The cellular uptake and cytotoxic effect of curcuminoids on breast cancer cells

AbstractObjectiveCurcuminoids (including curcumin) are natural antioxidants demonstrating potent chemopreventive properties against several forms of cancer. This study investigated the antiproliferative and induced apoptotic effects of curcuminoids on three cell lines isolated from human breast adenocarcinoma and ductal carcinoma (MDA-MB-231, MDA-MB-435S, and MCF-7).Materials and MethodsThis study developed a highly sensitive, reproducible assay method using high-pressure liquid chromatography to quantify the cellular uptake of curcuminoids by breast cancer cells and quantitate its effect on inhibition of proliferation and activation of apoptosis in breast cancer cells.ResultsResults indicate that curcuminoids inhibited cell proliferation and activation of apoptosis in the cell lines in this study. Both effects were observed to increase in proportion to the cellular uptake of curcuminoids; cellular uptake increased following an increase in the dosage of curcuminoids.ConclusionThe inhibition of proliferation and increased apoptosis of breast cancer cells appears to be associated with the uptake of curcuminoids by cancer cells

Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection

The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the “back to nature” approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control

Generation of a platform strain for ionic liquid tolerance using adaptive laboratory evolution.

BackgroundThere is a need to replace petroleum-derived with sustainable feedstocks for chemical production. Certain biomass feedstocks can meet this need as abundant, diverse, and renewable resources. Specific ionic liquids (ILs) can play a role in this process as promising candidates for chemical pretreatment and deconstruction of plant-based biomass feedstocks as they efficiently release carbohydrates which can be fermented. However, the most efficient pretreatment ILs are highly toxic to biological systems, such as microbial fermentations, and hinder subsequent bioprocessing of fermentative sugars obtained from IL-treated biomass.MethodsTo generate strains capable of tolerating residual ILs present in treated feedstocks, a tolerance adaptive laboratory evolution (TALE) approach was developed and utilized to improve growth of two different Escherichia coli strains, DH1 and K-12 MG1655, in the presence of two different ionic liquids, 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) and 1-butyl-3-methylimidazolium chloride ([C4C1Im]Cl). For multiple parallel replicate populations of E. coli, cells were repeatedly passed to select for improved fitness over the course of approximately 40 days. Clonal isolates were screened and the best performing isolates were subjected to whole genome sequencing.ResultsThe most prevalent mutations in tolerant clones occurred in transport processes related to the functions of mdtJI, a multidrug efflux pump, and yhdP, an uncharacterized transporter. Additional mutations were enriched in processes such as transcriptional regulation and nucleotide biosynthesis. Finally, the best-performing strains were compared to previously characterized tolerant strains and showed superior performance in tolerance of different IL and media combinations (i.e., cross tolerance) with robust growth at 8.5% (w/v) and detectable growth up to 11.9% (w/v) [C2C1Im][OAc].ConclusionThe generated strains thus represent the best performing platform strains available for bioproduction utilizing IL-treated renewable substrates, and the TALE method was highly successful in overcoming the general issue of substrate toxicity and has great promise for use in tolerance engineering

Tolerance characterization and isoprenol production of adapted Escherichia coli in the presence of ionic liquids

Ionic liquid (IL)-based pretreatment makes lignocellulosic biomass more accessible to enzymes and improves enzymatic digestibility. However, the ILs left in biomass slurry after pretreatment could inhibit activity of enzymes and microbial fermentation. Therefore, it is necessary to develop robust host strains that are IL-tolerant. In this study, we characterized IL tolerance and biofuel production of adapted Escherichia coli obtained by adaptive laboratory evolution (ALE). We found that IL-tolerant E. coli obtained via ALE by 1-butyl-3-methylimidazolium chloride ([C C Im]Cl) showed improved growth in the presence of four ILs, [C C Im]Cl, 1-ethyl-3-methylimidazolium chloride ([C C Im]Cl), 1-butyl-3-methylimidazolium acetate ([C C Im][OAc]), and 1-ethyl-3-methylimidazolium acetate ([C C Im][OAc]) compared to that of the parent strain. The growth of adapted strain E. coli MG1655-A1 was even promoted by [C C Im]Cl and [C C Im]Cl of certain concentrations. The adapted strains were further transformed by introducing mevalonate-based metabolic pathway and they showed significantly increased isoprenol titer compared to parent strain E. coli MG1655. Furthermore, they were shown to use [C C Im][OAc] and [C C Im][OAc] as carbon sources and assimilate the acetate ions. These results indicated that ALE provided promising host strains for one-pot biofuel production

Dimethyl Sulfoxide Assisted Ionic Liquid Pretreatment of Switchgrass for Isoprenol Production

