Search Results (1,860)

Human skin is continuously exposed to microbial invasion and oxidative stress, highlighting the need for safe and effective natural skin-protective agents. This study aims to investigate the antibacterial, antioxidant, and anti-tyrosinase activities of methanolic leaf extracts of Syzygium nervosum collected from Chiang Mai (SNLM-CM) and Phayao (SNLM-PY), Thailand. LC–QTOF–MS analysis revealed distinct phytochemical profiles between the extracts, suggesting that geographical origin influenced their biological activities. Antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli was evaluated, together with studies of bacterial membrane integrity. Antioxidant capacity was assessed using ABTS, DPPH, FRAP, and ORAC assays, while anti-tyrosinase activity and cytotoxicity toward normal human dermal fibroblasts (NHDF) were determined by MTT assay. Both extracts exhibited potent antibacterial activity, particularly against Gram-positive bacteria (S. aureus and S. epidermidis) likely through membrane disruption, as evidenced by propidium iodide uptake, intracellular DNA and protein leakage, and scanning electron microscopy observations. SNLM-CM showed stronger antioxidant activity, whereas SNLM-PY demonstrated greater anti-tyrosinase activity. The extracts maintained high NHDF viability at concentrations below 100 µg/mL and retained antibacterial efficacy when incorporated into a cleansing gel formulation. Overall, S. nervosum leaf extracts exhibit promising antibacterial, antioxidant, and anti-tyrosinase activities, warranting further investigation to optimize their safety and efficacy for dermatological and cosmetic use. Full article

Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: A chalcone derivative containing naphthalene and toluene moieties (A) was synthesized from 2-acetonaphthone and p-tolualdehyde and subsequently converted into a novel 4,5-dihydro-1H-pyrazole-1-carbothioamide derivative (B) through reaction with thiosemicarbazide. The cytotoxicity of compounds A and B against K562 CML cells was evaluated using the MTT assay. The active compound was further investigated for cytotoxic selectivity using HL-60 acute myeloid leukemia (AML) cells and healthy PBMCs. Apoptotic effects in K562 cells were analyzed using Annexin V/ethidium homodimer staining, whereas ABL1 inhibitory activity was determined using the ADP-Glo kinase assay. The potential interaction between the active compound and ABL1 was assessed by molecular docking analysis. Results: Compound B displayed potent cytotoxic activity against K562 cells with an IC₅₀ value of 6.92 ± 1.14 µM and demonstrated selectivity toward leukemic cells over PBMCs (SI = 5.4). Treatment with compound B markedly induced apoptosis in K562 cells. In addition, compound B inhibited ABL1 activity in a concentration-dependent manner. Molecular docking studies revealed a favorable binding orientation within the ATP-binding pocket of ABL1. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) analysis predicted favorable pharmacokinetic properties for compound B. Conclusions: These findings demonstrate that compound B possesses cytotoxic, pro-apoptotic, and ABL1 inhibitory activities against CML cells and may serve as a promising lead structure for the development of novel therapeutic agents targeting CML. Full article

Zearalenone is a common mycotoxin that impairs reproductive function, particularly by damaging ovarian granulosa cells. This study investigated the protective effect and underlying mechanism of scutellarin against zearalenone-induced injury in porcine ovarian granulosa cells. Cells were isolated and identified by follicle-stimulating hormone receptor immunofluorescence. Cell viability, cell-cycle distribution, and related molecular changes were evaluated using the MTT assay, flow cytometry, qRT-PCR, and Western blot. Scutellarin showed no obvious cytotoxicity within the tested range and attenuated the zearalenone-induced reduction in cell viability. Flow cytometry analysis demonstrated that scutellarin alleviated zearalenone-induced cell-cycle disturbance. At the molecular level, scutellarin upregulated the expression of cell-cycle-related factors, including CDK1, CDK2, CDK4, and PCNA, and increased the expression of Wnt/β-catenin signaling-related proteins, including WNT5A, β-catenin, c-MYC, and CCND1. WNT5A knockdown further indicated that scutellarin-mediated regulation of PCNA, CDK1, and CDK4 is WNT5A-dependent, whereas its effect on CDK2 may involve a WNT5A-independent mechanism. These findings indicate that scutellarin alleviates zearalenone-induced granulosa cell injury partly through WNT5A-associated modulation of cell-cycle-related proteins, providing mechanistic insights for its protective effects. Full article

