Study on multiscale structures and digestibility of cassava starch and medium-chain fatty acids complexes using molecular simulation techniques.

Effect of complexation of three medium-chain fatty acids (octanoic, decylic and lauric acid, OA, DA and LA, respectively) on structural characteristics, physicochemical properties and digestion behaviors of cassava starch (CS) was investigated. Current study indicated that LA was more easily to combine with CS (complex index 88.9%), followed by DA (80.9%), which was also consistent with their corresponding complexed lipids content. Following the investigation of morphology, short-range ordered structure, helical structure, crystalline/amorphous region and fractal dimension of the various complexes, all cassava starch-fatty acids complexes (CS-FAs) were characterized with a flaked morphology rather than a round morphology in native starch (control CS). X-ray diffraction demonstrated that all CS-FAs had a V-type crystalline structure, and nuclear magnetic resonance spectroscopy confirmed that the complexes made from different fatty acids displayed similar V6 or V7 type polymorphs. Interestingly, small-angle X-ray scattering analysis revealed that α value became greater following increased carbon chain length of fatty acids, indicating the formation of a more ordered fractal structure in the aggregates. Changes in rheological parameters G' and G'' indicated that starch complexed with fatty acids was more likely to form a gel network, but difference among three CS-FAs complexes was significant, which might be contributed to their corresponding hydrophobicity and hydrophilicity raised from individual fatty acids. Importantly, digestion indicated that CS-LA complexes had the lowest hydrolysis degree, followed by the greatest RS content, indicating the importance of chain length of fatty acids for manipulating the fine structure and functionality of the complexes.

Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Associations between serum perfluoroalkyl and polyfluoroalkyl concentrations and diabetes mellitus in the Korean general population: Insights from the Korean National Environmental Health Survey 2018-2020.

AIMS: Recent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. METHODS: We analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018-2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7-6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. RESULTS: In the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. CONCLUSIONS: These findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.

Individual and joint associations of per- and polyfluoroalkyl substances (PFAS) with gallstone disease in adults: A cross-sectional study.

Disturbances in the enterohepatic circulation are important biological mechanisms for causing gallstones and also have important effects on the metabolism of Per- and polyfluoroalkyl substances (PFAS). Moreover, PFAS is associated with sex hormone disorder which is another important cause of gallstones. However, it remains unclear whether PFAS is associated with gallstones. In this study, we used logistic regression, restricted cubic spline (RCS), quantile g-computation (qg-comp), Bayesian kernel machine regression (BKMR), and subgroup analysis to assess the individual and joint associations of PFAS with gallstones and effect modifiers. We observed that the individual associations of perfluorodecanoic acid (PFDeA) (OR: 0.600, 95% CI: 0.444 to 0.811), perfluoroundecanoic acid (PFUA) (OR: 0.630, 95% CI: 0.453 to 0.877), n-perfluorooctane sulfonic acid (n-PFOS) (OR: 0.719, 95% CI: 0.571 to 0.906), and perfluoromethylheptane sulfonic acid isomers (Sm-PFOS) (OR: 0.768, 95% CI: 0.602 to 0.981) with gallstones were linearly negative. Qg-comp showed that the PFAS mixture (OR: 0.777, 95% CI: 0.514 to 1.175) was negatively associated with gallstones, but the difference was not statistically significant, and PFDeA had the highest negative association. Moreover, smoking modified the association of perfluorononanoic acid (PFNA) with gallstones. BKMR showed that PFDeA, PFNA, and PFUA had the highest groupPIP (groupPIP = 0.93); PFDeA (condPIP = 0.82), n-perfluorooctanoic acid (n-PFOA) (condPIP = 0.68), and n-PFOS (condPIP = 0.56) also had high condPIPs. Compared with the median level, the joint association of the PFAS mixture with gallstones showed a negative trend; when the PFAS mixture level was at the 70th percentile or higher, they were negatively associated with gallstones. Meanwhile, when other PFAS were fixed at the 25th, 50th, and 75th percentiles, PFDeA had negative associations with gallstones. Our evidence emphasizes that PFAS is negatively associated with gallstones, and more studies are needed in the future to definite the associations of PFAS with gallstones and explore the underlying biological mechanisms.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGß), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGß: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGß. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGß only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGß only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGß differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation.

