An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy.

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO2) and oridonin (ORI). This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis, thereby enhancing ferroptosis therapy. Fused cell membranes (FM) were used to modify nanoparticles (ORI@CaO2@Fe-TCPP, NPs) to produce FM@ORI@CaO2@Fe-TCPP (FM@NPs). The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously, working in tandem with Fe3+ to induce ferroptosis. Photodynamic therapy (PDT) guided by porphyrin (TCPP) significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species (ROS). This self-amplifying strategy promoted robust ferroptosis, which could work synergistically with FM-mediated immunotherapy. In vivo experiments showed that FM@NPs inhibited 91.57% of melanoma cells within six days, a rate 5.6 times higher than chemotherapy alone. FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity. Thus, this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

Mesoporous Silica-Based Membranes in Transdermal Drug Delivery: The Role of Drug Loss in the Skin.

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes.

Analyzing water hyacinth plants from two South African rivers for the detection of seven pharmaceuticals and their metabolites.

Water hyacinth plants (Eichhornia crassipes Mart.) collected from two South African rivers were analyzed in order to investigate their suitability for judging the presence of pharmaceuticals in the water. Thereby, a number of drugs, including amitriptyline, atenolol, citalopram, orphenadrine, lidocaine, telmisartan, and tramadol, could be detected. Particularly for the latter substance, relatively high concentrations (more than 5000 ng g-1 dry plant material) were detected in the water plants. Subsequently, the plant extracts were also screened for drug-derived transformation products, whereby a series of phase-one metabolites could be tentatively identified.

Root uptake of cereal benzoxazinoids grants resistance to root-knot nematode invasion in white clover.

Plants synthesize a plethora of chemical defence compounds, which vary between evolutionary lineages. We hypothesize that plants evolved the ability to utilize defence compounds synthesized and released by neighbouring heterospecific plants. In two experiments, we incubated clover (Trifolium repens L.) seedlings with individual benzoxazinoid (BX) compounds (2,4-dihydroxy-1,4-benzoxazin-3-one, 2-hydroxy-1,4-benzoxazin-3-one, benzoxazolinone, and 6-methoxy- benzoxazolin-2-one), a group of bioactive compounds produced by cereals, to allow clover BX uptake. Subsequently, we transplanted the seedlings into soil and quantified BX root and shoot content and invasion of root-knot nematodes in clover roots up to 8 weeks after transplantation. We show that clover root uptake of BXs substantially enhanced clover's resistance against the root-knot nematode Meloidogyne incognita. This effect lasted up to 6 weeks after the clover roots were exposed to the BXs. BXs were absorbed by clover roots, and then translocated to the shoots. As a result of clover metabolization, we detected the parent BXs and a range of their transformation products in the roots and shoots. Based on these novel findings, we envisage that co-cultivation of crop species with complementary and transferable chemical defence systems can add to plant protection.

Effects of bioconversion by Battus polydamas on the chemical composition of Aristolochia spp. and evaluation of antimicrobial activity and biocompatibility.

Aristolochia plants are emblematic from an ethnopharmacological viewpoint and are know to possess numerous biological properties, including antiseptic. However, the medicinal potential of these species is debatable because of their representative chemical constituents, aristolochic acids (AAs) and aristolactams (ALs), which are associated, for instance, with nephropathy and cancer. These contrasting issues have stimulated the development of approaches intended to detoxification of aristoloquiaceous biomasses, among which is included the bioconversion method using larvae of the specialist phytophagous insect Battus polydamas, previously shown to be viable for chemical diversification and to reduce toxicity. Thus, eleven Aristolochia spp. were bioconverted, and the antimicrobial activities of the plant methanolic extracts and its respective bioconversion products were evaluated. The best results were found for Aristolochia esperanzae, Aristolochia gibertii, and Aristolochia ringens against Bacillus cereus, with MIC ranging from 7.8 to 31.25 µg/mL. These three species were selected for chemical, antioxidant, cytotoxic, hemolytic, and mutagenic analyses. Chemical analysis revealed 65 compounds, 21 of them possible bioconversion products. The extracts showed potential to inhibit the formation and degradation of B. cereus biofilms. Extracts of A. gibertii and its bioconverted biomass showed antioxidant activity comparable to dibutylhydroxytoluene (BHT) standard. Bioconversion decreased the hemolytic activity of A. esperanzae and the cytotoxicities of A. esperanzae and A. gibertii. None of the extracts was found to be mutagenic. The bioactivities of the fecal extracts were maintained, and biocompatibility was improved. Therefore, the results obtained in this study reveal positive expectations about the natural detoxification process of the Aristolochia species.

