Smoking induces cellular stress and genomic damage that may disrupt regulation of the p53 tumor-suppressor pathway. This cross-sectional study evaluated serum p53 concentrations in 154 Iraqi adults, including 92 smokers and 62 non-smoking controls, and examined the predicted interaction of nicotine with the MDM2–p53 complex using molecular docking and molecular dynamics simulations. Serum p53 was measured by sandwich ELISA, while smokers were classified as Cigarette, narghile, or Electronic-Cigarette users, and associations between cumulative smoking exposure and serum p53 were assessed. Nicotine was docked into the MDM2–p53 peptide complex structure (PDB ID: 4HFZ) using MOE 2019, followed by a 110-ns molecular dynamics simulation in Desmond. Serum p53 concentrations were significantly higher in smokers than in controls (4791.2 vs. 3024.1 pg/mL, p < 0.001). No significant differences were detected among smoking types (p = 0.547), and cumulative exposure was not significantly correlated with serum p53 in any subgroup. Docking identified a preferred nicotine-binding pose with a predicted score of −5.31 kcal/mol and interactions involving Val28 and Arg29. The simulated complex exhibited marked early conformational adjustment, followed by a comparatively stable trajectory supported by persistent and intermittent noncovalent interactions. These findings indicate that smoking is associated with elevated circulating p53 concentrations and suggest that nicotine may interact with residues within the MDM2–p53 binding region; however, further cellular and biochemical validation is required.
Prostate cancer (PCa) disproportionately affects men of African descent, and glutathione S-transferase Mu 1 (GSTM1) alongside glutathione S-transferase Theta 1 (GSTT1) have been reported to be potential genetic contributors due to their role in detoxification pathways. However, evidence on their association with PCa risk in African-origin populations remains limited. Therefore, this systematic review and meta-analysis evaluated the association between GSTM1 and GSTT1 polymorphisms and PCa risk in men of African descent. Following PRISMA guidelines, seven case-control studies published between 2006 and 2023 were included, with a total of 873 PCa cases and 1121 controls from North African, West African, Afro-Caribbean, and African-American populations. Random-effects models were used to calculate pooled effect sizes, with heterogeneity assessed using the I2 statistic. The results suggest that, for GSTM1, neither the null genotype nor the positive genotype demonstrated a significant association with PCa risk, a pattern that was consistent across populations. Funnel plot assessments and Egger's regression tests (p = 0.6876) were consistent with an absence of publication bias for GSTM1, although the small number of studies limits the power of these tests. However, GSTT1 analyses revealed considerable variability. While the null genotype showed no overall association, substantial heterogeneity (I2 = 68.3%) was observed. Visual inspection of funnel plots suggested potential asymmetry, but Egger's test (p = 0.5032) did not provide statistical evidence of publication bias, although this assessment is underpowered given the small number of studies. Notably, North African studies reported increased risk with the GSTT1 null genotype, whereas the Caribbean cohort showed a protective effect. The positive genotype also displayed conflicting trends, with protective effects in North Africa and elevated risks in Caribbean populations. These region-specific GSTT1 patterns should be regarded as hypothesis-generating, and the findings overall suggest that genetic risks may vary between populations and highlight the need for ancestry-focused studies that also consider environmental and lifestyle factors to better understand prostate cancer in men of African origin.
Biogenic synthesis of metal nanoparticles using medicinal plants has emerged as a sustainable and environmentally friendly strategy for producing multifunctional nanomaterials with promising biomedical applications. Here, an aqueous seed extract of Foeniculum vulgare was utilized as a natural reducing and stabilizing agent for the synthesis of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs). The synthesized nanoparticles were characterized by UV–Visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). UV–Visible analysis confirmed nanoparticle formation through characteristic surface plasmon resonance and absorption peaks, while FTIR spectra indicated the involvement of plant-derived phytochemicals in nanoparticle reduction and stabilization. XRD analysis verified the crystalline structure of both nanomaterials, with an average crystallite size of approximately 37 nm, whereas SEM revealed predominantly spherical nanoparticles with diameters ranging from 22 to 128 nm. EDX analysis further confirmed the elemental composition of the synthesized AgNPs and ZnONPs. The antimicrobial performance of the biogenic nanoparticles was investigated against Staphylococcus aureus , Pseudomonas aeruginosa , and Candida albicans using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration (MBC/MFC) assays. Both AgNPs and ZnONPs exhibited concentration-dependent antimicrobial activity; however, AgNPs produced larger inhibition zones and lower MIC and MBC/MFC values than ZnONPs. Among the tested microorganisms, C. albicans was the most susceptible, whereas P. aeruginosa exhibited the highest level of resistance. The in vivo toxicological profile was evaluated following oral administration of 10 mg/kg/day for 14 consecutive days. AgNP-treated animals showed only minor biochemical and histopathological alterations. In contrast, ZnONP treatment significantly increased serum ALT, AST, and urea levels and significantly decreased ALP activity and the hepato-somatic index compared with the control group ( P < 0.05). ZnONP-treated animals also exhibited more pronounced hepatic and renal histopathological alterations than AgNP-treated animals. These findings indicate that F. vulgare -mediated AgNPs provide superior antimicrobial performance with a more favorable short-term safety profile than ZnONPs under the experimental conditions. Collectively, the results highlight the potential of biogenic AgNPs synthesized from F. vulgare seed extract as promising antimicrobial nanomaterials for future biomedical and pharmaceutical applications.
