Search Results (2,579)

Cervical cancer is a major gynecological malignancy linked to hormonal dysregulation and genetic alterations. Chemotherapy is standard but limited by toxicity and chemoresistance, prompting interest in plant-derived adjuncts. This study examined the anticancer and immunomodulatory effects of Hesperidin (Hes), a citrus flavonoid, with Doxorubicin (DX) in HeLa cervical cancer cells. Cell viability was assessed by MTT assay, apoptotic markers (Bcl-2, Caspase-3) by RT-qPCR, and inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) by ELISA. Cytokine levels were normalized to 10⁴ viable cells, and mRNA expression of all four cytokines was quantified by RT-qPCR, confirming protein-level changes and showing the strongest IL-6 suppression with Hes+DX. Chou–Talalay combination index (CI) analysis demonstrated synergistic interactions (CI < 1.0) between Hes and DX across all tested concentrations, with strong synergism (CI < 0.7) at medium and high doses, particularly at 48 and 72 h. Hes alone showed dose-dependent cytotoxicity, while the combination markedly increased Caspase-3, reduced Bcl-2, and decreased IL-1β, IL-6, and TNF-α, indicating enhanced intrinsic apoptosis and complementary immunomodulation. These results suggest that Hes augments DX’s pro-apoptotic and anti-inflammatory effects, potentially allowing lower chemotherapy doses and reduced systemic toxicity in cervical cancer treatment. Full article

(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment but also with molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hottest topics. (2) Methods: We identified castalin from chestnut shells by using NRM and LC-MS/MS. We treated different cancer cell lines with castalin alone or in combination with a CHK1 inhibitor. Finally, we performed an RNA-seq analysis of HeLa cells treated with castalin. (3) Results: We demonstrated the ability of castalin to induce DNA damage, probably by increasing ROS production. Consistently, antioxidant treatment, with ascorbic acid, reduced the DNA damage induced by castalin. Finally, we demonstrated the potential synergistic effect of castalin with SRA737, a CHK1 inhibitor currently used in clinical trials. (4) Conclusions: We demonstrated the ability of castalin to induce DNA damage favoring NHEJ repair. Moreover, the use of castalin in combination with SRA737 increased the efficacy of the CHK1 inhibitor, reducing its possible side effects. Full article

Background/Objectives: Cervical cancer remains a major health challenge, especially in low-resource regions with limited diagnostic and advanced treatment options. Nanotechnology-based strategies offer promising alternatives to conventional chemotherapy by reducing systemic toxicity and enabling site-specific delivery. Methods: In this study, halloysite (Hall) was functionalized with green-synthesized 2 wt% zinc oxide (GZn) and silver (GAg) nanoparticles (NPs) using Tribulus terrestris extract (25 mM) to enhance cisplatin (Cp) and carboplatin (Cbpt) delivery for targeted cervical cancer therapy. Results: Structural and morphological analyses confirmed the successful integration of GZn and GAg NPs into the Hall without compromising its tubular integrity. Cp or Cbpt adsorption studies with varying times (0.15–12 h), as well as drug/Hall ratios (10–50) and pH levels (5; 6.6; 7.4; 9.0; and 10.5), revealed greater Cp adsorption than Cbpt, attributed to its higher reactivity and affinity toward the Hall surface. pH-responsive release studies biphasic drug release for non-PEGYlated formulations, with Cp (14% with 2 h) and Cbpt (10% with 0.5 h), whereas PEGYlated systems exhibited sustained release under acidic tumor-like conditions, achieving 14% in 72 h for Cp and 4.5% in 72 h for Cbpt. Release kinetics followed either Fickian or non-Fickian diffusion depending on pH and drug type, with the Korsmeyer–Peppas model offering a strong fit (R² > 0.85). In vitro assays revealed that Cbpt/GZn-Hall/PEG, Cp/GZn-Hall/PEG, and Cbpt/GAg-Hall/PEG induced dose-dependent cytotoxicity against HeLa while sparing HFF-1 fibroblasts. Conclusions: These findings indicate that green-synthesized nanohybrids are promising carriers for targeted Cp and Cbpt delivery, warranting further in vivo evaluation for cervical cancer therapy. Full article

