The study first describes chemical profiles of essential oils from Vietnamese Senecio scandens Buch.-Ham. ex D. Don. From the gas chromatography-mass spectrometry (GC-MS) analysis, the stem bark essential oil was characterized by the major compounds β-myrcene (19.7%), (E)-β-ocimene (9.5%), and limonene (5.4%), while the leaf essential oil was dominated by trans-cadina-1(6),4-diene (11.0%), caryophyllene oxide (10.9%), (E)-caryophyllene (9.0%), α-humulene (6.9%), germacrene D (6.8%), β-myrcene (6.7%), and cis-isolongifolanone (6.7%). The essential oils from the stem barks (IC50 = 8.75 ± 0.42 µg/mL) and leaves (IC50 = 12.40 ± 0.56 µg/mL) surpassed the standard allopurinol (IC50 = 14.7 ± 0.71 µg/mL) in the xanthine oxidase (XO) inhibitory activity. Additionally, they showed strong cytotoxic, antioxidant, and anti-inflammatory activities with IC50 values of 18.2-42.8 µg/mL. The stem bark sample further strongly inhibited the bacterium Bacillus cereus ATCC 11778 with the minimum inhibitory concentration (MIC) value of 64 µg/mL. In general, the stem bark essential oil consistently demonstrated stronger potency than the leaf essential oil. Molecular docking studies further supported that germacrene D, trans-cadina-1(6),4-diene, (E)-caryophyllene, and α-humulene exhibited stronger binding affinities with the XO than the reference ligand guanine. These interactions were primarily mediated by hydrophobic contacts with key residues, with germacrene D and trans-cadina-1(6),4-diene emerging as the most potent inhibitors.

Hydrazone derivatives are one of the scaffolds frequently used in new drug development studies. Due to the promising pharmacological effects of the hydrazone structure, fifteen new hydrazide-hydrazone compounds containing flurbiprofen 1,2,4-triazole were synthesized in this study and their in vitro anticancer effects were tested. All compounds were tested for cytotoxic effects against breast cancer cell lines (MCF-7 and MDA-MB231), and glioblastoma cell line (U87) by using MTT assay. Among the synthesized compounds, compounds 7a and 7c exhibited the most potent cytotoxic activity with IC50 values of 7.80 ± 1.20 µM and 2.40 ± 0.93 µM against MCF-7 cell line, while compound 7a showed the highest activity with IC50 value of 7.63 ± 1.05 µM against MDA-MB231 cell line. In addition, compounds 7c and 7n presented cytotoxic activity with IC50 values of 10.31 ± 4.63 µM and 10.81 ± 6.11 µM against U87 cell line. The possible cytotoxic effects of compounds on mouse fibroblast cell line (L929) were assessed for their safety and compounds 7a, 7c, and 7n were found less toxic than 5-fluorourasil. Additionally, compound 7c was further studied to investigate its effects on apoptosis and PI3K activity, which play a role in cancer development. The results showed that compound 7c increased apoptosis in MCF-7 cells and it displayed PI3K enzyme inhibitory activity. Our study revealed that the synthesized hydrazone compounds have the potential to be lead compounds for further studies on cancer.

In this study, the essential oil of Juniperus chinensis L. seeds was analyzed by GC-MS, identifying 25 compounds comprising 99.78% of the oil. α-Pinene (79.63 ± 0.45%) was the major component, followed by β-myrcene, β-pinene, and DL-limonene. The oil exhibited antimicrobial activity with inhibition zones of 11 mm (S. aureus), 6 mm (E. coli), and 4 mm (S. mutans). Antifungal effects were noted against Fusarium solani and Aspergillus niger. Cytotoxicity assays revealed selective effects on MDA-MB-231 breast cancer cells (IC50: 38 µg/mL), with no toxicity to MCF-10A normal cells. Molecular docking demonstrated strong binding affinity of α-cedrol to AKT-1 protein (-7.5 kcal/mol), supported by RMSD stability analysis and hydrogen bonding. ADME profiling confirmed favorable drug-likeness of α-cedrol. These results suggest that J. chinensis L. seed essential oil, particularly as a complex phytochemical mixture containing α-cedrol, holds promise as a natural source for antimicrobial and anticancer agents.

