-
Theranostics 2021Tanshinone, a type of diterpenes derived from , is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia...
Tanshinone, a type of diterpenes derived from , is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia (AML). However, the therapeutic function and the underlying mechanism of Tanshinone in AML are not clear, and the toxic effect of Tanshinone limits its clinical application. Our work utilizes human leukemia cell lines, zebrafish transgenics and xenograft models to study the cellular and molecular mechanisms of how Tanshinone affects normal and abnormal hematopoiesis. WISH, Sudan Black and O-Dianisidine Staining were used to determine the expression of hematopoietic genes on zebrafish embryos. RNA-seq analysis showed that differential expression genes and enrichment gene signature with Tan I treatment. The surface plasmon resonance (SPR) method was used with a BIAcore T200 (GE Healthcare) to measure the binding affinities of Tan I. methyltransferase assay was performed to verify Tan I inhibits the histone enzymatic activity of the PRC2 complex. ChIP-qPCR assay was used to determine the H3K27me3 level of EZH2 target genes. We found that Tanshinone I (Tan I), one of the Tanshinones, can inhibit the proliferation of human leukemia cells and in the xenograft zebrafish model, as well as the normal and malignant definitive hematopoiesis in zebrafish. Mechanistic studies illustrate that Tan I regulates normal and malignant hematopoiesis through direct binding to EZH2, a well-known histone H3K27 methyltransferase, and inhibiting PRC2 enzymatic activity. Furthermore, we identified and as two possible downstream genes of Tan I's effects on EZH2. Together, this study confirmed that Tan I is a novel EZH2 inhibitor and suggested and as two potential therapeutic targets for myeloid malignant diseases.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Abietanes; Animals; Animals, Genetically Modified; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Chromatin Immunoprecipitation; Enhancer of Zeste Homolog 2 Protein; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematopoiesis; Histones; Humans; Leukemia; Matrix Metalloproteinase 9; Neoplasm Proteins; Polycomb Repressive Complex 2; Protein Binding; RNA-Seq; Salvia miltiorrhiza; Surface Plasmon Resonance; Transcriptome; Xenograft Model Antitumor Assays; Zebrafish
PubMed: 34093860
DOI: 10.7150/thno.53170 -
Journal of Hazardous Materials Oct 2023In this study, we developed a colorimetric ozone passive sampler (OPS) incorporating o-dianisidine, a redox dye, into a polydimethylsiloxane sheet. The reaction between...
In this study, we developed a colorimetric ozone passive sampler (OPS) incorporating o-dianisidine, a redox dye, into a polydimethylsiloxane sheet. The reaction between ozone (O) and o-dianisidine result in a visible yellowish color change. Unlike previous passive methods that rely on nitrate extraction or the color disappearance of indigotrisulfonate, the OPS offered improved recognition of average O exposure. To optimize OPS based on time-weighted average (TWA), we extracted and quantified the amount of reacted o-dianisidine after exposing OPS to O by varying concentrations (0-200 ppb) within 8 h. Colorimetric changes of OPS were further analyzed by capturing images, and the effective absorbance of blue scale showed the best fit (EA, R =0.997). OPS validation on visual detection assessed by six parameters: limit of detection, limit of quantification, reproducibility, sampling rate, selectivity to interfering gases, and sensitivity to environmental factors. To enhance visibility, the OPS was assembled with coloration exposure guidelines, and a smartphone app was developed to quantify average O exposures. We further conducted field tests that showed the significant disparity between O concentrations and personal O exposures, which is considered more crucial for assessing health risks. The OPS was optimized to monitor O exposure levels and raise awareness among workers and occupants regarding invisible indoor hazards.
Topics: Humans; Colorimetry; Dianisidine; Reproducibility of Results; Levonorgestrel; Ozone
PubMed: 37703734
DOI: 10.1016/j.jhazmat.2023.132510 -
International Journal of Nanomedicine 2023Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The...
Development of Curcumin and Piperine-Loaded Bio-Active Self-Nanoemulsifying Drugs and Investigation of Their Bioactivity in Zebrafish Embryos and Human Hematological Cancer Cell Lines.
