Search Results (50)

Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article

Small non-coding microRNAs (miRNAs) play crucial roles in the degradation of the messenger RNAs (mRNAs) that are involved in various biological processes post-transcriptionally and translationally. Many plants, especially Musa spp. (plantains and bananas), which are important perennial herbs of the family Musaceae, experience significant yield loss due to abiotic stressors, yet only a few miRNAs involved in this response have been identified. This study employed in silico analyses of transcriptome shotgun assembly (TSA) and expressed sequence tag (EST) sequences to identify Musa miRNAs and their target genes. Leaf and root tissues from three Musa genomic groups (AAA, AAB, and ABB) under drought stress were analyzed using quantitative real-time PCR (qRT-PCR) to validate the expression of miRNAs. A total of 17 potential conserved miRNAs from 11 families were identified, with the minimal folding free energies (-kcal/mol) of precursors ranging from −136.00 to −55.70, as observed through RNA folding analysis. Six miRNAs (miR530-5p, miR528-5p, miR482a, miR397a, miR160h, and miR399a) showed distinct tissue-specific expression patterns in the roots and leaves across the three groups. A total of 59 target regulatory transcription factors and enzymes involved in stress response, growth, and metabolism were predicted. Of these, 11 targets were validated for miR530-5p, miR528-5p, miR482a, and miR397a, using qRT-PCR. These four stress-responsive miRNAs exhibited an inverse expression relationship with their target genes across two different tissues in Musa groups. This research provides insights into miRNA-mediated drought stress responsiveness in Musa spp., potentially benefiting future studies on gene regulation under drought stress. Full article

Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article

Background/Objectives: Camellia nitidissima Chi (C. nitidissima), a traditional Chinese “food and medicine homology” plant, has demonstrated potential anti-tumor properties. However, its mechanisms of anti-lung cancer activity via ferroptosis remain unclear. This study aimed to construct an integrated research system of “natural product extraction-purification, bioactivity evaluation, and computational drug screening” to explore the bioactive compounds in C. nitidissima leaves targeting HMOX-1-mediated ferroptosis and their anti-lung cancer mechanisms. Methods: Active fractions were prepared using ethanol extraction combined with polyamide column chromatography. The anti-lung cancer activity was evaluated using the NCI-H1975 cell model. Ferroptosis was verified via transmission electron microscopy (TEM), biochemical indicators, a PCR Array, and immunofluorescence. The bioactive compounds were identified using UPLC-Q Exactive MS, and their binding affinity to HMOX-1 was evaluated via molecular docking and dynamics simulations, followed by cellular validation. Results: The 95% F1 fraction from the extracts of C. nitidissima leaves exhibited the strongest anti-lung cancer activity, which could be significantly reversed by Ferrostatin-1. Furthermore, it induced typical ferroptosis-related structural damage in mitochondria, including shrinkage and a reduction in size, increased membrane density, and a reduction or even the disappearance of cristae structures. At the molecular level, this fraction significantly increased the levels of oxidative stress markers (ROS↑, MDA↑, Fe²⁺↑, and GSH↓) and upregulated the expression of key ferroptosis-related genes, including HMOX-1, CHAC1, and NOX1. Using UPLC-Q Exactive MS combined with computational simulation methods, four bioactive compounds with high affinity for HMOX1 were successfully identified, including isochlorogenic acid A (−8.4 kcal/mol), isochlorogenic acid C (−8.4 kcal/mol), apigenin (−7.8 kcal/mol), and chrysin (−7.3 kcal/mol). Cellular experiments validated that these compounds exhibited dose-dependent anti-proliferative effects. Conclusions: The leaves of C. nitidissima induce anti-lung cancer effects via HMOX-1-mediated ferroptosis. Isochlorogenic acid A/C, apigenin, and chrysin were identified as key bioactive components. These findings lay the foundation for the development of natural ferroptosis-targeted drugs. Full article

