Search Results (4,169)

Coordination complexes play a crucial role in modern research. 4-benzopyranone-2-carboxylic acid is a fascinating class of molecules with numerous applications, including the synthesis of pharmaceuticals and valuable chiral compounds. Antibacterial and tuberculostatic medicines, HIV protease inhibitors, intermediates in organic synthesis, and organic catalysis are only a few of the biological applications of chiral complexes. In this study, the synthesis of four metal complexes, C₃₀H₂₈N₂NiO₁₂ [Ni(bzpyr)₂(py)₂(H₂O)₂] (I), C₃₀H₂₄CoN₂O₁₀ [Co(bzpyr)₂(py)₂(H₂O)₂] (II), C₂₀H₂₀O₁₃Zn [Zn(bzpyr)₂(H₂O)₃] (III), and C₃₀H₂₂CuN₂O₉ [Cu(bzpyr)₂(py)₂(H₂O)] (IV), is reported via direct reactions of 4-benzopyranone-2-carboxylic acid with metal salts and pyridine in anhydrous ethanol. Single-crystal X-ray diffraction analysis revealed that complexes I and II crystallize in the chiral space group P-1, whereas III and IV crystallize in the centrosymmetric space group P2₁/c. The structures of these complexes were further characterized by infrared spectroscopy, UV-Visible Diffuse Reflectance Spectroscopy, electrospray ionization mass spectrometry (ESI-MS), elemental analysis, nuclear magnetic resonance, electron paramagnetic resonance spectroscopy and single-crystal X-ray diffraction. In addition, the cytotoxic activities of complexes I–IV were evaluated against the human tumor cell lines K562, A549, HepG2, MDA-MB-231, and SW480, and molecular docking studies were conducted on the four complexes. Full article

Aflatoxin B1 (AFB1), deoxynivalenol (DON), and ochratoxin A (OTA) are common mycotoxins that frequently co-occur in cereals and pose potential risks to animal and human health. This study investigated the cytotoxic effects of AFB1, DON, and OTA, individually and in binary and ternary combinations, in four human-derived cell lines representing major target organs (Caco-2, HepG2, HK-2, and SK-N-SH). Individual toxin exposure revealed cell type–dependent sensitivity, with DON generally exhibiting the strongest cytostatic effect. Combined exposure analysis showed distinct interaction patterns across cell models, including antagonistic effects of AFB1 + OTA in most cell lines, dose-dependent interactions of DON + OTA, and low-dose synergistic effects in specific combinations. Overall, the results demonstrate that mycotoxin interactions are highly dependent on dose and target cell type, and that low-dose co-contamination may enhance toxicological risks, underscoring the importance of considering combined mycotoxin exposure in health risk assessment. Full article

Cotinus coggygria Scop., a member of the Anacardiaceae family, is known for its antiseptic, anti-inflammatory, and antitumor properties. In the present study, the ethyl acetate/water leaf extract of C. coggygria was evaluated for antioxidant and anticancer activities. The extract exhibited strong radical-scavenging potential, effectively neutralizing DPPH, ABTS^•+, and superoxide radicals in a concentration-dependent manner. The cytotoxic effects of the extract on human hepatocellular carcinoma HepG2 cells were also investigated. Flow cytometry revealed significant S-phase cell cycle arrest, while fluorescent microscopy and annexin V-FITC/PI staining demonstrated induction of apoptosis. DNA damage was confirmed by alkaline comet assay. Molecular docking was used to evaluate the binding affinity and inhibitory potential of penta-O-galloyl-β-D-glucose, a representative of gallotannins found in C. coggygria extracts, towards cyclin-dependent kinase 2 and checkpoint kinase 1. A high inhibition ability was demonstrated, which could explain the observed cell cycle block. Collectively, these findings suggest that C. coggygria extract exerts strong antioxidant capacity and selective antiproliferative activity in HepG2 cells. The anticancer effects of C. coggygria extract were associated with DNA damage, cell cycle arrest, disruption of mitochondrial membrane potential, and apoptosis induction. The results show the potential of the herb as a natural therapeutic agent for hepatocellular carcinoma. Full article

