Maillard Reaction-Derived S-Doped Carbon Dots Promotes Downregulation of PPARγ, C/EBPα, and SREBP-1 Genes In-Vitro.

Carbon nanodots (CDs) are commonly found in food products and have attracted significant attention from food scientists. There is a high probability of CD exposure in humans, but its impacts on health are unclear. Therefore, health effects associated with CD consumption should be investigated. In this study, we attempted to create a model system of the Maillard reaction between cystine and glucose using a simple cooking approach. The CDs (CG-CDs) were isolated from cystine-glucose-based Maillard reaction products and characterized using fluorescence spectroscopy, X-ray diffractometer (XRD), and transmission electron microscope (TEM). Furthermore, human mesenchymal stem cells (hMCs) were used as a model to unravel the CDs' cytotoxic properties. The physiochemical assessment revealed that CG-CDs emit excitation-dependent fluorescence and possess a circular shape with sizes ranging from 2 to 13 nm. CG-CDs are predominantly composed of carbon, oxygen, and sulfur. The results of the cytotoxicity evaluation indicate good biocompatibility, where no severe toxicity was observed in hMCs up to 400 µg/mL. The DPPH assay demonstrated that CDs exert potent antioxidant abilities. The qPCR analysis revealed that CDs promote the downregulation of the key regulatory genes, PPARγ, C/EBPα, SREBP-1, and HMGCR, coupled with the upregulation of anti-inflammatory genes. Our findings suggested that, along with their excellent biocompatibility, CG-CDs may offer positive health outcomes by modulating critical genes involved in lipogenesis, homeostasis, and obesity pathogenesis.

Understanding the Interaction between Nanomaterials Originated from High-Temperature Processed Starch/Myristic Acid and Human Monocyte Cells.

High-temperature cooking approaches trigger many metabolically undesirable molecule formations, which pose health risks. As a result, nanomaterial formation has been observed while cooking and reported recently. At high temperatures, starch and myristic acid interact and lead to the creation of nanomaterials (cMS-NMs). We used a non-polar solvent chloroform to separate the nanomaterials using a liquid-liquid extraction technique. The physico-chemical characterization was carried out using dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). To determine the biological impact of these nanomaterials using different in vitro assays, including a cell viability assay, microscopic staining, and gene expression analysis, we adopted the THP-1 cell line as an in vitro monocyte model in our study. The TEM images revealed that fabricated cMS nanomaterials are smaller than 100 nm in diameter. There were significant concerns found in the cytotoxicity assay and gene expression analysis. At concentrations of 100-250 µg/mL, the cMS-NMs caused up to 95% cell death. We found both necrosis and apoptosis in cMS-NMs treated THP-1 cells. In cMS-NMs-treated THP-1 cells, we found decreased expression levels in IL1B and NFKB1A genes and significant upregulation in MIF genes, suggesting a negative immune response. These findings strongly suggest that cMS-NMs originated from high-temperature food processing can cause adverse effects on biological systems. Therefore, charred materials in processed foods should be avoided in order to minimize the risk of health complications.

Fabrication of myristic acid-potato starch complex nanostructures and assessment of their cytotoxic behavior.

