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Recent studies have implemented a calculated additive toxicity (CAT) approach that sums measured disinfection byproduct (DBP) concentrations weighted by their respective in vitro bioassay potencies to estimate their associated risk in disinfected waters. In this study, the CAT approach was used to systematically investigate 21 regulated and unregulated DBPs measured in drinking water at the household level. Water samples from the tap were collected from over 120 randomly selected participants supplied by eight public water systems using four distinct source water types, two types of disinfection processes, and across two seasons. The purpose of this study was to compare CAT using multiple biological end points, examine household variability, identify DBPs driving toxicity, and assess if current regulated DBPs are adequate predictors of unregulated DBPs. Our results support the significance of unregulated DBPs, particularly haloacetonitriles and iodoacetic acid, as drivers of toxicity. Simple linear models between regulated versus unregulated concentrations and CAT were overall weak with 67% considered poor (r 2 < 0.3). These results reveal that current regulatory monitoring approaches may not be adequately capturing true household exposure due to higher contribution of unregulated DBPs to CAT and poor predictability between regulated and unregulated DBP-mediated CAT.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.

BackgroundNatural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product.MethodsStarting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach.ResultsCalculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment.ConclusionsOverall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administrations Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

[Display omitted] Bacterial infection of biomedical implants is an important clinical challenge, driving the development of novel antimicrobial materials. The antibacterial effect of vertically aligned graphene as a nanoarray coating has been reported. In this study, vertically aligned graphene nanosheets decorated with silver nanoparticles were fabricated to enhance antibacterial effectiveness. Vertical graphene (VG) nanoflakes were synthesized by plasma-enhanced chemical vapor deposition (PECVD). Ag nanoparticles were attached to the surface of VG through using polydopamine and achieving a sustained release of Ag+. VG loaded with Ag nanoparticles (VGP/Ag) not only prevented bacterial adhesion for a long time, but also exhibited good biocompatibility. This work provides a new venue for designing antibacterial surfaces based on combination of graphene nanoarrays with other nanomaterials, and the results indicate that this approach could be very successful in preventing implant associated infections. [ABSTRACT FROM AUTHOR]

An efficient column chromatography of the CH2Cl2/MeOH crude extract from the soft coral Litophyton mollis (Macfadyen, 1936) yielded seven steroids, including five 4α-methylated steroids (1–5) and two 19-oxygenated steroids (6–7). Notably, both compounds 3 and 7 are new, identified as (22E)-4α,24-dimethyl-5α-cholesta-22,24(28)-dien-3β,8β-diol (3) and (22E,24R)-7β-acetoxy-24-methyl-cholesta-5,22-dien-3β,19-diol (7). The chemical structures and relative configurations were elucidated through comprehensive spectroscopic analyses, including 1D and 2D NMR, as well as HRESIMS analysis. The cytotoxicity of metabolites 1–7 was evaluated against three cancer cell lines: MCF-7, HepG2, and NCI-1299. Remarkably, metabolites 6 and 7 exhibited strong cytotoxic activity against MCF-7, with IC50 values of 8.6 and 8.4 μM, respectively, while also showing moderate effects against NCI-1299, with IC50 values of 15.7 and 15.1 μM, respectively. Additionally, steroids 4 and 5 displayed weak cytotoxicity against all three cell lines, with IC50 values in the ranges of 34.7–37.5 and 30.8–46.3 μM, respectively. [ABSTRACT FROM AUTHOR]

Borate bioactive glasses are an auspicious material for tissue engineering applications due to their enhanced dissolution rate, bioactivity, and capacity to integrate therapeutic ions. In this study, borate-based S49B4 bioactive glass doped with silver at mass fraction of 0.5, 1, and 3 wt% were studied for bioactivity, degradation, antibacterial, and cytocompatibility. Thermogravimetric analysis revealed that the bioactive glasses were thermally stable between 600 and 700 °C. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the successful synthesis of an amorphous phase of the doped borosilicate bioactive glasses and the incorporation of silver ion crystals within the structure, as well as associated contributions from borate and silicate network formers in the borosilicate bioactive glass. Morphological evaluation revealed that the borosilicate bioactive glasses exhibit a uniform and spherical shape across all formulations, with the mean particle size varying from 65 to 76 nm. An in-vitro acellular bioactivity in simulated body fluid medium showed that increasing the silver content increased the degradation rate and pH. Besides, scanning electron microscopy and Energy dispersive X-ray spectroscopy analysis revealed an upsurge in apatite production on the BBGs' surfaces as well as incremental Calcium-Phosphate ratio values of 1.50, 1.65 and 1.70 as the silver content increases. The antibacterial effect was tested against Escherichia coli and Staphylococcus aureus , while cytocompatibility was tested against human gingival epithelial cells. Silver integration at 1 wt percent yielded the most promising outcomes, which were particularly bactericidal at 79.8 % for Escherichia coli and 93.41 % for Staphylococcus aureus. Similarly, its Lactate Dehydrogenase percentage is significantly similar to the negative control employed in the study, indicating its biocompatibility. In contrast, 3 wt% silver exhibited the maximum bactericidal activity while also exhibiting mild cytotoxicity. In summary, our research indicates that elevated silver concentration enhances the bioactivity and antimicrobial characteristics of borosilicate bioactive glasses; nevertheless, a higher silver weight percent in this study also increases the possibility of cytotoxicity. It is therefore essential to carefully regulate the amount of silver doping at lower concentrations in order to maximize antibacterial action and minimize toxicity to human cells. The results presented here contribute to our understanding of the prospective use of silver doped borosilicate bioactive glasses as a possible material for tissue engineering applications. [ABSTRACT FROM AUTHOR]

• Essential oil from whole plant of Ocimum viride was studied for cytotoxicity against HL-60 cells. • Cytotoxicity was mediated by inducing apoptosis in the cells as observed by various microscopic and flow cytometry techniques. • Apoptotic pathway involved here was caspase −9 dependent intrinsic pathway. Initiator caspases −9 and −8 directly stimulated caspase-3 and −6, that ultimately leads to apoptotic activities in HL-60 cells. The present study discusses the apoptotic potential of essential oil from whole plant of Ocimum viride (EOV) against human promyelocytic leukemia HL-60 cells. IC 50 value of EOV on HL-60 cells was 0.087, 0.0503, and 0.034 µl/ml respectively at 6, 12, and 24 h. Several parameters were used to access the role of EOV in inducing apoptosis in human HL-60 cancer cells, including nuclear binding fluoroprobes, electron micrographs, DNA laddering, and annexin V-FITC/PI affinity assay. Quantification of BrdU incorporation was done to determine the degree of DNA damage. It was further determined that EOV has an effect on the DNA cell cycle and mitochondria, which was observed in the form of a prominent subdivision of G 0 peaks in the analysis of the DNA cell cycle, as well as a reduction in the mitochondrial membrane potential. A higher level of cytosolic cytochrome-c was associated with these events. Bcl-2 depletion and increase in ROS were also analysed. Both initiator caspases namely caspase-9 and -8 activated caspase-3 which eventually leads to apoptosis. These effects revealed that EOV has apoptosis inducing potential towards HL-60 cells and can be a promising candidate for further anticancer studies. [ABSTRACT FROM AUTHOR]

The anticancer potential of essential oils (EOs) has been widely investigated in several scientific studies. The use of these natural products can be an effective alternative to commercial medications that cause various side effects in cancer patients. In this context, this review critically discusses the anticancer potential of EOs obtained from Croton species of the Euphorbiaceae family. In addition, the ethnomedicinal uses, phytochemical constituents, and toxicity of these products were also reviewed. The literature was retrieved from different online databases, from the first report published in 2006 until June 2024. Traditionally, Croton species are commonly used to treat cancer in Asian, African, South American, and North American countries. The in vivo and in vitro anticancer activity of EOs from 17 species of Croton has been well reported in the literature, with emphasis on the efficacy of C. urucurana, C. argyrophyllus, C. matourensis, C. doctoris , and C. floribundus. Chemically, sesquiterpenes, monoterpenes, phenylpropene, monocyclic diterpene alcohol, and acetylenic fatty acid identified as major compounds in the EOs of these plants may be related to the observed anticancer activity. Regarding the mechanisms of action, it is likely that EOs from Croton species act in cell cycle arrest, DNA fragmentation, and apoptosis in different cancer cell lines. It is important to highlight that many of these EOs have not yet been evaluated for their biological safety in vivo toxicological tests, requiring caution when using these products. [Display omitted] • Essential oils from Croton species are rich in sesquiterpenes and monoterpenes. • 16 species of Croton are used for cancer treatment in traditional medicine. • Essential oils from Croton species exhibited anticancer potential in vitro and in vivo. • Essential oils from Croton species act in cell cycle arrest, DNA fragmentation, and apoptosis of cancer cells. [ABSTRACT FROM AUTHOR]

