Understanding PFAS toxicity through cell culture metabolomics: Current applications and future perspectives.

Per- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health.

Polyphenol Contents, Gas Chromatography-Mass Spectrometry (GC-MS) and Antibacterial Activity of Methanol Extract and Fractions of Sonneratia Caseolaris Fruits from Ben Tre Province in Vietnam.

Plants contain a large number of phytochemical components, many of which are known as bioactive compounds and responsible for the expression of various pharmacological activities. The extract of Sonneratia caseolaris fruit collected in Vietnam was investigated for its total phenolic and total flavonoid contents using methanol solvent and different fractions of S. caseolaris fruits (hexane, ethyl acetate, n-butanol, and aqueous). GC-MS analysis was conducted to identify the bioactive chemical constituents occurring in the active extract. Further, the antibacterial activity was tested in vitro on bacterial isolates, namely Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, using the disc diffusion method on tryptic soya agar (TSA) medium. The methanol extract showed high total flavonoid (82.3 ± 0.41 mg QE/g extract) and phenolic (41.0 ± 0.34 mg GAE/g extract) content. GC-MS of the methanol extract and different fractions of S. caseolaris fruits detected 20 compounds, principally fatty alcohols, fatty acids, phenols, lipids, terpenes derivatives, and carboxylic acids derivatives. A 50 mg/ml concentration of methanol extract had the strongest antibacterial activity on E. coli, S. aureus, and B. subtilis. Furthermore, ethyl acetate, aqueous, and n-butanol fractions inhibited S. aureus and B. subtilis the most. The results of the present study suggested that the fruits of S. caseolaris are rich sources of phenolic compounds that can contribute to safe and cost-effective treatments.

Differences in the Microbiological Profile of Raw and Pasteurized Breastmilk from Hospital and Community-Based Donors at the First Human Milk Bank in Vietnam.

Background: Microbiological quality is one of the key safety standards in human milk bank (HMB) operations. We describe the profiles of bacteria in donor human milk (DHM) before and after the pasteurization of samples collected from breastfeeding women in the hospital and from the community in the first HMB in Vietnam. Methods: Data were collected between February 2017 and January 2022 from an online HMB monitoring system. First, DHM samples were cultured, and the number of colony-forming units (CFU) were counted before (n = 708) and after pasteurization (n = 1146). The gram-staining method combined with the Vitek 2 Compact system were used to identify types of organisms at the Da Nang Hospital for Women and Children's Laboratory. Passing criteria for DHM included pre-pasteurization samples had a total colony count <105 CFU/mL and post-pasteurization was <10 CFU/mL. Results: During five years of operation, Da Nang HMB had 491 donors (48.7% were hospital and the rest community donors) who donated an average amount of 14.2 L over 45 days. Of this DHM volume, 84.9% of donor samples passed the pre- and post-pasteurization microbiological tests. DHM from community donors had a higher pass rate (87.8%) compared to that from hospital donors (79.5%). Before pasteurization, 15.4% of DHM samples had a bacteria count <103 CFU/mL, 63.0% had 103-<105 CFU/mL, and 21.6% had ≥105 CFU/mL. Most of the unpasteurized DHM samples (93.0%) had microorganism growth: with one organism (16.4%), two (33.9%), three or more (43.6%). After pasteurization, 17.9% samples had a bacteria count of 1−9 CFU/mL and 7.2% had ≥10 CFU/mL. DHM samples from community donors had a lower bacterial count and number of organisms than those from hospital donors both before and after pasteurization. The highest microorganisms from unpasteurized DHM samples were Staphylococcus epidermidis (74.2%), Acinetobacter sp. (52.1%), gram-positive bacillus (51.7%), Staphylococcus coagulase-negative (15.8%), and Staphylococcus aureus (10.5%). Common microorganisms from pasteurized DHM were gram-positive bacillus (21.0%), Staphylococcus epidermidis (3.9%), and Acinetobacter sp. (0.9%). Samples from the hospital tended to have a higher contamination with those microorganisms than those from community donors. Conclusions: The majority of DHM samples in Da Nang passed microbiological testing criteria. DHM from community donors had higher pass rates than hospital donors. Corrective actions are needed to improve HMB operations and hospital microbiological quality standards, as well as general improvements in water and sanitation.