Background and Rationale: Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) is a climbing medicinal plant with long-standing ethnopharmacological use, particularly in inflammatory and hepatic disorders and cancer-related conditions. There is a knowledge gap regarding how wild versus cultivated ecotypes differ in chemotype, bioactivity, and safety, and how this might support or refine traditional use. Study Objectives: This study aimed to compare wild and cultivated ecotypes of T. crispa from the Nile Delta (Egypt) in terms of quantitative and qualitative phytochemical profiles; selected in vitro biological activities (especially antioxidant and cytotoxic actions); genetic markers potentially associated with metabolic variation; and short-term oral safety in an animal model. Core Methodology: Standardized extraction of plant material from wild and cultivated ecotypes. Determination of total phenolics, total flavonoids, and major phytochemical classes (alkaloids, tannins, terpenoids). Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC₅₀ determination). Cytotoxicity against human cancer cell lines, with emphasis on HepG2 hepatoma cells and calculation of IC₅₀ values. Targeted genetic analysis to detect single-nucleotide polymorphisms (SNPs) in the gen1 locus that differentiate ecotypes. A 14-day oral toxicity study in rats, assessing liver and kidney function markers and performing histopathology of liver and kidney tissues. Principal Results: The wild ecotype showed a 43–65% increase in total flavonoid and polyphenol content compared with the cultivated ecotype, as well as substantially higher levels of key alkaloids, particularly berberine (around 12.5 ± 0.8 mg/g), along with elevated chlorogenic acid and borapetoside C. UHPLC-MS and NMR analyses confirmed the identity of the main bioactive constituents and defined a distinct chemical fingerprint for the wild chemotype. Bioassays demonstrated stronger antioxidant activity of the wild extract than the cultivated one and selective cytotoxicity of the wild extract against HepG2 cells (IC₅₀ ≈ 85 µg/mL), being clearly more potent than extracts from cultivated plants. Genetic profiling detected a C → T SNP within the gen1 region that differentiates the wild ecotype and may be linked to altered biosynthetic regulation. The 14-day oral toxicity study (up to 600 mg/kg) revealed no evidence of hepatic or renal toxicity, with biochemical markers remaining within physiological limits and normal liver and kidney histology. Conclusions and Future Perspectives: The wild Nile-Delta ecotype of T. crispa appears to be a stress-adapted chemotype characterized by enriched levels of multiple bioactive metabolites, superior in vitro bioactivity, and an encouraging preliminary safety margin. These findings support further evaluation of wild T. crispa as a candidate source for standardized botanical preparations targeting oxidative stress-related and hepatic pathologies, while emphasizing the need for: More comprehensive in vivo efficacy studies. Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species. Full article

Six new diterpenoids, including two verticillane ghardaqenoids A–B (1–2) and four dolabellane ghardaqenoids C–F (3–6), were isolated from the soft coral Heteroxenia ghardaqensis collected in the South China Sea. The structures of ghardaqenoids A, D, and E (1, 4, 5) were determined by X-ray diffraction. Ghardaqenoids B, C, and F (2, 3, 6) were identified on the basis of NMR data, DP4+, and ECD spectral data. In particular, compound 6 exhibited strong in vitro lipid-lowering activity in free fatty acid (FFA)-induced HepG2 cells and liver organoids. Further mechanistic studies revealed that compound 6 regulated AMPK-related proteins and genes, thereby inhibiting the accumulation of triglycerides (TG) and total cholesterol (TC). These findings suggested that pharmacological AMPK activation serves as a promising role in lipid-lowering therapeutic strategies. Full article