Utilization of Free and Dipeptide-Bound Formyline and Pyrraline by Saccharomyces Yeasts.

The utilization of the glycated amino acids formyline and pyrraline as well as their peptide-bound derivatives by 14 Saccharomyces yeasts, including 6 beer yeasts (bottom and top fermenting), one wine yeast, 6 strains isolated from natural habitats and one laboratory reference yeast strain (wild type) was investigated. All yeasts were able to metabolize glycated amino acids via the Ehrlich pathway to the corresponding Ehrlich metabolites. While formyline and small amounts of pyrraline entered the yeast cells via passive diffusion, the amounts of dipeptide-bound MRPs, especially the dipeptides glycated at the C-terminus, decreased much faster, indicating an uptake into the yeast cells. Furthermore, the glycation-mediated hydrophobization in general leads to an faster degradation rate compared to the native lysine dipeptides. While the utilization of free formyline is yeast-specific, the amounts of (glycated) dipeptides decreased faster in the presence of brewer's yeasts, which also showed a higher formation rate of Ehrlich metabolites compared to naturally isolated strains. Due to rapid uptake of alanyl dipeptides, it can be assumed that the Ehrlich enzyme system of naturally isolated yeasts is overloaded and the intracellularly released MRP is primarily excreted from the cell. This indicates adaptation of technologically used yeasts to (glycated) dipeptides as a nitrogen source.

Biodegradation capabilities of filamentous fungi in high-concentration heavy crude oil environments.

In this comprehensive study, we delved into the capabilities of five fungal strains: Aspergillus flavus, Aspergillus niger, Penicillium chrysogenum, Penicillium glabrum, and Penicillium rubens (the latter isolated from heavy crude oil [HCO]) in metabolizing HCO as a carbon source. Employing a meticulously designed experimental approach, conducted at room temperature (25 °C), we systematically explored various culture media and incubation periods. The results unveiled the exceptional resilience of all these fungi to HCO, with A. flavus standing out as the top performer. Notably, A. flavus exhibited robust growth, achieving a remarkable 59.1% expansion across the medium's surface, accompanied by distinctive macroscopic traits, including a cottony appearance and vibrant coloration. In an effort to further scrutinize its biotransformation prowess, we conducted experiments in a liquid medium, quantifying CO2 production through gas chromatography, which reached its zenith at day 30, signifying substantial bioconversion with a 38% increase in CO2 production. Additionally, we monitored changes in surface tension using the Du Noüy ring method, revealing a reduction in aqueous phase tension from 72.3 to 47 mN/m. This compelling evidence confirms that A. flavus adeptly metabolizes HCO to fuel its growth, while concurrently generating valuable biosurfactants. These findings underscore the immense biotechnological potential of A. flavus in addressing challenges related to HCO, thereby offering promising prospects for bioremediation and crude oil bioupgrading endeavors.

Mobility, speciation of cadmium, and bacterial community composition along soil depths during microbial carbonate precipitation under simulated acid rain.

An overexploitation of earth resources results in acid deposition in soil, which adversely impacts soil ecosystems and biodiversity and affects conventional heavy metal remediation using immobilization. A series of column experiments was conducted in this study to compare the cadmium (Cd) retention stability through biotic and abiotic carbonate precipitation impacted by simulated acid rain (SAR), to build a comprehensive understanding of cadmium speciation and distribution along soil depth and to elucidate the biogeochemical bacteria-soil-heavy metal interfaces. The strain of Sporosarcina pasteurii DSM 33 was used to trigger the biotic carbonate precipitation and cultivated throughout the 60-day column incubation. Results of soil pH, electrical conductivity (EC), and quantitative CdCO3/CaCO3 analysis concluded that the combination of biotic and abiotic soil treatment could reinforce soil buffering capacity as a strong defense mechanism against acid rain disturbance. Up to 1.8 ± 0.04 U/mg urease enzyme activity was observed in combination soil from day 10, confirming the sustained effect of urease-mediated microbial carbonate precipitation. Cadmium speciation and distribution analyses provided new insights into the dual stimulation of carbonate-bound and Fe/Mn-bound phases of cadmium immobilization under microbially induced carbonate precipitation (MICP). As confirmed by the microbial community analysis, outsourcing urea triggered diverse microbial metabolic responses, notably carbonate precipitation and dissimilatory iron metabolism, in both oxygen-rich topsoil and oxygen-depleted subsurface layers. The overall investigation suggests the feasibility of applying MICP for soil Cd remediation under harsh environments and stratagem by selecting microbial functionality to overcome environmental challenges.

