Increasing evidence highlights that excessive iron accumulation in the brain plays a vital role in neuronal senescence and is implicated in the pathogenesis of age-related neurodegenerative diseases, including Alzheimers disease (AD) and Parkinsons disease (PD). Therefore, the chemical compounds that eliminate an iron overload may provide better protection against oxidative stress conditions that cause the accumulation of senescent cells during brain aging. Ebselen has been identified as a strongly useful compound in the research on redox biology mechanisms. We hypothesized that ebselen could alleviate an iron overload-induced oxidative stress and consequently reverses the senescence-like phenotypes in the neuronal cells. In the present study, SH-SY5Y cells were treated with ferric ammonium citrate (FAC) before ebselen, and the evaluation of the cellular iron homeostasis, the indicators of oxidative stress, and the onset of senescence phenotypes and mechanisms were carried out accordingly. Our findings showed that ebselen ameliorated the FAC-mediated iron overload by decreasing the expression of divalent metal transporter 1 (DMT1) and ferritin light chain (FT-L) proteins. In contrast, it increased the expression of ferroportin 1 (FPN1) protein and its correlation led to a decrease in the expression of the cytosolic labile iron pool (LIP). Furthermore, ebselen significantly reduced reactive oxygen species (ROS) and rescued the mitochondrial membrane potential (ΔΨm). Notably, ebselen restored the biomarkers of cellular senescence by reducing the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and senescence-associated secretory phenotypes (SASP). This also suppressed the expression of p53 protein targeting DNA damage response (DDR)/p21 cyclin-dependent kinase (CDK) inhibitor through a mTORC1 signaling pathway. Potentially, ebselen could be a therapeutic agent for treating brain aging and AD by mitigating iron accumulation and restoring senescence in SH-SY5Y cells.

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer whose prevalence is rising, particularly in Thailand, is marked by elevated oxidative stress driven by chronic inflammation, parasitic infections, and dysregulated redox signaling. This study investigates the anticancer potential of tiliacorinine using a silico approach, including drug-likeness, ADMET, network pharmacology, molecular docking, and dynamics simulations. Tiliacorinine and 216 predicted targets were identified, with 79 overlapping CCA-related genes from GeneCards. GO and KEGG analyses revealed involvement in cell migration, membrane structure, kinase activity, and cancer-associated pathways. Network and PPI analyses identified ten key targets, including SRC, HIF1A, HSP90AA1, NFKB1, MTOR, MMP9, MMP2, PIK3CA, ICAM1, and MAPK1. Tiliacorinine showed the strongest affinity for MTOR (−10.78 kcal/mol, K_i = 12.62 nM), binding at the same site as known inhibitors with superior energy and specificity, supported by hydrogen bonding at ASP950 and hydrophobic interactions. Tiliacorinine also demonstrated strong binding to SRC, MMP9, and MAPK1. Molecular dynamics simulations revealed stable binding of tiliacorinine to MTOR, particularly at residues ASP950, TRP1086, and PHE1087. Comparative analysis with the MTOR–GDC-0980 complex confirmed consistent interaction patterns, reinforcing the structural stability and specificity of tiliacorinine. These results highlight its strong pharmacological potential and support its candidacy as a promising lead compound for cholangiocarcinoma therapy.

This study aimed to generate Car- and Pac-resistant cell lines from the human lung adenocarcinoma H1792 cell line, designated as H1792/Car and H1792/Pac, and perform transcriptome sequencing to identify potential targets. Common differentially expressed genes (Co-DEGs) in both resistant cell lines were identified, followed by hub gene identification. Online validation was conducted through GEPIA and Kaplan–Meier Plotter platforms, with experimental validation performed using real-time quantitative PCR (RT-qPCR). After six months, the H1792/Car and H1792/Pac cell lines exhibited a 10.7-fold and 5.6-fold increase in resistance to Car and Pac, respectively. Flow cytometry analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by Car or Pac. Transcriptomic sequencing identified 123 Co-DEGs, including 72 upregulated and 51 downregulated genes, consistently expressed in both H1792/Car and H1792/Pac cell lines. Among these, 13 hub genes were identified, with colony-stimulating factor 3 (CSF3) uniquely associated with post-progression survival (PPS) in adenocarcinoma patients undergoing chemotherapy. Notably, CSF3 expression was significantly elevated in both H1792/Car and H1792/Pac compared to parental cells. These findings underscore the value of drug-resistant models in uncovering critical biomarkers. CSF3 emerges as a promising guiding marker or potential molecular target for optimizing Car- and Pac-based doublet regimens.