The increasing use of Technology-Critical Elements (TCEs) in modern technology has led to widespread environmental release, raising questions about their biological effects, as emerging evidence suggests significant toxicity. We investigated the effects of three technology-critical elements, Indium oxide (In₂O₃), Lanthanum nitrate hexahydrate (La(NO₃)₃·6H₂O) and Cerium(III) nitrate hexahydrate (Ce(NO₃)₃·6H₂O), on human dermal fibroblasts (BJ) and hepatocarcinoma cells (HepG2), assessing their uptake, impact on viability, and induced cellular stress responses, quantified by markers of inflammation, oxidative stress, and membrane damage. Our results show a strong differential susceptibility: normal BJ fibroblasts proved vulnerable, whereas HepG2 cells were highly resistant. This divergence occurred despite substantial and comparable accumulation of all three TCEs in both cell lines, indicating that toxicity is uncoupled from the magnitude of the uptake. Mechanistically, the differential toxicity correlated strongly with opposing antioxidant responses. Additionally, low concentrations of cerium (III) nitrate (12.5–50 µg/mL) uniquely stimulated the proliferation of HepG2 cells (up to 129% of control). While these findings identify multiple mechanistic hazards regarding the potential of low-level technology-critical element exposure, they must be interpreted cautiously and warrant further investigation in more complex biological models. Full article

Background/Objectives: Compensated advanced chronic liver disease (cACLD) affects millions and carries risk for portal hypertension, large varices, and clinical decompensation. The HepQuant DuO^® test provides a blood-based assessment of liver function and physiology, generating a disease severity index (DSI) validated for risk stratification. A retrospective, real-world, observational analysis was conducted to evaluate the utility of HepQuant DuO’s DSI cutpoint (18.3) in guiding endoscopy and clinical management decisions for patients with cACLD in the United States. Methods: De-identified data from 87 cases with cACLD were extracted from physician-provided Statements of Medical Necessity documenting the reasons for the HepQuant DuO test. The primary endpoint was concordance of endoscopy decisions with DSI ≤ 18.3 (avoid) or >18.3 (proceed). The secondary endpoint was concordance of clinical management intensity with the same cutpoint. Results: Among the 55 cases analyzed for endoscopy decisions, overall concordance with DSI 18.3 was 93% (p < 0.001 by Fisher’s exact test): 96% of cases with DSI ≤ 18.3 avoided endoscopy, and 90% with DSI > 18.3 underwent endoscopy. For the 45 cases assessing management intensity, overall concordance was 89% (p < 0.001): 90% of cases with DSI ≤ 18.3 had reduced follow-up, and 89% with DSI > 18.3 had intensified management. The cohort exhibited broad functional heterogeneity not captured by standard labs or elastography. Conclusions: HepQuant DuO’s DSI cutpoint 18.3 demonstrated strong concordance with real-world clinical decisions, supporting its utility for risk stratification, optimizing endoscopy use, and tailoring management in cACLD. Full article

Background/Objectives: Elevated circulating non-esterified fatty acids (NEFAs) are closely associated with hepatic inflammatory injury in dairy cattle, simultaneously with the entry of lipopolysaccharide (LPS) into the liver. This study aimed to investigate the synergistic effects of NEFAs and LPS on pyroptosis in bovine hepatocytes. Methods: Primary bovine hepatocytes were allocated into control, NEFA, NEFA + LPS, NEFA + LPS + Caspase-1 inhibitor, and NEFA + LPS + NLRP3 inhibitor groups. Levels and activation of pyroptosis-related markers (NLRP3, ASC, Caspase-1, GSDMD, IL-18 and IL-1β) were measured. Results: NEFAs alone upregulated these markers in a dose-dependent manner. Compared to NEFAs alone, NEFA + LPS co-treatment significantly enhanced levels of the markers, increased IL-1β secretion, and promoted NLRP3/Caspase-1 co-localization and Caspase-1activity. Notably, these effects of NEFA + LPS were attenuated by the NLRP3 or Caspase-1 inhibitors. Similar results were obtained when repeating the experiments in carcinoma HepG2 cells. Also, a random liver section from the subclinical ketotic cows displayed a higher fluorescence intensity of NLRP3 and Caspase-1 and stronger co-localization than that from a healthy cow. Conclusions: NEFAs and LPS synergistically contribute to pyroptosis in bovine hepatocytes by enhancing NLRP3 inflammasome assembly and subsequent Caspase-1 activation, providing a potential target for mitigating hepatic injury. Full article