Review: Fish bile, a highly versatile biomarker for different environmental pollutants.

Ecotoxicological assessments encompass a broad spectrum of biochemical endpoints and ecological factors, allowing for comprehensive assessments concerning pollutant exposure levels and their effects on both fish populations and surrounding ecosystems. While these evaluations offer invaluable insights into the overall health and dynamics of aquatic environments, they often provide an integrated perspective, making it challenging to pinpoint the precise sources and individual-level responses to environmental contaminants. In contrast, biliary pollutant excretion assessments represent a focused approach aimed at understanding how fish at the individual level respond to environmental stressors. In this sense, the analysis of pollutant profiles in fish bile not only serves as a valuable exposure indicator, but also provides critical information concerning the uptake, metabolism, and elimination of specific contaminants. Therefore, by investigating unique and dynamic fish responses to various pollutants, biliary assessments can contribute significantly to the refinement of ecotoxicological studies. This review aims to discuss the multifaceted utility of bile as a potent biomarker for various environmental pollutants in fish in targeted monitoring strategies, such as polycyclic aromatic hydrocarbons, metals, pesticides, pharmaceuticals, estrogenic compounds, resin acids, hepatotoxins and per- and polyfluorinated substances. The main caveats of this type of assessment are also discussed, as well as future directions of fish bile studies.

Metabolization of the Amadori Product N-ε-Fructosyllysine by Probiotic Bacteria.

Glycation reactions in food lead to the formation of the Amadori rearrangement product (ARP) N-ε-fructosyllysine (fructoselysine, FL), which is taken up with the daily diet and comes into contact with the gut microbiota during digestion. In the present study, nine commercially available probiotic preparations as well as single pure strains thereof were investigated for their FL-degrading capability under anaerobic conditions. One of the commercial preparations as well as three single pure strains thereof was able to completely degrade 0.25 mM FL within 72 h. Three new deglycating lactic acid bacteria species, namely, Lactobacillus buchneri DSM 20057, Lactobacillus jensenii DSM 20557, and Pediococcus acidilactici DSM 25404, could be identified. Quantitative experiments showed that FL was completely deglycated to lysine. Using 13C6-labeled FL as the substrate, it could be proven that the sugar moiety of the Amadori product is degraded to lactic acid, showing for the first time that certain lactic acid bacteria can utilize the sugar moiety as a substrate for lactic acid fermentation.

Formation mechanism of lipid-derived volatile flavor compounds metabolized by inoculated probiotics and their improving effect on the flavor of low-salt dry-cured mackerel.

This study aimed to evaluate the contribution and mechanisms of Lactobacillus plantarum and Zygosaccharomyces mellis inoculation to the enhancement of aroma in low-salt dry-cured mackerel (LDCM). Inoculating probiotics significantly improved the LDCM's aroma, with mixed probiotics showing a superior effect. The contents of lipid-derived volatile flavor compounds (LVFCs), free fatty acid contents, and key enzyme activities significantly increased (p < 0.05) in probiotic-treated groups. The dominant species in the probiotics-treated groups were the inoculated Lactobacillus plantarum and Zygosaccharomyces mellis, which were the main producer of metabolic enzymes for the generation of LVFCs. Lactobacillus plantarum performed well in lipid hydrolysis and aldehydes reduction, while Zygosaccharomyces mellis played a main role in aldehyde production.

Mechanism of selenite tolerance during barley germination: A combination of tissue selenium metabolism alterations and ascorbate-glutathione cycle modulation.

