Search Results (19)

This study investigates the valorization of Nephelium lappaceum (rambutan) shell, an agro-industrial byproduct, as a sustainable source of bioactive compounds through comprehensive chemical and functional characterization. Phytochemical profiles were determined using spectrophotometrics and HPLC-DAD-MS/MS, revealing a composition dominated by ellagitannins (e.g., geraniin, corilagin, chebulagic acid) and ellagic acid derivatives, alongside significant levels of total phenolics (25,982.2 mg/100 g DW) and anthocyanins. The extract exhibited strong antioxidant activity (DPPH IC₅₀ = 8.02 μg/mL; TEAC = 5703.92 μmol TE/g), consistent with its high phenolic content. Biological evaluation demonstrated antimicrobial activity against a broad panel of Gram-positive and Gram-negative bacteria, including multidrug-resistant strains, with greater efficacy against Gram-positive species (Staphylococcus aureus, MIC = 2.5 mg/mL). The extract also showed significant antibiofilm activity, achieving up to 93% inhibition. Antitumoral assays revealed selective cytotoxicity, particularly against HeLa cells (IC₅₀ = 260 μg/mL; TI = 11.5), indicating preferential effects on tumor over non-tumor cells. Importantly, hemolytic assays confirmed low toxicity, with negligible erythrocyte membrane disruption across tested concentrations. Overall, these findings highlight rambutan shell as a rich source of phenolic bioactives with multifunctional biological properties and favorable safety profile, supporting its potential application in nutraceutical and pharmaceutical formulations within a circular economy framework. This study aligns with SDG 3 and SDG 9 by promoting the valorization of agro-industrial waste as a source of safe bioactive compounds for health-related applications. Full article

Background/Objectives: The aberrant epigenetic landscape of cancer cells has attracted wide attention, motivating the search for new epigenetically active drugs both for anticancer therapy and for overcoming the drug resistance promoted by epigenetic changes. The use of epi-drugs in cancer therapy requires consideration of the influence of applied treatment on epigenetic regulation of gene expression. Therefore, it is reasonable to screen epigenetically active compounds among the drugs widely used in clinical oncology. Methods: We applied the HeLa TI cell-based assay to analyze the epigenetic activity of 40 drugs including 22 chemotherapeutic, 2 immunotherapeutic, 13 targeted, and 3 palliative agents. Reactivation of the epigenetically silenced GFP reporter gene integrated into the genome of HeLa TI cells was assessed using flow cytometry. Results: Statistically significant increases in the proportions of GFP-positive cells were demonstrated for the alkylating agent chlorambucil; the antimetabolites cytarabine, fluorouracil, gemcitabine, and pemetrexed; the platinum-based compounds cisplatin, and oxaliplatin; the topoisomerase inhibitor topotecan; and the antimicrotubule agents docetaxel, vincristine, and eribulin. Epigenetic activity was also detected for the targeted-therapy agents AZD8055, wortmannin, and cetuximab, as well as for the corticosteroid dexamethasone. Thus, epigenetic activity was revealed for 15 drugs widely used in cancer therapy, which possess different modes of action. Conclusions: Our findings show that many anticancer therapy agents modulate the epigenetic landscape of cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance. Full article

Biological activities, including cell viability, oxidative stress, genotoxicity/antigenotoxicity, and antimicrobial activity, were evaluated for a visible-light-responsive TiO₂-based ICT complex with dihydroquercetin (DHQ) and compared with pristine TiO₂, its inorganic component. Pristine TiO₂ did not induce cytotoxicity in MRC-5 or HeLa cells within the tested concentration range (1–20 mg/mL), while TiO₂/DHQ displayed a significant reduction in cell viability in both cell lines at higher concentrations (≥10 mg/mL). The analysis of reactive oxygen species (ROS) production revealed that TiO₂/DHQ significantly reduced ROS levels in both cell types (MRC-5 and HeLa), with HeLa cells showing a more substantial reduction at lower concentrations. Genotoxicity assessment using the comet assay demonstrated that TiO₂ induced DNA damage in MRC-5 cells, while TiO₂/DHQ did not, indicating that DHQ mitigates the genotoxic potential of TiO₂. Furthermore, TiO₂/DHQ exhibited antigenotoxic effects by reducing H₂O₂-induced DNA damage in MRC-5 cells, supporting its protective role against oxidative stress. Preliminary antimicrobial tests revealed that TiO₂/DHQ exhibits antimicrobial activity against E. coli under visible-light excitation, while TiO₂ does not. These findings suggest that the TiO₂-based ICT complex with DHQ with enhanced antioxidant properties can potentially serve as a safe, non-toxic biocide agent. Full article