The emergence of tumor cell resistance is one of the major issues in current oncology practice. It reduces the effectiveness of therapy and worsens cancer patients' prognoses. However, it confirms a wide range of molecular interactions as well as the complexity of the human organism. Our previous research confirmed the functionality of the erythropoietin receptor (EPOR) in ovarian and breast cancer cells, as well as its relationship to these cells' sensitivity to specific therapies. The current study demonstrates that EPOR overexpression in human ovarian adenocarcinoma cells A2780 is directly linked to paclitaxel resistance. Furthermore, EPOR overexpression results in morphological changes that vary according to the pattern of EPOR isotypes expressed. In this regard, the most interesting result appears to be the change in the shape of the T clone, which has a tendency to form spheroidal structures. In addition, functional enrichment analysis demonstrated that EPOR-associated differentially expressed genes are involved in several biological and cell processes. Indeed, a T clone with a single 68 kDa EPOR isotype demonstrates significant resistance to paclitaxel therapy and is associated with the upregulation of tubulin beta 6.

Breast cancer, chronic inflammation, and antimicrobial resistance (AMR) represent major global health challenges that require novel multitarget therapeutic strategies. This study evaluated the phytochemical composition, antioxidant activity, cytotoxic potential, immunomodulatory effects, and antibacterial properties of leaf extracts from Acrostichum aureum, Argemone mexicana, and Ficus religiosa. Sequential solvent extraction followed by LC-MS analysis revealed distinct phenolic profiles among the species. A. aureum was enriched in ferulic acid, rutin, chlorogenic acid, and p-coumaric acid, whereas A. mexicana contained veratric acid, luteolin, and apigenin. F. religiosa showed elevated levels of chlorogenic and protocatechuic acids along with related metabolites. All extracts exhibited concentration-dependent antioxidant activity, with DPPH radical scavenging ranging from 48.12 ± 5.22% to 63.14 ± 6.25% at 100 µg/mL and nitric oxide inhibition from 72.15 ± 6.17% to 78.24 ± 5.24% at 1000 µg/mL. Fractionated extracts (petroleum ether, chloroform, ethyl acetate, and ethanol) displayed differential cytotoxicity against MCF-7 breast cancer cells. Notably, ethanolic fractions promoted pro-apoptotic signaling by increasing BAX expression (up to 2.5-fold) while suppressing BCL-2 (0.4-fold) and reducing inflammatory mediators IL-6 and TNF-α. Antibacterial assays further demonstrated species-specific activity patterns: A. mexicana and F. religiosa effectively inhibited Escherichia coli strains (up to 43.79% growth reduction), whereas A. aureum showed the strongest activity against multidrug-resistant Acinetobacter baumannii ATCC 17978 (26.88 ± 8.25%). These findings highlight a clear relationship between phytochemical composition and biological activity, indicating that these medicinal plants may serve as promising sources of multitarget phytotherapeutic agents. Further in vivo studies and bioactive compound isolation are required to validate their therapeutic potential.

Strategies for rationally designing gold-based chemotherapeutics remain limited by an incomplete understanding of how ligand electronics shape structure and biological function. Here, we establish a direct link between σ-donor strength, geometric distortion, and anticancer activity across a series of carbon-stabilized Au(III) bisphosphine macrocycles derived from N,N'-(1,2-phenylene)bis(2-(diphenylphosphino)benzamide) (dppbH2) and electronically tuned cyclometalated [C^N] templates. Systematic installation of substituents that modulate σ-donation to Au(III) produces predictable shifts in Au-C and Au-P bond lengths, trans bite angles, and square planar deformation. σ-donor character of complexes influences geometric distortion, aqueous stability, and up to an order-of-magnitude higher cytotoxicity in triple-negative breast cancer and estrogen receptor-positive models compared to cisplatin. Mechanism of action studies supports acute mitochondrial uncoupling and mtROS production, leading to cell death by this class of compounds. This electronic-structural-biological correlation provides a rare, experimentally validated design principle for Au(III) scaffolds and positions electronically tuned macrocycles as a chemically tractable platform for targeting intracellular pathways.