PURPOSE
Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.
METHODS
CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells.
RESULTS
Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and -19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 μg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63±0.23 μg/mL, 26.03 ± 1.5 μg/mL and 17.52 ± 0.22 μg/mL, respectively.
CONCLUSION
Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.
Topics: Animals; Humans; Pharmaceutical Preparations; Curcumin; Zebrafish; Drug Delivery Systems; Solubility; Administration, Oral; Surface-Active Agents; Hematologic Neoplasms; Leukemia; Emulsions; Nanoparticles; Biological Availability
PubMed: 37051315
DOI: 10.2147/IJN.S400330 -
Heliyon Jan 2021Various aromatic compounds that are structurally analogous to lignin were tested as possible/preferred substrates for purified laccase from newly isolated white rote...
Various aromatic compounds that are structurally analogous to lignin were tested as possible/preferred substrates for purified laccase from newly isolated white rote fungi, WRF03. The pH optima were tested using different substrates and kinetic studies were conducted at these pH optima. The pH optima in the presence of ABTS, α-naphthol, o-dianisidine, and catechol were 4.5 but 5.0 and 5.5 in the presence of guaiacol and pyrogallol, respectively. The initial velocities obtained from the kinetic study were analyzed using Graph Pad Prism 7 and Lineweaver-Burk plot to obtain kinetic constants ( and ) which were used to calculate substrate specificity. Amongst all the substrates tested, ABTS had the highest specificity-constant (181.51 Ms), and therefore, the most preferred substrate was followed by α-naphthol, -dianisidine, guaiacol, pyrogallol, and catechol. Resorcinol, orcinol, and veratryl alcohol did not display any considerable chemical shift in the presence of WRF03 laccase. Also, oxidation of phenolic substrates appeared to be dependent on the nature of the substituent groups and their relative position on the aromatic nucleus. Since most of these substrates are structural analogs of lignin and many recalcitrant environmental pollutants, the enzyme may find application in delignification, treatment of wastewater containing dyes, and polycyclic aromatic hydrocarbons (PAHs).
PubMed: 33537494
DOI: 10.1016/j.heliyon.2021.e06080 -
Polymers Dec 2020The pronouncedly low thermal conductivity of polymers in the range of 0.1-0.2 W m K is a limiting factor for their application as an insulating layer in microelectronics...
The pronouncedly low thermal conductivity of polymers in the range of 0.1-0.2 W m K is a limiting factor for their application as an insulating layer in microelectronics that exhibit continuously higher power-to-volume ratios. Two strategies can be applied to increase the thermal conductivity of polymers; that is, compounding with thermally conductive inorganic materials as well as blending with aromatic units arranged by the principle of π-π stacking. In this study, both strategies were investigated and compared on the example of epoxy-amine resins of bisphenol A diglycidyl ether (BADGE) and 1,2,7,8-diepoxyoctane (DEO), respectively. These two diepoxy compounds were cured with mixtures of the diamines isophorone diamine (IPDA) and -dianisidine (DAN). The epoxy-amine resins were cured without filler and with 5 wt.-% of SiO nanoparticles. Enhanced thermal conductivity in the range of 0.4 W·m·K was observed exclusively in DEO-based polymer networks that were cured with DAN (and do not contain SiO fillers). This observation is argued to originate from π-π stacking of the aromatic units of DAN enabled by the higher flexibility of the aliphatic carbon chain of DEO compared with that of BADGE. The enhanced thermal conductivity occurs only at temperatures above the glass-transition point and only if no inorganic fillers, which disrupt the π-π stacking of the aromatic groups, are present. In summary, it can be argued that the bisphenol-free epoxy-amine resin with an epoxy compound derivable from natural resources shows favorably higher thermal conductivity in comparison with the petrol-based bisphenol-based epoxy/amine resins.
PubMed: 33375238
DOI: 10.3390/polym13010065 -
Heliyon Jan 2021Kinetic and physicochemical properties of peroxidase purified using a novel and cost efficient protocol was investigated with a view to providing information on its...