The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health.

Characterizing Important Dietary Exposure Sources of Perfluoroalkyl Acids in Inuit Youth and Adults in Nunavik Using a Feature Selection Tool.

BACKGROUND: Previous studies have identified the consumption of country foods (hunted/harvested foods from the land) as the primary exposure source of perfluoroalkyl acids (PFAA) in Arctic communities. However, identifying the specific foods associated with PFAA exposures is complicated due to correlation between country foods that are commonly consumed together. METHODS: We used venous blood sample data and food frequency questionnaire data from the Qanuilirpitaa? ("How are we now?") 2017 (Q2017) survey of Inuit individuals ≥16 y of age residing in Nunavik (n=1,193). Adaptive elastic net, a machine learning technique, identified the most important food items for predicting PFAA biomarker levels while accounting for the correlation among the food items. We used generalized linear regression models to quantify the association between the most predictive food items and six plasma PFAA biomarker levels. The estimates were converted to percent changes in a specific PFAA biomarker level per standard deviation increase in the consumption of a food item. Models were also stratified by food type (market or country foods). RESULTS: Perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with frequent consumption of beluga misirak (rendered fat) [14.6%; 95% confidence interval (CI): 10.3%, 18.9%; 14.6% (95% CI: 10.1%, 19.0%)], seal liver [9.3% (95% CI: 5.0%, 13.7%); 8.1% (95% CI: 3.5%, 12.6%)], and suuvalik (fish roe mixed with berries and fat) [6.0% (95% CI: 1.3%, 10.7%); 7.5% (95% CI: 2.7%, 12.3%)]. Beluga misirak was also associated with higher concentrations of perfluorohexanesulphonic acid (PFHxS) and perfluorononanoic acid (PFNA), albeit with lower percentage changes. PFHxS, perfluorooctanoic acid (PFOA), and PFNA followed some similar patterns, with higher levels associated with frequent consumption of ptarmigan [6.1% (95% CI: 3.2%, 9.0%); 5.1% (95% CI: 1.1%, 9.1%); 5.4% (95% CI: 1.8%, 9.0%)]. Among market foods, frequent consumption of processed meat and popcorn was consistently associated with lower PFAA exposure. CONCLUSIONS: Our study identifies specific food items contributing to environmental contaminant exposure in Indigenous or small communities relying on local subsistence foods using adaptive elastic net to prioritize responses from a complex food frequency questionnaire. In Nunavik, higher PFAA biomarker levels were primarily related to increased consumption of country foods, particularly beluga misirak, seal liver, suuvalik, and ptarmigan. Our results support policies regulating PFAA production and use to limit the contamination of Arctic species through long-range transport. https://doi.org/10.1289/EHP13556.

LORE receptor homomerization is required for 3-hydroxydecanoic acid-induced immune signaling and determines the natural variation of immunosensitivity within the Arabidopsis genus.

The S-domain-type receptor-like kinase (SD-RLK) LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) from Arabidopsis thaliana is a pattern recognition receptor that senses medium-chain 3-hydroxy fatty acids, such as 3-hydroxydecanoic acid (3-OH-C10:0), to activate pattern-triggered immunity. Here, we show that LORE homomerization is required to activate 3-OH-C10:0-induced immune signaling. Fluorescence lifetime imaging in Nicotiana benthamiana demonstrates that AtLORE homomerizes via the extracellular and transmembrane domains. Co-expression of AtLORE truncations lacking the intracellular domain exerts a dominant negative effect on AtLORE signaling in both N. benthamiana and A. thaliana, highlighting that homomerization is essential for signaling. Screening for 3-OH-C10:0-induced reactive oxygen species production revealed natural variation within the Arabidopsis genus. Arabidopsis lyrata and Arabidopsis halleri do not respond to 3-OH-C10:0, although both possess a putative LORE ortholog. Both LORE orthologs have defective extracellular domains that bind 3-OH-C10:0 to a similar level as AtLORE, but lack the ability to homomerize. Thus, ligand binding is independent of LORE homomerization. Analysis of AtLORE and AlyrLORE chimera suggests that the loss of AlyrLORE homomerization is caused by several amino acid polymorphisms across the extracellular domain. Our findings shed light on the activation mechanism of LORE and the loss of 3-OH-C10:0 perception within the Arabidopsis genus.