Exposure to polylactic acid induces oxidative stress and reduces the ceramide levels in larvae of greater wax moth (Galleria mellonella).

Plastic biodegradation by insects has made significant progress, opening up new avenues for the treatment of plastic waste. Wax moth larvae, for example, have attracted the attention of the scientific community because they are known to chew, ingest, and biodegrade natural polymer bee waxes. Despite this, we know very little about how these insects perform on manufactured plastics or how manufactured plastics affect insect metabolism. As a result, we studied the metabolism of greater wax moths (Galleria mellonella) fed on molasses-supplemented polylactic acid plastic (PLA) blocks. An analysis of the central carbon metabolism (CCM) metabolites was performed using liquid chromatography triple quadrupole mass spectrometry (LC-QQQ-MS), while an analysis of untargeted metabolites and lipids was conducted using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS). In total, 169 targeted CCM metabolites, 222 untargeted polar metabolites, and 196 untargeted nonpolar lipids were identified within the insect samples. In contrast, compared to control larvae, PLA-fed larvae displayed significantly different levels of 97 CCM metabolites, 75 polar metabolites, and 57 lipids. Purine and pyrimidine metabolisms were affected by PLA feeding, as well as amino acid metabolism, carbohydrates, cofactors, vitamins, and related metabolisms. Additionally, PLA exposure disrupted insect energy metabolism and oxidative stress, among other metabolic disturbances. The larvae fed PLA have lower levels of several lipids, suggesting a reduction in lipid reserves, and ceramide levels are likely to have changed due to apoptosis and inflammation. The study indicates that G. mellonella larvae could ingest PLA but this process causes some metabolic stress for the host. Future studies of the molecular pathways of this biodegradation process might help to provide strategies for stress reduction that would speed up insect digestion of plastic.

Notes on Culturable Endophytic Microorganisms Isolated from 14 Medicinal Plants in Vietnam: A Diversity Analysis to Predict the Host-Microbe Correlations.

Endophytes can generate a cornucopia of marvelous bioactive secondary metabolites useful for mankind but their biodiversity and associations with host plants are still elusive. In this study, we explored the culturable endophytic microorganisms associated with 14 medicinal plants that are of high socio-economic value and/or reportedly endemic to northern Vietnam. Specifically, we isolated the endophytic microorganisms by applying surface sterilization methods and identified them based on morphological and rDNA sequence analyses. Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis (PCA) were used to analyze the correlations between the taxonomic affiliations of the culturable endophytes and the characteristics of their hosts. Most of the culturable endophytes obtained were bacteria (80), and few of those were actinomycetes (15) and fungi (8). Many of them are reported to be endophytes of medicinal plants for the first time. A number of plants (5) are also reported for the first time to contain microbial endophytes, while some plants with powerful pharmaceutical potential harbor unique endophytes. Furthermore, our results reveal a strikingly close relation between the compositions of bacterial and fungal isolates from plants having anti-bacterial activity and those from plants having anti-inflammatory activity, or between the compositions of the microbial endophytic isolates from plants having anti-cancer activity and those from plants having antioxidant activity. Altogether, the results provide new findings which can be inspiring for further in-depth studies to explore and exploit the relationships between medicinal plants and their associated endophytes in northern Vietnam and world-wide.

Antirheumatic therapy is associated with reduced complement activation in rheumatoid arthritis.