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized an in silico network pharmacology approach to elucidate the pharmacokinetic properties and molecular mechanisms of ε- and δ-viniferin against HCC within the context of metabolic and inflammatory liver pathologies. Methods: ADMET profiles were characterized using SwissADME and pkCSM. Therapeutic targets were identified by intersecting viniferin-associated molecules with disease genes from GeneCards. A protein–protein interaction (PPI) network was constructed, supplemented by GO and KEGG enrichment analyses. Molecular docking and 200 ns of molecular dynamics (MD) simulations evaluated the binding affinity and structural stability between viniferin isomers and identified hub proteins. Results: Both ε- and δ-viniferin showed favorable drug-like properties, including high gastrointestinal absorption and low hepatotoxicity. We identified 247 overlapping targets, with network analysis highlighting ten essential hub genes, including AKT1, HSP90AA1, ESR1, HIF1A, NFKB1, GSK3B, PTGS2, APP, MTOR, and PIK3CA. Enrichment analysis confirmed their involvement in critical oncogenic pathways. Molecular docking showed strong interactions with APP, HSP90AA1, and AKT1, while MD simulations validated the long-term stability of ε-viniferin within the APP binding pocket. Conclusions: These findings provide mechanistic insights into viniferin as a multi-target agent for HCC, justifying further experimental validation in pre-clinical models.

Plants produce a wide range of natural compounds that possess various beneficial properties, including antioxidant, anti-tyrosinase, antibacterial, and cytotoxic activities. The present study aims to investigate the phytochemicals by total phenolic content and GC-MS analysis and to evaluate the antioxidant and anticancer properties of the peels of Manihot esculenta Crantz. The total phenolic content in fractions A5 and E5, determined by the Folin-Ciocalteu method, was remarkably high with values of 395.77 ± 0.65 mg GAE/g and 617.21 ± 0.62 mg GAE/g, respectively. In terms of antioxidant activity assessed by DPPH scavenging assay, fractions A3, A4, A5, E3, E5, E7 and E8 showed significant activity with IC50 values of 385.83 ± 0.12, 507.87 ± 0.01, 504.69 ± 0.04, 537.56 ± 0.30, 534.04 ± 0.56, 552.78 ± 0.58 and 508.26 ± 0.33 µg/ml, respectively, compared to the standard IC50 value of 555.00 ± 0.35 µg/ml. In addition, the acetone and ethanol extracts showed moderate cytotoxicity against lung cancer cells (H1792) in the MTT assay, with IC50 values of 115.80 ± 2.57 µg/mL and 111.33 ± 2.25 µg/mL, respectively. GC-MS analysis of fractions A3 and E8 identified 6 and 11 components, respectively. The major component of fraction A3 was identified as 1,2-benzenedicarboxylic acid dinonyl ester (50.59%), while fraction E8 consisted mainly of n-hexadecanoic acid (17.45%). These results suggest that the peel extracts and specific fractions of M. esculenta Crantz. are rich in phenolics and exhibit promising antioxidant activity, making them suitable candidates for development into health-promoting products and medical cosmetics.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance the median survival of patients with lung adenocarcinoma (ADC) that harbor EGFR-sensitive mutations. However, most patients inevitably experience tumor relapse owing to drug resistance. We aimed to identify potential serum biomarkers for predicting post-EGFR-TKI treatment relapse in patients with advanced-stage lung ADC. Methods: Among 27 patients, including 6 and 21 with early and late relapse, respectively, differentially expressed proteins between patients with early and late relapses were identified using liquid chromatography and tandem mass spectrometry and subsequently validated using Western blotting. Predictive ability was assessed using the receiver operating characteristic curve and area under the curve (AUC) analysis. The association between the clinical variables and treatment response was evaluated using the chi-square test. Results: The serum expression levels of the translocated promoter region (TPR), junction plakoglobin (JUP), and fibrinogen alpha chain (FGA) were significantly higher in patients with late rather than early relapse. The findings indicated that TPR and FGA exhibited good diagnostic performance, with AUCs of 0.946 (p = 0.002; 95% confidence interval [CI], 0.84–1.05) and 0.809 (p = 0.034; 95% CI, 0.65–0.97), respectively. Conclusions: Our results suggest that the TPR and FGA levels are potential predictors of post-EGFR-TKI treatment relapse.