BACKGROUND: Lipids and carbohydrates perform essential functions in foods. In recent decades, food scientists have studied the effects of carbohydrate-lipid interactions on the functional properties of food. However, the ways in which carbohydrate-lipid complex-derived materials affect the biological system are unknown. In this study, a myristic acid-potato starch complex was created using a simple cooking approach. The complex was employed as a precursor for the fabrication of myristic acid-potato starch complex-based nanostructured materials (MPS-NMs) through a liquid-liquid extraction approach. A study was conducted on the structural and cytotoxic features of the fabricated MPS-NMs. RESULTS: Transmission electron microscopy images confirmed the formation of spherical nanostructures, 3-60 nm in size. After 24 h exposure, the chloroform fraction-based and n-hexane fraction-based MPS-NMs increased cell death by ~90% and ~ 82%, respectively. Chloroform fraction-based MPS-NMs (CMPS-NMs) triggers apoptotic cell death in human mesenchymal stem cells (hMSCs). n-Hexane fraction-based MPS-NMs (HMPS-NMs) treated cells have red color-intact nuclei, attributed to necrotic cell death. The CMPS-NMs and HMPS-NMs significantly decreased the mitochondria membrane potential and increased the intracellular reactive oxygen species (ROS) levels. We observed significant downregulation in flavin-containing monooxygenase (FMO), Ataxia Telangiectasia Mutated (ATM), and uridine diphosphate glucuronosyltransferases (UGT) gene expression levels in the exposed cells of CMPS-NMs and HMPS- NMs. In addition, we found upregulation of glutathione-disulfide reductase (GSR) and glutathione S-transferase A4 (GSTA4) genes in CMPS-NMs, and HMPS-NMs exposure. CONCLUSION: The cooking process may lead to the formation of nanostructured material in food systems. Chloroform fraction-based MPS-NMs and HMPS-NMs may contribute to cell metabolic disorders. © 2023 Society of Chemical Industry.

Mucilage-assisted fabrication of molybdenum trioxide nanostructures for photothermal ablation of breast cancer cells.

Nanostructures have been used for various biomedical applications due to their optical, antibacterial, magnetic, antioxidant, and biocompatible properties. Cancer is a prevalent disease that severely threatens human life and health. Thus, innovative and effective therapeutic approaches are urgently required for cancer. Photothermal therapy (PTT) is a promising approach to killing cancer cells. In this investigation, we developed a low-cost, simple, green technique to fabricate molybdenum trioxide nanostructures (MNs) using Opuntia ficus-indica mucilage as a template. Moreover, the MNs were functionalized with folic acid (FA) for cancer PTT. The X-ray diffractometer results revealed that the prepared MNs have an orthorhombic crystal phase. The transmission electron microscope image of MNs shows a flake shape with 20-150 nm diameter. The cytotoxicity of MNs and FA-conjugated MNs was studied in vitro. These cell viability assay results suggested that fabricated MoO3 nanostructures reduced 25% of cell viability in MCF-7 cells, even at high doses. However, even with high-dose treatment, FA/MNs do not cause significant cell death. Acridine orange/ethidium bromide (AO/EB) staining revealed DNA and chromatin condensation in MCF-7 cells exposed to MNs. Overall, the in vitro study results suggested that FA/MNs have excellent biocompatibility, which applies to biomedical applications. MNs dispersion temperature gradually increases from 26 to 58°C under 808 nm laser irradiation. We found significant mortality rates after NIR irradiation in MNs- or FA/MNs-treated MCF-7 cells. These findings suggest that FA/MNs can be used as an effective photothermal agent to treat breast cancer.

Association of CYP2R1 and CYP27B1 genes with the risk of obesity and vitamin D metabolism in Saudi women.

BACKGROUND: Epigenome, genetic variants, and other environmental factors involved in gene regulation are highly inter-dependent in several chronic diseases, including obesity, cardiovascular disease, and diabetes. The present study aimed at testing the associations and the mechanism involved in silencing of CYP2R1 gene in normal and obese Saudi women patients. Height, weight, BMI, 25-hydroxy vitamin D, parathyroid hormone, glycemic status, and lipid profile (TG, LDL, HDL, and TC) of CYP2R1 were measured in 100 women (31 normal and 69 obese patients). RESULTS: Our result shows that hypermethylation in site 2 of the CYP2R1 gene with body weight (p < 0.004), BMI (p < 0.002), waist circumference (p < 0.002), total-LDL (p < 0.027), total cholesterol (p < 0.022), and vitamin D (VD) (close to borderline significance p < 0.06) and site 4 of CYP2R1 with LDL (p < 0.041) in the four tested sites among normal and obese women was significantly associated. Moreover, we tested five different CpG sites in the CYP27B1 gene where site 5 correlated significantly with VD levels. CONCLUSION: Our present study clearly indicates that hypermethylation of specific sites in the CYP2R1 and CYP27B1 genes might regulate gene expression with special reference to the risk of obesity and vitamin D metabolism.