BACKGROUND: The complement system plays an important role in pathophysiology of cardiovascular disease (CVD), and might be involved in accelerated atherogenesis in rheumatoid arthritis (RA). The role of complement activation in response to treatment, and in development of premature CVD in RA, is limited. Therefore, we examined the effects of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) on complement activation using soluble terminal complement complex (TCC) levels in RA; and assessed associations between TCC and inflammatory and cardiovascular biomarkers. METHODS: We assessed 64 RA patients starting with MTX monotherapy (n = 34) or TNFi with or without MTX co-medication (TNFi±MTX, n = 30). ELISA was used to measure TCC in EDTA plasma. The patients were examined at baseline, after 6 weeks and 6 months of treatment. RESULTS: Median TCC was 1.10 CAU/mL, and 57 (89%) patients had TCC above the estimated upper reference limit (<0.70). Compared to baseline, TCC levels were significantly lower at 6-week visit (0.85 CAU/mL, p<0.0001), without significant differences between the two treatment regimens. Notably, sustained reduction in TCC was only achieved after 6 months on TNFi±MTX (0.80 CAU/mL, p = 0.006). Reductions in TCC after treatment were related to decreased C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin 6, and increased levels of total, high and low-density lipoprotein cholesterol. Similarly, baseline TCC was significantly related to baseline CRP, ESR and interleukin 6. Patients with endothelial dysfunction had higher baseline TCC than those without (median 1.4 versus 1.0 CAU/mL, p = 0.023). CONCLUSIONS: Patients with active RA had elevated TCC, indicating increased complement activation. TCC decreased with antirheumatic treatment already after 6 weeks. However, only treatment with TNFi±MTX led to sustained reduction in TCC during the 6-month follow-up period. RA patients with endothelial dysfunction had higher baseline TCC compared to those without, possibly reflecting involvement of complement in the atherosclerotic process in RA.

In silico screening of potential ß-secretase (BACE1) inhibitors from VIETHERB database.

For the purpose of discovering potential inhibitors of ß-amyloid (BACE1), which is a crucial element in Alzheimer's disease (AD) pathogenesis, an in silico study of naturally occurring compounds was performed using precise computational approaches. Autodock4 package was preliminary used to predict the binding affinities to BACE1 of more than four thousand compounds presented in the Vietnamese plants (VIETHERB) database. Based on docking results, twenty top-lead compounds having the largest docking energy to BACE1 were rigorously examined using steered molecular dynamics (SMD) simulations. Interestingly, SMD results found that the binding affinity values of three compounds, including myricetin 3-O-(3''-galloylrhamnopyranoside), quercetin 3-O-neohesperidoside, and hydroxysafflor yellow A, are remarkably higher than that of the well-known BACE1 inhibitor, 23I, and these compounds can thus be considered the promising candidates for inhibitors of BACE1.

In vitro antiviral activities of ethanol and aqueous extracts of Vietnamese traditional medicinal plants against Porcine Epidemic Diarrhea virus: a coronavirus family member.

Porcine epidemic diarrhea virus (PEDV) causes diarrhea in pigs leading to severe illnesses and high mortality rates. The development of medicinal agents to treat PEDV infection is therefore crucial. In this study, antiviral activities against PEDV of ethanol and aqueous extracts of 17 Vietnamese traditional medicinal plants were evaluated using the cytopathic effect-based assay. The results showed that 14 out of 17 medicinal plants could inhibit the cytopathic effect of PEDV. The ethanol extract of Stixis scandens was identified as the most active extract with its MIC (minimum inhibitory concentration) being 0.15 µg/mL. Other plant extracts also displayed strong antiviral activity against PEDV, including Anisomeles indica, Pericampylus glaucus and Croton kongensis. The results demonstrate that certain medicinal plants have a high antiviral potential and may serve as a lead to develop novel pharmaceutical agents to cure PED as well as the diseases caused by other coronaviruses.

Preservation of oil slick samples on adsorbent Teflon fabric: Potential for deployment aboard autonomous surface vessels.