• LaEO demonstrated strong inhibition against MDR A. baumannii. • LaEO demonstrated low toxicity in mammalian cells. • LaEO can potentiate the antibiotic effect of Imipenem and Gentamicin. This study investigated the antimicrobial and cytotoxic effects of Lippia alba essential oil (LaEO) against five clinical isolates of multidrug-resistant A. baumannii from various infection sites in public hospitals in Recife, Pernambuco, Brazil. Gas chromatography-mass spectrometry analysis revealed 36 compounds in LaEO, with carvacrol (48.62 %), ρ-cymene (7.17 %), γ-terpinene (5.09 %), and thymol (5.00 %) as the most abundant constituents. LaEO exhibited potent inhibition of bacterial growth at MIC values ranging from 64 to 128 μg/mL, with MBC values similar to MIC. Additionally, interactions between LaEO and clinical antimicrobials (imipenem and gentamicin) demonstrated additive and synergistic effects when combined. Cytotoxicity assessment using the MTT assay on peritoneal macrophages revealed no significant difference in cell viability compared to the control, with a CC50 exceeding 512 μg/mL. Hemolytic activity on human red blood cells was minimal, with less than 2 % hemolysis observed at bacterially inhibitory concentrations. [ABSTRACT FROM AUTHOR]

• The results evidenced the presence of reducing sugars, alkaloids, coumarins, cardiac glycosides, sesquiterpene lactones, tannins and quinones. • Hydroalcoholic extract of glucose exhibited a higher concentration of phenolic compounds (6.6 μg GAE/mg). • Hydroalcoholic extract of molasses demonstrated a higher concentration of phytates (40 μg PAE/mg). • Both extracts exhibited similar amounts of saponins (2.55 ± 0.18 μg DGE/mg). • Both extracts exhibited antioxidant potential using the DPPH, ABTS and FRAP assays. • Both extracts exhibited no cytotoxicity at the concentrations tested, demonstrating 100 % viability (LC50 > 300 μg/mL). Cordyceps militaris is an entomopathogenic fungus with therapeutic potential in humans. The focus is on its hydroalcoholic extracts, which were obtained from biomass cultured in vitro in molasses. The media were subjected to a colourimetric chemical screening, an in vitro antioxidant potential evaluation by DPPH, ABTS and FRAP, and a cytotoxicity test by MTT assay. The results evidenced the presence of reducing sugars, alkaloids, coumarins, cardiac glycosides, and sesquiterpene lactones in both extracts. Additionally, tannins and quinones were identified exclusively in EHM. EHG exhibited a higher concentration of phenolic compounds (6.6 µg GAE/mg), while EHM demonstrated a higher concentration of phytates (40 µg PAE/mg), and both exhibited similar amounts of saponins (2.55±0.18 µg DGE/mg). The antioxidant potential of the extracts was assessed using the DPPH, ABTS and FRAP assays. The results demonstrated that EHG exhibited a greater effect in both assays, with 60.98 % and 80.70 % inhibition, respectively. In contrast, no significant difference was observed in the DPPH assay, with an average inhibition of 77.83 %. Both extracts exhibited no cytotoxicity at the concentrations tested, demonstrating 100 % viability (LC 50 > 300 µg/mL). It was concluded that the use of different carbon sources in both enriched media for the in vitro culture of C. militaris resulted in a modified chemical profile of the obtained biomass, which exhibited greater phytochemical complexity when cultured with molasses. In contrast, the biomass cultured with glucose showed a notable antioxidant potential in vitro , and no extract exhibited cytotoxicity in the tested cell lines. [ABSTRACT FROM AUTHOR]

ABSTRACT Cancer chemotherapy is continuously challenged by serious complications like pronounced side effects and multidrug resistance (MDR). Natural products, such as curcumin, offer promising alternatives due to their diverse biological applications and low toxicity. However, curcumin's clinical utility is limited by poor bioavailability, rapid metabolism, and non‐specific (PAINS) activity. Building on previous findings, this study explored the structural modification of curcumin‐inspired benzothiazepane derivatives in an attempt to enhance their therapeutic potential through modifications of the two peripheral (hetero)aromatic rings and the benzothiazepane scaffold. In this way, eight new 2‐(hetero)aryl‐4‐(4‐(hetero)aryl‐2‐oxobut‐3‐en‐1‐ylidene)benzothiazepanes and two 4‐thiobutan‐2‐one “double Michael addition” derivatives were synthesized and tested for cytotoxicity against a panel of eight cancer cell lines. The screening results indicated that bis‐(4‐hydroxyphenyl) analogs bearing a chlorinated benzothiazepane ring exhibited the highest potency and broad‐spectrum activity at the low micromolar range. Bis‐substitutions with 3‐pyridinyl and 2‐furyl groups showed less potent but more specific activity profiles, potentially reducing PAINS effects. 2‐Aminothiophenol‐derived double Michael addition products demonstrated increased broad‐spectrum activity, highlighting the importance of the free aniline amino group for targeted effects. This study underscores the potential of benzothiazepane derivatives as viable cancer cell cytotoxic agents and provides useful insights for future optimization and evaluation. [ABSTRACT FROM AUTHOR]

The current work highlights the preparation and antitumor activity of new benzimidazole derivatives of the natural product vanillin as a novel aromatase inhibitor. All the newly reported hybrids were characterized using sophisticated analytical techniques like NMR, IR, and mass spectrometry. The anticancer results against five cancer cell lines exhibited compounds 6, 7, and 8 to be most sensitive with IC50 in the range 0.36–8.65 μM, whereas doxorubicin showed IC50 of 4.74 μM and 3.69 μM toward breast cancer cells, MCF-7 and MDA-MB-231, respectively. Also, compound 6 revealed promising aromatase inhibition with IC50 0.064 μM while 7 and 8 with IC50 1.16 and 2.87 μM, respectively. Compound 9-bearing morpholine heterocycle revealed a better antibacterial effect on S. aureus with 22 mm (ZI) and MIC of 25 µg/disk than amoxicillin. These synthesized compounds displayed desirable pharmacokinetic properties and interacted with active sites of the aromatase enzyme in docking study. In conclusion, compound 6 was found to be a promising molecule as an aromatase inhibitor for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Summary: Cephalaria syriaca, known as cephalaria, is an annual, pilose plant with pink‐purple flowers growing wild in wheat fields. Viscoelastic properties of gluten‐free doughs can be improved by adding cephalaria. However, this addition results in some undesirable properties in bread such as bitter taste and dark internal colour. This study aimed to reduce these effects by obtaining cephalaria obtained from distilled water and ethanol extracts and to increase the potential use of extracts in bread production. Different proportions of water and ethanol extracts obtained from oil‐free cephalaria were added to bread by creating a model with Mixture Design, and the optimum concentration was determined by farinograph trials. The antioxidative, antimicrobial, and cytotoxic effects of extract and the effect of cephalaria on yeast activity were examined. Cephalaria extracts had no measurable antimicrobial effect and no antifungal effect on Rhizopus stolonifer, while an antifungal effect was found against A. niger and P. expansum. The IC50 value was found to be 4.15 mg mL−1 for ethanol extract while the water extract had no effect on cells. The addition of extract had no negative effect on the number of yeasts in sourdough fermentation. The study has improved the usage of cephalaria by using water and ethanol extracts in dough. [ABSTRACT FROM AUTHOR]

In this work, we describe the synthesis and characterisation of the starting materials [Cp*IrCl2]2 and four new ruthenium(II) and iridium(III) complexes half sandwich, contain the fragments [(p-cymene)Ru]2+ and [Cp*Ir]2+; (Cp* = CpMe4Et) of stoichiometry: [Cp*IrCl2(2-aminopyridine)] (I), [Cp*IrCl2(4-aminopyridine)] (II), [Cp*IrCl2(adenine)] (III) and [(p-cymene)RuCl2(adenine)] (IV). The new compounds have been characterised by C, H, and N elemental analysis; infrared and 1H NMR spectroscopy with 1H–1H COSY, ESI/TOF mass spectrometry and thermogravimetry. A study of the cytotoxicity of these compounds against the Hela cell line was carried out, with results indicating a low activity. [ABSTRACT FROM AUTHOR]