Co-exposure to commercial food product ingredient E341 and E551 triggers cytotoxicity in human mesenchymal stem cells.

Several nano-toxicological studies have assessed the prospective health risks of engineered nanostructures. Still, nanoscale ingredients from food products are not explored well, and only a few have attended to the possible effects of food additive-based nanoparticles in food. The physicochemical properties of food additives and their fate on human health are still unknown. To fill this knowledge gap, we examined the physicochemical characteristics of food product isolate E341/E551. Additionally, we assessed the consequence of these nanoscale E341 and E551 as co-exposure on human mesenchymal stem cells (hMSCs). The transmission electron microscope (TEM) images revealed that food product isolate (E341/E551) consists of nanoscale particles. The E551 and E341 have 20-50 nm and 70-200 nm diameters, respectively. Co-exposure of food additives SiO2 (E551) and Tricalcium phosphate (E341) effect on the cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) level of hMSCs were studied. The cell viability reduction, mitochondrial membrane potential loss, and ROS generation in E341/E551 co-exposed cells were observed. Our study suggests that E341/E551 co-exposure elevated the ROS level and mitochondrial membrane potential depletion at a high dose. The oxidative stress-related genes MDM3, TNFSF10, and POR have exhibited significant upregulation in the E341/E551 treatment group. These results conclude that long-term over-exposure to E341/E551 may be triggers health risks in a human. Further in vivo studies are required for food industry implications due to nanoscale ingredients in E341 and E551.

Unveiling the Biocompatible Properties of Date Palm Tree (Phoenix dactylifera L.) Biomass-Derived Lignin Nanoparticles.

Searching for sustainable, ecofriendly, and renewable precursors for nanostructured material synthesis is a fascinating area pertaining to feasibility in various applications. Especially, lignin-based material preparation is essential for unraveling the usage of lignin by valorization. Hence, we have synthesized lignin nanoparticles (LNPs) using date palm tree (Phoenix dactylifera L.) biomass as a precursor in this investigation. The LNP's morphological and thermal features were assessed. Moreover, we have evaluated the LNP's cytocompatibility properties by adopting in vitro approach. The P. dactylifera L. (PD) biomass-derived LNP's morphological features show a spherical shape with a 10-100 nm diameter. The LNPs have a decreased cell viability of ∼8% at a high concentration exposure to human mesenchymal stem cells (hMSCs) for 48 h. However, the LNPs do not cause any cellular and nuclear morphology changes in hMSCs. The mitochondrial membrane potential assessment results confirm healthy mitochondria with high mitochondrial membrane potential in LNP-treated cells. The intracellular reactive oxygen species (ROS) generation assay results revealed that LNPs do not trigger ROS generation in hMSCs. We examined the upregulation of GSTM3 and GSR genes and the downregulation of SOD1 genes in LNP-treated hMSCs, but no significant changes were observed. Our study concluded that PD biomass-derived LNPs have a good cytocompatibility and an antioxidant property. Thus, they can be applicable for various biological, cosmetic, and environmental applications.

Plumbagin triggers redox-mediated autophagy through the LC3B protein in human papillomavirus-positive cervical cancer cells.