Background/Objectives: Plants of the Crassulaceae family have been utilized in traditional medicine because of their medicinal properties. Crassula capitella, an ornamental succulent plant, has not yet received significant attention from physiochemists or pharmacologists. The objective of this study was to investigate the in vitro phytochemical properties and biological activity of methanolic extracts obtained from the leaves (CCLE) and inflorescences (CCIE) of C. capitella. Methods: Phytochemical screening included GC/MS analysis. The in vitro investigation of biological properties includes the assessment of antibacterial activity, utilizing disk diffusion assays and measuring MIC and MBC values for Gram-positive and Gram-negative bacteria. Antioxidant properties were determined through IC50 values in DPPH and ABTS assays. Cytotoxicity properties were evaluated using the MTT assay in MCF-7 and HepG2 cells, along with an analysis of apoptosis gene expression. Additionally, the antidiabetic effects were examined through α-amylase or α-glucosidase inhibition assays. Results: GC/MS analysis revealed distinct differences. CCLE contained more terpenoids such as betulinaldehyde (30.53%) followed by lupeol (19%) and betulin (4.07%), whereas CCIE was rich in fatty acids. The TPC and TFC of CCIE (88.17 mg GAE/g and 57 mg QE/g) were significantly greater than those of CCLE. Compared with CCLE, CCIE exhibited greater antibacterial properties (MIC values of 6.25 µg/mL toward S. aureus), greater antioxidant properties (IC₅₀ values in the DPPH/ABTS assay), antitumor properties (IC₅₀ values of approximately 90–96 µg/mL), and antidiabetic properties (IC₅₀ values of 87–83 µg/mL in the α-amylase/α-glucosidase assay). Both bioactive extracts induced apoptosis in cancer cells by downregulating the expression of the tumorigenesis genes bcl-2 and bcl-xL. Conclusions: The findings provided the first evidence about the evaluated the potential antibacterial, antioxidant, anticancer, and antidiabetic activities of C. capitella, which is attributed to its robust chemical composition and position it as a compelling candidate for further in vivo and sub-clinical applications. Full article

Chalcone-based derivatives were designed as dual-acting ligands targeting the histamine H₃ receptor (H₃R) and monoamine oxidase B (MAO-B), based on the lead compound DL76. Three series of compounds (1–18) were synthesised and characterised, including simple chalcones (1–9) and piperidinyl chalcones (10–18). All piperidinyl derivatives exhibited nanomolar affinity for human H₃R (hH₃R), with compounds 10–12 achieving K_i values ≤ 30 nM. Simple chalcones showed potent human MAO-B (hMAO-B) inhibition (IC₅₀: 0.85–337 nM), especially 3,4-dichloro derivatives. Compound 15 was the most active hybrid, with a K_i of 46.8 nM for hH₃R and an IC₅₀ of 212.5 nM for hMAO-B. Molecular docking and 250 ns simulations revealed stabilising interactions at both binding sites and clarified structural features behind dual activity. Preliminary ADMET profiling showed low Caco-2 permeability and rapid microsomal metabolism, mainly via hydroxylation. Compound 15 exhibited micromolar cytotoxicity in SH-SY5Y and HepG2 cells, induced G2/M arrest, disrupted mitochondrial homeostasis, and was genotoxic in Peripheral Blood Mononuclear Cells (PBMCs). Additionally, for H₃R ligands (15, DL76, pitolisant), the study reports the first use of Surface Plasmon Resonance Microscopy (SPRM) to assess their interactions with this receptor. Therefore, piperidinyl chalcones show promise as ligands with dual action on H₃R and MAO-B, useful in the treatment of neurodegeneration and/or CNS cancers. Full article