Milk of lime (MOL), a suspension of calcium oxide and calcium hydroxide, is vital in the purification of sugar beet and cane juices. This study evaluates the application of Fourier Transform Near-Infrared (FT-NIR) spectroscopy combined with chemometric models—Partial Least Squares (PLS) and Principal Component Regression (PCR)—for rapid, non-destructive assessment of key MOL parameters: density, total lime content, calcium oxide availability, and sucrose content. Ninety samples were analyzed using both wet chemistry and FT-NIR. The predictive performance was assessed using the coefficient of determination (R²). High predictive accuracy was observed for density (PLS: R² = 0.8274; PCR: R² = 0.8795) and calcium oxide availability (PLS: R² = 0.9035; PCR: R² = 0.9115). Total lime content showed moderate accuracy (PLS: R² = 0.7748; PCR: R² = 0.7983), while sucrose content exhibited low predictive power (PLS: R² = 0.2312; PCR: R² = 0.3747). The weak performance was noted for %CaO (PLS: R² = 0.4893; PCR: R² = 0.2409), likely due to spectral overlap and matrix complexity. Despite these challenges, FT-NIR remains a viable, reagent-free method for monitoring MOL, with the potential to enhance process control in the sugar industry. Future work should focus on refining calibration strategies and addressing spectral interferences to improve predictive accuracy for complex matrices. Full article

In this study, we synthesized a novel trimethoprim derivative, 4-(((2-amino-5-(3,4,5-trimethoxybenzyl) pyrimidine-4-yl)imino)methyl)benzene-1,3-diol (HD), by the reaction of trimethoprim with 2,4-dihydroxybenzaldehyde. We then prepared metal complexes of this derivative with Cu(II), Co(II), Ni(II), Ag(I), and Zn(II) and functionalized them with ZnO and Au nanoparticles. Their structures were confirmed through ¹H NMR, mass spectrometry, FTIR, conductivity, thermal analysis, magnetic susceptibility, X-ray diffraction, UV-Vis spectroscopy, and TEM, revealing octahedral geometries for all complexes. Surface features were investigated using density functional theory (DFT) analysis. Pharmacokinetic parameters and target enzymes for HD and its complexes were computed using the SwissADME web tool, with the BOILED-Egg model indicating that HD and its Cu complex should be passively permeable via the blood-brain barrier and highly absorbed by the gastrointestinal tract (GIT), unlike the Ni, Co, Ag, and Zn complexes, which are predicted to show low GIT absorption. Molecular docking studies with the Caspase-3 enzyme (PDB code: 3GJQ) using the AutoDock 4.2 software demonstrated binding energies of −7.66, −8.36, −9.05, −8.62, −6.90, and −7.81 kcal/mol for HD and the Cu, Co, Ni, Ag, and Zn complexes, respectively, compared to −6.54 and −4.63 kcal/mol for TMP and 5-FU (5-fluorouracil), indicating a potential superior anticancer potential of the novel compounds. The anticancer activities of these complexes were evaluated using the MTT assay. The IC₅₀ values for 5-FU, TMP, HD, Cu-HD, HD@ZnONPs, Cu-HD@ZnONPs, HD@AuNPs, and Cu-HD@AuNPs were found to be 32.53, 80.76, 114.7, 61.66, 77, 53.13, 55.06, and 50.81 µg/mL, respectively. Notably, all derivatives exhibited higher activity against the HepG-2 cancer cell line than TMP, except for HD, which showed similar effectiveness to TMP. Real-time PCR analysis revealed that the Au-HD@AuNPs and Cu-HD@AuNPs significantly increased caspase-3 inhibition by 4.35- and 4.5-fold and P53 expression by 3.05- and 3.41-fold, respectively, indicating enhanced pro-apoptotic gene expression and apoptosis induction in HepG2 cells. Our findings demonstrate that these novel derivatives possess significant anticancer properties, with some complexes showing superior activity compared to standard drugs such as 5-Fluorouracil (5-FU) and Trimethoprim (TMP). This study highlights the potential of these nanocomposites as promising candidates for cancer therapy. Full article

