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Introduction: Colon cancer remains a major global health challenge, necessitating the development of novel, selective, and sustainable therapeutic strategies. Rhein, a bioactive anthraquinone isolated from Cassia italica, has demonstrated anticancer potential but suffers from limited bioavailability. To overcome these limitations, we investigated the green biosynthesis of Rhein–selenium nanoparticles (Rh-Se-NPs) and evaluated their anticancer efficacy.

Methods: Rhein was extracted from Cassia italica leaves and confirmed by 1H and 13C nuclear magnetic resonance spectroscopy. Rh-Se-NPs were synthesized via a green biosynthetic approach and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Cytotoxicity was assessed against DLD-1 and SW620 colon cancer cell lines, with FSU fibroblast cells serving as controls. Cell proliferation, migration, and apoptosis were evaluated through morphological analysis, wound healing assays, caspase activity measurements, and gene expression profiling of oncogenes and tumor suppressors.

Results and Discussion: Rh-Se-NPs exhibited spherical morphology (32 ± 5 nm, TEM), a hydrodynamic diameter of 90.4 nm (DLS), and high colloidal stability (zeta potential: 31.1 mV). Compared to free Rhein, Rh-Se-NPs demonstrated significantly enhanced cytotoxicity, reducing IC50 values by more than two-fold and increasing selectivity indices to 12.85 (DLD-1) and 6.93 (SW620). Functional assays confirmed inhibition of cell proliferation and migration. Apoptosis was evidenced by elevated caspase-9 and caspase-3 activities. Gene expression analysis revealed strong downregulation of oncogenes (CEA, FOXQ1, CXCL17, VEGFA) and marked upregulation of the tumor suppressor PTEN (up to 15.9-fold). This study demonstrates, for the first time, that Rh-Se-NPs act as a biocompatible phytochemical–selenium nanoplatform with dual anticancer mechanisms: apoptosis induction and oncogene suppression. The findings highlight Rh-Se-NPs as a promising, sustainable, and highly selective therapeutic strategy for colon cancer.

Endophytic fungi are an uncharted source of bioactive metabolites with varied therapeutic characteristics. In this research, an endophytic Aspergillus sp. (HAG1) was collected from Phragmites australis and identified using morphological and molecular methods. The large-scale fermentation, chromatographic purification, and spectroscopic approaches (FT-IR, UV-Vis, 1H NMR, and ESI-MS) resulted in the identification of three metabolites: vaccenic acid (C1), pipericine (C2), and guaiacylglycerol (C3). Of these, C3 is reported here for the first time as an endophyte-derived metabolite from P. australis. All the metabolites exhibited significant antioxidant, antibacterial, antibiofilm, and anti-inflammatory activity. The activities of C3 were the most effective in DPPH and ABTS scavenging, COX-1/COX-2 inhibition, and suppression of biofilm for bacteria, although C3 was inactive against acetylcholinesterase activity. Molecular docking and molecular dynamics (MD) simulations underscored a favorable binding with a high binding conformation stability of C3 for antioxidant (1DGF), anti-inflammatory (3NLO), and antibiofilm (5TZ1) targets. In addition, density function theory (DFT) calculations delivered insights regarding electronic structure, explaining observed reactivity and hydrogen bonding ability. Moreover, ADMET predictions indicated that C3 has favorable solubility, metabolic stability, and low toxicity when compared to C1 and C2.

The purpose was to investigate whether the eosinophil biomarker EMR1, ectopically expressed in colon cancer tumor cells, could be used to identify patients at risk for relapse after curative surgery. EMR1 mRNA levels were determined in primary tumors (n = 66) and lymph nodes (LNs; n = 377) from 121 colon cancer patients. Controls were resection margins of colon cancer tumors and LNs from patients with inflammatory bowel disease. Primary read-out was recurrency evaluated as disease-free survival time in the Kaplan–Meier survival model and hazard ratio calculation by uni- and multivariate Cox regression. High EMR1 levels in the regional LNs were associated with poor prognosis [hazard ratio 3.1 (1.2–8.0) at 5-year follow-up, p = 0.02]. Patients with a very poor prognosis were identified by combining EMR1 with CXCL17 analysis of LNs [hazard ratio 4.6 (1.1–19.7), p = 0.04]. High EMR1 levels in the primary tumor were associated with a good prognosis [hazard ratio 0.1 (0.02–0.9), p = 0.04]. Multivariate analysis strengthened the result for LNs but weakened the result for the primary tumor. These contradictory prognostic results probably relate to the prominent eosinophilia in the primary tumor, essentially lacking in LNs, where ectopically expressed EMR1 in tumor cells dominates. Thus, EMR1 expressed in tumor cells probably promotes tumor growth.