Blocking the p53-MDM2 and/or p53-MDMX protein-protein interaction (PPI) by small-molecule inhibitors has been tracked as a potentially effective cancer treatment approach. Herein, we present the discovery of a new series of spirooxindole-tethered pyrazolopyridine derivatives. The development of the new congeners was based on the analysis of the co-crystal structures of the inhibitors bound to both MDM2 and MDMX and studying the binding interactions between the substituents of small molecules and the three subpockets of the p53-MDM2/MDMX. The spirooxindoles 6b, 6k, and 6n attained the most pronounced activity in the MULTI-ARRAY MDM2-p53 complex assay with IC50 values of 1.26, 1.30, and 1.25 µM, respectively, in comparison with nutlin-3 (IC50 = 2.03 µM). The counterparts 6b, 6k, and 6n also revealed notable inhibitory potential against p53-MDMX. The antiproliferative efficacy of the most active target compounds was assessed in HCT-116 colon cancer cell line that overexpressed MDM2 and harbored wild-type p53. The derivative 6k accomplished the highest antiproliferative activity against HCT-116 compared to nutlin-3. Moreover, 6k displayed minimal toxicity compared to the reference nutlin-3 when examined on a normal cell line. Flow cytometric analysis revealed that 6k controlled cell growth via cell cycle arrest at the G1 phase and induced cell death via apoptosis. Additionally, compound 6k revealed a prominent effect in raising p53 levels with a 6.464-fold increase compared to the control. Molecular docking and molecular dynamics simulations justified the observed efficacy. Collectively, this study showcased a new class of potent p53-MDM2/MDMX dual inhibitors possessing a spirooxindole scaffold which can be subjected to future development.

Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (> 50 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that TP53 missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.

Resistance to 5-fluorouracil (5-FU) remains a major challenge in the treatment of colorectal cancer (CRC). Here, we identify ETS variant transcription factor 7 (ETV7) as significantly upregulated in CRC tissues and cell lines, with elevated expression associated with poor clinical prognosis. Functional assays demonstrate that ETV7 enhances CRC cell proliferation, invasion, and resistance to 5-FU. Mechanistically, ETV7 transcriptionally upregulates CXCL1, leading to increased neutrophil recruitment and enhanced formation of neutrophil extracellular traps (NETs). The resulting NETs-enriched tumor microenvironment promotes tumor aggressiveness and chemoresistance. Pharmacological inhibition of CXCL1 or degradation of NETs effectively attenuates ETV7-driven malignant phenotypes in vitro and in vivo. Collectively, these findings establish an ETV7-CXCL1-NETs axis that contributes to 5-FU resistance in CRC and suggest that targeting this pathway may improve chemotherapy response.

Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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Tumor mutational burden (TMB) and PD-L1 are established biomarkers for guiding immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC). As ICI use expands into early-stage disease, we explored the feasibility of using TMB, which can be determined via a comprehensive genomic profiling assay along with EGFR and ALK genomic alterations, as a biomarker for outcomes in both neoadjuvant and adjuvant settings. TMB-high status (≥10 mut/Mb) showed a numerically higher, but not statistically significant, rate of pathological complete response among patients receiving neoadjuvant ICI and significantly associated with more favorable time to recurrence in patients receiving adjuvant ICI, particularly among patients with PD-L1 expression <50%. TMB should be considered in future early-stage NSCLC ICI clinical trials to further validate these results.