Breast cancer (BC) is a complex disease driven by a combination of genetic mutations and epigenetic modifications. In particular, the overexpression of BET family proteins (BETs) has emerged as a key epigenetic aberration contributing to BC pathogenesis. CBL0137 (CBL), a small-molecule compound, has shown promise as an inhibitor of BETs in HeLa TI cells. In this study, we aimed to assess the anticancer effects of CBL in vitro and evaluate its impact on the expression of BETs in BC cells. Cells of three subtypes of BC (MCF7, MDA-MB-231, SKBR3) were used in this study. Cytotoxic effects were analyzed using the MTT assay. Effects on cell cycle and apoptosis were assessed using FACS with PI and FITC-Annexin staining. The level of BETs (BRD2, BRD3, BRD4) was determined by Western blotting. CBL demonstrated a significant reduction in BС cell viability with an IC50 value of approximately 1 μM for all cell lines after 72h of exposure and 20 μM after 24h. CBL treatment resulted in an increase in cells in the G2/M phase in MCF7 and SKBR3 cells after 24h and 72h of action, as well as in MDA-MB-231 cells after 24h. In MCF7 cells, the influence of CBL led to apoptotic changes characterized by a slight elevation in the early apoptotic population. Treatment of MDA-MB-231 cells with CBL resulted in a decrease in the expression of BRD2, BRD3, and BRD4 proteins, while treatment of MCF7 cells led to a reduction in BRD3 and BRD4 protein levels. No significant changes in the amount of BET proteins were observed in SKBR3 cells. In conclusion, the presented data offer valuable insights into the mechanisms of action of CBL, providing a basis for further investigation into its therapeutic potential in BC treatment. This research was funded by the RSF (no. 21-75-10163). Full article

The development of malignant tumors is caused by a complex combination of genetic mutations and epigenetic alterations, the latter of which are induced by either external environmental factors or signaling disruption following genetic mutations. Some types of cancer demonstrate a significant increase in epigenetic enzymes, and targeting these epigenetic alterations represents a compelling strategy to reverse cell transcriptome to the normal state, improving chemotherapy response. Curaxin CBL0137 is a new potent anticancer drug that has been shown to activate epigenetically silenced genes. However, its detailed effects on the enzymes of the epigenetic system of transcription regulation have not been studied. Here, we report that CBL0137 inhibits the expression of DNA methyltransferase DNMT3a in HeLa TI cells, both at the level of mRNA and protein, and it decreases the level of integral DNA methylation in Ca Ski cells. For the first time, it is shown that CBL0137 decreases the level of BET family proteins, BRD2, BRD3, and BRD4, the key participants in transcription elongation, followed by the corresponding gene expression enhancement. Furthermore, we demonstrate that CBL0137 does not affect the mechanisms of histone acetylation and methylation. The ability of CBL0137 to suppress DNMT3A and BET family proteins should be taken into consideration when combined chemotherapy is applied. Our data demonstrate the potential of CBL0137 to be used in the therapy of tumors with corresponding aberrant epigenetic profiles. Full article