In 2020, a dairy farm in northwest Germany reported several cows with severe respiratory disease, fever, and reduced milk production. Multiple direct and indirect diagnostic methods were used to identify the cause of the disease. However, the pathogens detected could not be correlated with the severity of the clinical symptoms, so further diagnostic steps were taken. Blood and nasal swab samples were examined using next-generation sequencing (NGS) as part of a metagenomic analysis. For the first time in Germany, Hepacivirus bovis genotype 2 was detected. Real-time RT-PCR assays confirmed the presence of BovHepV genotypes 1 and 2 in the herd between 2020 and 2023. Analyses of complete and partial genome sequences demonstrated the presence of different virus variants in the herd over several years. In addition, the sequence data indicated that cattle can be reinfected with viruses belonging either to different BovHepV subtypes or to the same subtype. Although no direct link could be established between the detection of bovine hepaciviruses and the observed clinical symptoms, the PCR and sequence data obtained provide valuable insights into the epidemiology and pathogenesis of BovHepV infections. Full article

Extensively drug-resistant (XDR) bacteria pose a serious global public health threat due to their high levels of resistance to multiple classes of antibiotics. This study aimed to characterize bacterial isolates obtained from clinical samples, evaluate their antibiotic resistance patterns, and investigate the antimicrobial and anticancer potential of essential oils (EOs) and their nanoemulsions (NEs). A total of 175 bacterial isolates were collected from various clinical sources, identified, and subjected to antibiotic susceptibility testing using both conventional methods and the VITEK^® 2 system. Among these, nine isolates were identified as extensively drug-resistant. Among the tested EOs, carvacrol exhibited the strongest antibacterial activity, with minimum inhibitory concentrations (MICs) ranging from 14 to 35 µg/mL, compared to 8 to 19 µg/mL for meropenem. To enhance its stability and efficacy, carvacrol nanoemulsions (CANE) were prepared via ultrasonication and characterized using zeta potential measurements, which indicated a positive surface charge of +14.2 mV, while dynamic light scattering (DLS) analysis revealed a narrow size distribution with a mean hydrodynamic diameter of 411.3 nm. High-resolution transmission electron microscopy (HR-TEM) showed spherical droplets ranging from 18 to 144 nm in size, with an average diameter of 69 ± 28 nm. The nanoemulsion formulation significantly enhanced antibacterial activity, with MICs reduced to 11 ± 0.0–23 ± 0.21 µg/mL, compared to 14 ± 0.13–35 ± 0.11 µg/mL for pure carvacrol oil. Gas chromatography–mass spectrometry (GC–MS) analysis identified major active constituents, including thymol, methoxyphenyl, estragole, and D-limonene, which are likely contributors to the observed antimicrobial and anticancer effects. In addition, carvacrol nanoemulsions demonstrated potent cytotoxicity against multiple human cancer cell lines (HepG2, MCF-7, PC-3, and Caco-2) while showing minimal toxicity toward normal cells. Confocal microscopy further confirmed apoptosis induction in treated cancer cells, suggesting a mitochondria-mediated apoptotic pathway. In conclusion, this study highlights the strong therapeutic potential of essential oils—particularly carvacrol and its nanoemulsion formulation—as dual-action agents exhibiting broad-spectrum antibacterial activity against XDR pathogens and selective cytotoxicity against cancer cells. Full article