In this communication, we report results of an experiment in which crude oil adsorbed on Teflon fabric is exposed to conditions expected in natural ocean-surface collection vehicle containers over a period of 3 months. Samples were recovered at designated time points and analyzed to determine degree of preservation of molecular signatures. Ratios of saturate hydrocarbons were preferentially preserved compared to those of aromatic compounds. Unsubstituted aromatic compounds such as naphthalene and dibenzothiophene were removed at higher rates relative to methyl-substituted homologues owing to differences in biodegradability and solubility. Ratios of important marker compounds persist over several months with sufficient fidelity for accurate determination of source-rock facies and thermal maturity. Collection and storage of oil samples on small pieces of adsorbent Teflon mesh broadens the opportunity space for collection of organic geochemistry data. Deployment of automated samplers equipped with such Teflon meshes aboard autonomous surface vehicles and human-operated vessels promises cheaper, better coverage of geochemical data in seep, slick, and spill surveys conducted for research, exploration, monitoring, and emergency response efforts.

Serum Short-Chain Fatty Acids and Associations With Inflammation in Newly Diagnosed Patients With Multiple Sclerosis and Healthy Controls.

Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by demyelination and neuroaxonal damage in the central nervous system. The etiology is complex and is still not fully understood. Accumulating evidence suggests that our gut microbiota and its metabolites influence the MS pathogenesis. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are metabolites produced by gut microbiota through fermentation of indigestible carbohydrates. SCFAs and kynurenine metabolites have been shown to have important immunomodulatory properties, and propionate supplementation in MS patients has been associated with long-term clinical improvement. However, the underlying mechanisms of action and its importance in MS remain incompletely understood. We analyzed serum levels of SCFAs and performed targeted metabolomics in relation to biomarkers of inflammation, and clinical and MRI measures in newly diagnosed patients with relapsing-remitting MS before their first disease modifying therapy and healthy controls (HCs). We demonstrated that serum acetate levels were nominally reduced in MS patients compared with HCs. The ratios of acetate/butyrate and acetate/(propionate + butyrate) were significantly lower in MS patients in a multivariate analysis (orthogonal partial least squares discriminant analysis; OPLS-DA). The mentioned ratios and acetate levels correlated negatively with the pro-inflammatory biomarker IFNG, indicating an inverse relation between acetate and inflammation. In contrast, the proportion of butyrate was found higher in MS patients in the multivariate analysis, and both butyrate and valerate correlated positively with proinflammatory cytokines (IFNG and TNF), suggesting complex bidirectional regulatory properties of SCFAs. Branched SCFAs were inversely correlated with clinical disability, at a nominal significance level. Otherwise SCFAs did not correlate with clinical variables or MRI measures. There were signs of an alteration of the kynurenine pathway in MS, and butyrate was positively correlated with the immunomodulatory metabolite 3-hydroxyanthranilic acid. Other variables that influenced the separation between MS and HCs were NfL, ARG1 and IL1R1, D-ribose 5-phosphate, pantothenic acid and D-glucuronic acid. In conclusion, we provide novel results in this rapidly evolving field, emphasizing the complexity of the interactions between SCFAs and inflammation; therefore, further studies are required to clarify these issues before supplementation of SCFAs can be widely recommended.

Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines.

Pyrido-fused quinazolinones were synthesized via copper-catalyzed cascade C(sp2)-H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2 catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2. Broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. The bioactive naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The remarkable feature of this protocol is that complicated heterocyclic structures are readily achieved in a single synthetic step from easily accessible reactants and catalysts. This pathway to pyrido-fused quinazolinones would be complementary to existing protocols.

Association Between Serum 25-Hydroxyvitamin D Concentrations and Chronic Pain: Effects of Drinking Habits.