To check the hard-soft nature of metals on biological interaction, heteroleptic compounds [FeII(L1)(L2)](1) and [FeIII(L1)(L2)]Cl (2) were prepared where ligands are (2-hydroxy-1-naphthylidene-o-aminophenol) [L1] and 1,10-phenanthroline [L2]. Complexes are characterized by Fourier transform infrared spectra (FTIR), high resolution mass spectrometry (HRMS), and UV-vis spectroscopic techniques. Square pyramidal geometry of the complex 1 was determined using computational study [density functional theory (DFT) function (B3LYP/ LANL2DZ)]. The characteristic Fe(II) to Fe (III) oxidation and Fe(III) to Fe(II) reduction peaks were observed in the desired potential range for complexes 1 and 2, respectively. Iron complexes demonstrated anticancer effective hydrolytic DNA cleavage efficacy and efficient groove binding prosperity toward DNA with intrinsic and apparent binding constant values of the order of 105  M-1. The complexes displayed good binding capabilities to carrier protein bovine serum albumin (BSA). The experimental DNA and BSA binding nature was validated through molecular docking study. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET)drug screening profiling indicates that complex 1 satisfies all of Lipinski rule with good cell permeability, solubility, lipophilicity, and nontoxicity. Complexes show efficient anticancer activity in MCF-7 cell lines through apoptotic pathway. Complex 1 is found to have better biological activity compared to 2 due to softer nature of Fe(II) ion.

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer, with limited treatment options due to the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. This characteristic renders TNBC resistant to hormone-based and HER2-targeted therapies, leaving cytotoxic chemotherapy as the predominant strategy and highlighting the urgency for novel interventions. In this study, we investigated the mechanism of action of GL24, a potent 4-(phenylsulfonyl)morpholine-based small molecule with selective tumor suppression effects on metastatic TNBC cells, while being ineffective against TNBC cells derived from the primary tumor site, using gene co-expression analysis. By considering the distinct phenotypic responses induced by GL24, we tailored our co-expression analysis approach, selecting gene pairs that exhibited differential co-expression in effective cells while excluding gene pairs that also showed differential patterns in non-effective cells. Constructing a co-expression network from these differential pairs, followed by enrichment analysis and functional annotation, revealed specific gene interactions and molecular pathways associated with GL24-mediated TNBC inhibition. These insights supported the previously established findings that showed convergence on apoptosis based on differentially expressed genes, while also providing complementary information by highlighting pathways involved in metabolic alterations, proliferation, and migration or invasion. This expanded understanding advances the knowledge of the mechanisms of GL24 in combating TNBC.

The phenolic compound profile of ethanolic extract of Stropharia inuncta (Fr.) Quél., a natural macrofungus species, and the effects of this chemical structure on antioxidant, anticholinesterase and antiproliferative activities were evaluated. Antioxidant capacity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and Rel Assay Diagnostics kits; DPPH: 72.653 ± 1.857 mg Trolox equivalents (TE)/g, FRAP: 86.873 ± 1.125 mg TE/g, otal antioxidant status (TAS): 4.049 ± 0.057 mmol/L, total oxidant status (TOS): 9.642 ± 0.038 μmol/L, oxidative stress index (OSI): 0.238 ± 0.002, respectively. Within the scope of anticholinesterase activity, IC50 values of the extract on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined as 55.007 ± 1.411 μg/mL and 82.993 ± 1.501 μg/mL, respectively. Antiproliferative effect was evaluated on A549 human lung adenocarcinoma cell line after 24 h of incubation; significant decrease in cell viability was observed especially at concentrations of 100 and 200 μg/mL. Phenolic content was analyzed by LC-MS/MS method and the highest levels of gallic acid (3713.45 ± 12.26 mg/kg), quercetin (2911.40 ± 6.19 mg/kg), and 4-hydroxybenzoic acid (2167.69 ± 4.71 mg/kg) were detected. Also compounds such as vanillic acid, catechinhydrate and acetohydroxamic acid were found at significant levels. The findings show that S. inuncta is a rich natural source of phenolic compounds and this chemical structure contributes to versatile biological activities. The limited information in the literature on the biological activities and phenolic compound profile of this species positions the study as a contribution to the field.