INTRODUCTION: In this study, we analyzed the effect of plumbagin (PL) on cultured SiHa cervical cancer cells using fluorescence microscopy and flow cytometry techniques to identify the mode of cell death and to elucidate whether cells die through apoptosis or non-apoptosis. MATERIAL AND METHODS: The cell death was analyzed using MTT assay. The cellular morphological changes were assessed using acridine orange/ethidium bromide dual staining. DNA damage and cell cycle progression were analyzed using a comet assay and flow cytometry respectively. RESULTS: Morphological and cytological features revealed that PL induced autophagic cell death in cancer cells. The results of a cell cycle analysis indicated that the proportion of cells in sub-G0 phase increased. Translocation of LC-3B protein from the cytoplasm to the autophagosome was found in 31% of PL-treated cells, suggesting that PL provoked autophagic cell death. In this study, it was observed that plumbagin treatment caused cleavage of DNA in SiHa cancer cells, and morphological analysis provided very strong evidence supporting the occurrence of autophagic cell death as a result of plumbagin treatment. CONCLUSIONS: In addition, a Cytoscape-based protein-PL interaction network analysis provided very strong evidence in support of the specific mode of cell death in the context of autophagy, which has also been one of the desired endpoints in human papillomavirus-positive cervical cancer therapy and apoptotic cell death-resistant cancer treatment. Thus, this study is the first to test PL against the SiHa cervical cancer cell line, providing leads for further testing on non-apoptotic cell death for application in cervical cancer management.

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study.

This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO4)-where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline-to two genotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox-cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)-phenolate complex[Cu(tdp)(phen)]+ offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.

Simultaneous fabrication of carbon nanodots and hydroxyapatite nanoparticles from fish scale for biomedical applications.

Fish industries and markets produce large quantities of fish scales, skins, shells, and bone wastes post processing that contaminate the environment and cause health risks in humans. In this context, we have developed a novel and simple integrated process to valorize the Lethrinus lentjan fish scales by fabricate carbon nanodots (CDs) and hydroxyapatite nanoparticles (HA NPs) simultaneously. The fish scale treatment was carried out by hydrothermal method at 280 °C that produced CDs and HA NPs simultaneously. Under hydrothermal treatment, organic and inorganic substances of fish scale is transformed to CDs and HA NPs respectively. As TEM images confirmed that fish scale derived CDs were spherically shaped and ~3 to 15 nm in size. The CDs exhibited excitation-dependent emission in photoluminescence. The HA NPs were ~8 to 12 nm in diameter and ~50 to 100 nm in length with rod shape. Also, HA NPs possess spherical shape nanostructures with 15-50 nm in diameter. Furthermore, we assessed the cytotoxic behavior of synthesized nanostructures using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. These results showed that synthesized CDs and HA NPs did not cause significant changes in cell viability and morphology, indicating biocompatibility. Additionally, the synthesized CDs and HA NPs were exploited as fluorescent probes for cellular imaging and osteogenic differentiation of stem cells respectively. Overall, the study results indicate that low-cost fish waste was valorized by producing CDs and HA NPs concurrently. The synthesized nanostructures can be applicable for bio-imaging and bone tissue engineering applications.

Colonic Bacteria-Transformed Catechin Metabolite Response to Cytokine Production by Human Peripheral Blood Mononuclear Cells.

Human gut microbes are a profitable tool for the modification of food compounds into biologically active metabolites. The biological properties of catechins have been extensively investigated. However, the bioavailability of catechin in human blood plasma is very low. This study aimed to determine the biotransformed catechin metabolites and their bioactive potentials for modulating the immune response of human peripheral blood mononuclear cells (PBMCs). Biotransformation of catechin was carried out using in-vitro gut microbial biotransformation method, the transformed metabolites were identified and confirmed by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-MS). Present observations confirmed that the catechin was biotransformed into 11 metabolites upon microbial dehydroxylation and C ring cleavage. Further, immunomodulatory potential of catechin metabolites was analyzed in peripheral blood mononuclear cells (PBMCs). We found up-regulation of anti-inflammatory cytokine (IL-4, IL-10) and down-regulation of pro-inflammatory (IL-16, IL-12B) cytokine may be due to Th2 immune response. In conclusion, biotransformed catechin metabolites enhance anti-inflammatory cytokines which is beneficial for overcoming inflammatory disorders.

Phoenix dactylifera lignocellulosic biomass as precursor for nanostructure fabrication using integrated process.