Safe natural antifungal and anticancer agents are increasingly needed. This study investigated β-conglycinin glycoproteins from chickpea, soybean, and lupin seeds for their dual antifungal and anticancer potential. Proteins were isolated and tested against Aspergillus spp. (A. flavus, A. niger, A. parasiticus) and colon cancer cell lines (DLD-1, SW620, HCT8, HT29). MIC values, sporulation, aflatoxin inhibition, and cell wall integrity assays (β-1,3-glucan, chitin, SEM imaging, and leakage) reflected the antifungal activity of the studied proteins, while cell viability, apoptosis markers, migration assays, and biomarker expression evaluated their anticancer activity. Bioinformatic analyzed the structural and physicochemical properties. Lupin β-conglycinin showed the most decisive antifungal action, reducing growth, sporulation, and aflatoxin production while disrupting fungal walls. It selectively reduced the viability of colon cancer cells while sparing normal cells, induced apoptosis (via caspase-3 and -9 activation), inhibited migration, and downregulated tumor biomarkers (CEA, FOXQ1, VEGFA, CXCL16, CXCL17, LGR5, and LGR6). Structural modeling revealed a compact 3D conformation, a high ratio of hydrophilic to hydrophobic residues, and a unique N-linked glycosylation site. This study provides the first integrated evidence of β-conglycinin's dual role, particularly from lupin, as both a fungal toxin inhibitor and an anticancer agent, highlighting its potential as a safe natural therapeutic.

Ferrite nanoparticles (NPs) have emerged as promising candidates for cancer therapy. In this study, Mg-doped copper ferrite NPs, MgₓCu₁₋ₓFe2O4 (x = 0.0, 0.5, and 1.0), were synthesized via a citrate–nitrate combustion method and evaluated for their anticancer potential. Structural and morphological characteristics were analyzed using powder X-ray diffraction, field-emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Cytotoxicity against human cancer cell lines was assessed using MTT and flow cytometry assays, along with analyses of reactive oxygen species (ROS) generation and apoptosis. Among the compositions studied, Cu0.5Mg0.5Fe2O4 demonstrated the highest cytotoxic efficacy, with IC₅₀ values of 17.2 ± 0.15 µg/mL (PC-3) and 25.04 ± 0.28 µg/mL (Caco-2). Flow cytometric analysis revealed increased total apoptosis of 42.08% and 34.95% in PC-3 and Caco-2 cells, respectively. Gene expression analysis revealed downregulation of Bcl-2 and Cyclin D and upregulation of BAX, P53, and Caspase-3, indicating ROS-mediated mitochondria-dependent apoptosis. The enhanced anticancer activity of Cu0.5Mg0.5Fe2O4 is attributed to its optimized size, surface charge, and composition, which promote cellular uptake, ROS generation, DNA damage, and interactions with cellular components. These findings highlight the potential of mixed-metal ferrite nanoparticles as effective nanomaterial-based cancer therapeutics.

Adipose mesenchymal stem cell-derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF-β1, Smad3, IL-6, BAX, Wnt-7, FN, and miRNA145-5p are determined using qRT-PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup-shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA-145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.

BACKGROUND: Scientists have faced difficulties in synthesizing natural substances with potent biological activity from cost-effective sources. Endophytic fungi metabolites with nanoparticles have been utilized to develop a friendly, suitable procedure to address this problem and ameliorate the average amount of antioxidant, antimicrobial, and anticancer materials. Therefore, this study utilized endophytic fungi as a source of the natural extract with biosynthesized manganese nanoparticles (MnNPs) in the form of nanocomposites.

METHODS: Thirty endophytic fungi were isolated and were assessed for their antioxidant activity by 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial activity. The most potent isolate was identified utilizing 18S rRNA and was applied to purify and separate their natural antimicrobial products by Flash column chromatography. In addition, the most potent product was identified based on instrumental analysis through Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and Gas chromatography-mass spectrometry (GC.MS). The purified product was combined with biosynthsesized manganese nanoparticles (MnNPs) for the production of nanocomposite (MnNCs). Later on, the physicochemical features of MnNPs and its MnNCs were examined and then they were assessed for determination their biological activities.

RESULTS: The most potent isolate was identified as Aspergillus terreus with accession number OR243300. The antioxidant and antimicrobial product produced by the strain A. terreus was identified as an amide derivative consisting of 3-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-4-oxopentanoic acid (HDOCOX) with the chemical formula C₁₃H₁₈O₅. Furthermore, purified HDOCOX, MnNPs and Mn-HDOCOX-NPs nanocomposite (MnNCs) showed significant antimicrobial effectiveness. The minimum inhibitory concentrations (MICs) determined for MnNCs were 10 µg/mL against C. albicans and E.coli. Furthermore, MnNCs were reduced hepatocellular carcinoma viability.

CONCLUSION: The use of HDOCOX, either alone or in combination with MnNPs, is a potential candidate for inhibiting pathogenic microbes and the development of an anticancer drug pipeline.

Introduction: Chitosan have been leveraged to create chitosan nanocapsules within a bio-based nanocarrier system, enhancing efficacy and overcoming widespread microbial resistance. To generate chitosan nanocapsules (CNCs) that act as inhibitory agents against pathogenic microbes, this study combined titanium nanoparticles (TiO2 NPs) with chitosan nanoparticles (Cs NPs).