Hepatocellular carcinoma (HCC) poses a significant global public health challenge, with conventional therapies often limited by severe adverse reactions. This study utilized network pharmacology and molecular docking to identify anti-HCC compounds from Ganoderma applanatum triterpenoids (GAT). Sixty compounds were screened using Swiss ADME, with potential targets predicted subsequently. Intersection analysis with HCC-associated targets identified 339 overlapping targets. Subsequent protein-protein interaction (PPI) network analysis identified nine core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that GAT inhibits HCC progression by modulating cancer-associated signaling pathways such as PI3K-Akt, MAPK, Ras, and Rap1 signaling. A compound-target network identified core compounds. Molecular docking demonstrated strong binding affinities between four compounds (applanaic acid C, methyl gibbosate A, bovistol, lucidone A) and three targets (AKT1, MAPK1, SRC). Toxicity predictions indicated low acute oral toxicity for applanaic acid C (LD50 > 300 mg/kg) and lucidone A (LD50 > 5000 mg/kg). Moreover, immunotoxicity risks were noted, which require key attention during subsequent drug development. This study systematically elucidates the multi-target and multi-pathway anti-HCC mechanisms of GAT providing a foundation for developing natural product-derived therapeutics. Further experimental validation of the efficacy and safety profiles is warranted for these potential lead compounds.

Glioblastoma (GBM) is one of the most aggressive and treatment-refractory brain tumors. Temozolomide (TMZ) remains the standard chemotherapeutic agent but is frequently compromised by DNA-repair mechanisms, whereas tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis only in a subset of tumors due to strong intrinsic resistance. Here, we identify the Mu-2-related death-inducing gene (MUDENG/MuD) as the µ-subunit of adaptor protein complex 5 (AP5M1). TurboID-based proximity labeling revealed reproducible interactions with AP5B1 and AP5M1 subunits, as well as additional associations with AP1-3 complexes and nuclear proteins involved in cell-cycle regulation. These findings establish MuD as a multifunctional component of the AP5 complex that modulates cell-fate signaling in a context-dependent manner. Using MuD-mutant GBM cell lines, we demonstrate that MuD suppresses TRAIL-induced apoptosis by interfering with extrinsic and intrinsic pathways downstream of Bid, whereas it promotes TMZ-induced cytotoxicity through p53-dependent cell-cycle control and DNA-damage responses. Gene set enrichment analysis (GSEA) and functional profiling further revealed distinct MuD-associated interactomes linked to receptor endocytosis and genotoxic-stress pathways. Together, these results uncover opposing roles of MuD in TRAIL- and TMZ-mediated cell death, with MuD suppressing apoptotic signaling in response to TRAIL while modulating p53-dependent genotoxic stress responses that influence TMZ-induced cytotoxicity in glioblastoma.

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

The aim of the present study was to investigate the prevalence of oral manifestations among patients undergoing chemotherapy.

Melanoma, an aggressive cancer with a poor prognosis, is difficult for early diagnosis, and there are limited drug treatments. Biologically active molecules, especially polyphenols and flavonoids, have a great therapeutic potential; however, their applications are limited by low aqueous solubility and bioavailability.

Nitrosylcobalamin (NO-Cbl) is a vitamin B12 analog designed to exploit the "Trojan horse" vulnerability created by the heightened need of cancer cells for cobalamin and one-carbon metabolism. Building on our recent biophysical studies confirming the affinity of NO-Cbl for intrinsic factor, this work aimed to investigate the mechanistic basis for the selective anticancer activity of NO-Cbl through the cobalamin transport axis and lysosomal processing.