Nano‐sized bivalent metal complexes, specifically [M(L)2] with L = 2‐((E)‐((4,5‐dimethyl‐2‐(((E)‐4‐methylbenzylidene)amino)phenyl)‐imino)methyl)benzenethiol] (C23H22N2S) and M = Cu (II) (C1), Co (II) (C2), Ni (II) (C3), and Zn (II) (C4), underwent synthesis and subsequent characterization. Elemental analyses, infrared, NMR, mass, electronic, magnetic susceptibility, conductivity assessments, and X‐ray diffraction studies were used to assess our bivalent metal complexes. DFT studies were used to study the tautomeric equilibrium of the tridentate thio‐Schiff base ligand (HL), via the DFT\B3LYP method in connection with a 6–311G* correlation consistent basis set. Two tautomers, which are thione and thiol forms, were studied to estimate the predominant one. The metal formed four coordinated with the tridentate N2S donor thio‐Schiff base to form octahedral geometry complexes. The SEM, TEM, XRD, AFM, and EDX of the studied complexes unveiled distinct and strong diffraction peaks, signifying their crystalline nature and providing evidence of their particle sizes being within the nano‐size. The crystal sizes calculated for all complexes were determined to be ranging from 27.73 to 76.39 nm. The interactions between metal complexes and calf thymus DNA, and their potential for mimicking insulin activity, were investigated in a controlled lab setting by measuring their ability to inhibit alpha‐amylase. The antimicrobial potential of thio‐Schiff base ligand (HL) plus complexes (C1–C4) were tested. The viscosity and UV–Vis absorption determinations were utilized to assess the calf thymus DNA (CT‐DNA) interaction with the nano‐sized metal (II) chelates. Our flow cytometry data indicate significant levels of apoptosis and cell cycle arresting in both liver and breast cancer cell lines. [ABSTRACT FROM AUTHOR]

In recent years, nanotechnology has revolutionized various sectors, particularly in nanomedicine, where nanomaterials are used for diagnosis, monitoring, control, prevention, and treatment. Among these, silver nanoparticles (AgNPs) stand out due to their remarkable antimicrobial and cytotoxic properties. Traditional chemical synthesis of AgNPs poses significant environmental and health risks. This study introduces a novel, eco‐friendly synthesis method using royal jelly (RJ), a nutrient‐rich secretion from honeybees, to produce AgNPs with potent anticancer effects. Our research provides a detailed investigation into RJ‐mediated AgNPs' modulation of the VEGFa/PI3K/Akt/MMP‐2 pathway in HeLa and A549 cancer cell lines. AgNP characterization was performed by applying UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) in combination with selected area electron diffraction (SAED). Cell signaling system components were determined by ELISA analysis. The cells were subjected to staining with hematoxylin and eosin to visualize the treatment's effects. This study focuses on the green synthesis of AgNPs using RJ and its bioactivity against cancer cells. It provides a detailed characterization of the nanoparticles and examines their effects on cancer cells, specifically HeLa cervical cancer and A549 lung cancer cell lines. Green synthesized AgNPs demonstrate significant cytotoxic effects against HeLa and A549 cancer cell lines. The underlying molecular mechanisms contributing to their anticancer activity were elucidated. Our findings revealed a significant decrease in arginase activity upon exposure to AgNPs, accompanied by reductions in PI3K and phosphorylated and total Akt levels, indicative of pathway inhibition. Additionally, RJAgNP demonstrated a capacity to reduce nitric oxide levels and suppress angiogenesis‐related factors like VEGF and MMP‐2 and inflammation‐related factors like TNF‐α and COX‐2, thus impeding angiogenesis and metastasis. Moreover, our results shed light on the involvement of reactive oxygen intermediates (ROIs) in mediating apoptotic pathways, as evidenced by the increase in malondialdehyde (MDA) concentration and the corresponding decrease in Akt levels, ultimately promoting death in cancer cells. Our study contributes significantly to the field of nanomedicine and cancer therapy by introducing the use of green synthesis AgNPs using RJ and providing in‐depth insights into their molecular mechanisms of anticancer action. Our research findings demonstrate the anticancer potential of RJ‐AgNPs by targeting the VEGFa/PI3K/Akt/MMP‐2 pathway and modulation of ROS/RNS in cancer cells. [ABSTRACT FROM AUTHOR]

Synthesis of 5‐alkynyl furopyrimidine nucleoside analogs, with free‐ribose groups, was carried out, and their biological activity was evaluated. The substituents introduced at the C‐5 included propargyl and homopropargyl alcohols, 4‐methylphenyl (p‐tolyl), and 4‐pentylphenyl substituted alkynyl groups (56%–88%). Subsequently, alkyne function was coordinated to dicobalt hexacarbonyl unit, yielding the corresponding dicobalt hexacarbonyl 5‐alkynyl furopyrimidine nucleosides (51%–75%). All compounds contained 4‐pentylphenyl group attached at the C‐6 position of the bicyclic base, in line with most active antiviral structures. The antiproliferative effect of these modified nucleosides on cancer cells of different phenotypes was determined using in vitro studies. The tested compounds show antiproliferative effects with median inhibitory concentration (IC50) values of 16–23 and 9–15 μM for HeLa and K562 cells, respectively. The determination of reactive oxygen species (ROS) formation in K562 cells in the presence of modified nucleosides may suggest that the mode of action of the examined compounds may be attributed to the induction of oxidative stress. [ABSTRACT FROM AUTHOR]

Novel (E)-3-(dimethylamino)-1-(quinolin-3-yl)prop-2-en-1-one and (E)-3-(dimethylamino)-1-(quinolin-3-yl)but-2-en-1-one (2) were synthesized in excellent yields by reacting 3-acetylquinoline with DMF-DMA and DMA-DMA respectively. Subsequently, 2 were used as the precursors for the synthesis of 3-(pyrazolo[1,5-a]pyrimidin-7-yl)quinolines and 3-(5-methylpyrazolo[1,5-a]pyrimidin-7-yl)quinolines (4). All the synthesized compounds were subjected to structure elucidation and evaluated for their antiparasitic potential with special reference to their anti-malarial properties. The in-vitro studies of the synthesized compounds revealed moderate anti-malarial efficacy for compounds 4b, 4c, 4d, 4k, 4l and 4m. Compounds 4g and 4i showed highest activity displaying IC50 values of 2.10 and 2.77 μ M, respectively, for the chloroquine-sensitive strain of P. falciparum, and 4.26 and 2.87 μ M, respectively, for the chloroquine-resistant strain. The in-vitro cytotoxicity of the compounds showed CC50 as >500 µM and thus, found to be safe. Molecular docking of the novel series of ligand 4a–4n against the target protein P. falciparum PfLDH enzyme target (PDB ID 1LDG) revealed good binding energies ranging from –8.06 to –11.02 kcal/mol with low inhibition constants summed up as 1.04, 473.55, 352.51, 290.9, 437.86, 1.23, 41.18, 26.81, 162.76, 300.38, 70.2, 29.84, 4.14, 8.4 µM, respectively. The lower the inhibition constant (µM), the greater is the binding affinity and lower the medication required to inhibit the activity of the target receptor. (E)-3-(dimethylamino)-1-(quinolin-3-yl)but-2-en-1-one with 3-aminopyrazole under ultrasonic irradiation in aqueous medium yielded novel 3-(pyrazolo[1,5-a]pyrimidin-7-yl)quinolines and 3-(5-methylpyrazolo[1,5-a]pyrimidin-7-yl)quinolines. Antimalarial studies against Pf3D7 strain resulted in moderate activity with compound 4g showing highest activity. Molecular docking analysis of the compounds reveals the potentiality of the series to serve as antimalarial agents against CQ-sensitive (Pf3D7) and multi-drug-resistant (PfK1). [ABSTRACT FROM AUTHOR]