Kinetic and physicochemical properties of peroxidase purified using a novel and cost efficient protocol was investigated with a view to providing information on its possible biotechnological potentials. peroxidase was purified to homogeneity in two steps, involving ATPS and size exclusion chromatography on Sephadex G-100 with a yield of 84.12 %. In-gel activity staining revealed the presence of one isoform of peroxidase. The purified peroxidase is monomeric with native and subunits molecular weight of 38.9 and 43.5 kDa respectively. Kinetic parameters - , , of the purified enzyme were 2.5 units/mg protein, 0.020 ± 0.04 mM and 1.37 ± 0.18 mM respectively. Its optimum pH and temperature were 5 and 30 °C respectively. The purified enzyme cross-linked BSA into an insoluble matrix with the aid of caffeic acid. The study concluded that the purification scheme adopted is rapid and efficient, the purified enzyme exhibited some physiochemical properties that make it suitable for various biotechnological applications.
PubMed: 33521366
DOI: 10.1016/j.heliyon.2021.e06032 -
Ecotoxicology and Environmental Safety Jan 2021The environmental effects of additives have attracted increasing attention. Sodium dehydroacetate (DHA-S), as an approved preservative, is widely added in processed...
The environmental effects of additives have attracted increasing attention. Sodium dehydroacetate (DHA-S), as an approved preservative, is widely added in processed foods, cosmetics and personal care products. However, DHA-S has been recently reported to induce hemorrhage and coagulation aberration in rats. Yet little is known about the ecotoxicological effect and underlying mechanisms of DHA-S. Here, we utilized the advantage of zebrafish model to evaluate such effects. DHA-S induced cerebral hemorrhage, mandibular dysplasia and pericardial edema in zebrafish after 24 h exposure (48-72 hpf) at 50 mg/L. We also observed the defective heart looping and apoptosis in DHA-S-treated zebrafish through o-dianisidine and acridine orange staining. Meanwhile, DHA-S induced the deficiency of Ca and vitamin D3 in zebrafish. We further demonstrated that DHA-S stimulated Ca influx resulting in Ca-dependent mitochondrial damage in cardiomyocytes. Additionally, DHA-S inhibited glucose uptake and repressed the biosynthesis of amino acids. Finally, we identified that sodium bicarbonate could rescue zebrafish from DHA-S induced cardiovascular toxicity. Altogether, our results suggest that DHA-S is a potential risk for cardiovascular system.
Topics: Animals; Apoptosis; Calcium; Cardiotoxicity; Cell Line; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Edema, Cardiac; Embryo, Nonmammalian; Embryonic Development; Heart; Myocardium; Pericardium; Pyrones; Rats; Zebrafish
PubMed: 33396133
DOI: 10.1016/j.ecoenv.2020.111613 -
Nanotoxicology Jun 2018Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining attention. We previously found that silica nanoparticles (SiNPs) could induce vascular...
Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining attention. We previously found that silica nanoparticles (SiNPs) could induce vascular endothelial damage. However, the subsequent toxicologic response to SiNPs-induced endothelial damage was still largely unknown. In this study, we explored the inflammation-coagulation response and thrombotic effects of SiNPs in endothelial cells and zebrafish embryos. For in vitro study, swollen mitochondria and autophagosome were observed in ultrastructural analysis. The cytoskeleton organization was disrupted by SiNPs in vascular endothelial cells. The release of proinflammatory and procoagulant cytokines including IL-6, IL-8, MCP-1, PECAM-1, TF and vWF, were markedly elevated in a dose-dependent manner. For in vivo study, based on the NOAEL for dosimetry selection, and using two transgenic zebrafish, Tg(mpo:GFP) and Tg(fli-1:EGFP), SiNPs-induced neutrophil-mediated inflammation and impaired vascular endothelial cells. With the dosage higher than NOAEL, SiNPs significantly decreased blood flow and velocity, exhibiting a blood hypercoagulable state in zebrafish embryos. The thrombotic effect was assessed by o-dianisidine staining, showed that an increasing of erythrocyte aggregation occurred in SiNPs-treated zebrafish. Microarray analysis was used to screen the possible genes for inflammation-coagulation response to SiNPs in zebrafish, and the JAK1/TF signaling pathway was further verified by qRT-PCR and Western blot assays. For in-deepth study, il6st was knocked down with specific morpholinos. The whole-mount in situ hybridization and qRT-PCR analysis showed that the expression jak1 and f3b were attenuated in il6st knockdown groups. In summary, our data demonstrated that SiNPs could induce inflammation-coagulation response and thrombotic effects via JAK1/TF signaling pathway.
