusions These findings provide a mechanistic rationale for repurposing MET as an adjuvant agent to enhance therapeutic efficacy and overcome drug resistance in combination treatment strategies.
Preeclampsia (PE) is a severe pregnancy-specific complication characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, which can cause multi-organ damage and life-threatening outcomes for both mothers and foetuses. Its pathogenesis remains incompletely elucidated, with placental dysfunction widely recognized as a core pathogenic factor. This study integrated multiple placental transcriptome and single-cell sequencing datasets from the Gene Expression Omnibus (GEO) database, employing a multi-dimensional bioinformatics approach - including differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, molecular subtype clustering, single-cell resolution analysis, and intercellular communication analysis - to systematically identify PE-related key genes, construct a diagnostic model, define molecular subtypes, and explore potential molecular mechanisms. Results showed 10 differentially expressed genes (DEGs) were identified in PE placental tissues; WGCNA pinpointed the turquoise module as the core PE-associated module. Further screening using 11 machine learning algorithms identified 9 feature genes with high diagnostic value (DDR1, DIO2, FSTL3, HK2, HTRA4, LEP, SERPINA3, TMEM45A, TREM1). A diagnostic model built with the 'Stepglm[forward]' algorithm exhibited excellent performance in both training and validation sets (average AUC = 0.865). Molecular subtype analysis classified PE samples into two subtypes (C1, C2) with significantly distinct immune infiltration profiles, where the C1 subtype showed higher immune cell infiltration. Single-cell analysis identified 11 cell types in PE placental tissue and highlighted TMEM45A as a key DEG. Intercellular communication analysis revealed the VEGF signalling pathway as the core driver of abnormal cellular crosstalk in PE, primarily mediating signal transduction between villous cytotrophoblast cells (VCT), extravillous trophoblast cells (EVT), and endothelial cells. Hypoxia scoring analysis demonstrated significantly higher hypoxia levels in the PE group compared to normal controls, with TMEM45A expression positively correlated with hypoxia scores. This study provides novel insights into the molecular pathogenesis of PE and offers potential biomarkers and a theoretical basis for its early diagnosis and targeted therapy.
This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer-Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.
Objective This review introduces the ‘nanomaterial-microbiome-brain interface’ as a conceptual framework uniting three systems: gut microbiota, nanoparticles, and neurodegeneration.Main Findings We synthesize evidence showing that titanium dioxide, silver, and zinc oxide nanoparticles differentially alter microbial composition. These microbial shifts intersect with established gut-brain mechanisms, including short-chain fatty acid production and immune modulation, providing plausible pathways linking nanomaterial exposure to neurological outcomes.Conclusion We propose the ‘nanomaterial-microbiome-brain interface’ as a novel conceptual framework with twofold relevance—serving both as a potential contributor to Parkinson’s disease pathogenesis through unintentional environmental exposure, and as an underexplored avenue for therapeutic intervention. Critical knowledge gaps persist. Addressing these gaps will require integrated approaches that bridge nanomaterial research, microbiome science, and neurodegeneration studies.
Ex vivo expansion of human adipose-derived stem cells (hADSCs) remains challenging because reduced-serum culture conditions can compromise short-term cell function. Here, we evaluated a microenvironment-inspired tri-component preconditioning regimen composed of platelet-rich plasma (PRP), Lactobacillus plantarum cell-free supernatant (Lp-SN), and resveratrol-loaded PLGA nanoparticles (RSV-PLGA-NPs) as a reduced-serum culture support strategy. Using a Box-Behnken design, we identified a formulation space in which PRP, Lp-SN, and RSV-PLGA-NPs were associated with improved hADSC viability and increased expression of selected stemness-associated genes in vitro. Omission-control experiments comparing the full formulation with partial combinations and blank PLGA NPs showed attenuated responses when individual components were removed, whereas the NP carrier alone had no significant effect. These findings support the utility of this tri-component system as a preliminary ex vivo preconditioning approach for short-term hADSC culture support. However, the results should be interpreted within the limits of the present in vitro study, as long-term expansion, post-treatment differentiation capacity, and in vivo performance were not evaluated.
Sol-gel process proved to be an effective approach to synthesize borosilicate-based bioactive glasses with significant crystallization induced during devitrification verified by Na2CaSiO4 phase. A progressive growth of hydroxyapatite (HA) phase in the size range of 17-26 nm was observed. Fourier transform infra-red (FTIR) spectroscopy suggested the presence non-bridging oxygen (NBO) and BO3 groups that facilitated rapid ion exchange. While bands at 550-650 cm-1 (PO43-) and 1524 cm-1 (CO32-) confirmed the formation of carbonated HA. The porous architecture of bioactive glass facilitated rapid in-vitro mineralization while crystalline bioactive glass improved dimensional stability and controlled degradation which renders it ideal for hard tissue engineering scaffolds where structural integrity is important besides biological functions.