Radiation-induced bystander response (RIBR) is a response induced in non-irradiated cells that receive bystander signals from directly irradiated cells. X-ray microbeams are useful tools for elucidating the mechanisms underlying RIBR. However, previous X-ray microbeams used low-energy soft X-rays with higher biological effects, such as aluminum characteristic X-rays, and the difference from conventional X-rays and γ-rays has often been discussed. The microbeam X-ray cell irradiation system at the Central Research Institute of Electric Power Industry has been upgraded to generate higher energy titanium characteristic X-rays (Ti_K X-rays), which have a longer penetration distance sufficient to irradiate 3D cultured tissues. Using this system, we irradiated the nuclei of HeLa cells with high precision and found that the pan-nuclear induction of phosphorylated histone H2AX on serine 139 (γ-H2AX) in the non-irradiated cells increased 180 and 360 min after irradiation. We established a new method to quantitatively evaluate bystander cells, using the fluorescence intensity of γ-H2AX as an indicator. The percentage of bystander cells increased significantly to 23.2% ± 3.2% and 29.3% ± 3.5% at 180 and 360 min after irradiation, respectively. Our irradiation system and the obtained results may be useful for studies of cell competition as well as non-targeted effects. Full article

Localized surface plasmon resonance (LSPR) is the cause of the photo-thermal effect observed in topological insulator (TI) bismuth selenide (Bi₂Se₃) nanoparticles. These plasmonic properties, which are thought to be caused by its particular topological surface state (TSS), make the material interesting for application in the field of medical diagnosis and therapy. However, to be applied, the nanoparticles have to be coated with a protective surface layer, which prevents agglomeration and dissolution in the physiological medium. In this work, we investigated the possibility of using silica as a biocompatible coating for Bi₂Se₃ nanoparticles, instead of the commonly used ethylene-glycol, which, as is presented in this work, is not biocompatible and alters/masks the optical properties of TI. We successfully prepared Bi₂Se₃ nanoparticles coated with different silica layer thicknesses. Such nanoparticles, except those with a thick, ≈200 nm silica layer, retained their optical properties. Compared to ethylene-glycol coated nanoparticles, these silica coated nanoparticles displayed an improved photo-thermal conversion, which increased with the increasing thickness of the silica layer. To reach the desired temperatures, a 10–100 times lower concentration of photo-thermal nanoparticles was needed. In vitro experiments on erythrocytes and HeLa cells showed that, unlike ethylene glycol coated nanoparticles, silica coated nanoparticles are biocompatible. Full article

In this article, a hybrid ${\mathrm{TiO}}_2$/Au/graphene layer-based surface plasmon resonance (SPR) sensor with improved sensitivity and capability for cancer detection is presented. The finite element method (FEM) was used for numerical analysis. The proposed SPR biosensor was structured based on the angular analysis of the attenuated total reflection (ATR) method for the detection of various types of cancer using the refractive index component. The resonance angle shifted owing to the increment of normal and cancerous cells’ refractive index, which varied between 1.36 and 1.401 for six different types of normal and cancerous cells. According to numerical results, the obtained sensitivities for skin (basal), cervical (HeLa), adrenal gland (PC12), blood (Jurkat), and breast (MCF-7 and MDA-MB-231) cancer cells were 210 deg/RIU, 245.83 deg/RIU, 264.285 deg/RIU, 285.71 deg/RIU, 292.86 deg/RIU, and 278.57 deg/RIU, respectively. Furthermore, the detection accuracy (DA), figure of merits (FOM), and signal-to-noise ratio (SNR) were also obtained, with values of 0.263 deg⁻¹, 48.02 RIU⁻¹, and 3.84, respectively. Additionally, the distribution of the electric field and the propagation of the magnetic field for resonant and non-resonant conditions of the proposed structure were illustrated. It was found that an enhanced field was exhibited on the surface of the plasmonic material for resonant conditions. We also measured the penetration depth of 180 nm using decayed electric field intensity. Furthermore, the impact of using a ${\mathrm{TiO}}_2$/Au/graphene layer was demonstrated. We further conducted analyses of the effects of the thickness of the gold layer and the effects of additional graphene layers on overall sensitivities for six different types of cancer. The proposed T${\mathrm{iO}}_2$/Au/graphene layered structure exhibited the highest overall sensitivity in terms of detecting cancerous cells from healthy cells. Moreover, the proposed sensor was numerically analyzed for a wide range of biological solutions (refractive index 1.33–1.41), and the sensor linearity was calculated with a linear regression coefficient (R²) of 0.9858. Finally, numerical results obtained in this manuscript exhibited high sensitivity in comparison with previously reported studies. Full article