The present study investigates the pro- and anti-apoptotic responses of HepG2 liver cancer cells to Ornithogalum sigmoideum (O. sigmoideum) and Smilax excelsa (S. excelsa) extracts, aiming to identify their potential as anti-cancer agents. Methanolic extracts of O. sigmoideum and S. excelsa were prepared, and their phytochemical profiles were analyzed by Gas Chromatography–Mass Spectrometry (GC-MS). Cytotoxicity and IC50 values were determined in HepG2 cells using the MTT assay. The relative mRNA expression of apoptotic genes (BAX, BCL-2, and Caspase-3) was quantified by qPCR, and the treatment effect size was calculated using Cohen’s d. GC-MS analysis revealed distinct phytochemical profiles; S. excelsa was rich in phenolic compounds, while fatty acid esters and alcohols dominated Ornithogalum extracts. O. sigmoideum bulb extract exhibited the strongest cytotoxicity (IC50 = 125.57 µg/mL), followed by the leaves (IC50 = 156.43 µg/mL), whereas Smilax showed minimal toxicity (IC50 = 304.15 µg/mL). Mechanistically, the O. sigmoideum leaf extract showed gene expression patterns consistent with pro-apoptotic signaling, including upregulation of BAX and Caspase-3 mRNA. O. sigmoideum extracts, especially from leaf parts, exhibit significant cytotoxicity, and the transcriptomic profile is consistent with apoptotic pathway activation in HepG2 cells, positioning it as a candidate for further mechanistic investigation. Full article

Wound dressings play a crucial role in promoting tissue regeneration while protecting damaged tissue from microbial infections. The aim of this study is to produce antimicrobial PVA-chitosan membranes for wound dressing applications using Stevia rebaudiana Bertoni leaf extract (stevia) as a natural bioactive agent. Although widely recognized as a natural sweetener, stevia contains a high concentration of diterpene glycosides, particularly stevioside and rebaudioside A, together with phenolic compounds that contribute to its biological activities. Therefore, stevia was first evaluated against selected microorganisms and demonstrated effective antimicrobial activity. PVA-chitosan (P/Ch) membranes were prepared by solvent casting method by incorporating different amounts of stevia (P/Ch, P/Ch@20, P/Ch@40, and P/Ch@60). The antimicrobial activity of stevia was also successfully maintained in P/Ch membranes. Good antibacterial activity was observed against Bacillus subtilis and Escherichia coli, whereas the antifungal activity against Candida albicans was comparatively modest. Contact surface analysis showed complete bactericidal activity in Gram-negative and spore-forming bacteria. The cytocompatibility of the membranes was investigated by MTT assay. All formulations maintained a high cell viability (>80%) while the P/Ch@40 membrane increased the metabolic activity to above 100% at higher extract concentrations. In conclusion, stevia-incorporated membranes exhibited high antimicrobial activity, acceptable characteristic properties, and good cytocompatibility, suggesting that they are promising alternative biomaterials for tissue engineering applications. Full article

Four novel alkaloids, including three γ-lactam alkaloids (1–3) and one diketopiperazine (4), along with eight previously known compounds (5–12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the tentative stereochemical assignments of the side-chain double bonds in 2 and 3, were elucidated through comprehensive spectroscopic analysis and in comparison with the literature’s data. All isolated compounds were evaluated for their anti-leukaemic activities against human leukaemia cell lines K562 and RS4;11 using the MTT assay. Compounds 4, 6, 7, and 9–12 exhibited notable cytotoxic activities against both RS4;11 and K562 cell lines, with IC₅₀ values ranging from 5.02 ± 2.33 to 31.85 ± 0.50 μM. The results of Western blotting and Annexin V-FITC/PI staining elucidated that compounds 4, 7, and 10 could induce apoptosis in both RS4;11 cells and K562 cells. Full article