Bacillus cereus is a spore-forming foodborne pathogen that causes emetic and diarrheal food poisoning. An emetic strain of B. cereus produces spores and an emetic toxin called cereulide, which exhibits high heat resistance. In this study, we investigated the effects of epigallocatechin gallate (EGCg), theaflavin-3'-gallate (TF2b), and theaflavin-3,3'-gallate (TF3), polyphenolic components of tea extracts, on the survivability, spores, and toxin of B. cereus. Among them, EGCg at 62.5 μg/mL and 250 μg/mL showed bacteriostatic and bactericidal effects on B. cereus by damaging the cellular membrane, causing leakage of cellular nucleic acid related substances, and thus inhibiting the growth of B. cereus. However, no significant effects were shown on spore germination by EGCg, TF2b, or TF3 at a concentration of 250 μg/mL in this investigation. Their inhibitory effects were primarily confined to the outgrowth of daughter cells after spore germination. Furthermore, quantitative polymerase chain reaction (qPCR) showed that they suppressed the activity of cesA, a gene associated with cereulide production. At concentrations of 125 µg/mL for TF2b and 62.5 µg/mL for TF3, a discernible attenuation of cytotoxic effects induced by cereulide on HEp-2 cells was evident. [ABSTRACT FROM AUTHOR]

Man-made vitreous fibers (MMVF) comprise diverse materials for thermal and acoustic insulation, including stone wool. Depending on dimension, durability, and dose, MMVF might induce adverse health effects. Therefore, early predictive in vitro (geno)toxicity screening of new MMVF is highly desired to ensure safety for exposed workers and consumers. Here, we investigated, as a starting point, critical in vitro screening determinants and pitfalls using primary rat alveolar macrophages (AM) and normal rat mesothelial cells (NRM2). A stone wool fiber (RIF56008) served as an exemplary MMVF (fibrous vs. ground to estimate impact of fiber shape) and long amosite (asbestos) as insoluble fiber reference. Materials were comprehensively characterized, and in vivo-relevant in vitro concentrations defined, based on different approaches (low to supposed overload: 0.5, 5 and 50 µg/cm2). After 4–48 h of incubation, certain readouts were analyzed and material uptake was investigated by light and fluorescence-coupled darkfield microscopy. DNA-strand break induction was not morphology-dependent and nearly absent in both cell types. However, NRM2 demonstrated material-, morphology- and concentration-dependent membrane damage, CINC-1 release, reduction in cell count, and induction of binucleated cells (asbestos > RIF56008 > RIF56008 ground). In contrast to NRM2, asbestos was nearly inactive in AM, with CINC-1 release solely induced by RIF56008. In conclusion, to define an MMVF-adapted, predictive in vitro (geno)toxicity screening tool, references, endpoints, and concentrations should be carefully chosen, based on in vivo relevance, and sensitivity and specificity of the chosen cell model. Next, further endpoints should be evaluated, ideally with validation by in vivo data regarding their predictivity. [ABSTRACT FROM AUTHOR]

Lemna aequinoctialis (duckweed) is the smallest and fast-growing aquatic plant species producing protein-rich biomass with high protein nutritional value, phytoremediation capacity, and nutrient removal from wastewater. Duckweed may also be used as a new potential bioreactor for biological products, such as vaccines, antibodies, and pharmaceutical proteins. Based upon the potential importanc of L. aequinoctialis in phytoremediation and as a bioreactor the aim of this study was to (1) characterize the chemical and nutritional profiles of L. aequinoctialis biomass utilizing an integrated multi-trophic aquaculture system (IMTA) and a pond, and (2) investigate the cytotoxic potential of different concentrations of organic extracts and fractions using the MTT bioassay. EDXRF and ICP-MS analyses indicated the presence of trace elements in lower amounts in relation to the biomass of L. aequinoctialis in the lagoon, emphasizing the importance of plant inclusion management to reduce bioaccumulation of these elements. Analysis of mineral profiles, fatty acids, and amino acids indicated a satisfactory nutritional composition for the use of biomass as a bioproduct. Pigment analysis showed a high concentration of carotenoids, especially astaxanthin. After standardizing the controls, the MTT cell viability test was carried out utilizing rat hepatoma cell line (HTC), which are metabolizing cells that were treated with aqueous or ethanolic extracts and the dichloromethane, ethyl acetate, and methanol fractions at different concentrations. No apparent cytotoxic potential was observed following treatments, since there was no significant reduction in cell viability. Therefore, this study provides information regarding the biomass of L. aequinoctialis derived from the IMTA system, which might support further research into the application of this species as a bioproduct. [ABSTRACT FROM AUTHOR]

Artemisia turcomanica extract was utilized to green synthesize Ag, ZnO, and Ag-doped ZnO nanoparticles (NPs). The aim of this research was to assess the anticancer activity of these NPs against AGS gastric cancer cells. Ag-doped ZnO, undoped ZnO, and Ag NPs were synthesized and characterized by X-ray powder diffraction, UV–visible spectroscopy, Field Emission Scanning Electron Microscope, Fourier Transform Infrared Spectrometer, Transmission Electron Microscopy, and zeta potential. The anti-proliferative activity of the biogenic synthesized NPs was evaluated against AGS cancer cells. Apoptosis induction and cell cycle arrest were determined using flow cytometry. The expression levels of Caspase 3 (CASP3), Caspase 9 (CASP9), BCL2-associated X (BAX), and BCL2 apoptosis regulator (BCL2) genes were measured by qRT-PCR. The size of the ZnO, Ag, and Ag-doped ZnO NPs is estimated between 24 and 45, 17 and 31, and 11 and 49 nm, respectively. The zeta potential values of Ag, ZnO, and Ag-doped ZnO NPs were measured – 17.05 ± 0.36, – 17.60 ± 0.42, and – 16.20 ± 0.56 mV, respectively, which indicates the proper stability of NPs. The spherical synthesized NPs and plant extract showed a cytotoxic effect on AGS cancer cells. Inhibitory concentration (IC50) values of the extract, Ag, ZnO, and Ag-doped ZnO NPs were 234.65, 18.32, 9.15, and 5.31 μg/mL, respectively, which indicated great anticancer activity of Ag-doped ZnO NPs. Early apoptosis induced by treatment using extract, Ag, ZnO, and Ag-doped ZnO NPs were 3.26, 5.86, 15.40, and 11.3%, and 7.05, 15.5, 11.10, and 23.55% of the cells were engaged in late apoptosis, respectively. This indicated the ideal apoptotic effects of Ag-doped-ZnO NPs. The biosynthesized Ag-doped-ZnO NPs also could arrest the AGS cells in the sub-G1 phase of the cell cycle. The Ag-doped-ZnO NPs could significantly up-regulate the expression of pro-apoptotic (CASP3, CASP9, BAX) and down-regulate the expression of BCL2 genes compared to other treated groups (P < 0.001). These findings confirmed that the synthesized biogenic NPs are good candidates for cancer therapy in the biomedical field as an anticancer agent. The biogenic synthesis of Ag-doped ZnO nanoparticles was performed using Artemisia turcomanica extract. For the synthesis of Ag-doped ZnO NPs, Zinc acetate was mixed with AgNO3. Then, A. turcomanica extract was added. The color change of the solution indicated the synthesis of Ag-doped ZnO NPs. After cellular uptake of Ag-doped ZnO nanoparticles into the cancer cells, ROS generation, mitochondrial damage, apoptosis induction, and cell cycle arrest in sub-G1 occurred. [ABSTRACT FROM AUTHOR]

This research work explores the green synthesis of silver nanoparticles using Quassia indica (QI-Ag NPs), a natural plant extract, as a stabilizing and reducing agent. The synthesized QI-Ag NPs were characterized using various analytical techniques, including UV-Visible spectroscopy, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Transmission Electron Microscopy (HR-TEM) and Selected Area Electron Diffraction (SAED). The UV-Visible analysis revealed a characteristic peak at 430 nm, indicating the successful formation of AgNPs. XRD analysis unveiled the crystalline nature of the nanoparticles, with four distinctive peaks corresponding to the silver crystallographic planes. SEM and EDX provided insights into the morphology and chemical composition of the QI-AgNPs. Moreover, TEM and SAED elucidated the structural attributes and crystallinity of the nanoparticles. The Ag NPs exhibited a spherical structure and crystalline nature, as supported by both SAED and XRD findings. The zeta potential of QI-Ag NPs exhibited a value of −24.2 mV. The synthesized QI-Ag NPs were evaluated for their photocatalytic potential, demonstrating a remarkable 97% degradation of Crystal Violet dye. Furthermore, comprehensive studies encompassing antioxidant, antimicrobial and cytotoxicity assessments were conducted, showcasing the multifaceted applications of these nanoparticles. This research underscores the promising potential of Q. indica-mediated silver nanoparticles as environmentally benign and versatile nanomaterials. [ABSTRACT FROM AUTHOR]