Agricultural residue is an inevitable byproduct of agricultural activities. Valorization of agricultural residue is necessary to avoid wastage. In this study, we developed an integrated process for fabricating various nanostructures using Phoenix dactylifera (PD) lignocellulosic biomass as a sustainable bioprecursor. The PD biomass was treated using a hydrothermal method at 180 °C to derive the liquid fraction containing carbon nanodots (CDs). After pretreatment, the biomass was treated with an alkali solution to disassociate the lignin and cellulose. The extracted lignin was dissolved in tetrahydrofuran and subjected to a dialysis process. During the dialysis process, the lignin transformed into lignin nanoparticles (LNPs). The cellulose-containing fraction was transformed into cellulose nanostructures (CNs) via a sequential process (bleaching and acid hydrolysis). The structural properties, morphological features, crystallinity, and thermal stability of the fabricated CDs, LNPs, and CNs were analyzed. The synthesized CDs and LNPs had a spherical shape with different sizes: 2-10 nm (CDs) and 100-900 nm (LNPs). The CNs exhibited a fibrillated architecture and were 5-10 nm wide and 400-700 nm long. A biocompatibility analysis indicated that the synthesized nanostructures are nontoxic to human mesenchymal stem cells at concentrations of up to 200 µg/mL. This process is suitable for synthesizing nanostructures using different types of plant lignocellulosic biomass.

Sulforaphane alleviates cadmium-induced toxicity in human mesenchymal stem cells through POR and TNFSF10 genes expression.

Sulforaphane is a dietary compound possessing anti-inflammatory, antioxidant, anti-diabetic, anti-carcinogenic, and anti-aging properties. The role of sulforaphane in the context of cadmium (Cd)-induced toxicity through the alteration of nuclear morphology, mitochondrial membrane potential, and gene expression patterns, however, remains unclear. Thus, we assessed the protective role of sulforaphane against Cd-induced nuclear and mitochondrial damage in human mesenchymal stem cells (hMSCs). Cells were exposed to Cd and sulforaphane, either alone or in combination, for 48 h. The cell viability was assessed by adopting MTT assay. The nuclear morphology was investigated using Acridine orange/Ethidium bromide (AO/EB) dual staining and Hoechst staining. The mitochondrial membrane potential loss and lysosomal staining were analyzed using JC-1 staining and LysoRed staining respectively. The gene expression was studied using quantitative real-time PCR analysis. After 48 h of exposure to Cd, the viability of hMSCs decreased in a dose-dependent manner. In contrast, a single treatment with the phytochemical sulforaphane did not cause any remarkable reduction in hMSC viability. Combined treatment with Cd and sulforaphane resulted in a marked recovery in cell viability compared to that observed in cells treated with Cd alone. Analysis of nuclear morphology indicated that Cd induced necrotic cell death, while combined Cd and sulforaphane treatment prevented nuclear morphology changes. Cd ions also significantly attenuate the mitochondrial membrane potential (MMP) and alter gene expression in hMSCs; however, we observed that sulforaphane improves MMP under conditions of Cd-sulforaphane co-treatment of hMSCs. The gene expression results indicate that POR, TNFRSF1A and TNFSF10 genes expression are significantly upregulated by Cd-sulforaphane co-treatment than Cd or sulforaphane treatment alone. Our study results clearly indicate that sulforaphane can protect hMSCs against Cd-induced changes in nuclear morphology, attenuation of MMP, and alteration of gene expression patterns. Thus, intake of sulforaphane-enriched vegetables and fruits will be helpful to overcome Cd-induced toxicity in humans.

Synthesis of SiO2 nanostructures from Pennisetum glaucum and their effect on osteogenic differentiation for bone tissue engineering applications.