Background: Glioblastoma (GBM) is characterised by therapeutic resistance and high invasiveness, so the development of new treatments is essential. Oncolytic virotherapy using the vesicular stomatitis virus (VSV) is a promising approach as it is inherently tumour-selective and immunostimulatory. This study evaluated the antitumour efficacy of a recombinant VSV engineered to co-express mouse interleukin-12 and granulocyte-macrophage colony-stimulating factor (rVSV-dM51-mIL12-mGMCSF) using in vitro and in vivo U-87 MG models. Methods: The oncolytic activity of rVSV-dM51-mIL12-mGMCSF was evaluated in vitro against human U-87 MG and mouse GL-261 glioblastoma cells using flow cytometry (MOI 0.1) and MTT assays (MOIs 0.1 and 0.001). In vivo, tumour progression was monitored in U-87 MG xenograft mice for 30 days after inoculation. At the study endpoint, tumour tissues from treated and control animals were subjected to immunohistochemical (IHC) analysis; the H-score method was used to quantify expression of the Ki-67 proliferation marker, VSV glycoprotein (VSV-G), and mIL-12. Results: rVSV-dM51-mIL12-mGMCSF demonstrated oncolytic activity against both cell lines in vitro; however, its cytotoxicity was lower compared to the parental control virus (rVSV-dM51-GFP). In contrast, treatment in vivo resulted in greater tumour growth inhibition. IHC analysis revealed a significant reduction in the Ki-67 H-score alongside high levels of VSV glycoprotein and mIL-12 expression. These results confirm that, although the payloads do not enhance direct viral oncolysis in vitro, they significantly improve antitumour efficacy in vivo. Conclusions: rVSV-dM51-mIL12-mGMCSF effectively inhibited tumour growth in the U-87 MG xenograft model, supporting further evaluation of glioblastoma-directed oncolytic virotherapy. Full article

Amyloidosis encompasses a spectrum of diseases in which insoluble protein aggregates are deposited in various parts of the body, including the brain, giving rise to Alzheimer’s disease, prion disease, and Parkinson’s disease, and also being a manifestation of Type II diabetes. The soluble protein gets aggregated as insoluble plaques by an unknown phenomenon, leading to the disease. If an agent is developed that can dissociate or disintegrate these plaques, it can be proposed as a lead molecule for amyloid dissociation. In the present study, we have taken the aqueous extract of a herb, Shankhapushpi (Convolvulus pluricaulis), and synthesized zinc oxide nanoflowers (ZnO-NFs-Skp). The plant extract was characterized using phytochemical analysis, and the ZnO-NFs-Skp were characterized using various photophysical tools like dynamic light scattering, zeta potential, XRD, FTIR, and scanning electron microscopy (SEM). The in vitro cytotoxicity of the ZnO-NFs-Skp was assessed in the PC12 cell line using an MTT assay and a fluorescent dual-staining assay. The effect of ZnO-NFs-Skp on zebrafish embryos was evaluated for in vivo biocompatibility. Finally, the amyloid degradation of the ZnO-NFs, after incubation with preformed insulin amyloids, the model amyloid protein used for the amyloid study, was evaluated at different time intervals using the Thioflavin T fluorescence assay. The results indicated that the Shankhapushpi extract had alkaloids, coumarins, and glycosides. The hydrodynamic diameter of ZnO-NF-Skp was found to be 181 nm, and the zeta potential was −17.7 mV. SEM imaging showed a carnation flower-like morphology with a petal thickness of 30 ± 5 nm. The ZnO-NFs-Skp did not induce any toxicity up to a dose of 160 μg/mL, both in vitro and in vivo. The amyloid degradation study revealed 38% degradation of the IA, 24 h after incubation at 37 °C. SEM analysis also evidenced the degradation of IA. Compared to ZnO nanoparticles (18%), ZnO-NFs-Skp could degrade almost double (35%) the amount of IA after 12 h incubation, as shown by the ThT assay. Overall, the data suggested that Shankhapushpi-mediated ZnO-NFs (ZnO-NFs-Skp) are biocompatible and have a good capacity to degrade amyloids. In the future, amyloid degradation using Aβ-42 and the prion protein needs to be investigated. Full article