The evaluation of antimicrobial, antioxidant, and anticancer activity against PANC-1 cell by Ag nanoparticles (AgNPs) synthesized using aqueous plant extract from turnera subulata has been reported. The AgNPs against human pancreatic cancer cell line PANC-1 cells were tested using MTT assay. The antibacterial and antioxidant properties have been evaluated. The sharp peaks at 400 nm in surface plasmon resonance (SPR) correspond to AgNPs. The carboxyl (C=O) and amine (N–H) functional organic moeities adsorbed over the AgNPs. X-ray diffraction (XRD) confirmed the peaks due to diffraction from 111, 200, 220, and 311 planes of face centered cubic (FCC) structure of silver. The AgNPs have a size of 23.9 nm from HRSEM and with an average diameter of 75.9nm by DLS measurements. The antioxidant properties of AgNPs were demonstrated by the DPPH degrading activity, nitric oxide and super oxide scavenging methods. The anticancer study revealed that AgNPs(25-500 µg/ml) had shown cytotoxicity against PANC-1 cells. The morphology of the cells has been evaluated by dual AO/ETBr staining and DAPI nuclear staining. The expressions of Bcl-2 and P53 genes were evaluated by RT-PCR using 114µg/ml dose of AgNPs. The expression of p53 mRNA in the PANC-1 cell line treated with synthesized AgNPs increased 1.8-fold compared to untreated cells. The expression of Bcl-2 was inhibited in the cells (p <.05) to 0.8-fold which treated with synthesized AgNPs (p <.05, p = 02) compared to the control. The upregulation of p53 and downregulation of Bcl-2 of the prepared AgNPs make them as a viable therapeutic agent against pancreatic cancer. [ABSTRACT FROM AUTHOR]

The biological activities of different parts of the Rheum ribes plant were evaluated comparatively. Extracts showing strong biological activity were identified and it was determined which of the extract-loaded nanoparticles showed stronger activity. Cytotoxic activity of R. ribes extracts was calculated on glial (C6) and fibroblast (NIH 3T3) cells using XTT assay. Spectrophotometry was used to evaluate the impact of these compounds on the enzyme activities of human carbonic anhydrase I and II (hCA I and hCA II). The findings showed that chitosan NPs with extracts loaded on them have a lower IC50 value and more cytotoxic activity in C6 cells than chitosan NPs with only extracts. R. ribes young shoots ultrasonic methanol extract (RYU) was shown to have the strongest antiproliferative efficacy against C6 cells. Results showed that RYU and ultrasonic methanol extract of R. ribes radix (RRU) were determined as the best carbonic anhydrase inhibitors. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. At a concentration of 10 µg/mL, it was found that none of the R. ribes extracts exhibited cytotoxic action toward the NIH 3T3 cell line. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. It was observed that none of the extracts of R. ribes at a concentration of 10 µg/mL showed cytotoxic activity in the NIH 3T3 cell line. [ABSTRACT FROM AUTHOR]

Trigonella coerulescens subsp. ayvalikensis is an annual local endemic taxon distributed only in Ayvalık/Balıkesir district and evaluated in the Vulnerable Category (VU). Trigonella L. is an important genus with medicinal and economic value in the Fabaceae family. Seeds of the genus Trigonella are known to contain several groups of secondary metabolites, the most abundant compounds being steroidal saponins, as well as flavones, isoflavones, and polysaccharides. In our study, the cytotoxic effect on two different cancer cell lines namely, PC-3 (prostate) and SW480 (colon), was investigated by extracting Trigonella coerulescens subsp. ayvalikensis with different solvents. The cytotoxic effects of extracts obtained from plant seeds with different solvents (hexane, methanol, ethanol, acetone) were investigated. The MTT test was used to examine the cytotoxic effect, which was studied with PC-3 and SW480 cancer cell lines. The different concentrations (23.45 µg/µL, 46.875 µg/µL, 93.75 µg/µL, 187.5 µg/µL, 375 µg/µL) of seed extracts were applied to the cells at different times points (24h, 48h and 72h) and absorbance was taken at 550 nm in the spectrophotometer. As a result of cytotoxic studies, it was observed that hexane extract had the most reducing effect on PC-3 compared to the control groups. In the SW480 cell line, a proliferative effect was observed in extracts prepared with methanol, hexane, and acetone in the early period of 24 hours. In the later period (72 hours), the extract prepared with hexane and acetone showed the most cytotoxic effect on SW480 cells. [ABSTRACT FROM AUTHOR]

This study is aimed to investigate the effects of Hypericum perforatum olive oil extract on the cytotoxic and metastatic properties of human colorectal cancer cells and human bone marrow-derived mesenchymal stem cells. In addition, ALDH3A1 and Vimentin expressions were evaluated by qRT-PCR and western blot analysis. Total phenolic and flavonoid contents and antioxidant activity of methanol extracts prepared with oil enrichment were measured using spectrophotometry-based methods. The cytotoxic effects of the extracts on SW-480 and bone marrow-derived mesenchymal stem cells were evaluated by MTT assay, resulting in IC50 values of 4.8 mg/ml and 4.9 mg/ml, respectively. It was determined that cell migration and colony formation were significantly reduced at the IC50 values determined for SW-480 and human bone marrow-derived mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

This investigation was performed to analyze the biological efficiency of metabolites extracted from actinobacterium, SRV02 strain. The doses of MIC and MBC signifies the control of bacterial strains and maximum inhibition. The presence of chemical metabolite-rich ethyl acetate extracts was responsible for the bactericidal effects. Furthermore, the cytotoxic capability of an ethyl acetate extract rich in metabolites was evaluated using non-small cell lung cancer cell lines. The changes in cell morphology were confirmed through different AO/EB, Hoechst and DCFH-DA fluorescent staining. Fourier transform infrared spectroscopy (FT-IR) and Gas Chromatography Mass Spectrometry (GC-MS) analysis were used to confirm the presence of chemical components in the crude ethyl acetate extract. The FT-IR analysis revealed the presence of alkanes (C-H stretch), primary amines (with C = C stretch), alkanes (C = C stretch), aliphatic amines (C –N stretch), then carboxylic acids (O –H bend) and alkanes (C– H) stretching vibrations. The compounds including Hexadecane, Eicosane, Heptadecane, Cyclohexane and Hexadecenoic acid were confirmed using GC-MS analysis. Overall, this result provides the therapeutic roles of secondary metabolites derived from actinobacterial strain and it could be useful for biomedical applications. [ABSTRACT FROM AUTHOR]

The 21st‐century toxicity testing program recommends the use of cytotoxicity data from human cells in culture for rapid in vitro screening focusing on biological pathways of potential toxicants to predict in vivo toxicity. Liver is the major organ for both endogenous and exogenous chemical metabolism of xenobiotics. Therefore, this review was undertaken to evaluate side by side five different currently used commercial cytotoxicity assay kits for purpose of rapid predictive screening of potential hepatotoxicants. The test compounds for this review were selected from the NIH LiverTox and FDA Liver Toxicity Knowledge Base (LTKB) databases. Human liver HepG2, HepaRG, and rat liver Clone 9 cell cultures were used as the in vitro liver models. Five commercial assay kits representing different biomarkers or pathways were selected for this review. These kits are Vita‐Orange Cell Viability Assay Kit (Sigma‐Aldrich), CellTiter‐Glo Cell Viability Assay Kit (Promega), CytoTox‐ONE Homogeneous Membrane Integrity Assay Kit (Promega), DNA Quantitation Fluorescence Assay Kit (Sigma‐Aldrich), and Neutral Red Based In Vitro Toxicology Assay Kit (Sigma‐Aldrich). This review found that these kits can all be used for rapid predictive cytotoxicity screening of potential hepatotoxicants in human liver HepG2 and rat liver Clone 9 cells in culture as in vitro liver models without compromising quality and accuracy of endpoint measurements as well as the length of toxicity screening time. Unraveling the structure–activity relationship of potential hepatotoxins would help to classify their hepatotoxic effects. Therefore, in addition to the current regulatory hepatotoxicity testing strategies, development and regulatory approval of hepatotoxins need to be discussed in order to identify potential gaps in the safety assessment. The overall results of our study support the hypothesis that a battery of rapid, simple, and reliable assays is an excellent tool for predicting in vivo effects of suspected liver toxins. The human liver HepaRG cells do not appear to be an ideal in vitro liver model for this purpose. Five commercial cytotoxicity assay kits used for screening hepatotoxins were evaluated using HepG2, HepaRG, and Clone 9 cell cultures as in vitro models. This study supports the hypothesis that a battery of these assays is an excellent tool for predicting in vivo effects of liver toxins. [ABSTRACT FROM AUTHOR]