Parallel electromembrane extraction of peptides with monoterpene and medium-length fatty acid deep eutectic solvents.

BACKGROUND: Electromembrane extraction (EME) involves the process of mass transfer of charged analytes from an aqueous sample through an organic liquid membrane into an aqueous acceptor medium under the influence of an electrical field. Successful solvation of the analyte within the liquid membrane is of paramount importance and involves molecular interactions with the liquid membrane. In this comprehensive investigation, parallel EME was examined using a training set of 13 model peptides employing deep eutectic solvents as the liquid membrane. These deep eutectic solvents were formulated by mixing specific monoterpenes (thymol, menthol, camphor) with medium-chain fatty acids (1-octanoic acid and 1-decanoic acid). RESULTS: From an array of different liquid membrane compositions explored, it was revealed that the combination of camphor and 1-decanoic acid (in a 1:1 w/w ratio) with 2% di (2-ethylhexyl) phosphate (DEHP) delivered the most efficient extraction system. The solvation of the model peptides within this liquid membrane predominantly relied on ionic interactions between protonated basic functionalities and DEHP, along with hydrogen bond interactions between the deprotonated acid functionalities (hydrogen bond acceptor) and 1-decanoic acid (hydrogen bond donor). Selectivity was modulated by the pH of the sample and acceptor solutions, with a direct correlation to the polarity and net charge of the model peptides. The ionization of 1-decanoic acid in the interfacial region between the sample and liquid membrane emerged as an important factor influencing the selectivity. SIGNIFICANCE AND NOVELTY: Although parallel EME of peptides has been reported previously, the current liquid membrane provides an extraction system with sufficient stability for the first time. Selective extraction of peptides through EME holds substantial promise within the realm of next-generation environmentally-friendly sample preparation methodologies. The findings presented in this paper contribute significantly to our fundamental understanding of these processes, and may serve as an important reference for the development of future methods in this field.

No Effects of Decanoic Acid on Locomotor Activity and Antioxidant Defences in an Experimental Animal Model of Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Medium-chain triglycerides such as decanoic acid (C10), which is one of the fatty acids that constitute dietary fats, are of substantial interest for their potential therapeutic effects on neuropsychiatric disorders. However, the effects of C10 on attention-deficit/hyperactivity disorder (ADHD) remain to be studied. We explored the effects of C10 on behavioural activity and antioxidant defences in an experimental animal model of ADHD. METHODS: To establish an experimental animal model of ADHD, neonatal rats were subjected to unilateral striatal lesions using 6-hydroxydopamine (6-OHDA). The rats sequentially underwent open-field and Y-maze tests before treatment [postnatal day 25 (PN25)]. After the subcutaneous administration of either vehicle or C10 solution (250 mg/kg) for 14 days, the behavioural tests were repeated on PN39. Next, we examined the effects of C10 on the expression of the constitutive antioxidant enzymes catalase and glutathione peroxidase-1/2 and the phase II transcription factor nuclear factor erythroid 2-related factor 2 in four different regions of the rat brain. RESULTS: Injection of 6-OHDA unilaterally into the striatum resulted in elevated locomotor activity on PN39. The administration of C10 for a period of 14 days did not alter the locomotor hyperactivity. Moreover, the administration of C10 had no significant effects on the expression of proteins related to antioxidant defences in the hippocampus, prefrontal cortex, striatum or cerebellum of both control and lesioned rats. CONCLUSIONS: The lack of significant effects of C10 in our study may depend on the dose and duration of C10 administration. Further exhaustive studies are needed to verify the efficacy and effects of different doses and treatment durations of C10 and to explore the underlying mechanisms.

[Determination of seven perfluoroalkyl and polyfluoroalkyl substances in serum of pregnant women and evaluation of neonatal neurobehavior based on high performance liquid chromatography-tandem mass spectrometry].

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 µm) at an oven temperature of 40 ℃, injection volume of 10 µL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.36(-0.64, 0.08)) and general assessment(ß(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(ß(95% CI): 0.38(-0.74, 0.01)) and total NBNA(ß(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(ß(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.54(-0.73, 0.35)) and general assessment(ß(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(ß(95% CI): 0.67(-1.2, 0.14)) and total NBNA(ß(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(ß(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(ß(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(ß(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.