Flavonoid biosynthesis is proposed to play a critical role in floral organ development in Paeonia species. However, its specific involvement in stamen petalization remains unclear. This study identified and characterized 13 gene families related to flavonoid biosynthesis across four Paeonia species. Comparative and phylogenetic analysis revealed that most flavonoid biosynthesis-related genes experience lineage-specific expansion in P. ludlowii. Genes belonging to the same family were commonly clustered on chromosomes and displayed highly conserved domain and motif compositions. The cis-element analysis identified Cis-acting elements associated with light, hormonal, and stress responses, implicating their regulatory roles in flavonoid biosynthesis. To further investigate the role of these genes in stamen petalization of P. lactiflora, expression profiling analyses were performed on ‘Fen Yu Nu’ (normal stamens) and ‘Lian Tai’ (petaloid stamens) cultivars using transcriptomic data released previously. Three quercetin-related genes revealed distinct stage-specific patterns in ‘Fen Yu Nu’ and ‘Lian Tai’. Notably, PlaF3’H03 exhibited significant upregulation during petaloid stamen development in ‘Lian Tai’, suggesting its role in stamen transformation. Molecular docking identified PlaF3’H07 as a key enzyme with strong substrate-binding affinity (ΔG = −4.7 kcal/mol), supporting its catalytic function in quercetin synthesis. The expression pattern of key flavonoid biosynthetic genes was also confirmed across three developmental stages of floral buds by real-time quantitative PCR. This study provides insights into the genetic basis underlying stamen petalization in P. lactiflora and offers potential targets for genetic improvement of floral traits in Paeonia and other ornamental plants. Full article

Crohn’s disease is an inflammatory bowel disease (IBD) that currently lacks satisfactory treatment options. Therefore, new targets for new drugs are urgently needed to combat this disease. In the present study, we investigated the transcriptomics-based mRNA expression of intestinal biopsies from patients with Crohn’s disease. We compared the mRNA expression profiles of the ileum and colon of patients with those of healthy individuals. A total of 72 genes in the ileum and 33 genes in the colon were differentially regulated. Among these, six genes were overexpressed in both tissues, including IL1B, TCL1A, HCAR3, IGHG1, S100AB, and OSM. We further focused on OSM/oncostatin M. To confirm the responsiveness of intestinal tissues from patients with Crohn’s disease to oncostatin M inhibition, we examined the expression of the oncostatin M using immunohistochemistry in patient biopsies as well as in kindlin-1^−/− and kindlin-2^−/− knockout mice, which exhibit an inflammatory bowel disease (IBD) phenotype, and found strong oncostatin M expression in all samples examined. Next, we conducted a drug-repurposing study using the supercomputer MOGON and bioinformatic methods. A total of 13 candidate compounds out of 1577 FDA-approved drugs were identified by PyRx-based virtual drug screening and AutoDock-based molecular docking. Their lowest binding energies (LBEs) ranged from −10.46 (±0.08) to −8.77 (±0.08) kcal/mol, and their predicted inhibition constants (pK_i) ranged from 21.62 (±2.97) to 373.78 (±36.78) nM. Ecamsule has an interesting stereostructure with two C₂-symmetric enantiomers (1S,4R-1′S,4′R and 1R,4S-1′R,4′S) (1a and 1b) and one meso diastereomer (1S,4R-1′R,4′S) (1c). These three stereoisomers showed strong, albeit differing, binding affinities in molecular docking. As examined by nuclear magnetic resonance and polarimetry, the 1S,4R-1′S,4′R isomer was the stereoisomer present in our commercially available preparations used for microscale thermophoresis. Ecamsule (1a) was chosen for in vitro validation using recombinant oncostatin M and microscale thermophoresis. Considerable dissociation constants were obtained for ecamsule after three repetitions with a K_d value of 11.36 ± 2.83 µM. Subsequently, we evaluated, by qRT-PCR, the efficacy of ecamsule (1a) as a potential drug that could prevent oncostatin M activation by inhibiting downstream inflammatory marker genes (IL6, TNFA, and CXCL11). In conclusion, we have identified oncostatin M as a promising new drug target for Crohn’s disease through transcriptomics and ecamsule as a potential new drug candidate for Crohn’s disease through a drug-repurposing approach both in silico and in vitro. Full article