Selenite is widely used to increase Selenium (Se) content in cereals, however excessive selenite may be toxic to plant growth. In this study, barley was malted to elucidate the action mechanism of selenite in the generation and detoxification of oxidative toxicity. The results showed that high doses (600 µM) of selenite radically increased oxidative stress by the elevated accumulation of superoxide and malondialdehyde, leading to phenotypic symptoms of selenite-induced toxicity like stunted growth. Barley tolerates selenite through a combination of mechanisms, including altering Se distribution in barley, accelerating Se efflux, and increasing the activity of some essential antioxidant enzymes. Low doses (150 µM) of selenite improved barley biomass, respiratory rate, root vigor, and maintained the steady-state equilibrium between reactive oxygen species (ROS) and antioxidant enzyme. Selenite-induced proline may act as a biosignal to mediate the response of barley to Se stress. Furthermore, low doses of selenite increased the glutathione (GSH) and ascorbate (AsA) concentrations by mediating the ascorbate-glutathione cycle (AsA-GSH cycle). GSH intervention and dimethyl selenide volatilization appear to be the primary mechanisms of selenite tolerance in barley. Thus, results from this study will provide a better understanding of the mechanisms of selenite tolerance in crops.

The contribution of inoculated probiotics to increased protein-derived volatile flavor compounds.

This study aimed to evaluate the contribution and mechanisms of Lactobacillus plantarum and Zygosaccharomyces mellis inoculation to the enhancement of protein-derived volatile flavor compounds (PVFCs) in low-salt dry-cured mackerel (LDCM). The contents of PVFCs (3-methylbutanal and phenylacetaldehyde), intermediates (α-ketoisocaproate and phenylpyruvic acid), precursor (α-ketoisocaproate and phenylpyruvic acid), and key enzyme activities (protease and transaminase) significantly increased (p < 0.05) in probiotic-treated groups. The dominant species in the probiotics-treated groups were the inoculated Lactobacillus plantarum and Zygosaccharomyces mellis, which were the main producer of key enzymes for the generation of PVFCs. Lactobacillus plantarum performed well in protein degradation and amino acid transamination, resulting in generating more 3-methylbutanal and phenylacetaldehyde, while Zygosaccharomyces mellis played a main role in phenylethanol production. The synergistic action of Lactobacillus plantarum and Zygosaccharomyces mellis could promote the formation of 3-methyl-1-butanol.

Bioactive profiles of edible vegetable oils determined using 10D hyphenated comprehensive high-performance thin-layer chromatography (HPTLC×HPTLC) with on-surface metabolism (nanoGIT) and planar bioassays.

Introduction: Vegetable oils rich in unsaturated fatty acids are assumed to be safe and even healthy for consumers though lipid compositions of foods vary naturally and are complex considering the wealth of minor compounds down to the trace level. Methods: The developed comprehensive high-performance thin-layer chromatography (HPTLC×HPTLC) method including the on-surface metabolization (nanoGIT) and bioassay detection combined all steps on the same planar surface. The pancreatic lipolysis (intestinal phase) experiment and the subsequent analysis of the fatty acid composition including its effect-directed detection using a planar bioassay was performed without elaborate sample preparation or fractionation to ensure sample integrity. Thus, no sample part was lost, and the whole sample was studied on a single surface regarding all aspects. This made the methodology as well as technology miniaturized, lean, all-in-one, and very sustainable. Results and discussion: To prioritize important active compounds including their metabolism products in the complex oil samples, the nanoGIT method was used to examine the pancreatic lipolysis of nine different vegetable oils commonly used in the kitchen and food industry, e.g., canola oil, flaxseed oil, hemp oil, walnut oil, soybean oil, sunflower oil, olive oil, coconut oil, and palm oil. The digested oils revealed antibacterial and genotoxic effects, which were assigned to fatty acids and oxidized species via high-resolution tandem mass spectrometry (HRMS/MS). This finding reinforces the importance of adding powerful techniques to current analytical tools. The 10D hyphenated nanoGIT-HPTLC×HPTLC-Vis/FLD-bioassay-heart cut-RP-HPLC-DAD-HESI-HRMS/MS has the potential to detect any potential hazard due to digestion/metabolism, improving food safety and understanding on the impact of complex samples.

Mineralization of Few-Layer Graphene Made It Bioavailable in Chlamydomonas reinhardtii.