Fungi are a prolific source of diverse bioactive metabolites, yet many remain unexplored. Among these, depsidones are a rare class of compounds with significant biological potential, but they are seldom reported in mushrooms. This study investigated the medicinal fungus Ganoderma lucidum, known for its extensive therapeutic use in traditional medicine. Fruiting bodies were extracted using petroleum ether, ethyl acetate, n-butanol, and methanol. Extracts were screened phytochemically and assessed for total phenolic content and antioxidant activity using the DPPH assay. Ethyl acetate extract exhibited the highest phenolic yield and antioxidant potential and was subsequently evaluated for cytotoxicity against HepG2, HCT116, MCF7, and A549 cancer cell lines. It showed notable anticancer activity with minimal toxicity to normal Vero cells. UHPLC/Q-TOF-MS/MS analysis of G. lucidum ethyl acetate extract tentatively identified nine minor depsidones including mollicellin G, simplicildone I, mollicellin B, talaromyone B, simplicildone A, purpactin C, emeguisin B, mollicellin E, and simplicildone D on the basis of high-resolution negative-mode detection and characteristic MS/MS fragmentation patterns. Molecular docking revealed strong binding affinities between these compounds and cancer-related targets (AKT1, CDK2, ERK1, TNFα), with simplicildone D and mollicellin G demonstrating particularly high interactions. These findings provide mechanistic insights into the observed bioactivity and highlight G. lucidum as a promising source of therapeutic depsidones for future anticancer drug development. Full article

Background/Objectives: Wastewaters containing antibiotics pose risks to human health and soil ecosystems. In this study, the white-rot fungus Coriolopsis gallica (a basidiomycete exhibiting high laccase production) was used for the biotransformation of three antibiotics (50 mg L⁻¹): tetracycline, chloramphenicol, and sulfanilamide. Methods: The biotransformation process was investigated in liquid and solid media using high-performance liquid chromatography (HPLC) and the bacterial growth inhibition agar well diffusion method, respectively. Results: Among the three antibiotics tested, tetracycline showed the highest biotransformation efficiency, achieving a 100% removal rate in the liquid medium and a 100% decrease in the growth inhibition of Escherichia coli in the solid medium. Chloramphenicol and sulfanilamide were partially removed (20% and 16%, respectively) after 12 days of treatment in more than one step without the loss of their antibacterial activities. The presence of these antibiotics in the culture medium of C. gallica enhanced laccase activity, indicating that this ligninolytic enzyme might participate in the biotransformation process. Conclusions: Thus, the results reported in this article extend our knowledge of the catalytic potential of C. gallica and give further perspectives for its application in the biodegradation of antibiotics. To the best of our knowledge, this is the first study wherein C. gallica was used for the treatment of tetracycline, chloramphenicol, and sulfanilamide. Full article

Two series of tricyclic thieno[3,2-d]pyrimidines were synthesized, achieving yields of up to 97%. The tricyclic thieno[3,2-d]pyrimidines examined in this study are synthetic analogs of the deoxyvasicinone alkaloids, where the thiophene ring substitutes for the benzene ring. A systematic investigation was conducted on the scaffold-hopping strategy of these alkaloids, emphasizing the selective synthesis and anticancer properties of thieno[3,2-d]pyrimidines. The anticancer evaluation was performed on human cancer cell lines, specifically cervical HeLa and colon HT-29 carcinoma cells. Additional bioassays included cell migration analyses, cell cycle progression, apoptosis, and molecular docking analyses. Furthermore, molecular docking studies showed that the most active small molecule 6e is likely to disrupt the cell cycle process through targeting CDKs (Cyclin-dependent kinases), leading to the inhibition of tumor cell proliferation. Full article

