Peptide-hormones, including pancreatic peptide-YY(PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), insulin, and leptin function as satiety signals, while ghrelin promotes hunger. These hormones are also involved in glucose homeostasis and body-weight regulation. The aim of this cross-sectional analysis was to examine the association of these peptide-hormones with obesity-markers, insulin-resistance, and dyslipidemia (total-cholesterol (TC), low-density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol (HDL-C), triglyceride (TG)). Sixteen-obese (OB) adults and 21 normal-weight (NW) age-and gender-matched counterparts were recruited. OB-participants showed significantly higher levels of leptin, insulin, Homeostatic-Model Assessment of Insulin Resistance (HOMA-IR), and TG. NW participants had significantly higher levels of ghrelin. GLP-1 was positively correlated with insulin, HOMA-IR, and obesity-markers except percent body fat. Leptin was positively correlated with all markers (except glucose and dyslipidemia). PYY was positively correlated with BMI, insulin and HOMA-IR. Ghrelin was inversely correlated with all of the markers except glucose, TC, and LDL-C. In the regression analysis model, leptin was positively associated with obesity markers and insulin resistance. Our results indicate a significant difference in peptide hormones among OB and NW Lebanese individuals. Since there is controversial evidence regarding body-weight and peptide-hormones in the literature, this study highlights a step forward towards finding ethnic based strategies to treat obesity and its consequences. Full article

It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington’s effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin. Full article

The aim of the current study was to assess the cadmium (Cd) phytoremediation potential of Helianthus annuus L. that was exposed to 50, 100, and 150 mg/kg of cadmium for 15, 30, and 60 days with application of EDTA (Ethylenediaminetetraacetic acid) in the soil and IAA (indole acetic acid) as a foliar spray. The results indicated that the concentration, duration of exposure, and amount of Cd affect the phytoremediation potential. The maximum Cd was observed at 60 days (32.05, 16.86, and 10.63%) of Cd application, compared to 15 (2.04, 0.60, and 1.17%) or 30 days (8.41, 3.93, and 4.20%, respectively), in a dose-dependent manner. The application of EDTA in the soil and foliar IAA enhanced the Cd accumulation in the plants at 15, 30, and 60 days of exposure, with maximum accumulation at 60 days. Exposed plants with foliar IAA application showed 64.82%, 33.77%, and 25.84% absorption at 50, 100, and 150 mg/kg, respectively. Apart from higher absorption, the cadmium translocation to the edible part of the plants ceased, i.e., the seeds had 0% accumulation. The interesting fact was recorded that efficient phytoremediation was recorded at 15 days of exposure, whereas maximum phytoremediation was recorded at 60 days of exposure. To minimize the stress, the host also produced stress-related metabolites (i.e., flavonoids, phenolics, proline, and sugar) and antioxidants (i.e., catalases and ascorbate peroxidases). From the current evidence, it could be assumed that the use of EDTA and IAA, along with hyperaccumulating plants, could be a possible green method to remediate Cd-contaminated soil efficiently in a short period of time. Full article

Vitamin B6 may alleviate diabetes by regulating insulin secretion and increasing insulin sensitivity, but its mechanism remains to be explored. In this study, vitamin B6-mediated autophagy and high glucose-induced apoptosis were tested to investigate the mechanism by which vitamin B6 regulates insulin release. The results showed that 20 mM glucose increased the apoptosis rate from 10.39% to 22.44%. Vitamin B6 reduced the apoptosis rate of RIN-m5F cells from 22.44% to 11.31%. Our data also showed that the vitamin B6 content in processed eggs was decreased and that the hydrothermal process did not affect the bioactivity of vitamin B6. Vitamin B6 increased the number of autophagosomes and the ratio of autophagosome marker protein microtubule associated protein 1 light chain 3 beta to microtubule associated protein 1 light chain 3 alpha (LC3-II/LC3-I). It also decreased the amount of sequetosome 1 (SQSTM1/p62) and inhibited the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K) under normal and high glucose stress. Another study showed that vitamin B6 inhibited the apoptosis rate, whereas the autophagy inhibitor 3-methyladenine (3-MA) blocked the protective effect of vitamin B6 against apoptosis induced by high glucose. The hydrothermal process decreased the vitamin B6 content in eggs but had no effect on the cytoprotective function of vitamin B6 in RIN-m5f cells. In conclusion, we demonstrated that vitamin B6-mediated autophagy protected RIN-m5f cells from high glucose-induced apoptosis might via the mTOR-dependent pathway. Our data also suggest that low temperatures and short-term hydrothermal processes are beneficial for dietary eggs. Full article