Silica nanostructures were fabricated from Pennisetum glaucum (pearl millet) seed husk by acid-pretreatment and calcination. The fabricated silica nanostructure (SN) functional groups, crystalline nature, surface morphology, and particle size were analyzed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy, respectively. Additionally, the cytocompatibility of SNs was analyzed on human mesenchymal stem cells (hMSCs) in an MTT assay, propidium iodine (PI) staining, and acridine orange/ethidium bromide (AO/EB) staining. We observed peaks at 1090 and 800 cm-1, which were assigned to symmetric, asymmetric, and bending vibrations of O-Si-O. The SNs showed an amorphous nature with a spherical shape and were 20-60 nm in diameter. The MTT assay results indicated that SNs exhibited cytocompatibility in hMSCs. The PI staining and AO/EB staining results suggested that SNs do not affect nuclear morphology at up to 400 µg/mL. Furthermore, SNs effect on osteogenic differentiation in hMSCs was studied. These results indicate that SNs induced osteogenic differentiation in hMSCs by upregulation of ALP, BSP, ON and RUNX2 genes. Our process could valorize the Pennisetum glaucum agricultural residues to high value products for bone tissue engineering applications.

Evaluation of antibacterial and cytotoxic properties of green synthesized Cu2O/Graphene nanosheets.

Graphene nanocomposites have received attention for the therapy and detection of diseases. In this study, we developed a simple and green chemistry approach for synthesizing Cu2O/graphene nanocomposites (Cu2O/G) using date palm fruit syrup as a reducing agent. The graphene oxide surface anchored with Cu(OH)2 and reduced it to fabricate Cu2O-anchored graphene nanosheets using date palm fruit syrup. Physicochemical characteristics of the synthesized nanocomposites were analyzed. Scanning electron microscopy images revealed 50-70 nm Cu2O nanostructures anchored on the surface of crumpled graphene sheets. The Cu2O/G nanocomposites inhibited the gram-negative and gram-positive bacterial growth at 300 µg. When compared with Cu2O nanoparticles and graphene oxide nanosheets (GO), Cu2O/G nanocomposite exhibited outstanding bactericidal activity. The cytotoxic properties of the prepared nanocomposites were studied in human mesenchymal stem cells (hMSCs). The Cu2O/G nanocomposites did not reduced cell viability by up to 200 µg/mL and slightly induced cell death at high concentrations. However, Cu2O nanoparticles and GO have significantly reduced the cell viability in hMSCs. The microscopic images of cellular and nuclear morphology suggested that the Cu2O/G composites did not cause major changes to hMSCs. The Cu2O nanoparticles and GO remarkably triggers the cellular damages, nuclear condensation and DNA fragmentation in hMSCs. Our study results revealed that Cu2O/G has excellent antibacterial activity with good biocompatibility. Thus, Cu2O/G could be used as a promising antibacterial agent in various purposes.

Fabrication and cytotoxicity assessment of cellulose nanofibrils using Bassia eriophora biomass.

Cellulose nanofibrils (CNs) are eco-friendly, biodegradable, biocompatible, renewable, cost-effective, and possess excellent mechanical properties. We fabricated CNs from Bassia eriophora biomass, and the structure and morphology were investigated by transmission electron microscopy that revealed 2-6 µm long fibrillated structures with diameters of 15-40 nm. CNs biocompatibility was assessed using in vitro based assays, including cell viability assay, AO/EB staining, Hoechst staining, JC-1 staining, and gene expression analysis. The assessment of cellular and nuclear morphologies of human mesenchymal stem cells (hMSCs) showed that CNs do not affect cell viability and morphology. JC-1 staining results revealed that CNs do not cause mitochondrial membrane potential of hMSCs. Cell-based in vitro assays revealed that CNs are biocompatible even at high concentrations. The CNs effect on cell cycle regulated gene expression was studied that results suggested that CCND1 and CCND3 gene expression levels increased slightly, when compared with control. But CCNG1, CYCS3, and CCNC1 genes has no significant difference was observed. Overall, our results suggested that CNs can be used for tissue engineering and regenerative medicine.

Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines.

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a⁻m led to their apoptotic cell death.

Antimicrobial activity of nanoemulsion on drug-resistant bacterial pathogens.