Topics: Animals; Blood Coagulation; Cells, Cultured; Embryo, Nonmammalian; Endothelium, Vascular; Humans; Inflammation; Janus Kinase 1; Nanoparticles; Signal Transduction; Silicon Dioxide; Thrombosis; Zebrafish
PubMed: 29658397
DOI: 10.1080/17435390.2018.1461267 -
Acta Crystallographica. Section E,... Mar 2018The title compound, (systematic name: ,'-dibenzyl-3,3'-dimeth-oxy-1,1'-biphenyl-4,4'-di-amine), CHNO, was synthesized by the reduction of a Schiff base prepared a...
The title compound, (systematic name: ,'-dibenzyl-3,3'-dimeth-oxy-1,1'-biphenyl-4,4'-di-amine), CHNO, was synthesized by the reduction of a Schiff base prepared a condensation reaction between -dianisidine and benzaldehyde under acidic conditions. The mol-ecule lies on a crystallographic inversion centre so that the asymmetric unit contains one half-mol-ecule. The biphenyl moiety compound is essentially planar. Two intra-molecular N-H⋯O hydrogen bonds occur. The dihedral angle between the terminal phenyl and phenyl-ene rings of a benzidine unit is 48.68 (6)°. The methyl-ene C atom of the benzyl group is disordered over two sets of sites, with occupancy ratio 0.779 (18):0.221 (18). In the crystal, mol-ecules are connected by hydrogen bonding between -dianisidine O atoms and H atoms of the terminal benzyl groups, forming a one-dimensional ladder-like structure. In the data from DFT calculations, the central biphenyl showed a twisted conformation.
PubMed: 29765704
DOI: 10.1107/S2056989018001688 -
Indoor Air Mar 2021With an increasing use of indoor disinfectants such as chlorine (Cl ) and hypochlorous acid, a convenient sampler for estimating exposure to oxidants, such as effective...
With an increasing use of indoor disinfectants such as chlorine (Cl ) and hypochlorous acid, a convenient sampler for estimating exposure to oxidants, such as effective chlorine, is necessary. Here, we developed a personal passive air sampler (PPAS) composed of a redox dye, o-dianisidine, in a polydimethylsiloxane (PDMS) sheet. o-Dianisidine readily reacts with gaseous oxidants generated by bleach usage, and its color changes as the reaction progresses; hence, personal exposure to effective chlorine could be easily detected by the naked eye, while cumulative exposure could be determined by measuring concentrations of o-dianisidine reacting with it. The PPAS was calibrated, and a sampling rate of 0.00253 m /h was obtained using a small test chamber. The PPAS was tested with the help of ten volunteers whose personal exposure to Cl -equivalent gas was estimated after bathrooms were cleaned using spray and liquid-type household disinfection products, and the accumulated exposure-gas concentrations ranged from 69 to 408 ppbv and 148 to 435 ppbv, respectively. These PPAS-derived exposure concentrations were approximately two orders lower than those estimated using ConsExpo, suggesting a significant overestimation by prevailing screening models, possibly due to the ignorance of transformation reactions.
Topics: Air Pollutants; Air Pollution, Indoor; Chlorine; Dimethylpolysiloxanes; Disinfectants; Disinfection; Environmental Monitoring; Humans; Hypochlorous Acid; Inhalation Exposure
PubMed: 32978992
DOI: 10.1111/ina.12747