Background/Objectives: Microalgae are recognized as prolific producers of bioactive metabolites with pharmaceutical potential. This study aimed to isolate and characterize cytotoxic constituents from selected cytotoxic microalgae, collected in Hue city, Vietnam. Methods: Microalgal samples were collected from freshwater bodies, morphologically identified, and maintained in laboratory culture. Thirteen strains were successfully isolated and cultivated in BG11, Z8, and BBM media to determine optimal growth conditions. Cytotoxic effects of extracts/compounds were determined using the sulforhodamine B assay on human lung cancer (SK-LU-1) and human liver cancer (HepG2) cell lines. The methanol extract was partitioned with n-hexane and CH₂Cl₂, followed by extensive chromatographic separation and HPLC purification to afford twelve compounds, including two new and ten known compounds. The structures were elucidated by HR-ESI-MS and NMR spectra, chemical methods, and comparing compounds in the literature. Results: From the phytoplankton samples collected across six freshwater bodies in Hue city, Vietnam, thirteen microalgal strains were successfully isolated and purified under laboratory conditions. These strains were morphologically and taxonomically identified to be Microcystis aeruginosa HU05, Microcystis viridis HU13, Anabaena circinalis HU08, Aphanizomenon flos-aquae HU02, Dolichospermum smithii HU04, Calothrix braunii HU14, Nostoc muscorum HU12, Nostoc punctiforme HU11, Raphidiopsis raciborskii HU03, Lyngbya spiralis HU15, Planktothrix stagnina HU16, Phormidium subtilis HU06, and Scenedesmus quadricauda HU07. All methanol extracts of those microalgae were evaluated for cytotoxic activity. The MeOH extracts of M. viridis (HU13) and D. smithii (HU04) exhibited significant cytotoxic effects, with IC₅₀ values of 6.19 ± 0.80 and 4.89 ± 0.76 µg/mL for M. viridis, and 9.51 ± 0.84 and 8.32 ± 0.94 µg/mL for D. smithii against SK-LU-1 and HepG2 cell lines, respectively. Furthermore, chemical studies of D. smithii HU04 led to the isolation of two new compounds, smithioside A (1) and smithioside B (2) and ten known ones, 3,4,5-trimethoxyphenyl-1-O-β-D-glucopyranoside (3), 4′-hydroxy-3′-methoxyphenol-β-D-[6-O-(4″-hydroxy-3″,5″-dimethoxylbenzoate)]-glucopyranoside (4), 4′-hydroxy-2′,6′-dimethoxyphenol 1-O-β-D-(6-O-syringoyl)glucopyranoside (5), mallophenol B (6), pisoninol II (7), guaiacylglycerol (8), (E)-asarone (9), deacetylsarmentamide B (10), (E)-2-hexenyl-β-D-glucopyranoside (11), and 5,6-dihydropyridin-2(1H)-one (12). The cytotoxic activity of all isolated compounds was also evaluated against SK-LU-1 and HepG2 cancer cell lines. Compound 12 showed the strongest activity, with IC₅₀ values of 9.13 ± 0.89 µM (SK-LU-1) and 7.64 ± 0.46 µM (HepG2). Compounds 5 and 6 exhibited moderate cytotoxic activity on both human cancer cell lines with IC₅₀ values ranging from 25.99 to 51.47 µM. Conclusions: These results highlight the potential of Dolichospermum smithii HU04 as a source of bioactive compounds, particularly in anticancer applications. These findings suggest that D. smithii HU04 extracts could be developed for therapeutic purposes targeting cancer. Full article

Copper(II) complexes have great potential as antitumor and antimicrobial agents, and their coumarin derivatives bearing histamine substituents possess versatile structural and biological properties. The present article describes the synthesis of novel copper(II)–coumarin–histamine complexes and ligands and their characterization by IR, NMR, X-ray diffraction, and elemental analysis. Their antimicrobial activity (MIC, MBC/MFC) was tested against 11 reference strains. Cytotoxicity was evaluated using the MTT assay against 15 selected cancer cell lines and normal HMEC-1 cells. It presents three new ligands and three new complexes with copper(II) ions and selected histamine-containing coumarin derivatives. The new copper(II) complexes demonstrated markedly higher anticancer activity than their corresponding ligands across all evaluated cancer cell lines. The highest anticancer activity against the Hep3B liver cancer cell line was demonstrated by the copper(II) complex (3b), which also showed the strongest inhibition of S. epidermidis ATCC 12228 and S. aureus ATCC 6538. The copper(II) ions play a crucial role in the antitumor activity of these derivatives. Despite limited antimicrobial effects, the tested complexes, particularly 3a and 3b, demonstrate promising anticancer potential, especially against the Hep3B cancer cell line. Only 3b demonstrated antimicrobial activity against S. epidermidis ATCC 12228 and S. aureus ATCC 6538. Full article