Introduction: Currently, there are no effective medications for treating all the clinical conditions of patients with COVID-19. We aimed to evaluate the antiviral activity of compounds derived from L-tyrosine against the B.1 lineage of SARS-CoV-2 in vitro and in silico. Methodology: The cytotoxicities of 15 halogenated compounds derived from L-tyrosine were evaluated in Vero-E6 cells by the MTT assay. The antiviral activity of the compounds was evaluated using four strategies, and viral quantification was performed by a plaque assay and qRT-PCR. The toxicity of the compounds was evaluated by ADMET predictor software. The affinity of these compounds for viral or cellular proteins and the stability of their conformations were determined by docking and molecular dynamics, respectively. Results: TODC-3M, TODI-2M, and YODC-3M reduced the viral titer >40% and inhibited the replication of viral RNA without significant cytotoxicity. In silico analyses revealed that these compounds presented low toxicity and binding energies between −4.3 and −5.2 Kcal/mol for three viral proteins (spike, Mpro, and RdRp). TODC-3M and YODC-3M presented the most stable conformations with the evaluated proteins. Conclusions: The most promising compounds were TODC-3M, TODI-2M, and YODC-3M, which presented low in vitro and in silico toxicity, antiviral potential through different strategies, and favorable affinities for viral targets. Therefore, they are candidates for in vivo studies. Full article

Bladder cancer, the fourth most common cancer type among men, remains a therapeutic challenge due to its heterogeneity and frequent development of chemoresistance. Cisplatin-based chemotherapy, often combined with gemcitabine, is the standard treatment, yet resistance and off-target effects in non-cancerous tissues limit its efficacy. This study evaluated the effects of cisplatin, gemcitabine, and the APC/C inhibitor proTAME, both individually and in combination, on cell migration and MMP2/MMP9 expression in RT4 bladder cancer and ARPE-19 normal epithelial cells. Molecular docking analyses were conducted to investigate the interactions of these compounds with MMP2 and MMP9. IC20 values for gemcitabine, cisplatin, and proTAME were applied in scratch-wound healing and quantitative real-time PCR (qRT-PCR) assays. Docking results predicted that proTAME may interact favorably with MMP2 (−9.2 kcal/mol) and MMP9 (−8.7 kcal/mol), showing high computational binding affinities and potential key hydrogen bonds; however, these interactions require further experimental validation. Scratch-wound healing and qRT-PCR assays demonstrated that proTAME-containing combinations were associated with reduced cell migration and decreased MMP2 and MMP9 expression in RT4 cells. Cisplatin combined with proTAME showed the most pronounced reduction in MMP expression and cell migration, with proTAME alone also exhibiting notable inhibitory effects. In ARPE-19 cells, gemcitabine and cisplatin upregulated MMP2 and MMP9 expression, suggesting a potential stress response, whereas proTAME mitigated this effect. These differential effects show the importance of tumor-specific responses in RT4 cells, where proTAME shows promise in enhancing the efficacy of chemotherapy by modulating MMP-related pathways involved in tumor migration and invasion. In conclusion, this study highlights the potential of proTAME as a repurposed agent in bladder cancer treatment due to its association with reduced cell migration and MMP downregulation. While these in vitro and in silico findings suggest a promising role for proTAME in combination therapies, further validation in advanced preclinical models is necessary to assess its therapeutic applicability and safety. Full article

A couple presented to the office with an apparently healthy infant for a thorough clinical assessment, as they had previously lost two male children to a neurodegenerative disorder. They also reported the death of a male cousin abroad with a comparable condition. We aimed to evaluate a novel coding pathogenic variant c.1097T>A, PLA2G6, within the affected family, previously identified in a deceased cousin, but its clinical significance remained undetermined. A 200 bp PCR product of target genome (including codon 366 of PLA2G6) was amplified followed by enzymatic digestion (MboI) and sequencing. Structural pathogenic variant analysis was performed using PyMOL 2.5.4. In RFLP analysis, the mutant-type allele produced a single band of 200 bp, and the wild-type allele manifested as two bands of 112 bp and 88 bp. The pathogenic variant was identified in nine family members, including two heterozygous couples with consanguineous marriages resulting in affected children. It was predicted to be deleterious by multiple bioinformatic tools. The substitution of nonpolar isoleucine with polar asparagine of iPLA2 (Ile366Asn) resulted in a eense pathogenic variant (ATC>AAC). A missense variant (p. Ile366Asn) in the PLA2G6 gene is associated with clinically evident infantile neuroaxonal dystrophy, which is transmitted in an autosomal recessive pattern, and is also predicted to be dysfunctional by bioinformatic analyses. Full article