Skin cancer is a widespread type of cancer representing 30% of all cancer types worldwide. Resveratrol (RSV) is an anticancer drug used for skin cancer treatment. Several limitations of RSV such as poor aqueous solubility, first-pass metabolism, and instability limit their topical use. The study aimed to develop and optimize RSV-loaded invasomes for topical administration as well as assess their efficacy in vivo. The optimized RSV-loaded invasomes showed small particle size (208.7 ± 74 nm), PDI (0.3 ± 0.03), high % entrapment efficiency (77.7 ± 6%), and negative zeta potential (−70.4 ± 10.9 mV). They showed an initial burst effect followed by controlled drug release for 24 h. RSV-loaded invasomal gel revealed the highest skin deposition percentage (65%) in ex vivo rat skin, the highest potency (low IC50 of 6.34 μg/mL), and the highest cellular uptake when tested on squamous cancerous cells (SCCs) when compared to other formulations. The antitumor effect of topical RSV-loaded invasomes was also evaluated in vivo in Ehrlich-induced mice models. The results revealed that RSV-loaded invasomal gel exhibited the smallest tumor volume with no signs of organ toxicity indicating its safety in skin cancer treatment. Upregulation of BAX and Caspase-3 gene levels and downregulation of NF-kB and BCL2 protein levels were demonstrated using RT-PCR and ELISA tests, respectively. Interestingly, the present study is the first to develop RSV-loaded invasomal gel for topical skin cancer treatment. According to our results, invasomes are considered promising lipid-based nanosystems for topical RSV delivery having high skin penetration ability and anticancer effect in the treatment of skin carcinoma. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT) is an infectious disease which kills humans and animals as a result of hematological distortions, oxidative stress, tissue and neuroinflammations. This study reports on the differences in cytotoxicity, antitrypanosomal, antioxidant, and anti‐inflammatory activities of ethanol extracts from Clausena anisata fruit (CFE), Azadirachta indica (neem) leaf (NLE), and stem bark (NSBE), medicinal plants used to treat HAT in its endemic communities. The extracts remarkably inhibited Trypanosoma brucei brucei (GUTat 3.1) parasite in vitro with CFE recording the highest effect with an IC50 of 0.0055 (0.0955) μg/mL. The IC50 of the standard Coptis japonicum was 0.5957 (0.0693) μg/mL. Also, the antitrypanosomal activity of NLE was 123.34% higher than that of NSBE. The percentage number of wells containing viable T. b. brucei parasites was very significantly (p < 0.001) reduced for all the extracts after 48 h of incubation. Furthermore, the extracts did not show cytotoxicity against the liver (HepG2) cells (CC50s > 100 μg/mL and SI = 13.12–32,025.45). NSBE contained the highest quantity of phenolic compounds and flavonoids and also produced the highest antioxidant and anti‐inflammatory activity in the DPPH free radical scavenging assay (IC50 = 4.99 ± 0.018) and protein denaturation assay (IC50 = 0.1805 ± 0.0002 μg/mL). In addition, phytochemical analysis showed that NLE contained the highest number of classes of phytochemical constituents (seven) among the extracts. These results indicate that CFE, NLE, and NSBE possessed significant antitrypanosomal activity as a result of their antioxidant and anti‐inflammatory actions. However, a different mechanism was also involved in the antitrypanosomal activity of CFE and NLE, since their antitrypanosomal activity is greater than NSBE which demonstrated the highest antioxidant and anti‐inflammatory activities. Due to the remarkable antitrypanosomal action of CFE, its constituents are being isolated for possible development into novel antitrypanosomal agents. [ABSTRACT FROM AUTHOR]

Aims: This study aims to prepare and investigate the potential of theobromine derivative-loaded chitosomes as an effective anticancer drug. Background: N-Benzyl-2-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide (T-1-BA) exhibited promising anticancer potential. Loaded chitosomes, highlighting their suitability as a drug delivery system. The study builds on the significance of targeted drug delivery systems for enhanced anticancer efficacy. Objectives: To prepare T-1-BA-loaded chitosomes (T-1-BA-PC-CS complex) using the thin film hydration technique. To examine the colloidal characteristics, entrapment efficiency, and stability of the T-1-BA-PC-CS complex. To assess the in vitro anticancer efficacy of the T-1-BA-PC-CS complex against Hct116 and A549 cancer cell lines comparing the free T-1-BA, blank chitosomes, and the standard EGFR inhibitor, Lapatinib. Methods: The T-1-BA-PC-CS complex was prepared through the thin film hydration technique. Colloidal characteristics, including particle size, PDI, and zeta potential, were examined. In vitro anticancer efficacy was assessed through IC50 values, comparative analyses, SI calculations, cell cycle analysis, flow cytometry, and wound healing assays. Results: The T-1-BA-PC-CS complex demonstrated reduced IC50 values against Hct116 and A549 cell lines, indicating enhanced cytotoxicity compared to free T-1-BA and blank chitosomes. Comparative analyses highlighted superior anticancer activity. SI values indicated preferential cytotoxic effects on cancer cell lines. Flow cytometry analysis revealed cell cycle alterations and increased apoptosis. Wound healing assays showed a significant impact on migration and wound healing in A549 cells. Conclusion: The findings suggest that the T-1-BA-PC-CS complex holds great promise as an anticancer therapeutic by efficiently inducing favorable alterations in cell cycle phases and apoptosis, demonstrating its potential for further development in cancer treatment. [ABSTRACT FROM AUTHOR]

AbstractThe development of efficient strategies for overcoming cancer remains a standing objective in medicinal chemistry. Design and synthesis of new potent compounds contribute efficiently to chemotherapy strategy since molecular hybridization was found an efficient strategy for designing new candidates of possible potent anticancer activities. Isoindole and 1,3,4-thiadiazole as well as glycosyl structures are known in literature with their broad-spectrum activities, the most important of which is anticancer activity. In this study, novel hybrid compounds incorporating more than motif were synthesized. A multistep synthetic pathway starting from the simple 2-amino-1,3,4-thiadiazole-2-thiol and the commercially available phthalic anhydride was applied for the preparation of the hybrid heterocyclic system. Glycosylation by acetylated glycosyl bromide and reaction with a series of monosaccharides afforded the corresponding glycosylthio-1,3,4-thiadiazole based isoindole products and the hydrazinyl-sugar derivatives, respectively. 1,3,4-Thiadiazolyl-isoindolyl-sugar compounds and related arylidenes were prepared. The cytotoxicity activity was investigated against human cancerous MCF-7, PC-3, A-549 and normal BJ-1 cells. The iodobutylthio-1,3,4-thiadiazolyl derivative exhibited the most potent activity against A-549 cell. The hybrid thiadiazolyl-sugar-based isoindole structure with the hydrazinyl-per-O-acetylated-D-galactose moiety exhibited the most potent activity against MCF-7 cell. Docking into epidermal growth factor (EGFR) revealed that the later bioactive compounds presented promising energy scores showing good affinity and various binding interactions into EGFR active site. In addition, Molecular dynamics (MD) simulation was performed to investigate the stability of the EGFR enzyme’s binding domain applying a 100 ns simulation analysis on the docked complex of EGFR with the potent compound 10 which showed that the sugar hydrazone 10 remained in the EGFR binding cavity over the 100 ns simulation with different orientations. [ABSTRACT FROM AUTHOR]