Osteoarthritis (OA) presents a significant therapeutic challenge, necessitating innovative biomaterial strategies to reduce chronic inflammation and promote cartilage regeneration. This study developed a hybrid gelatine (GE)/polyvinyl alcohol (PVA) hydrogel crosslinked with genipin (GNP) to effectively deliver Hydroxytyrosol (HT). A 6% GE was incorporated with 3% and 5% PVA concentrations, followed by 0.1% (w/v) GNP. The physicochemical and biocompatibility properties were further evaluated. Physicochemical analysis identified the GPVA5%-GNP formulation as optimal, featuring an interconnected porous structure, optimal swelling ratio (640.43 ± 22.28%), improved hydrophilicity (44.50 ± 1.81°), controlled biodegradation, and enhanced compressive strength (96.88 ± 0.72%). Chemical tests confirmed thermal and structural stability, while biocompatibility assays showed over 95% cell viability. The therapeutic potential was evaluated using an IL-1β-induced inflammatory model in human chondrocytes. MTT assays revealed that HT at 12.5, 25, and 50 μM restored metabolic activity in a dose-dependent manner over 14 days, outperforming the 9 μM Glucosamine Sulphate positive control. The 50 μM HT dose yielded the best metabolic recovery, supported by Live/Dead imaging that showed increased viable cell density from Day 1 to Day 7. Overall, the GPVA5%-GNP hydrogel loaded with 50 μM HT offers a robust protective environment that reduces catabolic stress and promotes cell proliferation, making it a promising localized therapy for cartilage regeneration in OA.
Escalation of antimicrobial resistance amongst Klebsiella pneumoniae (K. pneumoniae) represents a remarkable worldwide health concern. This study reports the green biosynthesis of copper, silver and magnesium oxide trimetallic nanocomposites (CuO-AgO-MgO TNCs) using banana peel extract as a safe and sustainable reducing and stabilizing agent and emphasizes its inhibitory activity against carbapenem-resistant K. pneumoniae (CRKP) strains. The TNCs were characterized by ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, transmission electron microscope (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis, confirming their crystalline structure (average size 125 nm) and elemental composition (Cu, Ag, Mg, O). Cytotoxicity assessment using WI-38 normal cells showed minimal toxic effect with an IC50 of 193.49 ± 2.85 µg/mL. Antibacterial activity was evaluated against genotypically diverse CRKP strains. Well diffusion assay (WDA) showed inhibition zones of 18-38 mm, while the broth microdilution assay provided minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 8 to 1024 µg/mL and 128 to 2048 µg/mL, respectively. Time-kill assays indicated rapid bacterial growth reduction within 2 h, and antibiofilm assays showed 25-91% inhibition of biofilm formation. The image provided by SEM revealed pronounced morphological alterations in treated bacterial cells. Our findings exhibited biogenic CuO-AgO-MgO TNCs with potent antibacterial and antibiofilm activities against CRKP while showing negligible toxicity towards normal cells, highlighting their potential as a safe and effective alternative antimicrobial strategy.
The advancements in the areas of real-time RNA biosensor technology and their application to more precise diabetes care have laid the groundwork for new and potentially efficient strategies for monitoring and management of the disease. At the same time, many researchers are now studying the influence of environmental factors, and more specifically, exposure to endocrine-disrupting chemicals (EDCs), that can impact not only the diabetes disease process itself, but also the reliability and consistency of biosensors to monitor these stressors. The current review summarizes recent advances in RNA sensor technology designed for diabetes care, evaluates the connection between it and point-of-care (POC) diagnostics, and purposefully analyzes the existing evidence on how such EDCs can affect biosensor accuracy, stability, and general clinical usefulness.