Ecklonia cava and its major compound dieckol, both natural marine products, possess antioxidant, anti-inflammatory, and metabolic-regulating effects. Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is transmitted by mosquitoes and causes serious illnesses in humans. This study aimed to evaluate the anti-ZIKV potential of Ecklonia cava and dieckol. The antiviral activity of Ecklonia cava extract (ECE), prepared with 80% ethanol, was assessed in ZIKV-infected Vero E6 cells through MTT assay, plaque assay, and quantitative polymerase chain reaction (qPCR), demonstrating no cytotoxicity and a significant reduction in viral titers and ZIKV mRNA levels. In addition, ECE decreased the expression of tumor necrosis factor-α and interferon-induced protein with tetratricopeptide repeats in the ZIKV-infected cells. Dieckol, the primary active compound in ECE, exhibited potent anti-ZIKV activity, with a half maximal inhibitory concentration (IC₅₀), value of 4.8 µM. In silico molecular docking analysis revealed that dieckol forms stable complexes with key ZIKV proteins, including the envelope, NS2B/NS3, and RNA-dependent RNA polymerase (RdRp) protein, exhibiting high binding energies of −438.09 kcal/mol, −1040.51 kcal/mol, and −1043.40 kcal/mol, respectively. Overall, our findings suggest that ECE and dieckol are promising candidates for the development of anti-ZIKV agents. Full article

Huntington’s disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington’s Disease are caused by a pathological increase in the number of Cytokine-Adenine-Guanine (CAG) repeats on the first exon of the Huntingtin gene, which causes a protein to have an excessive number of glutamine residues; this alteration leads to a change in the protein’s conformation and function. Therefore, the purpose of this work was to design, synthesize and evaluate an antisense oligonucleotide (ASO; 95 nucleotides) HTT 90-5 directed to the Huntingtin CAG repeats in primary leukocyte culture cells from a patient with Huntington’s Disease; approximately 500,000 leukocytes per well extracted from venous blood were used, to which 100 pMol of ASO were administered, and the expression of Huntingtin was subsequently evaluated at 72 h by RT-PCR. Our results showed that the administration of the HTT 90-5 antisense decreased the expression of Huntingtin mRNA in the primary culture leukocyte cells from our patient. These results suggest that the use of long antisense targeting the CAG Huntingtin cluster may be an option to decrease the expression of Huntingtin and probably could be adjusted depending on the number of CAG repeats in the cluster. Full article

Mango (Mangifera indica), a nutritionally rich tropical fruit, is significantly impacted by UV-B radiation, which induces oxidative stress and disrupts physiological processes. This study aimed to investigate mango pulp’s molecular and biochemical responses to UV-B stress (96 kJ/mol) from the unripe to mature stages over three consecutive years, with samples collected at 10-day intervals. UV-B stress affected both non-enzymatic parameters, such as maturity index, reactive oxygen species (ROS) levels, membrane permeability, and key enzymatic components of the ascorbate-glutathione (AsA-GSH) cycle. These enzymes included glutathione reductase (GR), gamma-glutamyl transferase (GGT), glutathione S-transferases (GST), glutathione peroxidase (GPX), glucose-6-phosphate dehydrogenase (G6PDH), galactono-1,4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX), ascorbate oxidase (AAO), and monodehydroascorbate reductase (MDHAR). Transcriptomic analysis revealed 18 differentially expressed genes (DEGs) related to the AsA-GSH cycle, including MiGR, MiGGT1, MiGGT2, MiGPX1, MiGPX2, MiGST1, MiGST2, MiGST3, MiG6PDH1, MiG6PDH2, MiGalLDH, MiAPX1, MiAPX2, MiAAO1, MiAAO2, MiAAO3, MiAAO4, and MiMDHAR, validated through qRT-PCR. The findings suggest that UV-B stress activates a complex regulatory network in mango pulp to optimize ROS detoxification and conserve antioxidants, offering insights for enhancing the resilience of tropical fruit trees to environmental stressors. Full article

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC−25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription–quantitative polymerase chain reaction (RT−qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2−related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO−1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin−treated SCC−25 cells significantly decreased in a dose− and time−dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin−treated SCC−25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO−1 in fucoxanthin−treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration−dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO−1, and TFR1 were below −5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC−25 cells, highlighting its potential as a treatment for tongue cancer. Full article