The resuscitation of bacteria through biofilms presents a critical challenge in controlling microbial pathogenesis and addressing antimicrobial resistance. Continuous antibiofilm activity, particularly on frequently contacted surfaces, is therefore critical. In this study, a scalable is introduced, one‐step fabrication of Fe2O3/AgBr nanoimprints using a polymerizable sol–gel (PSG) approach to create functional nanostructured thin films with strong antimicrobial properties. Fe2O3, a visible‐light photocatalyst, is coupled with AgBr, a photosensitizer and dark‐active antimicrobial, forming a heterojunction that demonstrated potent antibacterial activity against Escherichia coli and Pseudomonas putida under both dark and light conditions. The heterojunctions exhibit significant biofilm inhibition in the dark, particularly against the robust biofilm‐forming P. putida, while visible light irradiation ensures complete biofilm clearance. These surfaces also achieve optimal reactive oxygen species (ROS) production, selectively targeting bacteria without compromising the integrity of mammalian cells. The biocompatibility is confirmed through MTT, TBARS, and apoptosis assays, demonstrating the non‐cytotoxic nature of the substrates. Moreover, the surfaces enable cell patterning and recovery of mammalian cells from microbial contamination, highlighting their potential in creating bacterial‐free environments for cell culture. This innovative method offers a promising route to next‐generation, self‐cleaning antimicrobial coatings, combining continuous biofilm inhibition with excellent biocompatibility and scalability. [ABSTRACT FROM AUTHOR]

AbstractFree radicals are ubiquitous in biological systems, being responsible for pathogenesis of degenerative diseases and participating in vitally important biochemical processes, which are mediated by radical regulatory agents. The effects of the aliphatic amine substituents in the catechol-derived Mannich bases on their antioxidant and pro-oxidant activity were investigated. It has been found that the presence of catechol moiety in the structure of Mannich bases allows them to act as Cu(II) reductants, efficient Fe(II) chelators and potent DPPH radical scavengers. It has been found that the plausible mechanism of the DPPH radical scavenging proceeds via quinone formation, followed by their interaction with ethanol via the Michael addition reaction. In the neutrophil respiratory burst assay, several compounds have demonstrated a weak antioxidant activity at the micromolar level (0.1–10 µM), whereas at the millimolar level (0.1 mМ) a strong pro-oxidant effect has been observed. Additionally, at the highest used concentrations a pronounced cytotoxicity against dermal fibroblasts DF-2 and an immunosuppressive effect against T-lymphocytes have been observed for all the synthesized compounds. It has been demonstrated that the oxidation of catechols in the presence of low-molecular thiols results in the formation of covalent adducts, which provides an insight into their cytotoxicity and detoxification pathways. [ABSTRACT FROM AUTHOR]

Background: Fagonia cretica L. (Family: Zygophyllaceae), is a wild shrub mostly found in Mediterranean districts and extensively used in folk medicine for a vast array of purposes such as antidiabetic and anticancer during the early stages. The goal of the current study was to validate the antioxidant, anti-inflammatory, and cytotoxic properties of Egyptian F. cretica using in vitro studies, metabolic profiling, and in silico approaches. Methods: The plant was collected from the Egyptian desert and the alcoholic extract was prepared from its aerial parts, total phenolic and total flavonoid contents were evaluated spectrophotometrically. Antioxidant potential was assessed via 1,1 diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. Anti-inflammatory activity was validated through in vitro COX-2, COX-1, and nitric oxide inhibition. Cytotoxicity was tested against liver (HepG2), breast (MCF-7), and intestinal (CACO2) carcinoma cell lines followed by assessment of its impact on the levels of apoptotic markers namely topoisomerase I and caspase 9 enzymes. Chemical profiling of the extract was performed using LC-HRMS technique. Saponin rich extract was prepared and tested for affecting topo I and caspase 9 enzymes. In silico studies were conducted on anti-inflammatory (COX-2 and COX-1) and cytotoxicity (topoisomerases I, IIα, and IIβ) targets using Autodock vina in PyRx platform. Results: Total phenolic and total flavonoid content of the extract were 2.4 ± 0.12 mg GAE/g and 0.18 ± 0.01 mg RE/g, respectively. In vitro results revealed antioxidant activity calculated as 1.4 ± 0.1 mg AEAC/g. In vitro anti-inflammatory assays unveiled inhibition of COX-2 and COX-1 enzymes with IC50 values of 13.02 ± 0.61 and 26.51 ± 0.83 µg/ml, respectively and nitric oxide with IC50 of 147.05 ± 9.61 µg/ml. Cytotoxicity on MCF-7, HepG2, and CACO2 cell line with IC50 values of 6.9 ± 0.53, 7.6 ± 0.42, and 9.2 ± 0.35 µg/ml, respectively, in addition to in vitro topoisomerase I inhibition (IC50 = 13.57 ± 0.71 µg/ml) and caspase 9 induction by 5.66 folds. Metabolic profiling using LC-HRMS technique resulted in dereplication of 21 compounds including triterpenoid saponins, flavonoids, diterpenoids, etc. Interestingly, saponin rich fraction and non-saponin fraction exhibited similar effects on topoisomerase I and caspase 9. In silico investigation unveiled high binding affinities of almost all the detected metabolites to the active sites of COX-2, COX-1, topo I, IIα, and IIβ enzymes. Conclusion: Collectively, we can conclude that F. cretica is a new source of many phytochemicals, and a significant natural source as cytotoxic and anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

There is an urgent need for preventive and therapeutic drugs to effectively treat and prevent viral diseases from resurfacing as they emerge during the COVID-19 pandemic. This study aims to assess the antiviral effects of four natural compounds commonly used in traditional medicine to treat SARS-CoV-2 infection. A cytotoxicity, dose-dependent, and plaque reduction assay was performed on Vero CCL-81 cells to figure out their effects on the cells. Quantification of cytokines was assessed. In silico analysis for the selected compound was also evaluated. Results revealed that the compounds could disrupt the viral replication cycle through direct inhibition of the virus or immune system stimulation. The cytotoxicity assay results revealed that the compounds were well tolerated by the cells, indicating that the compounds were not toxic to the cells. This study evaluated the antioxidant capacities of propolis, curcumin, quercetin, and ginseng using ABTS, FRAP, and CUPRAC assays, revealing that propolis exhibited the highest antioxidant activity of ABTS with 1250.40 ± 17.10 μmol Trolox eq/g, with FRAP values reaching 1200.55 ± 15.90 μmol Fe2⁺ eq/g and CUPRAC values of 1150.80 ± 14.20 μmol Trolox eq/g at 1000 µg/mL, highlighting its potential as a potent natural antioxidant. The results of the plaque reduction assay revealed that the compounds could reduce the size and number of plaques, indicating that the compounds could inhibit the virus replication cycle. Subsequently, using molecular docking to analyze the effect of propolis, curcumin, quercetin, and ginseng as inhibitors, it was unveiled that the four compounds are likely to have the potential to inhibit the protease activity, spike protein S1, and RNA polymerase of SARS-CoV-2 and the virus titer was reduced by 100% after post-infection using propolis as an inhibitor control. [ABSTRACT FROM AUTHOR]

Nanotechnology involves the synthesis and application of nanoparticles across various fields, including medicine, agriculture, environmental remediation, and electronics. The green synthesis of nanoparticles using plant extracts is increasingly being explored to produce eco‐friendly nanoparticles and mitigate potential adverse effects in biomedical applications. Titanium dioxide (TiO2) has garnered attention due to its low cost, availability, chemical stability, and biocompatibility. This study used an eco‐friendly and simple green synthesis approach to fabricate and characterize titanium dioxide nanoparticles (TiO2 NPs) using Agave americana leaf extract. The UV–vis spectra revealed a strong peak at 385 nm. X‐ray diffraction analysis confirmed the tetragonal crystalline structure of TiO2 (rutile), with a particle size of 14.56 nm. Fourier transform infrared spectroscopy indicated characteristic stretching vibrations of TiO2 at 471 cm−1. TiO2 NPs exhibited a significant cytotoxic effect against cancer cells while demonstrating lower toxicity to normal cells, highlighting their selective anticancer properties. Additionally, TiO2 NPs demonstrated a strong photocatalytic activity of 93% under UV light exposure over 180 min. These findings strongly support the utilization of Agave americana leaves as a valuable source of antioxidants and highlight the efficacy of biosynthesized TiO2 NPs in environmental and biological applications. [ABSTRACT FROM AUTHOR]