Background: Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis, antihistaminic, anti-inflammatory, and anticancer. Also, trifluoromethyl (CF₃) group has also been widely used in drug and agrochemical design. Methods: In this study, a series of new theophylline derivatives containing substituted trifluoromethyl and trifluoromethoxy groups were synthesized. The structures of these new compounds were confirmed by NMR, FT-IR, and elemental analyses. Additionally, the anticancer activities of the molecules were analyzed against VEGFR-2, CYP P450, and estrogen receptor by molecular docking method. Furthermore, in vitro biological effects of the compounds were comprehensively evaluated in cancer (A549 and HeLa) and normal (BEAS-2B) cells. Cell viability was assessed by MTT assay, and selectivity index (SI) values were calculated to determine tumor-specific toxicity. Results: N(7)-substituted theophyllines were prepared by the reaction of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theophylline) and trifluoromethyl substituted benzyl halide compounds. The synthesized N(7)-substituted theophyllines were obtained as white powder in high yield. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as ¹H, ¹³C, ¹⁹F NMR, and FT-IR spectroscopy, and elemental analysis. The highest interaction was recorded as −5.69 kcal/mol for 3-CF₃ substituted against VEGFR-2 structure while the best binding affinity was determined for 4-OCF₃ substituted with −6.69 kcal/mol against Human Cytochrome P450 with in silico analysis. The in vitro anticancer activities of the molecules were also evaluated against A549 and HeLa cells, and displayed considerably higher cytotoxicity with 2-CF₃, 3-CF_3, and 4-CF₃ substituted molecules in Hela and A549 cell line. To elucidate the molecular mechanism, apoptosis-related gene expression changes were analyzed by RT-qPCR in A549 and HeLa cells treated with compound 2-CF₃. Significant upregulation of pro-apoptotic markers and downregulation of anti-apoptotic genes were observed. Consistently, ELISA-based quantification confirmed increased protein levels of Caspase-3, BAX, and Cytochrome C, and decreased BCL-2, validating the apoptotic mechanism at the protein level. Also, the antibacterial and antibiofilm activity details of the molecules were evaluated against DNA Gyrase, and SarA crystal structures by molecular docking method. The highest interaction was recorded as −5.56 kcal/mol for 2-CF₃ substituted with H-bonds with Asn46, Val71, Asp73, and Thr165 against DNA Gyrase crystal structure while 3-CF₃ substituted has the best binding affinity against SarA. The in vitro antimicrobial effects of the molecules were also evaluated. Conclusions: The synthesized molecules may provide insight into the development of potential therapeutic agents to the increasing antimicrobial resistance and biofilm-forming capacity of microorganisms. Additionally, compound 2-CF₃ substituted exhibited promising and selective anticancer activity through apoptosis induction, supported by gene and protein level evidence. Full article

Alterations in gene expression induced by ionizing radiation (IR) were commonly explained by transcriptional activation. However, the weak correlation between mRNA and protein levels following IR indicates the significant role for post-transcriptional regulation. microRNAs (miRNAs) bound to AGO2 play a significant role in post-transcriptional regulation; however, their role in radiation response is not clear. miRNA sequencing was performed to analyze the miRNAome of glioma cells. The effect of IR on Let-7 miRNAs and their association with AGO2 was examined using RT-qPCR and RNA immunoprecipitation (RIP) assays. Clonogenic assays were performed to measure radiosensitivity following Let-7a overexpression or knockdown. DNA damage (γH2AX foci) and cell cycle distribution were analyzed by immunofluorescence and flow cytometry. Let-7 miRNA regulatory networks were identified through target prediction and pathway enrichment analysis. AGO2-Let-7 binding decreased post IR, indicating impaired RISC loading. Let-7 overexpression increased radiosensitivity, DNA damage and G2/M cell cycle arrest in glioma and other cells (HeLa and MDA-MB-231). Let-7 miRNAs mainly targeted cell cycle and DNA damage response (DDR) pathways. Our study showed radiation impairs AGO2-miRNA binding, while restoring Let-7-AGO2 interaction enhances radiosensitivity by modulating DNA repair and cell cycle checkpoint activation. Targeting AGO2-miRNA dynamics represents a promising approach to improve radiotherapy outcomes. Full article

Fridericia platyphylla, a member of the Bignoniaceae family, is widely recognized as a rich source of flavonoids with significant biopharmacological potential. This study aimed to perform a chemical annotation of its metabolites and to evaluate the antitumor activity of the hydroalcoholic extract from its leaves. The chemical diversity of this specimen was analyzed using liquid chromatography coupled with tandem mass spectrometry and Molecular Networking. Fifteen significant phenolic compounds were annotated, including phenolic acid derivatives, flavonoid glycosides, and flavone aglycones. Furthermore, the antiproliferative activities against human cervical cell lines, adenocarcinoma HPV 18 positive (HeLa) and carcinoma HPV 16 positive (SiHa), in vitro, exhibited distinct inhibitory effects, with IC₅₀ values of 44.78 and 66.97 µg mL⁻¹, respectively. The extract inhibited cell migration and exhibited cytotoxic effects by reducing the viability of HeLa and SiHa cells, suggesting its potential as a therapeutic candidate for cervical cancer. Therefore, given the significant antiproliferative and anti-migratory activity, these results open up prospects for investigating F. platyphylla leaf extract in the development of alternative therapies for cervical cancer. Full article