The surface of Ti₃C₂ MXene nanosheets (TC NSs) was first modified with the antioxidants sodium ascorbate (SA) and dopamine (DA) (DSTC NS) to improve their stability in oxidative and hydration environments and thereby improve their bioapplications. This novel approach not only improved MXene stability by arresting oxidation but also increased the available functional groups for further functionalization with various biomolecules. The DSTC NSs were then sequentially conjugated with enzyme glucose oxidase (GOx) and photosensitizer Ce6 to render the obtained CGDSTC NSs with glucose starvation and photodynamic therapeutic properties and thus attain high efficiency in killing cancer cells through the cooperative effect. The as-synthesized CGDSTC NSs demonstrated tremendous photothermal effect with conversion efficiency of 45.1% and photodynamic (ROS generation) properties upon irradiation with 808 and 671 nm lasers. Furthermore, it was observed that the enzymatic activity of CGDSTC NSs increased upon laser irradiation due to enhanced solution temperature. During in vitro studies, the CGDSTC NSs exhibited cytocompatability to HePG2 and HeLa cells under nonstimulus conditions. However, they elicited more than 90% cell-killing efficiency in the presence of glucose and laser irradiation via the cooperative effect between starvation therapy and phototherapy. These results indicate that CGDSTC NSs could be used as potential therapeutic agents to eradicate cancers with no or few adverse effects. This surface modification approach is also simple and facile to adopt in MXene-based research. Full article

The first Z-stereoselective method was developed for the synthesis of unsaturated acids containing a 1Z,5Z,9Z-triene moiety in 61–64% yields using the new Ti-catalyzed cross-coupling of oxygen-containing and aliphatic 1,2-dienes as the key synthetic step. It was shown for the first time that trienoic acids with non-methylene-interrupted Z-double bonds show moderate cytotoxic activities against tumor cell lines (Jurkat, K562, U937, HL60, HeLa), human embryonic kidney cells (Hek293), normal fibroblasts and human topoisomerase I (hTop1) inhibitory activity in vitro. The synthesized acids efficiently initiate apoptosis of Jurkat tumor cells, with the cell death mechanism being activated by the mitochondrial pathway. A probable mechanism of topoisomerase I inhibition was also hypothesized on the basis of in silico studies resorting to docking. The activation and inhibition of the most versatile intracellular signaling pathways (CREB, JNK, NFkB, p38, ERK1/2, Akt, p70S6K, STAT3 and STAT5 tyrosine kinases) responsible for cell proliferation and for initiation of apoptosis were studied by multiplex assay technology (Luminex xMAP). Full article

Hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ (HAp) is an important bioactive material for bone tissue reconstruction, due to its highly thermodynamic stability at a physiological pH without bio-resorption. In the present study, the Ag:HAp and the corresponding Ag:HAp + D3 thin films (~200 nm) coating were obtained by vacuum deposition method on Ti substrate. The obtained samples were exposed to different UV irradiation times, in order to investigate the UV light action upon thin films, before considering this method for the thin film’s decontamination. The effects of UV irradiation upon Ag:Hap + D3 are presented for the first time in the literature, marking a turning point for understanding the effect of UV light on composite biomaterial thin films. The UV irradiation induced an increase in the initial stages of surface roughness of Ag:HAp thin film, correlated with the modifications of XPS and FTIR signals. The characteristics of thin films measured by AFM (RMS) analysis corroborated with XPS and FTIR investigation highlighted a process of recovery of the thin film’s properties (e.g., RMS), suggesting a possible adaptation to UV irradiation. This process has been a stage to a more complicated UVA rapid degradation process. The antifungal assays demonstrated that all the investigated samples exhibited antifungal properties. Moreover, the cytotoxicity assays revealed that the HeLa cells morphology did not show any alterations after 24 h of incubation with the Ag:HAp and Ag:HAp + D3 thin films. Full article