The interaction of perfluoroalkyl acids and a family history of diabetes on arthritis: analyses of 2011-2018 NHANES.

Whether a family history of diabetes (FHD) and exposure to perfluoroalkyl acids (PFAAs) are correlated with an increased risk of developing arthritis remains unclear. This cross-sectional study was conducted to explore the correlations between FHD or exposure to PFAAs and arthritis as well as their interaction using the National Health and Nutrition Examination Survey (NHANES). In total, 6,194 participants aged ≥ 20 years from the 2011-2018 NHANES were enrolled. PFAAs are a cluster of synthetic chemicals, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). FHD was evaluated using self-reported questionnaires. Arthritis was classified into three types, rheumatoid arthritis (RA), osteoarthritis (OA), and others, which were diagnosed using questionnaires. Generalized linear models (GLMs) were used to test the correlation between FHD and arthritis. To examine the joint effects of PFAAs and FHD on arthritis, interaction terms were applied in the GLM. Arthritis incidence was 26.7% among all participants. FHD was associated with both RA [OR = 1.70 (95% CI: 1.15-2.50)] and other types of arthritis [OR = 1.62 (95% CI: 1.21-2.16)]. However, the relationship between FHD and OA was not significant after adjustment (P = 0.18). Interaction outcomes indicated that higher PFDA levels increased the association between FHD and arthritis. FHD is associated with an increased incidence of arthritis, which may be increased by PFDA. Given the heavy burden of arthritis, preventive measures for arthritis and reduction of PFAAs exposure for patients with FHD are required.

Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice.

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice. A single administration of 0.1 mmole/kg of PFDA, not PFOA, elevated serum ALT and bilirubin levels and caused cholestasis in WT mice. PFDA increased total and various bile acid species in serum but decreased them in the liver. Furthermore, in mouse livers, PFDA, not PFOA, down-regulated mRNA expression of uptake transporters (Ntcp, Oatp1a1, 1a4, 1b2, and 2b1) but induced efflux transporters (Bcrp, Mdr2, and Mrp2-4). In addition, PFDA, not PFOA, decreased Cyp7a1, 7b1, 8b1, and 27a1 mRNA expression in mouse livers with concomitant hepatic accumulation of cholesterol. In contrast, in PPARα-null mice, PFDA did not increase serum ALT, bilirubin, or total bile acids, but produced prominent hepatosteatosis; and the observed PFDA-induced expression changes of transporters and Cyps in WT mice were largely attenuated or abolished. In CAR-null mice, the observed PFDA-induced bile acid alterations in WT mice were mostly sustained. These results indicate that, at the dose employed, PFDA has more negative effects than PFOA on liver function. PPARα appears to play a major role in mediating most of PFDA-induced effects, which were absent or attenuated in PPARα-null mice. Lack of PPARα, however, exacerbated hepatic steatosis. Our findings indicate separated roles of PPARα in mediating the adaptive responses to PFDA: protective against hepatosteatosis but exacerbating cholestasis.

Enzymatic production process of capric acid-rich structured lipids: Development of formulation as a new therapeutic approach.

The present work reports an optimization of the synthesis of MLM-type (medium, long, medium) structured lipids (SL) through an acidolysis reaction of grape seed oil with capric acid catalyzed by Rhizopus oryzae lipase immobilized. At first, tests were carried out by preparing the biocatalysts using enzyme loadings (0.15 to 1 g of enzymatic powder) for each gram of support. Enzyme loading was used 0.3 g of enzymatic powder, and hydrolytic activity of 1860 ± 23.4 IU/g was reached. Optimized conditions determined by the Central Composite Rotatable Design (CCRD) revealed that the acidolysis reaction reached approximately 59 % incorporation degree (%ID) after 24 h, in addition to the fact that the biocatalyst could maintain the incorporation degree in five consecutive cycles. From this high incorporation degree, cell viability assays were performed with murine fibroblast cell lines and human cervical adenocarcinoma cell lines. Concerning the cytotoxicity assays, the concentration of MLM-SL to 1.75 and 2 % v/v were able to induce cell death in 56 % and 64 % of adenocarcinoma cells, respectively. Human cervical adenocarcinoma cells showed greater sensitivity to the induction of cell death when using emulsions with MLM-SL > 1.75 % v/v compared to emulsions with lower content indicating a potential for combating carcinogenic cells.