Hesperidin (HSP) is a polyphenolic compound employed widely in the therapy of epithelial ovarian cancer (EOC). However, the low bioavailability, attributed to first-pass metabolism, low dissolution and poor tumour specificity, hampered its clinical effectiveness. Therefore, HSP-loaded folic acid-PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HSP-PEGylated PLGA FA NPs) were synthesized to improve dissolution and target specificity of HSP for the management of EOC. The NPs were synthesized by nanoprecipitation and assessed for entrapment efficiency, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and in vitro dissolution. Additionally, antioxidant assay, cytotoxicity, cellular uptake and flow cytometric were performed on folate receptor overexpressing SKOV3 cell line. Physico-chemical characterization supported the formation of HSP-PEGylated PLGA FA NPs with entrapment efficiency ∼89.34%, particle size ∼205 nm, and a zeta potential of ∼ -25 mV, demonstrating their physical stability. The NPs enhanced HSP release at pH 5.5 compared to pH 7.4. The NPs showed greater cytotoxicity at an IC50 value of ∼29 µM/mL and enhanced early apoptosis ∼44% as compared to HSP-PEGylated PLGA NPs ∼32% towards the FA receptor overexpressed EOC cell line. The developed formulation shows promising potential as a targeted NP system for the management of EOC.
Nanomaterials are gaining prominence in regenerative medicine because their nanoscale features enable precise drug delivery, cellular regulation and targeted tissue repair. A particularly exciting opportunity lies in their application to immunomodulatory bone regeneration, where nanoscience and immunology intersect to address persistent challenges in bone healing. The recent progress in nanoparticle (NP) design, fabrication and characterization, with emphasis on their dual role as therapeutic carriers and modulators of immune responses, has been highlighted in this study. Both top-down and bottom-up synthesis strategies are discussed, illustrating how particle size, morphology and surface chemistry influence cell-nanosystem interactions. The immune system's responses to nanomaterials are explored in some detail, from beneficial adaptive memory formation to adverse inflammatory reactions, underscoring the delicate balance between efficacy and safety. Limitations of conventional NP systems include cytotoxicity, instability and regulatory hurdles, are examined in conjunction with advanced characterization techniques that relate material properties to biological outcomes. By integrating fundamental nanoscience with immunological perspectives, these fundamental insights into the rational design of nanomaterials for bone regeneration are discussed. The ultimate objective is to provide guidelines for developing safer, more effective strategies that can translate into meaningful clinical applications.
Background A Disintegrin and Metalloproteinase with Thrombospondin motifs 7 (ADAMTS7) plays a critical role in atherosclerosis by degrading the extracellular matrix and modulating smooth muscle cell (SMC) proliferation, migration, and phenotypic transformation. This study investigated the association between the ADAMTS7 single-nucleotide polymorphism (SNP) rs1045130 and large artery atherosclerotic (LAA) stroke.Materials and Methods Genotyping analyses were conducted on two independent case-control cohorts comprising 1,027 LAA patients and 1,043 age-matched controls, followed by the quantification of ADAMTS7 expression and its downstream molecular effects.Results ADAMTS7 was highly expressed in endothelial cells, SMCs, and macrophage-derived foam cells of vulnerable human aortic plaques. Furthermore, individuals carrying the rs1045130 A allele or GA/AA genotype had a significantly higher susceptibility to LAA stroke, poorer short-term outcomes, and an increased risk of one-month recurrence. Mechanistically, the G > A mutation disrupts the ADAMTS7-miR-654-5p interaction, leading to elevated ADAMTS7 expression and subsequent promotion of foamed vascular SMCs (VSMCs) proliferation and migration.Conclusions The rs1045130 G > A variant is associated with increased LAA stroke incidence and worse prognosis. The mutation promotes the proliferation and migration of foamed VSMCs by disrupting the miR-654-5p/ADAMTS7 axis, potentially accounting for the higher disease risk and poorer prognosis observed in affected individuals.
Targeting the inflammation-related molecules with nonsteroidal anti-inflammatory drugs (NSAIDs) represents a promising approach for cancer prevention/therapy. We evaluated the in vitro anticancer effects of sulindac, ketoprofen, celecoxib and the antidepressant fluoxetine, both free and coupled with synthesized dendrons and dendrimers, on the proliferation and apoptosis of human MCF-7 (human mammary adenocarcinoma), SKLU-1 (human lung adenocarcinoma) and as a control the normal monkey kidney (COS-7) cell line. The antiproliferative activity and cytotoxicity of tested NSAIDs on MCF-7 and SKLU-1 cell lines were assessed by the sulforhodamine B (SRB) assay. The tested dendrons with NSAIDs showed activity against the tumour cell lines. Significant inhibition of the growth of cancer cells was observed for the Janus dendrimers with sulindac-celecoxib, which was selective against MCF-7; and Janus dendrimers with fluoxetine were highly cytotoxic. The fluoxetine-dendrimer could be a candidate for the development of new pharmacological strategies for the treatment and prevention of MCF-7 cancer.