The production cost and viscosity of certain ionic liquids (ILs) are among the major factors preventing the establishment of economically viable IL-based biomass pretreatment technologies. Recently, mixtures of an IL with an organic solvent have been proposed for cellulose processing and biomass pretreatment. Dimethyl sulfoxide (DMSO) is an inexpensive organic solvent that is industrially produced from lignin, a byproduct of the pulping process. We carry out a mechanistic study of DMSO-assisted IL pretreatment of switchgrass. The physical structures of biomass samples are studied by X-ray diffraction (XRD), N₂ adsorption analysis, and small angle neutron scattering (SANS). Both dry and aqueous suspensions of biomass samples are measured by SANS which provides unique information on biomass pretreatment. A mixture of 42 wt % [C₂C₁Im]­[OAc] and 58 wt % DMSO is proposed as the optimal pretreatment solution, and the recycling and reuse of the mixture of solvents are also studied. The fermentability of the hydrolysates generated after pretreatment is evaluated using an E. coli strain engineered to produce isoprenol. This study suggests an avenue for developing more efficient and cost-effective IL-based processes for the production of lignocellulosic biofuels and bioproducts

Improvement of Trehalose Production by Immobilized Trehalose Synthase from Thermus thermophilus HB27

Trehalose is a non-reducing disaccharide with a wide range of applications in the fields of food, cosmetics, and pharmaceuticals. In this study, trehalose synthase derived from Thermus thermophilus HB27 (TtTreS) was immobilized on silicalite-1-based material for trehalose production. The activity and the stability of TtTreS against pH and temperature were significantly improved by immobilization. Enzyme immobilization also led to a lower concentration of byproduct glucose, which reduces byproduct inhibition of TtTreS. The immobilized TtTreS still retained 81% of its initial trehalose yield after 22 cycles of enzymatic reactions. The immobilized TtTreS exhibited high operational stability and remarkable reusability, indicating that it is promising for industrial applications

MOESM1 of Furfural tolerance and detoxification mechanism in Candida tropicalis

Additional file 1: Table S1. Strains and plasmids used in this study. Table S2. Primers used in this study. Figure S1. Furfural tolerance test evaluated by methylene blue staining. Furfural of 1, 3, 5, 7, and 9 g/L was added into the culture at mid-exponential phase. After having been stained by Methylene blue solvent 30 min, cells were observed and photoed by optical microscope. Figure S2. PCR confirmation of the specific integration in sequential ctADH1 disruption. Lane M, DNA makers; Lane A, PCR from C. tropicalis YE genome with primers ADH1-F and ADH1-R resulting in the band of 1.2 kb (ADH1); Lane B, PCR from C. tropicalis Y1 genome with primers ADH1-F and ADH1-R resulting in the band of 1.2 and 4.3 kb (ADH1 and ADH1a-HisG-URA3-HisG-ADH1b); Lane C, PCR from C. tropicalis Y2 genome with primers ADH1-F and ADH1-R resulting in the band of 1.2 and 1.7 kb (ADH1 and ADH1a-HisG-ADH1b); Lane D, PCR from C. tropicalis Y4 genome with primers ADH1-F and ADH1-R resulting in the band of 1.7 and 2.9 kb (ADH1a-HisG-ADH1b and ADH1-URA3). Figure S3. Sensitivity experiment of C. tropicalis T4, T3, T2, and YE (parent strain). Cells of C. tropicalis T4, T3, T2, and YE were inoculated into 5 ml YPD medium containing 3 g/L furfural. The cultures were incubated for 10 h at 30 °C. Figure S4. SDS-PAGE of alcohol dehydrogenase 1 expressed in E. coli. Lane M, protein molecular weight markers (Thermo Scientific, #26610, USA); Lane A, E. coli PCA cells after IPTG induction; Lane B, E. coli PCA cells before IPTG induction; Lane C, E. coli PC cells without IPTG induction; Lane D, E. coli PEA cells after IPTG induction; Lane E, E. coli PEA cells before IPTG induction; Lane F, E. coli PE cells without IPTG induction. Molecular weight of alcohol dehydrogenase 1 is around 43 kDa. Figure S5. In vivo furfural degradation in recombined E. coli. (A) Furfural degradation of E. coli PCA (with pCS-ADH1) and PC (with pCS-27) in M9 medium; (B) Furfural degradation of E. coli PEA (with pET-ADH1) and PE (with pETDuet-1) in M9 medium

Origin of Topological Hall‐Like Feature in Epitaxial SrRuO3 Thin Films

Abstract The discovery of topological Hall effect (THE) has important implications for next‐generation high‐density nonvolatile memories, energy‐efficient nanoelectronics, and spintronic devices. Both real‐space topological spin configurations and two anomalous Hall effects (AHE) with opposite polarity due to two magnetic phases have been proposed for THE‐like feature in SrRuO3 (SRO) films. In this work, SRO thin films with and without THE‐like features are systematically Investigated to decipher the origin of the THE feature. Magnetic measurement reveals the coexistence of two magnetic phases of different coercivity (Hc) in both the films, but the hump feature cannot be explained by the two channel AHE model based on these two magnetic phases. In fact, the AHE is mainly governed by the magnetic phase with higher Hc. A diffusive Berry phase transition model is proposed to explain the THE feature. The coexistence of two Berry phases with opposite signs over a narrow temperature range in the high Hc magnetic phase can explain the THE like feature. Such a coexistence of two Berry phases is due to the strong local structural tilt and microstructure variation in the thinner films. This work provides an insight between structure/micro structure and THE like features in SRO epitaxial thin films