Fatty acids-modified liposomes for encapsulation of bioactive peptides: Fabrication, characterization, storage stability and in vitro release.

The fragile membranes of liposomes limit their application by the food industry. In this study, we hypothesized that interactions between fatty acids with different chain lengths and phospholipids might enhance liposome stability. Decanoic acid modified liposomes (Lipo-DA) and stearic acid modified liposomes (Lipo-SA) were fabricated for encapsulation of hydrophilic peptides. Fluorescence spectroscopy and FTIR analysis showed molecular interactions existed between alkyl chains and phospholipids, resulting in greater compactness and hydrophobicity of the membranes in Lipo-DA and Lipo-SA. This led to a reduction in melting point characterized by differential scanning calorimetry analysis. Lipo-DA and Lipo-SA could delay the release of hydrophilic peptides compared with unmodified liposomes in simulated digestion. Moreover, Lipo-DA showed better stability during storage, while Lipo-SA exhibited precipitation, resulting in the lowest peptide retention. Our study showed that decanoic acid is suitable to enhance the stability of liposomes, although this approach has yet to be tested in food products.

Occurrence and pattern of legacy and emerging per- and Poly-FluoroAlkyl substances (PFAS) in eggs of loggerhead turtle Caretta caretta from western Mediterranean.

Per-and Poly-FluoroAlkyl Substances (PFAS) are a class of persistent, toxic, and mobile and chemicals both from industrial sources and from the use and disposal of Consumers products containing PFAS, whose concentration in marine food webs could pose a toxicological risk for biota and humans. In 2021, unhatched eggs were sampled from 41 loggerhead turtle Caretta caretta nests from the Italian shores of the Campania Region (Southern Italy). Whole eggs were analysed for the presence of 66 legacy and emerging PFAS with Liquid Chromatography coupled to Hybrid High Resolution Mass Spectrometry. A median Σ66 Per- and Poly-FluoroAlkyl Substances value of 3.34 ng/g egg fresh weight was found; perfluoroctane sulfonate (PFOS) represented the most contributing congener (47%), followed by perfluoro-n-undecanoic acid, perfluoro-n-tridecanoic acid, perfluoro-n-decanoic acid, perfluoro-n-decanoic acid, and perfluoro-n-tetradecanoic acid, respectively. Such compounds showed a log-norm distribution, suggesting found concentrations could represent the baseline levels in the considered sampling area. Emerging ChloroPolyFluoroPolyEthers Carboxylic Acids (ClPFECAs) were found in 20 out of 41 samples in the range 0.01-1.59 ng/g. Four samples had 20-100 fold higher concentration compared to that of other samples, suggesting the presence of hot spot areas possibly related to presence of fluoropolymer-based marine litter turtles may ingest. The analysis of two paired eggs/liver samples recovered from stranded animals revealed PFAS concentration in the same order of magnitude, supporting the role of vitellogenin in their selective transfer to yolk. Significant (P = 0.0155) Kendall negative correlation coefficient of -0.2705 among PFOS content in eggs and the recorded hatching success prompts for further investigation on associated exposure assessment and related eco-toxicity risk. This work reports for the first time PFAS presence in georeferenced loggerhead turtle eggs of the Mediterranean Sea and results represent a starting point to study PFAS time-trends in this vulnerable species.

Structural and pharmacological characterization of a medium-chain fatty acid receptor GPR84 in common carp (Cyprinus carpio).

The medium-chain fatty acid receptor GPR84, a member of the G protein-coupled receptor family, is mainly expressed in macrophages and microglia, and is involved in the regulation of inflammatory responses and retinal development in mammals and amphibians. However, structure, tissue distribution, and pharmacology of this receptor have rarely been reported in fish. In this study, we cloned the coding sequence (CDS) of common carp GPR84 (ccGPR84), examined its tissue distribution, and explored its cellular signaling function. The results showed that the CDS of ccGPR84 is 1191 bp and encodes a putative protein with 396 amino acids. Phylogenetic and chromosomal synteny analyses revealed that ccGPR84 was evolutionarily conserved with Cyprinids. Real-time quantitative PCR (qPCR) indicated that ccGPR84 was predominantly expressed in the intestine and spleen. Luciferase reporter assay demonstrated that nonanoic acid, capric acid (decanoic acid), undecanoic acid and lauric acid could inhibit cAMP signaling pathway and activate MAPK/ERK signaling pathway, while the potencies of these four fatty acids on the two signaling pathways were different. Lauric acid has the highest inhibitory potency on cAMP signaling pathway, followed by undecanoic acid, nonanoic acid, and capric acid. While for MAPK/ERK signaling pathway, nonanoic acid has the highest activation potency, followed by undecanoic acid, capric acid, and lauric acid. These findings lay the foundation for revealing the roles of different medium-chain fatty acids in the inflammatory response of common carp.