Doxorubicin (DOX) is a chemotherapeutic agent is used for various cancer cells. To characterize the chemical structural components and metabolic inhibition, we applied a DOX to HCT116 colon cancer cells using an independent metabolites profiling approach. Chemical metabolomics has been involved in the new drug delivery systems. Metabolomics profiling of DOX-applied HCT116 colon cancer cellular metabolisms is rare. We used ¹H nuclear magnetic resonance (NMR) spectroscopy in this study to clarify how DOX exposure affected HCT116 colon cancer cells. Metabolomics profiling in HCT116 cells detects 50 metabolites. Tracking metabolites can reveal pathway activities. HCT116 colon cancer cells were evenly treated with different concentrations of DOX for 24 h. The endogenous metabolites were identified by comparison with healthy cells. We found that acetate, glucose, glutamate, glutamine, sn-glycero-3-phosphocholine, valine, methionine, and isoleucine were increased. Metabolic expression of alanine, choline, fumarate, taurine, o-phosphocholine, inosine, lysine, and phenylalanine was decreased in HCT116 cancer cells. The metabolic phenotypic expression is markedly altered during a high dose of DOX. It is the first time that there is a metabolite pool and phenotypic expression in colon cancer cells. Targeting the DOX-metabolite axis may be a novel strategy for improving the curative effect of DOX-based therapy for colon cancer cells. These methods facilitate the routine metabolomic analysis of cancer cells. Full article

The aim of this study was to evaluate the nutritional value of cottonseed protein concentrate (CPC) as a single dietary protein source and the optimal protein level for grass carp (Ctenopharyngodon idellus). An 8-week feeding trial was conducted by feeding juvenile grass carp (initial body weight: 4.68 ± 0.01 g) with six experimental diets containing graded levels of protein provided by CPC. The results showed that the optimal CPC level (CPC4) improved the growth performance and health status of grass carp. The optimal dietary protein level was estimated to be 38.61 and 38.66% based on specific growth rate (SGR) and feed efficiency (FE), respectively. The CPC4 group significantly increased the total antioxidant capacity (T-AOC) content and glutathione peroxidase (GSH-Px) activity in the hepatopancreas (p < 0.05). In addition, the CPC4 group increased the muscle T-AOC and glutathione (GSH) content and improved muscle hardness, and the gene expression of MRFs, fgf6a, myhc-7, myhc-1, myhc-4, igf-II, and tor was upregulated while mstn gene expression was downregulated (p < 0.05). Correlation analysis revealed that the optimal dietary CPC level promoted grass carp growth, health, and flesh quality by regulating the relative abundance of intestinal microbes. Furthermore, CPC6 upregulated the ko00480 (Glutathione metabolism) and ko00620 (Pyruvate metabolism) pathways compared to CPC1 (p < 0.05), possibly indicating that low dietary CPC levels adversely affected amino acid metabolism in the intestinal microbiota of grass carp, while a high level of CPC will meet the metabolic needs of the body by increasing the utilization of energy. Full article