The prevalence of obesity has risen sharply in recent years, prompting the need for safer and more biocompatible therapeutic alternatives to conventional anti-obesity drugs. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized using pomegranate husk extract via two green approaches: conventional heating and microwave-assisted synthesis. Structural and morphological characterizations confirmed successful nanoparticle formation. Microwave-assisted ZnO nanoparticles (MA-ZnO NPs) exhibited smaller particle dimensions and narrower polydispersity compared with conventionally synthesized ZnO NPs. Both types of ZnO NPs demonstrated notable antioxidant activity (>62% scavenging in DPPH and ABTS assays) and strong inhibitory effects against pancreatic lipase and α-amylase (>70%), comparable to standard drugs such as orlistat and acarbose. Cytotoxicity assays using Vero cells confirmed high biocompatibility, with >60% cell viability. This work presents a comparative evaluation of two green synthesis methods and highlights the potential of biogenic ZnO NPs as multifunctional agents for oxidative stress reduction and enzyme inhibition in obesity management.
The first metal organic framework based on phthalocyanine was synthesized (MOF P). A green synthesis route was employed to fabricate zinc oxide (ZnO) nanoparticles using Amaranthus spinosus extract. The as-synthesized ZnO was subsequently integrated into MOF P, yielding a novel MOF P/ZnO nanocomposite. It was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), Fourier transform infra-red spectroscopy (FT-IR), Energy dispersive X-ray analysis (EDAX), elemental analysis, and Ultraviolet-visible (UV-Vis) spectroscopy. This study demonstrates a novel therapeutic platform based on phthalocyanine-integrated metal-organic frameworks (MOFs) and ZnO nanoparticles for targeted and efficient cancer therapy. MTT assay results demonstrated a dose-dependent reduction in cell viability following MOF P/ZnO treatment. Flow cytometry analysis of apoptosis revealed a marked increase in early and late apoptotic cells. Moreover, ROS levels were significantly elevated in treated cells.
Natural products remain an invaluable source of anticancer agents, with flavonoids and phenolic compounds being particularly recognized for their ability to modulate tumour suppressor pathways. Carissa macrocarpa (C. macrocarpa) is an edible plant rich in secondary metabolites. This study sought to identify the secondary metabolites of C. macrocarpa leaves using LC-MS/MS, evaluate their cytotoxic and pro-apoptotic effects in colorectal cancer cell lines (HT-29 and LS174T), and elucidate potential molecular interactions with p53 through in silico docking, thereby uncovering mechanistic insights into its anticancer activity. LC-MS/MS revealed abundant flavonoid glycosides, particularly derivatives of kaempferol, quercetin, and isorhamnetin. Biological assays demonstrated potent cytotoxicity of the extracts, with the total extract showing the strongest effect against LS174T cells (IC50 = 0.5 µg/mL). Extracts induced apoptosis, caused G1/S/G2 cell cycle arrest, and upregulated p53 expression. Docking confirmed strong binding affinities (-7.87 to -9.28 kcal/mol) for glycosylated flavonoids such as kaempferol-3-O-robinoside-7-O-rhamnoside, hesperidin, and isorhamnetin-3-O-rutinoside. Also, 100 ns molecular dynamics studies confirmed the stable binding of both kaempferol-3-O-robinoside-7-O-rhamnoside and hesperidin against the p53 pocket. In conclusion, this integrative study demonstrates that C. macrocarpa exerts anticancer effects in colorectal cancer cells by modulating p53 and provides a mechanistic rationale for its therapeutic potential.
Despite considerable research and various treatment approaches, dental decay remains a global health challenge. The use of synthetic antimicrobial agents can promote the development of resistance and may lead to adverse side effects. Streptococcus mutans is a key contributor to oral diseases, more so than other oral pathogens. Probiotics, however, play a beneficial role in maintaining oral health. Specifically, Lactobacillus acidophilus in the mouth can hinder harmful bacteria by competing for nutrients. Yet, evidence suggests they may also promote tooth decay. Our research focuses on membrane vesicles (MVs) isolation from L. acidophilus, and in vitro and in vivo antibacterial screening against S. mutans. The isolated MVs were consistent with previously reported vesicle size, zeta potential, and spherical morphology. They exhibit significant antimicrobial properties, prevent biofilm formation, hinder bacterial adhesion and invasion, and reduce the expression of virulence genes brpA, comDE, and spaP against S. mutans. In the in vivo model, they effectively eliminated S. mutans infection, strengthening the significance of our in vitro findings. Further proteomics study reveals the presence of possible antimicrobial peptides revealed by the DBAASP database. This study highlights the potential of MVs as a therapeutic strategy that could offer alternatives to traditional treatments and help tackle antibiotic resistance.