Isomangiferin is a natural C-glycosylated xanthone, an isomer of mangiferin. The biological properties of isomangiferin are not clearly known. The antioxidant effect of this xanthone was assessed with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) tests. Isomangiferin’s cytoprotective effects against menadione in human keratinocytes HaCaT were evaluated via an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. Additionally, the inhibition of elastase and hyaluronidase by isomangiferin was tested spectrophotometrically. Antielastase activity was analyzed in silico and by evaluating the degradation of elastin fibers and elastin in tendons using image analysis. The results indicated that the antioxidant properties of the tested xanthone were stronger than those of ascorbic acid (the IC₅₀ values for isomangiferin and ascorbic acid were 27.04 ± 1.8 and 164.6 ± 3.29 µM; 9.57 ± 0.05 and 35.83 ± 0.45 µM; and 70.44 ± 1.4 and 315.85 ± 4.49 µM in ABTS, DPPH and FRAP tests, respectively). Isomangiferin at a concentration of 95 µM (40 µg/mL) effectively protected HaCaT cells from death. This compound also demonstrated a moderate ability to inhibit hyaluronidase activity. The ability to inhibit elastase was demonstrated via image analysis and supported by docking studies, which indicated that isomangiferin binds with elastase not directly within the catalytic site but in the S4 subpocket. This study shows a promising direction for the development of new agents that mitigate oxidative stress-induced aging by protecting both elastin fibers and hyaluronic acid from degradation. Full article

Since lung cancer remains a leading cause of cancer-related mortality, effective adjunct strategies against this disease are needed. This study evaluated an extract prepared from organically cultivated Capsicum annuum treated with deep-seawater-derived ion minerals during cultivation (ODSW-CE) in Lewis lung carcinoma (LLC1) cells and LLC1 tumor-bearing mice. Targeted HPLC-DAD analysis identified and quantified lutein and β-carotene as representative carotenoids. ODSW-CE reduced MTT-derived cell viability and colony-forming ability in vitro and suppressed tumor growth in vivo. In tumor-bearing mice, ODSW-CE was associated with lower hematological inflammatory indices, reduced TNF-α and IL-1β levels in plasma and lung tissue, and attenuated histopathological alterations in tumor and lung tissues. These changes were accompanied by reduced expression of proteins associated with TLR4/MyD88/NF-κB signaling. ODSW-CE also modulated survival and apoptosis-related proteins, decreasing PI3K, p-Akt, and p-mTOR expression, increasing Bax and cleaved caspase-3 expression, and decreasing Bcl-2 expression. Additionally, in tumor tissue, Keap1 expression increased, whereas Nrf2, xCT, and GPX4 expression decreased. Overall, ODSW-CE suppressed LLC1 tumor growth and was associated with coordinated modulation of tumor-associated inflammatory signaling, survival pathways, apoptosis-related proteins, and redox defense. Full article