(-)-Epigallocatechin-3-Gallate Reduces Perfluorodecanoic Acid-Exacerbated Adiposity and Hepatic Lipid Accumulation in High-Fat Diet-Fed Male C57BL/6J Mice.

Perfluorodecanoic acid (PFDA), an enduring and harmful organic pollutant, is widely employed in diverse food-related sectors. Our previous studies have provided evidence that PFDA has the potential to facilitate obesity and hepatic fat accumulation induced by high-fat diet (HFD) intake. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, has been suggested to possess potential preventive effects against metabolic abnormalities and fatty liver. The purpose of this research was to investigate the effects of EGCG on PFDA-exacerbated adiposity and hepatic lipid accumulation in HFD-fed mice. The results showed that EGCG reduced body weight gain; tissue and organ weights; blood glucose, serum insulin, HOMA-IR, leptin, and lipid parameters; serum inflammatory cytokines (IL-1ß, IL-18, IL-6, and TNF-α); and hepatic lipid accumulation in PFDA-exposed mice fed an HFD. Further work showed that EGCG improved liver function and glucose homeostasis in mice fed an HFD and co-exposed to PFDA. The elevated hepatic mRNA levels of SREBP-1 and associated lipogenic genes, NLRP3, and caspase-1 in PFDA-exposed mice fed an HFD were significantly decreased by EGCG. Our work provides evidence for the potential anti-obesity effect of EGCG on co-exposure to HFD and PFDA and may call for further research on the bioactivity of EGCG to attenuate the endocrine disruption effects of long-term exposure to pollutants.

Levofloxacin-Fatty Acid Systems: Dual Enhancement Through Deep Eutectic Formation and Solubilization for Pharmaceutical Potential and Antibacterial Activity.

Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.

Capric Acid and Myristic Acid Permeability Enhancers in Curved Liposome Membranes.

Liposomes are considered as advanced drug delivery systems for cancer treatment. A generation of pH-sensitive liposomes is being developed that use fatty acids (FAs) as a trigger for drug release in tumor tissues. However, FAs are also known to enhance permeability, and it is unclear whether FAs in liposomes may cause drug leakage or premature drug release. The passive permeability of the drug through the membrane of the liposome is thus a crucial factor for timely drug delivery. To investigate how the curvature and lipid composition of liposomes affect their passive permeability, coarse-grained molecular dynamics were performed. The permeability was determined with a counting method. Flat bilayers and three liposomes with varying diameters were studied, which had varying lipid compositions of dipalmitoylphosphatidylcholine, cholesterol, and deprotonated or neutral saturated FAs. The investigated permeants were water and two other small permeants, which have different free energy profiles (solubility) across the membrane. First, for the curvature effect, our results showed that curvature increases the water permeability by reducing the membrane thickness. The permeability increase for water is about a factor of 1.7 for the most curved membranes. However, a high curvature decreases permeability for permeants with free energy profiles that are a mix of wells and barriers in the headgroup region of the membrane. Importantly, the type of experimental setup is expected to play a dominant role in the permeability value, i.e., whether permeants are escaping or entering the liposomes. Second, for the composition effect, FAs decrease both the area per lipid (APL) and the membrane thickness, resulting in permeability increases of up to 55%. Cholesterol has a similar effect on the APL but has the opposite impact on membrane thickness and permeability. Therefore, FAs and cholesterol have opposing effects on permeability, with cholesterol's effect being slightly stronger in our simulated bilayers. As all permeability values were well within a factor of 2, and with liposomes usually being larger and less curved in experimental applications, it can be concluded that the passive drug release from a pH-sensitive liposome does not seem to be significantly affected by the presence of FAs.