In the field of regenerative medicine, acrylated epoxidized vegetable oils are emerging as a promising avenue of exploration. The aim of this study is to evaluate the degradability of two formulations of acrylated epoxidized soybean oil (AESO): pure AESO and AESO diluted with soybean oil (SO) for potential bioprintability applications. The comprehensive investigation of these two polymeric formulations included optimization of polymerization conditions, confirmation of cytocompatibility, and, most importantly, the study of their degradability. The results reveal that AESO, used as a biomaterial for biomedical applications, undergoes a distinctive degradation process, combining both enzymatic and oxidative degradation (AESO/SO samples lose 29.45% of their weight after 60 days). This phenomenon is the result of a complex interplay of factors, including the chemical composition and physical characteristics of the polymer, the unique tissue environment in which it is implanted, and the duration of implantation. [ABSTRACT FROM AUTHOR]

A ruthenium(II) aquo complex [Ru(dipic)(PPh3)2(OH2)], (1 A), bearing O,N,O‐coordinated 2,6‐dipicolinate was synthesized via reaction of [Ru(PPh3)3Cl2] with 2,6‐dipicolinic acid. Crystal structure of 1 A was determined. Utilizing 1 A as a synthon, three new complexes were synthesized. Reaction of 1 A with a bidentate NHC‐ligand, viz. 1‐methyl‐3‐(2′‐pyridyl)imidazole (IMeCN), afforded [Ru(dipic)(IMeCN)(PPh3)], (2 A). Similar reactions of 1 A with two pincer ligands, viz. 2,6‐bis(1′‐methyl imidazolyl)pyridine (IMeCNC) and 2,2′;6′,2"‐terpyridine (trpy), respectively yielded [Ru(dipic)(IMeCNC)(PPh3)], (3 A) and [Ru(dipic)(trpy)(PPh3)], (3 B). Structure of 2 A was optimized by DFT method. Structures of 3 A and 3 B were determined by X‐ray crystallography. In both 3 A and 3B the 2,6‐dipicolinate ligand was found to be N,O‐coordinated with one carboxy end remaining unbound to the metal center. Anticancer property of 2 A, 3 A and 3 B was studied and compared. Cytotoxicity of 3 A, studied against three selected cancer cell lines, viz. chronic myelogenous leukemia cell line (K562), hepatocellular carcinoma cell line (HepG2) and breast adenocarcinoma cell line (MCF7), was found to be the most promising. It displayed the best activity against K562, while it did not have any appreciable effect on its normal counterpart, viz. the human peripheral blood mononuclear cells (hPBMC). The comparative cytotoxicity studies indicated that presence of the C,N,C‐coordinated pincer NHC ligand in 3 A, together with presence of the free carboxylate end of N,O‐coordinated dipic ligand, are presumably responsible for its superior cytotoxic behavior. [ABSTRACT FROM AUTHOR]

AbstractA new indigotin alkaloid, named talarindigotin A (1), along with the analogue 5H, 6H-quinindolin-11-one (2) were isolated from the mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041. Their structures were assigned on the basis of NMR, HRMS, and single-crystal X-ray diffraction analysis. In the cytotoxic bioassay, compound 1 showed great cytotoxicity against HepG2, Hela, HCT116, and Huh7 human cancer cell lines with IC50 values ranging from 2.08 to 4.58 μM. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells. [ABSTRACT FROM AUTHOR]

Borate bioactive glasses (BGs) have become indispensable in biomedicine for their exceptional bioactivity and tunable degradation characteristics. This study presents the synthesis and comprehensive evaluation of BGs within the x B 2 O 3 -CaO-Na 2 O-K 2 O-MgO-P 2 O 5 system, featuring varying compositions of B 2 O 3 (x = 40, 55, and 70 mol.%), using both sol-gel and melting techniques. A systematic investigation of their structural evolution, degradation kinetics, apatite-forming capabilities, and cytotoxicity has been conducted. The results demonstrate that the borate BGs with elevated B 2 O 3 content significantly accelerates the degradation rate and enhances bioactivity across both synthesis methods, as B 2 O 3 content increases from 40 to 70 mol%. Notably, the sol-gel derived BG samples demonstrate pronounced degradation, with mass loss reaching up to 90 %, and superior hydroxyapatite formation in simulated body fluid, surpassing the performance of their melting-derived counterparts. Cytotoxicity assays with MC3T3-E1 cells reveal no significant inhibitory effects from any of the borate bioglasses. Moreover, ab initio molecular dynamics simulations have been utilized to elucidate the relationship between structural alterations and in vitro bioactivity, with a particular emphasis on the boron coordination number. These findings provide a promising strategy for the development of borate BGs with tailored degradation profiles and excellent bioactivity, making them as strong candidates for various biomedical applications. [ABSTRACT FROM AUTHOR]

AbstractPesticides are diluted in products called solvents for spraying fields and for cell viability studies. This study aimed to determine whether pesticide solvents can alter the toxicity of endosulfan and Vero cell viability. Thus, the cytotoxicity of some diluents commonly used in pesticide solutions was evaluated by the neutral red incorporation technique and cell growth. Vero cells were exposed to endosulfan dissolved in sunflower (Helianthus annus, Linnaeus) oil, corn (Zea mays, Linnaeus) oil, dimethylsulfoxide (DMSO), and Tween 80, at a concentration of 1 µg L−1 for a period of 96 h. The results showed that both DMSO and Tween 80 induced a significant increase in cytotoxicity compared to sunflower oil and corn oil. Moreover, Tween 80 had a significant cytotoxic effect (P < 0.05) when compared to DMSO. The solvent can alter the toxicity of endosulfan, decreasing Vero cell viability, as was the case with DMSO and Tween 80. [ABSTRACT FROM AUTHOR]

This investigation aimed to study the effects of ZnO-added fluorophosphate glass on in vitro degradation, apatite-forming ability, cytotoxicity, antioxidant efficacy, and antibacterial activity. In this regard, fluorophosphate glasses with varying zinc oxide (ZnO) content (0, 1, 2, 4, and 8 mol%) were synthesized by the standard melt quenching technique and subsequently in vitro degradation of the glass samples was analyzed by water solubility test. The apatite-forming ability of the glasses was studied by simulated body fluid (SBF) immersion analysis. Variations in the elemental and structural properties of the glasses before and after SBF immersion were assessed using an X-ray diffractometer, a Fourier transform infrared spectrometer, and a scanning electron microscope coupled with energy-dispersive X-ray spectrometer. The cytotoxicity assessment for ZnO-added fluorophosphate glasses was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The antioxidant efficacy of the glass samples was evaluated using 2,2-diphenyl-1-picrylhydrazyl assay. Variations were observed in lower concentrations of ZnO compared to higher concentrations in mechanical, structural, and biological properties. Amongst the concentrations, 2 mol% ZnO-added fluorophosphate glass demonstrated superior antioxidant activity compared to the zinc-free fluorophosphate glass. The optimized 2 mol% of ZnO was evaluated against different bacterial strains such as Escherichia coli , Klebsiella pneumonia , Proteus vulgaris , Staphylococcus epidermidis , Pseudomonas aeruginosa , and Staphylococcus aureus using the agar diffusion method. A distinct transparent inhibitory zone was observed against all the bacterial strains, following exposure to the 2 mol% of ZnO containing fluorophosphate glass compared to the zinc-free glass sample. These findings suggest that 2 mol% of ZnO containing fluorophosphate glass is well-suited for biomedical applications involving cellular activity. [ABSTRACT FROM AUTHOR]

Hydrogels are interesting materials as delivery systems of various therapeutic agents, mainly due to the water-swollen network and the localized and sustained drug release. Herein, single-component starch-based hydrogels with enhanced degradation rates were produced by applying a facile synthesis and proposed for a novel delivery system of therapeutic molecules. Starch was oxidized with sodium periodate in water and mild conditions to generate aldehyde derivatives that, after a freeze-thaw procedure, were allowed to compact and stable hydrogels. Oxidized starch was also cross-linked with asparagine through a Schiff base reaction to link the active molecule directly to the polysaccharide structure. The materials were structurally and morphologically characterized, and the ability to adsorb and release over time an active molecule was proven by qNMR spectroscopy. The cytotoxicity was evaluated on CAL-27 cell line (oral squamous cell carcinoma). Results indicated that synthesized hydrogels lead to a "frozen proliferative" state on cells due to the swelling capability in the cell medium. This behavior was confirmed by flow cytometry data indicating the hydrogels induced less "early apoptosis" and more "late apoptosis" in the cells, compared to the untreated control. Since the proposed materials are able to control the cell proliferation, they could open a new scenario within the field of precise therapeutic applications. [ABSTRACT FROM AUTHOR]