Background: Chemoresistance remains a major obstacle in managing cholangiocarcinoma (CCA). The cannabis plant contains several phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), which exhibit anticancer properties. However, to the best of our knowledge, their effects on CCA have not been previously investigated. This study aimed to explore the molecular mechanisms underlying the anticancer effects of CBD, CBG, and CBN in CCA cells. Methods: KKU-100 and KKU-452 cells were treated with varying concentrations of CBD, CBG, and CBN for 24 and 48 h. Cytotoxicity was assessed using the MTT assay, and half maximal inhibitory concentration (IC₅₀) values were calculated. KKU 452 cells were further analyzed for apoptosis, mitochondrial membrane potential (MMP), and Ki67 expression using flow cytometry. Proteomics profiling was performed to compare the effect of these cannabinoids with those of gefitinib and cisplatin. Results: Monotherapy with CBD, CBG, or CBN induced dose-dependent cytotoxicity at 24 and 48 h with lower IC₅₀ values than those of cisplatin and comparable efficacy to that of gefitinib. At low doses, CBD, CBG, and CBN induced early apoptosis, while higher doses triggered late apoptosis. MMP loss increased by 2.5-, 4.9-, and 1.7-fold, respectively, after 6 h. Ki67, highly expressed in KKU-452 cells (Ki67-positive ratio = 3.16 ± 0.16), was significantly reduced after the cannabinoid treatment, with Ki67-positive ratios of 0.38 ± 0.22, 0.38 ± 0.13, and 0.32 ± 0.23 for CBD, CBG, and CBN, respectively. Proteomics analysis identified 2781 proteins affected by CBD, CBG, CBN, cisplatin, and gefitinib. All three cannabinoids downregulated key upstream regulatory proteins (LARP1, TFEB, and BCR). Similar patterns of LARP1 and TFEB downregulation were also observed with cisplatin and gefitinib. CBN showed the closest similarity to cisplatin, followed by gefitinib, by targeting CDK4/6 and PCGEM1 proteins. CBD and CBG exhibited the greatest similarity to each other, also influencing MASTL expression. Conclusions: CBD, CBG, and CBN exhibit potential anticancer activity in CCA by suppressing proliferation, reducing Ki67 expression, and inducing apoptosis through MMP disruption. The identification of shared molecular targets, including LARP1 and TFEB, provides new mechanistic insight and supports the potential development of cannabinoid-based therapeutic strategies for cholangiocarcinoma. Full article

Paclitaxel (PTX), a taxane-derived chemotherapeutic agent, is frequently used in the treatment of breast cancer (BC). Its anticancer effects are primarily associated with microtubule stabilization, disruption of cell-cycle progression, and triggering of apoptotic cell death. In the present study, we investigated the effects of PTX on the expression of genes involved in cancer-related pathways, energy metabolism, and drug resistance in four molecularly distinct BC cell lines: MCF-7, BT-474, SK-BR-3, and MDA-MB-231. The half-maximal inhibitory concentrations (IC₅₀) of PTX in BC cell lines and the non-tumorigenic hTERT-HME1 breast epithelial cell line were determined by the MTT assay to assess cell cytotoxicity. BC cells were exposed to nine different concentrations of PTX for 24, 48, and 72 h to evaluate concentration- and time-dependent effects. Following treatment, total RNA was isolated and converted into cDNA, and RT-qPCR analysis was performed to investigate PTX-mediated alterations in the expression of genes associated with cancer-related pathways. The impact of PTX on the cell-cycle phase distribution and apoptotic cell death was evaluated by flow cytometry. Treatment with PTX for 48 h at concentrations of 12.60 nM in MCF-7, 5.09 nM in BT-474, 16.09 nM in SK-BR-3, and 36.66 nM in MDA-MB-231 cells reduced cell viability and increased apoptosis. PTX treatment also altered the expression of genes involved in apoptosis, cell-cycle regulation, angiogenesis, epithelial–mesenchymal transition, hypoxia-related signaling, energy metabolism, telomere maintenance, and therapy resistance. Collectively, these findings demonstrate that PTX elicits heterogeneous molecular and cellular responses across molecularly distinct BC cell lines, particularly in cell viability, apoptosis, metabolic regulation, and treatment response. These in vitro findings suggest potential molecular mechanisms that could explain why some cells are more sensitive to PTX than others, but further experimental and clinical validation is needed to confirm this. Full article