The selection of sows that are reproductively fit and produce large litters of piglets is imperative for success in the pork industry. Currently, low heritability of reproductive and litter-related traits and unfavourable genetic correlations are slowing the improvement of pig selection efficiency. The integration of biomarkers as a supplement or alternative to the use of genetic markers may permit the optimization and increase of selection protocol efficiency. Metabolite biomarkers are an advantageous class of biomarkers that can facilitate the identification of cellular processes implicated in reproductive condition. Metabolism and metabolic biomarkers have been previously implicated in studies of female mammalian fertility, however a systematic analysis across multiple biofluids in infertile and high reproductive potential phenotypes has not been explored. In the current study, the serum, urinary and salivary metabolomes of infertile (INF) sows and high reproductive potential (HRP) sows with a live litter size ≥ 13 piglets were examined using LC-MS/MS techniques, and a data pipeline was used to highlight possible metabolite reproductive biomarkers discriminating the reproductive groups. The metabolomes of HRP and INF sows were distinct, including significant alterations in amino acid, fatty acid, membrane lipid and steroid hormone metabolism. Carnitines and fatty acid related metabolites were most discriminatory in separating and classifying the HRP and INF sows based on their biofluid metabolome. It appears that urine is a superior biofluid than saliva and serum for potentially predicting the reproductive potential level of a given female pig based on the performance of the resultant biomarker models. This study lays the groundwork for improving gilt and sow selection protocols using metabolomics as a tool for the prediction of reproductive potential. Full article

MicroRNA regulates multiple pathways in inflammatory response, adipogenesis, and glucose and lipid metabolism, which are involved in metabolic syndrome (MetS). Thus, this systematic review aimed at synthesizing the evidence on the relationships between circulating microRNA and risk factors for MetS. The systematic review was registered in the PROSPERO database (CRD42020168100) and included 24 case-control studies evaluating microRNA expression in serum/plasma of individuals ≥5 years old. Most of the studies focused on 13 microRNAs with higher frequency and there were robust connections between miR-146a and miR-122 with risk factors for MetS, based on average weighted degree. In addition, there was an association of miR-222 with adiposity, lipid metabolism, glycemic metabolism, and chronic inflammation and an association of miR-126, miR-221, and miR-423 with adiposity, lipid, and glycemic metabolism. A major part of circulating microRNA was upregulated in individuals with risk factors for MetS, showing correlations with glycemic and lipid markers and body adiposity. Circulating microRNA showed distinct expression profiles according to the clinical condition of individuals, being particularly linked with increased body fat. However, the exploration of factors associated with variations in microRNA expression was limited by the variety of microRNAs investigated by risk factor in diverse studies identified in this systematic review. Full article

Bacterial volatile organic compounds (BVOCs) released from selected soil microbes have been shown to trigger the alteration of plant growth. However, the substances responsible for such bioactivity and the mechanism of how plants interpret and respond to BVOCs remain largely elusive. Here, we established a model bioassay system using Arabidopsis and Bacillus spp. and found that Bacillus BVOCs interfere with the normal growth of Arabidopsis seedlings. Moreover, through a bioassay-guided purification, we identified isovaleric acid (IVA) as a volatile compound that exhibits inhibitory growth activity towards Arabidopsis seedlings. Our data provide novel molecular insights into how short-chain fatty acids released from soil microbes can affect plant growth through interkingdom signals. Full article

Fruits such as apples are a dietary source of polyphenols and have health benefits. We studied the benefits of apple polyphenols in reducing intestinal infections. We explored the potential roles of apple polyphenols in combating Clostridioides difficile-induced intestinal infections by modulating the intestinal microbiota and metabolism in our study. Mice fed with apple polyphenols exhibited higher survival rates and improved diarrhea symptoms in a C. difficile infection mouse model given once-daily apple polyphenol extract (200 or 400 mg/kg bw) or phosphate-buffered saline. Feeding polyphenols enhanced anti-inflammatory effects and colon barrier integrity. In addition, apple polyphenols mitigated intestinal microbiota disorders in C. difficile infection, modulating the intestinal microbiota and increasing the abundance of beneficial microbiota. Apple polyphenols also improved fecal metabolic alterations in C. difficile-infected mice and modulated the expression of pathways related to intestinal inflammation. Our results suggest that apple polyphenol extract is a potential prebiotic agent that affects the intestinal microbiota and metabolism, thereby positively influencing intestinal infections. Full article

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO₂max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population. Full article