Methods: A.flavus was used for the biosynthesis of TiO2NPs. Dynamic light scattering (DLS), zeta potential, atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD), were utilized to assess the physicochemical properties of TiO2NPs and their CNCs. These techniques clarified particle diameter, charge stability, specific surface area, surface morphology, shape, dimensional forms, and structural parameters, respectively.

Results: The findings showed that TiO2NPs and their nanocapsules achieved an encapsulation efficacy of over 86.7 ± 1.8% at 1.5% w/v chitosan concentration, with particle sizes of 40.7, 40.6, and 87.3 nm for TiO2NPs, CsNPs, and CNCs, respectively. Nanoparticle stability was confirmed by a zeta potential greater than –30.1 ± 4.5mV for TiO2NPs. Furthermore, TiO2NPs and their nanocapsules suppressed both Gram-positive and Gram-negative bacteria, with CNCs exhibiting more potent inhibitory effects than either TiO2NPs or CsNPs. The minimum inhibitory concentrations (MICs) of CNCs against Salmonella typhimurium and Aspergillus fumigatus were remarkably low, at 20 and 10 μg mL−1, respectively. TEM images of S. typhimurium and A. fumigatus treated with CNCs exhibited asymmetric cell deformations, wrinkled external surfaces, cell depressions, and declined cell counts. Cytotoxicity studies showed that CNCs exhibited non-cytotoxic behavior on normal human melanocytes (HFB4). In contrast, CNCs reduced the viability of human colon carcinoma (HCT-116) and hepatocellular carcinoma (HepG-2).

Conclusion: Nanomaterials, both alone or in nanocapsules, offer a promising alternative for inhibiting harmful microorganisms and represent a potential pathway for the development of anticancer medications. The findings indicate that CNCs are safe and effective against multidrug-resistant bacteria and fungi, making them a viable alternative to current antibiotic therapies.

Introduction: Proteases play an important role in tumor progression. The predictive efficacy of proteases PRSS3 and PRSS22 mRNA levels for predicting relapse in surgically treated colon cancer (CC) patients was assessed.

Methods: mRNA expression was quantified in 371 half lymph nodes (LNs) from 121 CC patients, 77 control LNs (13 patients), 66 primary colon tumors, and 30 normal colon tissues of these patients. Patients were also stratified according to their CEA mRNA level. The occurrence of relapse following curative surgery was evaluated using the Cox regression and Kaplan-Meier survival model analyses. Protein expression was examined through immunohistochemistry.

Results: PRSS22 was superior to PRSS3 in identifying patients at risk of recurrence. Thus, high PRSS22 levels in LNs identified 76.5% of those who recurred, while PRSS3 only identified 17.6% of these patients and these were in TNM stages III and IV. The Kaplan-Meier analysis indicated that CC patients exhibiting elevated PRSS22 levels in lymph nodes experienced a reduction in survival time, averaging 37 months over the follow-up period (p = 0.009) and a 3-fold increased hazard risk (1.3–6.0; p = 0.01). In the group with low PRSS22 levels, only one patient experienced relapse at the 12-year follow-up when CEA mRNA analysis was included. A fraction of CEA-positive tumor cells expressed PRSS22 protein.

Conclusion: The importance of the secreted serine protease, S1 family member PRSS22 in tumor progression is highlighted. It shows promise as a biomarker for CC prognosis and as a target to prevent tumor spread by inhibiting its enzymatic activity.

Introduction: The prognostic value of determining mRNA levels of two markers for regulatory T cells, IL-10 and FoxP3, in lymph nodes (LNs) and primary tumors of colon cancer (CC) patients receiving curative surgery was investigated.

Methods: mRNA levels were determined by real-time qRT-PCR in 370 LNs from 120 CC patients representing all four TNM stages, 66 primary tumors, 30 normal colon tissue samples and appropriate cell lines. Protein expression was analyzed by immunohistochemistry. Patients were followed for 12 years.

Results: High levels of IL-10 mRNA in LNs were associated with poor prognosis with shorter mean survival time of 10 and 32 months (p = 0.001 and p = 0.004) at 5- and 12-year follow-up with hazard ratios of 12.4 and 6.3, respectively. No association between IL-10 level and prognosis was seen in the primary tumor. High levels of FoxP3 mRNA were associated with good prognosis, both in LNs and primary tumor. The difference in survival time was, however, small. Analysis of IL-10 mRNA in combination with LGR6 or CXCL17 mRNA in LNs generated patients with different risk of recurrence – low-, high- and very high risk. Immunohistochemistry identified IL-10 and FoxP3 positive cells located at the outer rim of tumor aggregates.

Conclusion: Level determinations of IL-10 mRNA in LNs are useful for prediction of outcome for CC patients after curative surgery. Low levels indicate that the patients do not require further treatment, while IL-10 in combination with LGR6 or CXCL17 can be used to identify patients at very high risk of recurrence.