PURPOSE: Although the explanation for inconsistencies in the reported association between serum 25-hydroxyvitamin D [25(OH)D] levels and chronic pain (CP) has not yet been determined, understanding this discrepancy is necessary for the development of vitamin D supplementation as an effective treatment for CP. The aim of this cross-sectional study was to examine the relationship between 25(OH)D concentrations and CP according to drinking habits in Japanese subjects. PATIENTS AND METHODS: We distributed invitation letters to 2314 individuals older than 40 years in Shika town, a rural area in Japan, and 724 subjects (386 females; mean age: 63.9 ± 10.4 years) were recruited. CP was defined as persistent pain lasting at least 3 months in any part of the body. Serum concentrations of 25(OH)D, a biomarker of the vitamin D status, were measured using a radioimmunoassay. A serum 25(OH)D level <20 ng/mL was defined as serum 25(OH)D deficiency. Drinking habits were assessed using a self-administered questionnaire. There were three choices, "rarely drink", "sometimes" and "everyday". Respondents who answered "rarely drink" were labelled as non-drinkers and the others as drinkers. RESULTS: The prevalence of CP was 40.6%. A significant interaction between CP and drinking habits on 25(OH)D concentrations was observed (p = 0.098). A one-way analysis of covariance was performed to compare 25(OH)D concentrations between the subjects with and without CP in each drinking group, and the serum 25(OH)D levels of subjects with CP were significantly lower than those without CP among drinkers (p = 0.007). A logistic regression analysis revealed a correlation between serum 25(OH)D deficiency and CP in drinkers after adjustments for several confounding factors (odds ratio: 0.499; 95% confidence interval: 0.268 - 0.927; p = 0.028). CONCLUSION: The present results suggest that low serum 25(OH)D concentrations are associated with the development of CP in drinkers.

Immune response in probiotic-fed New Zealand black-footed abalone (Haliotis iris) under Vibrio splendidus challenge.

Vibriosis disease is a major constraint for sustainable molluscan aquaculture. Development of strategies to enhance disease resistance during grow out would greatly reduce stock mortality and boost production yields. In this study, New Zealand black-footed abalone (Haliotis iris) were fed a commercial diet enhanced with multi-strain probiotics (Exiguobacterium JHEb1, Vibrio JH1 and Enterococcus JHLDc) for four months, then challenged with an injection of pathogenic Vibrio splendidus. Host immune responses in haemocytes were characterized using flow cytometry by measuring total haemocyte counts (THC) and viability, degree of apoptosis, and production of reactive oxygen species (ROS) 48 h post-challenge. Probiotic-fed abalone had significantly higher survival rates compared to control animals after the bacterial challenge. Infected probiotic-fed abalone also had significantly higher haemocyte viabilities, slightly lower proportions of haemocytes undergoing early apoptosis, and lower proportions of ROS-producing haemocytes compared to infected control-fed abalone. In addition, metabolite profiles of muscle tissues generated via gas chromatography-mass spectrometry (GC-MS) delivered complimentary evidence to support a perturbed ROS-regulatory system in infected abalone through changes in key metabolites associated with glutathione biosynthesis. The results of this study provide valuable information to assist in farm management practices, leading to enhance production and sustainability of the New Zealand abalone aquaculture industry.

Global mapping of interventions to improve quality of life of patients with depression during 1990-2018.

PURPOSE: The number of patients with depressive disordered globally increased and affects people of all ages and countries and has a significant and negative impact on the quality of life (QoL). Depression if left untreated may lead to severe consequences. However, there are several types of effective treatments, but often patients need support from health staff to find suitable treatments. This study aims to examine the global trend of the publications as well as the development of interventions for depressing treatment. METHODS: We download and analyzed 15,976 scientific research from the Web of Science from 1990 to 2018. A text mining based on Latent Dirichlet and terms' co-occurrence in titles and abstracts to identify hidden research topics and research landscapes. RESULTS: We found that the number of papers related to non-pharmacological treatment (such as cognitive-behavioral, mindfulness, or family and social support) to improve the QoL of patients with depression has increased. The number of papers on this serious health issue in low-middle income countries (LMICs) was not as high as in high-income countries (HICs). CONCLUSION: It is necessary to increase support of the treatment of depression in LMICs as well as applied non-pharmacological interventions to patients with depression.

Robust chemical bonding of PMMA microfluidic devices to porous PETE membranes for reliable cytotoxicity testing of drugs.