Plants of the genus Porophyllum (Asteraceae) have traditional medicinal uses, but only 8 of 25 species have been studied. This study aimed to profile volatile compounds, phenolics, and fatty acids in dried leaves and stems of Porophyllum gracile and assess biological activities of extracts obtained using different solvents. GC-MS, HPLC-DAD, and GC-FID analyses identified over 120 compounds, including fatty acids, chlorogenic acid derivatives, quercetin derivatives, terpenes, ketones, aldehydes, and alcohols. Antioxidant activity in vitro (ABTS, DPPH, and FRAP assays) suggested a strong electron-transfer-mediated mechanism. In ARPE-19 cells under doxorubicin-induced oxidative stress, hexane and ethanolic extracts from leaves and stems significantly reduced intracellular reactive oxygen species, in some cases outperforming vitamin E. No antiproliferative activity was detected against cancer cell lines (MDA-MB-231, HeLa, A549, HCT 116, 22Rv1), nor cytotoxicity toward non-cancerous cells (ARPE-19, hFOB 1.19). This first detailed phytochemical characterization of P. gracile demonstrates its cellular antioxidant potential and supports its application as a natural antioxidant source in functional foods or nutraceuticals. Future work should elucidate mechanisms, isolate active compounds, and evaluate bioavailability in in vivo models. Full article

Erythrina caffra is a traditional plant used to treat cancer and inflammation. The study aimed to assess and isolate anticancer compounds from E. caffra bark. The plant material was extracted sequentially in n-hexane, dichloromethane, ethyl acetate and methanol. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and 3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate the crude extracts’ antioxidant and anticancer activities, respectively. Column chromatography was used to purify the potent extracts of the stem bark in order to isolate the bioactive compounds. The crude extracts of the E. caffra bark demonstrated antioxidant and anticancer activity, with the dichloromethane (DCM) extract producing the most favorable activity. Three compounds, namely Hexacosanyl isoferulate, Tetradecyl isoferulate, and 1-Heneicosanol, were detected in fractions from the DCM extract. All the isolated compounds showed significant anticancer potential, with the hydroxycinnamic acid compounds showing better anticancer effects in the cervical (HeLa) and breast cancer (MCF-7) cells. The compounds showed greater activity than even the standard drug, 5-fluorouracil, in the MCF-7 cells, with the tetradecyl isoferulate and hexacosanyl isoferulate fractions having IC₅₀ values of 123.62 and 58.84 µg/mL, respectively. The compounds were observed to be capable of triggering caspase cascade events, leading to apoptotic cell death. Overall, E. caffra extracts contained important bioactive compounds that induced apoptotic cell death in HeLa and MCF-7 tumor cells, warranting further investigations in vitro and in vivo. Full article

Background: Magnolia alejandrae is a tree endemic to Tamaulipas, Mexico, distributed in the forests of the Sierra Madre Oriental. Objective: Our objective was to analyze the secondary metabolite profile of different parts of M. alejandrae and evaluate their antiproliferative activity in vitro. Methods: Different extracts of leaf, bark, and fruit were obtained using conventional and unconventional extraction methods with solvents of different polarity. The extracts were analyzed by Ultra-Performance Liquid Chromatography-Mass Spectra (UPLC-MS), and their antiproliferative activity against cancer cell lines was determined. Results: The primary yields of the extracts obtained from M. alejandrae ranged from 8.32% to 36.19%. Three hundred and twelve secondary metabolites previously reported from the Magnolia genus were detected. The most frequent were magnone A, pinoresinol, and yangambin. Honokiol and magnolol were not detected. Two of the extracts (FSW and BSW) had antiproliferative activity (IC₅₀ < 140 µg/mL) against HeLa, MCF-7, A549, U373, and PC3 cancer cell lines. The higher activity was against the A549 cell line. Conclusions: M. alejandre extracts showed secondary metabolites previously reported and unreported in other species. Interestingly, some extracts had antiproliferative activity against cancer cell lines. Therefore, M. alejandrae is a source of molecules that could be explored to develop new drugs. Full article