Numerous studies have emphasized the toxicity of graphene-based nanomaterials to algae, however, the fundamental behavior and processes of graphene in biological hosts, including its transportation, metabolization, and bioavailability, are still not well understood. As photosynthetic organisms, algae are key contributors to carbon fixation and may play an important role in the fate of graphene. This study investigated the biological fate of 14C-labeled few-layer graphene (14C-FLG) in Chlamydomonas reinhardtii (C. reinhardtii). The results showed that 14C-FLG was taken up by C. reinhardtii and then translocated into its chloroplast. Metabolomic analysis revealed that 14C-FLG altered the metabolic profiles (including sugar metabolism, fatty acid, and tricarboxylic acid cycle) of C. reinhardtii, which promoted the photosynthesis of C. reinhardtii and then enhanced their growth. More importantly, the internalized 14C-FLG was metabolized into 14CO2, which was then used to participate in the metabolic processes required for life. Approximately 61.63%, 25.31%, and 13.06% of the total radioactivity (from 14CO2) was detected in carbohydrates, lipids, and proteins of algae, respectively. Overall, these results reveal the role of algae in the fate of graphene and highlight the potential of available graphene in bringing biological effects to algae, which helps to better assess the environmental risks of graphene.

ß-(1 → 3)(1 → 6)glucan from Schizophyllum commune 227E.32: High yield production via glucose/xylose co-metabolization.

A co-metabolization of xylose and glucose by Schizophyllum commune 227E.32 wild mushroom for exopolysaccharide (EPS) production is presented. Cultivations performed with S. commune 227E.32 at different xylose concentrations demonstrated that the concentration of 50 g·L-1 of xylose achieved the highest EPS production, around 4.46 g·L-1. Scale-up in a stirred tank reactor (STR) was performed. 10 % inoculum showed the highest cost/benefit ratio regarding sugar conversion and EPS production (Y P/S = 0.90 g·g-1), achieving 1.82 g·L-1 of EPS. Isolation, purification, and characterization were conducted with EPS produced in flasks and STR. GC-MS analysis showed glucose as main monosaccharide constituents for both isolates. 13C NMR and HSQC-edited showed that both EPS isolated consisted of a ß-D-Glcp (1 â†’ 3) main chain, partially substituted at O-6 with nonreducing ß-D-Glcp ends on every third residue, similar to ß-D-glucan isolated from S. commune basidiomes known as schizophyllan (SPG). The Mw was determined by GPC to 1.5 × 106 Da (flasks) and 1.1 × 106 Da (STR). AFM topographs revealed a semi-flexible appearance of the ß-D-glucan, consistent with the triple helical structures adopted by SPG and overall contour length consistent with a high molar mass.

Influence of Different Diets on the Degradation of Sulfasalazine by Colon Bacteria Determined Using MimiCol3.

The microbiome of the colon is characterized by its great diversity. This varies not only intra- but also interindividually and is influenced by endogenous and exogenous factors, such as dietary and lifestyle factors. The aim of this work was to investigate the extent to which the degradation of the drug sulfasalazine is influenced by different microbiota. Therefore, the in vitro model MimiCol3 was used, which represents the physiological conditions of the ascending colon. In addition to a representative physiological volume, the pH value, redox potential and an anaerobic atmosphere are important to provide the bacteria with the best possible growth conditions. Stool samples were taken from three healthy subjects, comparing omnivorous, vegetarian and meat-rich diets, and cultured for 24 h. However, the nutrient medium used for cultivation led to the alignment of the bacterial composition of the microbiota. The previously observed differences between the diets could not be maintained. Nevertheless, the similar degradation of sulfasalazine was observed in all microbiota studied in MimiCol3. This makes MimiCol3 a suitable in vitro model for metabolism studies in the gut microbiome.

Bacterial responses to plant antimicrobials: the case of alkannin and shikonin derivatives.

Alkannin, shikonin and their derivatives (A/S) are secondary metabolites produced in the roots of certain plants of the Boraginaceae family such as Lithospermum erythrorhizon Siebold & Zucc. and Alkanna tinctoria (L.) Tausch. These naphthoquinones express anti-cancer, wound healing, and antimicrobial activities. To study the interactions between endophytic bacteria isolated from A. tinctoria and the antimicrobials A/S, endophytic bacteria known to be resistant to the compounds were screened for their effect on A/S in liquid medium. Thereafter, the strain Pseudomonas sp. R-72008, was selected and tested for its ability to modify A/S in nutrient medium and minimal medium with A/S as sole carbon source. Bacterial growth was recorded, and high performance liquid chromatography-diode array and ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry analyses were performed to detect and quantify metabolites. In nutrient medium inoculated with R-72008, a decrease in the amount of A/S monomers initially present was observed and correlated with an increase of A/S oligomers. Moreover, a significant decrease of initial A/S monomers in minimal medium was correlated with bacterial growth, showing for the first time that a bacterial strain, Pseudomonas sp. R-72008, was able to use the naphthoquinones A/S as sole carbon source. This study opens new perspectives on the interactions between bacteria and plant antimicrobials.