Gestational diabetes mellitus (GDM), a common perinatal disease, is related to increased risks of maternal and neonatal adverse perinatal outcomes. We aimed to establish GDM risk prediction models that can be widely used in the first trimester using four different methods, including a score-scaled model derived from a meta-analysis using 42 studies, a logistic regression model, and two machine learning models (decision tree and random forest algorithms). The score-scaled model (seven variables) was established via a meta-analysis and a stratified cohort of 1075 Chinese pregnant women from the Northwest Women’s and Children’s Hospital (NWCH) and showed an area under the curve (AUC) of 0.772. The logistic regression model (seven variables) was established and validated using the above cohort and showed AUCs of 0.799 and 0.834 for the training and validation sets, respectively. Another two models were established using the decision tree (DT) and random forest (RF) algorithms and showed corresponding AUCs of 0.825 and 0.823 for the training set, and 0.816 and 0.827 for the validation set. The validation of the developed models suggested good performance in a cohort derived from another period. The score-scaled GDM prediction model, the logistic regression GDM prediction model, and the two machine learning GDM prediction models could be employed to identify pregnant women with a high risk of GDM using common clinical indicators, and interventions can be sought promptly. Full article

Clostridioides difficile infection (CDI) is responsible for an increasing number of cases of post-antibiotic diarrhea worldwide, which has high severity and mortality among hospitalized elderly patients. The disruption of gut microbiota due to antibacterial medication facilitates the intestinal colonization of C. difficile. In the present study, a murine model was used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the effects of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the brain metabolome for the first time. Four different metabolomic-based methods (targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS, targeted GC-MS/MS, and untargeted GC-MS) were applied, resulting in the identification of 217 unique metabolites in the brain extracts, mainly glycerophospholipids, glycerolipids, amino acids, carbohydrates, and fatty acids. Univariate and multivariate statistical analysis revealed that CDI, as well as the subsequent treatments, altered significantly several brain metabolites, probably due to gut dysbiosis, and affected the brain through the gut–brain axis. Notably, none of the therapeutic approaches completely restored the brain metabolic profile to the original, healthy, and non-infected phenotype, even after 10 days of treatment. Full article

A higher postprandial triglycerides response and hemorheological abnormalities may increase the incidence of metabolic disorders and negatively interfere with the aging process. A single session of preprandial endurance exercise was found to be effective in reducing triglyceride levels after a high-fat diet. However, whether the exercise-induced reduction in postprandial triglyceride levels influences hemorheological indicators remains unknown. This study aims to investigate the effects of postprandial lipemia on hemorheological properties and oxidative stress. Eight healthy young male participants completed two experimental trials. On day 1, the participants were randomly assigned to walk for 1 h at 50% VO₂max (EE trial) or rest (CON trial). On day 2, participants rested and consumed a high-fat meal in the morning. Results: The postprandial area under the curve (AUC) of plasma TG concentration was significantly lower in EE compared to CON (EE: 9.2 ± 1.9; CON: 10.9 ± 1.7 mmol/L·h⁻¹; p = 0.013; Cohen’s d = 0.036). No significant difference was observed in hemorheological properties and MDA (p > 0.05). Endurance exercise effectively decreased postprandial TG concentration but did not influence the postprandial hemorheological properties and oxidative stress indicators. Full article

Exosomes released from tumor cells treated with cancer-targeting drugs reflect altered metabolic processes within the cells. Therefore, metabolites in exosomes can be used as markers to predict the therapeutic response or identify therapeutic targets. In this study, metabolite changes in exosomes were investigated by co-administration of the herbal extract SH003 and docetaxel (DTX), which exert a synergistic anti-cancer effect on lung cancer cells. Exosomes released from cells treated with SH003 and DTX were purified, and untargeted metabolic profiling was performed by liquid chromatography–tandem mass spectrometry. Analysis of altered metabolic-based pathways showed that the combined treatment synergistically increased pyrimidine metabolism compared with single-drug treatment. Additionally, xenobiotic metabolism by cytochrome P450 was specifically increased in cells treated with the combination. However, the released exosomes and increased metabolites in exosomes did not affect the anti-cancer effect of SH003 and DTX. Therefore, our study suggests that metabolite profiling can be used to evaluate the efficacy of combined treatments. Furthermore, such exosome-based metabolism may facilitate understanding the physiological endpoints of combination therapy in human biofluids. Full article