Here, we report a simple yet reliable method for bonding poly(methyl methacrylate) (PMMA) to polyethylene terephthalate (PETE) track-etched membranes using (3-glycidyloxypropyl)trimethoxysilane (GLYMO), which enables reliable cytotoxicity tests in a microfluidic device impermeable to small molecules, such as anti-cancer drugs. The porous PETE membranes treated with 5% GLYMO were assembled with microfluidic channel-engraved PMMA substrates after air plasma treatment for 1 minute, followed by heating at 100 °C for 2 minutes, which permits irreversible and complete bonding to be achieved within 1 h. The bonding strength between the two substrates (1.97 × 107 kg m-2) was robust enough to flow culture medium through the device without leakage even at a gauge pressure of above 135 kPa. For validation of its utility in drugs testing, we successfully demonstrated that human lung adenocarcinoma cells cultured in the PMMA devices show more reliable cytotoxicity results for vincristine in comparison to conventional polydimethylsiloxane (PDMS) devices due to the inherent property of PMMA of it being impervious to small molecules. Given that the current organ-on-a-chip fabrication methods mostly rely on PDMS, this bonding strategy will expand simple fabrication capability using various thermoplastics and porous track-etched membranes, and allow us to create 3D-micro-constructs that more precisely mimic organ-level physiological conditions.

Analyzing Social Media Data to Understand Consumer Information Needs on Dietary Supplements.

Despite the high consumption of dietary supplements (DS), few reliable, relevant, and comprehensive online resources could satisfy information seekers. This research study aims to understand consumer information needs on DS using topic modeling, and to evaluate accuracy in correctly identifying topics from social media. We retrieved 16,095 unique questions posted on Yahoo! Answers relating to 438 unique DS ingredients mentioned in sub-section, "Alternative medicine" under the section, "Health" . We implemented an unsupervised topic modeling method, Correlation Explanation (CorEx) to unveil the various topics in which consumers are most interested. We manually reviewed the keywords of all the 200 topics generated by CorEx and assigned them to 38 health-related categories, corresponding to 12 higher-level groups. We found high accuracy (90-100%) in identifying questions that correctly align with the selected topics. The results could guide us to generate a more comprehensive and structured DS resource based on consumers' information needs.

Relationship between the Intake of n-3 Polyunsaturated Fatty Acids and Depressive Symptoms in Elderly Japanese People: Differences According to Sex and Weight Status.

n-3 polyunsaturated fatty acids (PUFAs) have been shown to have preventive effects against depression. In this study, we aimed to investigate the associations between the intake of n-3 PUFAs and depression among people according to sex and weight status. We utilized cross-sectional data from the Shika study in Japan. The study was conducted between 2013 and 2016. Data were collected from adults older than 65 years. Invitation letters were distributed to 2677 individuals, 2470 of whom participated in the study (92.3%). We assessed depressive states using the Japanese short version of the Geriatric Depression Scale (GDS-15). We assessed the intake of n-3 PUFAs using the validated food frequency questionnaire. One thousand six hundred thirty-three participants provided data, among which 327 (20.0%) exhibited depressive symptoms. When we performed the stratified analysis by sex and weight status, there were significant inverse relationships between total n-3 PUFAs, individual n-3 PUFAs, and n-3/n-6 PUFAs ratio and depressive symptoms in overweight/obese females. No correlations were observed between n-3 PUFAs intake and depressive states in males. The results demonstrated a relationship between n-3 PUFAs deficiencies and depressive states, particularly in overweight/obese females. Dietary modifications may help to prevent depressive symptoms in overweight/obese females.

Monobutyrin Reduces Liver Cholesterol and Improves Intestinal Barrier Function in Rats Fed High-Fat Diets.