Elastic solutions of a differential system of vibrational responses of a bidirectional porous functionally graded plate (BPFG) are described by employing high-order normal and shear deformation theory, in the present study. Natural frequency values are computed for the plates with simply supported boundary conditions and taking into consideration the thickness stretching effect. Grading of the effective material property for the BPFG plate is defined according to a power-law distribution. Navier’s approach is applied to determine the governing differential equations solution of the studied model derived by Hamilton’s principle. To confirm the reliability of the solution and the model accuracy, a comparison study with various studies that are presented in the literature is carried out. Numerical illustrations are presented to discuss the influences of the plate geometry, the porosity, the volume fraction distribution, and the nonlocality on the vibration behaviors of the model. The dynamic responses of unidirectional and bidirectional porous functionally graded nanoplates are analyzed in detail, employing two parametric numerical examples. Numerical results show the sensitivity of frequencies to the studied parametric factors and their dependence on porosity and nonlocality coefficients. Frequencies of BPFG with uneven/even distribution porosity decrease when increasing the transverse and axial power-law indexes ($P\ne 0$), and the same effect appears when increasing the nonlocal parameter. Full article

Enhancer–promoter interactions (EPIs) play a key role in epigenetic regulation of gene expression, dominating cellular identity and functional diversity. Dissecting these interactions is crucial for understanding transcriptional regulatory networks and their significance in cell differentiation, development, and disease. Here, we propose a novel deep learning framework, EPIFBMC (Enhancer-Promoter Interaction prediction with FBMC network) that leverages DNA sequence and genomic features for accurate EPI prediction. The FBMC network consists of three key modules: the Four-Encoding module first encodes the DNA sequence in multiple dimensions to extract key sequence information; then the BESL (Balanced Ensemble Subset Learning) adopts an integrated subset learning strategy to optimize the feature-learning process of positive and negative samples; finally, the MCANet module completes the training of EPI prediction based on a Multi-channel Network. We evaluated EPIFBMC on three cell line datasets (HeLa, IMR90, and NHEK), and validated its generalizability across three independent datasets (K562, GM12878, HUVEC) through cross-cell-line experiments, comparing favorably with state-of-the-art methods. Notably, EPIFBMC balances genomic feature richness and computational complexity, significantly accelerating training speed. Ablation studies identified two key DNA sequence features—positional conservation and positional specificity score—which showed critical predictive value across a benchmark dataset of six diverse cell lines. The computational testing show that EPIFBMC shows excellent performance in the EPI prediction task, providing a powerful tool for decoding gene regulatory networks. It is believed that it will have important application prospects in developmental biology, disease mechanism research, and therapeutic target discovery. Full article

Background: Many cancer cell lines, such as Hepa 1-6 (liver), A549 (lung), Hela (cervical), and MCF7 (breast), do not overexpress tyrosinase, an enzyme needed to activate the prodrug quercetin into its active form, o-quinone. In addition, these cancers do not rely on extracellular tyrosine for growth, as they can produce small amounts intracellularly. Methods: We investigate two therapeutic strategies using nanocapsules containing polyhemoglobin–tyrosinase (PolyHb–Tyr–nano) for action on (1) the intracellular activation of quercetin to o-quinone and (2) the depletion of intracellular tyrosine. We applied these strategies to the four cell lines listed above. Results: (1) PolyHb–Tyr–nano activates quercetin intracellularly, increasing o-quinone levels and reducing cancer cell viability. (2) PolyHb–Tyr–nano alone suppresses tumor growth by lowering intracellular tyrosine. Furthermore, PolyHb–Tyr–nano shows selective cytotoxicity, with an LD₅₀ of 0.7808 mg/mL in Hepa 1-6, compared with an extrapolated LD₅₀ of 84,181 mg/mL in the normal liver cells. In contrast, quercetin activation results in an LD₅₀ of 2.73 mg/mL in Hepa 1-6 and 74.18 mg/mL in normal hepatocytes. Conclusions: PolyHb–Tyr–nano offers dual therapeutic functions: (1) quercetin prodrug activation and (2) intracellular tyrosine depletion. Full article