The appearance of drug-resistant (DR) bacteria in the community is a crucial development, and is associated with increased morbidity, mortality, healthcare costs, and antibiotic use. Natural oil nanoemulsions (NEs) have potential for antimicrobial applications. In the present study, we determined the antimicrobial activity of an NE against DR bacterial pathogens in vitro. The NE comprised Cleome viscosa essential oil, Tween 80 nonionic surfactant, and water. We found that an NE with a droplet size of 7 nm and an oil:surfactant (v/v) ratio of 1:3 was effective against methicillin-resistant Staphylococcus aureus (MRSA), DR Streptococcus pyogenes, and DR extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Fourier-transform infrared (FTIR) spectroscopy revealed that NE treatment modified the functional groups of lipids, proteins, and nucleic acids in DR bacterial cells. Scanning electron microscopy (SEM) showed damage to the cell membranes and walls of NE-treated DR bacteria. These alterations were caused by bioactive compounds with wide-spectrum enzyme-inhibiting activity in the NE, such as ß-sitosterol, demecolcine, campesterol, and heneicosyl formate. The results suggest that the nanoemulsion is effective against DR bacteria, and acts by inhibiting the drug efflux mechanism of DR strains.

Assessment of sulforaphane-induced protective mechanisms against cadmium toxicity in human mesenchymal stem cells.

Cd is a hazardous substance and carcinogen that is present in the environment; it is known to cause toxic effects in living organisms. Sulforaphane is a naturally available phytochemical with antioxidant, anti-inflammatory, and anticarcinogenic properties. However, the effects of sulforaphane on Cd toxicity in human mesenchymal stem cells (hMSCs) are unknown. In the present study, we investigated the molecular mechanisms of the effects of sulforaphane on Cd toxicity in hMSCs by using MTT assays, acridine orange/ethidium bromide staining, Hoechst staining, LysoRed staining, assessment of mitochondrial membrane potential, and gene expression analysis. Cd decreased hMSC viability in a dose-dependent manner with an IC50 value of 56.5 µM. However, sulforaphane did not induce any significant reduction in cell viability. Nuclear morphological analysis revealed that Cd induced necrotic cell death. Additionally, Cd caused mitochondrial membrane potential loss in hMSCs. The treatment of Cd-exposed cells with sulforaphane (Cd-sulforaphane co-treatment) resulted in a significant recovery of the cell viability and nuclear morphological changes compared with that of cells treated with Cd only. The gene expression pattern of cells co-treated with Cd-sulforaphane was markedly different from that of Cd-treated cells, owing to the reduction in Cd toxicity. Our results clearly indicated that sulforaphane reduced Cd-induced toxic effects in hMSCs. Overall, the results of our study suggested that sulforaphane-rich vegetables and fruits can help to improve human health through amelioration of the molecular effects of Cd poisoning.

Sulforaphane mitigates cadmium-induced toxicity pattern in human peripheral blood lymphocytes and monocytes.

Cadmium (Cd) is a highly toxic and widely distributed heavy metal that induces various diseases in humans through environmental exposure. Therefore, alleviation of Cd-induced toxicity in living organisms is necessary. In this study, we investigated the protective role of sulforaphane on Cd-induced toxicity in human peripheral blood lymphocytes and monocytes. Sulforaphane did not show any major reduction in the viability of lymphocytes and monocytes. However, Cd treatment at a concentration of 50µM induced around 69% cell death. Treatment of IC10-Cd and 100µM sulforaphane combination for 24 and 48h increased viability by 2 and 9% in cells subjected to Cd toxicity, respectively. In addition, IC25 of Cd and 100µM sulforaphane combination recovered 17-20% of cell viability. Cd induced apoptotic and necrotic cell death. Sulforaphane treatment reduced Cd-induced cell death in lymphocytes and monocytes. Our results clearly indicate that when the cells were treated with Cd+sulforaphane combination, sulforaphane decreased the Cd-induced cytotoxic effect in lymphocytes and monocytes. In addition, sulforaphane concentration plays a major role in the alleviation of Cd-induced toxicity.