Background Cuproptosis, a recently identified cell death form, is closely associated with amyotrophic lateral sclerosis (ALS), a debilitating neurological disease characterized by motor neuron degeneration. This study investigated the potential involvement of Cuproptosis-Related Genes (CRGs) in ALS pathogenesis. Methods The ALS-related peripheral blood dataset (GSE112681) from the Gene Expression Omnibus (GEO) database was used to identify CR-DEGs, followed by enrichment analysis. CIBERSORT algorithm and correlation analysis revealed the immune cell infiltration in ALS patients and the correlation between immune cells and CR-DEGs. Machine learning algorithms were used to identify key CR-DEGs, perform GSEA, and construct a risk model. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) was used to detect the expression level of key CR-DEGs. Consensus clustering analysis was used to divide 397 ALS patients into two subclusters (C1 and C2) based on key CR-DEGs. Multivariate Cox regression analyzed clinical attributes and survival. Model accuracy was validated using receiver operating characteristic (ROC) curves, calibration curves, and two external datasets. Results Eight CR-DEGs including Nuclear Factor Erythroid 2-Like 2 (NFE2L2), Ferredoxin 1 (FDX1), Lipoyltransferase 1 (LIRT1), Glutaminase (GLS), and Dihydrolipoamide S-Succinyltransferase (DLST) involved in tricarboxylic acid (TCA) cycle and various mitochondrial metabolic pathways, were identified. Various types of immune cells infiltrated in the peripheral blood of ALS patients, which was correlated with CR-DEGs. Machine learning algorithms identified five key CR-DEGs enriched in multi-substance metabolism, immune- and ALS-related pathways. The nomogram constructed based on CR-DEGs highly predicted ALS incidence risk and prognosis. RT-qPCR results indicated that compared to normal individuals, the expression levels of NFE2L2, FDX1, and LIPT1 were increased in the peripheral blood of ALS patients, whereas those of GLS and DLST were decreased. Subsequently, GSEA results demonstrated significant upregulation of cuproptosis, apoptosis, multiple immune responses, and substance metabolism pathways in C1, which corresponded to a shortened survival period. Conversely, C2 exhibited upregulation of the myogenesis pathway, indicating a relatively favorable prognosis. The nomogram confirmed cuproptosis as a significant prognostic risk factor, especially for ALS patients with early- and bulbar-onset symptoms. Nomogram based on cuproptosis levels accurately predicted ALS prognosis and survival. Conclusions This study offers initial insights into the association between CR-DEGs and ALS and presents a risk prediction model for future investigations into ALS mechanisms and potential biomarkers.
Biogenic synthesis of metal nanoparticles using medicinal plants has emerged as a sustainable and environmentally friendly strategy for producing multifunctional nanomaterials with promising biomedical applications. Here, an aqueous seed extract of Foeniculum vulgare was utilized as a natural reducing and stabilizing agent for the synthesis of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs). The synthesized nanoparticles were characterized by UV–Visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). UV–Visible analysis confirmed nanoparticle formation through characteristic surface plasmon resonance and absorption peaks, while FTIR spectra indicated the involvement of plant-derived phytochemicals in nanoparticle reduction and stabilization. XRD analysis verified the crystalline structure of both nanomaterials, with an average crystallite size of approximately 37 nm, whereas SEM revealed predominantly spherical nanoparticles with diameters ranging from 22 to 128 nm. EDX analysis further confirmed the elemental composition of the synthesized AgNPs and ZnONPs.The antimicrobial performance of the biogenic nanoparticles was investigated against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration (MBC/MFC) assays. Both AgNPs and ZnONPs exhibited concentration-dependent antimicrobial activity; however, AgNPs produced larger inhibition zones and lower MIC and MBC/MFC values than ZnONPs. Among the tested microorganisms, C. albicans was the most susceptible, whereas P. aeruginosa exhibited the highest level of resistance.The in vivo toxicological profile was evaluated following oral administration of 10 mg/kg/day for 14 consecutive days. AgNP-treated animals showed only minor biochemical and histopathological alterations. In contrast, ZnONP treatment significantly increased serum ALT, AST, and urea levels and significantly decreased ALP activity and the hepato-somatic index compared with the control group (P < 0.05). ZnONP-treated animals also exhibited more pronounced hepatic and renal histopathological alterations than AgNP-treated animals. These findings indicate that F. vulgare-mediated AgNPs provide superior antimicrobial performance with a more favorable short-term safety profile than ZnONPs under the experimental conditions. Collectively, the results highlight the potential of biogenic AgNPs synthesized from F. vulgare seed extract as promising antimicrobial nanomaterials for future biomedical and pharmaceutical applications.