Conventional gelatin-based hydrogels lack responsiveness to the tumor microenvironment and exhibit low drug-loading efficiency for hydrophobic drugs, which limits their application in targeted cancer therapy. In this study, a reduction-responsive gelatin hydrogel was developed by grafting hydrophobic tert-butoxycarbonyl (Boc) groups onto gelatin chains, followed by EDC/NHS-mediated chemical cross-linking with L-cysteine dimethyl ester dihydrochloride, which contains disulfide bonds. The success of Boc grafting was confirmed by ¹H NMR, and free amine quantitative analysis. Rheological characterization confirmed the formation of a stable elastic network with controllable gelation times (5–12 min), demonstrating excellent injectability. Reduction-triggered degradation was observed in the presence of DTT or GSH, with the cleavage of disulfide bonds further evidenced by the detection of free sulfhydryl (-SH) groups via X-ray Photoelectron Spectroscopy. Microscale thermophoresis (MST) demonstrated measurable binding between Boc-modified gelatin and hydrophobic drugs, with dissociation constants (K_d) of 0.46 ± 0.37 μM for curcumin and 0.14 ± 0.14 μM for camptothecin. Drug loading assays show dramatically enhanced encapsulation efficiency for hydrophobic drugs (62.7% for curcumin, 66.6% for camptothecin) compared to unmodified hydrogels (7.2% and 16.8%, respectively). In vitro release kinetics follow the Korsmeyer–Peppas model, indicating a non-Fickian diffusion–erosion mechanism, and can be precisely tuned by gelatin concentration and reducing agent levels. Complete drug release occurs within approximately 325 min in 15 mM GSH. MTT and hemolysis assays confirm high biocompatibility. Collectively, this reduction-responsive system offers a promising platform for controlled, site-specific delivery of hydrophobic anticancer agents. Full article

This study investigates the combined effects of cisplatin (CDDP) and ε-viniferin (ε-VNF), a natural stilbenoid, on oxidative stress and apoptosis in HeLa cells. Cytotoxicity was assessed using the MTT assay, and IC₅₀ values were determined as 28 µM for CDDP and 21 µM for ε-VNF. Synergistic and antagonistic combination ratios of these doses were tested. Oxidative stress was evaluated via Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), Superoxide Dismutase (SOD), Reduced Glutathione (GSH), and Malondialdehyde (MDA). Apoptosis was measured using Annexin V-FITC/PI staining and caspase-9 activation assays. TAS levels significantly increased in all combination groups compared to the control (control: 266.7 ± 0.1 µmol/L; 20% combo: 2466.7 ± 1.0 µmol/L). OSI values decreased accordingly (control: 22.5 ± 7.1; 10% combo: 1.6 ± 0.5). GSH levels decreased in the combination groups (e.g., 20%: 0.8 ± 0.2 µM vs. control: 1.4 ± 0.1 µM), while MDA levels increased (20%: 3.8 ± 0.5 µM vs. control: 0.5 ± 0.1 µM). Caspase-9 positive cells increased markedly (20%: 55.0% vs. control: 13.2%), supporting activation of the mitochondrial apoptotic pathway. Annexin V analysis revealed increased late apoptosis (20%: 76.1%) and early apoptosis (20%: 17.0%). Full article

The growing demand for durable and environmentally sustainable bioactive textiles has created a need for functionalization strategies that minimize the release of active agents during use and laundering. In this study, a novel chloroxylenol-functionalized vinyl sulfone reactive dye was synthesized through the coupling of chloroxylenol with diazotized para-ester and characterized using FTIR, UV–Vis, ¹H-NMR, and ¹³C-NMR spectroscopy. The synthesized dye was applied to cotton fabric through an exhaust dyeing process, enabling simultaneous coloration and biofunctionalization in a single step. The dye exhibited high substantivity toward cotton, achieving dye exhaustion and fixation values of 95% and 91%, respectively. The dyed fabric demonstrated excellent antibacterial activity against Staphylococcus aureus (99.99%) and Escherichia coli (94%), antiviral activity of 87%, and antifungal activity of 86% before laundering. After 20 laundering cycles, antibacterial activity remained at 96% against S. aureus and 91% against E. coli, while antiviral and antifungal activities remained at 83% and 82%, respectively, confirming the durability of the bioactive functionality. Optical density measurements further verified substantial bacterial growth inhibition, whereas MTT assays using L929 fibroblasts demonstrated acceptable biocompatibility with cell viability exceeding 80% at the highest tested concentration. The dyed fabrics also exhibited excellent ultraviolet protection (UPF 119) with UVA and UVB blocking efficiencies of 99.35% and 98.98%, respectively, together with good colorfastness properties. Furthermore, UV–Vis analysis of the washing liquor indicated negligible dye release under the investigated laundering conditions. These findings demonstrate an effective and sustainable one-step strategy for producing durable multifunctional bioactive textiles while reducing processing steps and minimizing the potential release of active agents during use. Full article