Butyric acid has been shown to reduce high-fat diet-related metabolic disturbances and to improve intestinal barrier function due to its potent anti-inflammatory capacity. This study investigates whether a butyric acid ester, monobutyrin (MB) affects lipid profiles and gut barrier function in a dose-response manner in rats fed butter- or lard-based high-fat diets. Four-week-old male Wistar rats were fed butter-based diets containing 0, 0.25, 0.75 and 1.5 MB g/100 g (dry weight basis) or 0.5 glycerol g/100 g, and diets with lard (La) containing 0 and 0.5 MB g/100 g or a low-fat control diet for 3⁻4 weeks. Lipid profiles in blood and liver tissue, intestinal permeability and cecal short-chain fatty acids were examined. The results showed a dose-dependent decrease in liver total cholesterol for 1.5 MB (p < 0.05) and liver triglycerides for 0.75 MB (p < 0.05) and 1.5 MB (p = 0.08) groups compared to the high-fat control group. Furthermore, a lower excretion of mannitol in urine in the 1.5 MB group indicated improved intestinal barrier function. When MB was supplemented in the lard-based diet, serum total cholesterol levels decreased, and total amount of liver high-density lipoprotein-cholesterol increased. Thus, MB dietary supplementation can be effective in counteracting lipid metabolism disturbances and impaired gut barrier function induced by high-fat diets.

Monovalerin and trivalerin increase brain acetic acid, decrease liver succinic acid, and alter gut microbiota in rats fed high-fat diets.

PURPOSE: Short-chain fatty acids (SCFA) are known for their anti-inflammatory properties and may also prevent against the development of metabolic diseases. This study investigated possible effects of two valeric acid esters, monovalerin (MV) and trivalerin (TV) in rats fed high-fat diets. METHODS: Four groups of rats were given a low-fat diet (LF) or a high-fat control diet (HFC) with or without supplementation of MV or TV (5 g/kg) for 3 weeks (n = 7/group). SCFA (caecum, blood, liver and brain), succinic acid (liver), microbiota (caecum), lipid profile (liver and blood) and the inflammatory biomarker, lipopolysaccharide-binding protein (blood) were analysed at the end of the experiment. RESULTS: Supplementation of MV and TV to a high-fat diet increased 1.5-fold the amounts of acetic acid in the brain and 1.7-fold serum concentration of valeric acid, whereas liver succinic acid was reduced by 1.5-fold. Although liver triglyceride levels were higher in both MV and TV groups compared with the LF group, liver LDL/HDL ratio was lower in the MV group (P < 0.05). The caecal microbiota composition was altered, with threefold higher abundance of Bacteroidetes and higher ratio of Bacteroidetes/Firmicutes in the MV group compared with the HFC and LF groups. Acetic acid in the brain was negatively correlated with TM7, family S24-7 and rc4-4, and positively associated to Tenericutes and Anaeroplasma. CONCLUSIONS: The present study shows that MV and TV in the specified dose can affect caecal microbiota composition and, therefore, bacterial metabolites in the liver, serum and brain as well as the lipid profile in the liver.

Relationship between Dietary n-6 Fatty Acid Intake and Hypertension: Effect of Glycated Hemoglobin Levels.

The relationship between dietary n-6 fatty acids and hypertension is not clear. The metabolic products of n-6 fatty acids include those that control blood pressure, such as prostaglandin and thromboxane, and that differ depending on the extent of glucose tolerance. This cross-sectional study investigated the association of dietary n-6 fatty acid intake on hypertension, and the effects of glycated hemoglobin (HbA1c) value in 633 Japanese subjects aged 40 years and older. Dietary intake was measured using a validated brief self-administered diet history questionnaire. We defined hypertension as the use of antihypertensive medication or a blood pressure of 140/90 mmHg. The prevalence of hypertension was 55.3%. A high n-6 fatty acids intake inversely correlated with hypertension in subjects with HbA1c values less than 6.5% (odds ratio, 0.857; 95% confidence interval, 0.744 to 0.987). On the contrary, in subjects with an HbA1c value of 6.5% or higher, the n-6 fatty acids intake was significantly associated with hypertension (odds ratio, 3.618; 95% confidence interval, 1.019 to 12.84). Regular dietary n-6 fatty acid intake may contribute to the prevention and treatment of hypertension in a healthy general population. By contrast, in subjects with diabetes, regular n-6 fatty acids intake may increase the risk of hypertension.