Miniaturized method for the quantification of persistent organic pollutants and their metabolites in HepG2 cells: assessment of their biotransformation.

Biotransformation can greatly influence the accumulation and, subsequently, toxicity of substances in living beings. Although traditionally these studies to quantify metabolization of a compound have been carried out with in vivo species, currently, in vitro test methods with very different cell lines are being developed for their evaluation. However, this is still a very limited field due to multiple variables of a very diverse nature. So, an increasing number of analytical chemists are working with cells or other similar biological samples of very small size. This makes it necessary to address the development of analytical methods that allow determining their concentration both inside the cells and in their exposure medium. The aim of this study is to develop a set of analytical methodologies for the quantification of polycyclic aromatic hydrocarbons, PAHs (phenanthrene, PHE), and polybrominated diphenyl ethers, PBDEs (2,2',4,4'-tetrabromodiphenyl ether, BDE-47), and their major metabolites in cells and their exposure medium. Analytical methodologies, based on miniaturized ultrasound probe-assisted extraction, gas chromatography-mass spectrometry-microelectron capture detector (GC-MS-µECD), and liquid chromatography-fluorescence detector (LC-FL) determination techniques, have been optimized and then applied to a biotransformation study in HepG2 at 48 h of exposure. Significant concentrations of the major metabolites of PHE (1-OH, 2-OH, 3-OH, 4-OH-, and 9-OH-PHE) and BDE-47 (5-MeO-, 5-OH-, and 3-OH-BDE-47) were detected and quantified inside the cells and in the exposure medium. These results provide a new method for determination and improve information on the metabolization ratios for a better knowledge of the metabolic pathways and their toxicity.

Remnant cholesterol, stronger than triglycerides, is associated with incident non-alcoholic fatty liver disease.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of triglycerides within the liver. However, whether the circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol, remnant-C) are related to the occurrence of NAFLD has not yet been studied. This study aims to assess the association of triglycerides and remnant-C with NAFLD in a Chinese cohort of middle aged and elderly individuals. Methods: All subjects in the current study are from the 13,876 individuals who recruited in the Shandong cohort of the REACTION study. We included 6,634 participants who had more than one visit during the study period with an average follow-up time of 43.34 months. The association between lipid concentrations and incident NAFLD were evaluated by unadjusted and adjusted Cox proportional hazard models. The potential confounders were adjusted in the models including age, sex, hip circumference (HC), body mass index (BMI), systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), diabetes status and cardiovascular disease (CVD) status. Results: In multivariable-adjusted Cox proportional hazard model analyses, triglycerides (hazard ratio[HR], 95% confidence interval [CI]:1.080,1.047-1.113;p<0.001), high-density lipoprotein cholesterol (HDL-C) (HR, 95% CI: 0.571,0.487-0.670; p<0.001), and remnant-C (HR, 95% CI: 1.143,1.052-1.242; p=0.002), but not total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), were associated with incident NAFLD. Atherogenic dyslipidemia (triglycerides>1.69 mmol/L, HDL-C<1.03 mmol/L in men or<1.29 mmol/L in women) was also associated with NAFLD (HR, 95% CI: 1.343,1.177-1.533; p<0.001). Remnant-C levels were higher in females than in males and increased with increasing BMI and in participants with diabetes and CVD compared with those without diabetes or CVD. After adjusting for other factors in the Cox regression models, we found that serum levels of TG and remnant-C, but not TC or LDL-C, were associated with NAFLD outcomes in women group, non-cardiovascular disease status, non-diabetes status and middle BMI categories (24 to 28 kg/m2). Discussion: In the middle aged and elderly subset of the Chinese population, especially those who were women, non-CVD status, non-diabetes status and middle BMI status (24 to 28 kg/m2), levels of triglycerides and remnant-C, but not TC or LDL-C, were associated with NAFLD outcomes independent of other risk factors.