Titanium dioxide nanoparticles (nano-TiO₂), as a common nanomaterial, are widely used in water purification, paint, skincare and sunscreens. Its safety has always been a concern. Prior studies have shown that ultraviolet A (UVA) can exacerbate the toxicity of nano-TiO₂, including inducing cell apoptosis, changing glycosylation levels, arresting cell cycle, inhibiting tumor cell and bacterial growth. However, whether the combination of UVA and nano-TiO₂ cause cell necrosis and its mechanism are still rarely reported. In this study, we investigated the cytotoxicity and phototoxicity of mixture crystalline nano-TiO₂ (25% rutile and 75% anatase, 21 nm) under UVA irradiation in HeLa cells. Our results showed that the abnormal membrane integrity and the ultrastructure of HeLa cells, together with the decreased viability induced by nano-TiO₂ under UVA irradiation, were due to cell necrosis rather than caspase-dependent apoptosis. Furthermore, nano-TiO₂ and UVA generated the reactive oxygen species (ROS) and caused the mitochondrial permeability transition pore (mPTP) of HeLa cells to abnormally open. Cell viability was significantly increased after adding vitamin C (VC) or cyclosporin A (CsA) individually to inhibit ROS and mPTP. Clearance of ROS could not only impede the opening of mPTP but also reduce the rate of cell necrosis. The results suggest the possible mechanism of HeLa cell necrosis caused by nano-TiO₂ under UVA irradiation through the ROS-mPTP pathway. Full article

Atomic force microscopy (AFM) is an effective platform for in vitro manipulation and analysis of living cells in medical and biological sciences. To introduce additional new features and functionalities into a conventional AFM system, we investigated the photocatalytic nanofabrication and intracellular Raman imaging of living cells by employing functionalized AFM probes. Herein, we investigated the effect of indentation speed on the cell membrane perforation of living HeLa cells based on highly localized photochemical oxidation with a catalytic titanium dioxide (TiO₂)-functionalized AFM probe. On the basis of force–distance curves obtained during the indentation process, the probability of cell membrane perforation, penetration force, and cell viability was determined quantitatively. Moreover, we explored the possibility of intracellular tip-enhanced Raman spectroscopy (TERS) imaging of molecular dynamics in living cells via an AFM probe functionalized with silver nanoparticles in a homemade Raman system integrated with an inverted microscope. We successfully demonstrated that the intracellular TERS imaging has the potential to visualize distinctly different features in Raman spectra between the nucleus and the cytoplasm of a single living cell and to analyze the dynamic behavior of biomolecules inside a living cell. Full article

High throughput reconstruction of in vivo cellular environments allows for efficient investigation of cellular functions. If one-side-open multi-channel microdevices are integrated with micropumps, the devices will achieve higher throughput in the manipulation of single cells while maintaining flexibility and open accessibility. This paper reports on the integration of a polydimethylsiloxane (PDMS) micronozzle array and bidirectional electrokinetic pumps driven by DC-biased AC voltages. Pt/Ti and indium tin oxide (ITO) electrodes were used to study the effect of DC bias and peak-to-peak voltage and electrodes in a low conductivity isotonic solution. The flow was bidirectionally controlled by changing the DC bias. A pump integrated with a micronozzle array was used to transport single HeLa cells into nozzle holes. The application of DC-biased AC voltage (100 kHz, 10 V_pp, and V_DC: −4 V) provided a sufficient electroosmotic flow outside the nozzle array. This integration method of nozzle and pumps is anticipated to be a standard integration method. The operating conditions of DC-biased AC electrokinetic pumps in a biological buffer was clarified and found useful for cell manipulation. Full article