PubMed

Front Immunol. 2024 Oct 11;15:1462805. doi: 10.3389/fimmu.2024.1462805. eCollection 2024.ABSTRACTINTRODUCTION: Resveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation).METHODS: Twenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet.RESULTS: Res increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation.DISCUSSION: There findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites.PMID:39464877 | PMC:PMC11502325 | DOI:10.3389/fimmu.2024.1462805

J Environ Health Sci Eng. 2024 Jul 10;22(2):533-544. doi: 10.1007/s40201-024-00912-2. eCollection 2024 Dec.ABSTRACTBiological mechanisms of exposure to Trihalomethanes (THMs) in swimming pools remain unclear. Investigation of short-term changes in metabolomic profiles due to exposure to THMs during swimming can help to understand the health effects-related mechanisms. With this in view, we aimed to assess exposure of swimmers to THMs in chlorine and ozone-chlorine swimming pools using the metabolomics approach from September 2020 to January 2021 in Tehran. Two parallel panels of 29 healthy adult subjects swam over 60 min in either of swimming pools. Blood samples were collected before and 2 h after swimming to assess metabolomic profile using Hydrogen-Nuclear Magnetic Resonance Spectroscopy (H-NMR). Differential metabolites between the two groups were identified by multivariate analysis methods such as Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) and Random Forest (RF). The levels of THMs in exhaled air as a biomarker of exposure and the metabolic profile as a biomarker of the effect changed significantly between two participants of swimming pools. Based on the significant metabolites, the biochemical pathways were identified by the method of Metabolite Setts Enrichment Analysis (MSEA) and by using the Metaboanalyst platform. The pathways of tryptophan metabolism, galactose metabolism and fructose and mannose metabolism were the most important biochemically significant pathways in individuals after exposure to THMs. Finally, findings from metabolic changes in our study indicate that exposure to THMs in swimming pools can activate the mechanisms of central nervous system disorders, increased uric acid, increased risk of bladder cancer and oxidative stress.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-024-00912-2.PMID:39464829 | PMC:PMC11499471 | DOI:10.1007/s40201-024-00912-2

Trop Life Sci Res. 2024 Oct;35(3):23-56. doi: 10.21315/tlsr2024.35.3.2. Epub 2024 Oct 7.ABSTRACTMacodes limii J.J. Wood & A.L. Lamb is a terrestrial jewel orchid native to Sabah, recognised for its sparkling golden-yellow venations, uniformly distributed on its leaves. Despite its high ornamental value, the exploration of the plant's medicinal potential remains ambiguous. The current study was conducted to gain a fundamental understanding of the metabolite composition and regulation in M. limii plants from two different growing environments: wild and in vitro cultivation, as well as to analyse their phytochemical contents and antioxidant activity. The metabolite profiling of the M . limii plant extracts through gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has tentatively identified compounds from various classes including sugars, carbohydrates, sugar alcohols, amino acids, organic acids, phenolic derivatives and lipid and lipid-like compounds. Subsequently, the multivariate statistical analysis confirmed the existence of significant metabolite variations across distinct growth environments. Notably, the leaf extract derived from wild-grown plants displayed the highest levels of total phenolic and flavonoid content, contributing significantly to its higher antioxidant activity as measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The discovery has offered a fundamental understanding of the metabolites in M. limii jewel orchids, indicating that in vitro regenerated plants may represent a viable alternative for further investigating their therapeutic potential, thus helping to alleviate the impact on wild populations.PMID:39464667 | PMC:PMC11507973 | DOI:10.21315/tlsr2024.35.3.2

Front Vet Sci. 2024 Oct 11;11:1366128. doi: 10.3389/fvets.2024.1366128. eCollection 2024.ABSTRACTOmics methodologies, such as genomics, transcriptomics, proteomics, metabolomics, lipidomics and microbiomics, have revolutionized biological research by allowing comprehensive molecular analysis in livestock animals. However, despite being widely used in various animal species, research on donkeys has been notably scarce. China, renowned for its rich history in donkey husbandry, plays a pivotal role in their conservation and utilization. China boasts 24 distinct donkey breeds, necessitating conservation efforts, especially for smaller breeds facing extinction threats. So far, omics approaches have been employed in studies of donkey milk and meat, shedding light on their composition and quality. Similarly, omics methods have been utilized to explore the molecular basis associated with donkey growth, meat production, and quality traits. Omics analysis has also unraveled the critical role of donkey microbiota in health and nutrition, with gut microbiome studies revealing associations with factors such as pregnancy, age, transportation stress, and altitude. Furthermore, omics applications have addressed donkey health issues, including infectious diseases and reproductive problems. In addition, these applications have also provided insights into the improvement of donkey reproductive efficiency research. In conclusion, omics methodologies are essential for advancing knowledge about donkeys, their genetic diversity, and their applications across various domains. However, omics research in donkeys is still in its infancy, and there is a need for continued research to enhance donkey breeding, production, and welfare in China and beyond.PMID:39464628 | PMC:PMC11502298 | DOI:10.3389/fvets.2024.1366128

ACS Omega. 2024 Oct 10;9(42):42757-42765. doi: 10.1021/acsomega.4c04047. eCollection 2024 Oct 22.ABSTRACTSince the emergence and rapid dissemination of Coronavirus disease 2019 (COVID-19), over 774 million individuals globally have achieved recovery to today. There is some case flashing into here and there all over the world. Neutralizing Antibody (NAb) against Severe Acute Respiratory Syndrome Coronavirus-Type 2 (SARS-CoV-2) play a paramount role in conferring effective and lasting protection for several months. This protective effect decreases with time thus increasing the chance of reinfection. Therefore, we can provide the body with a lasting protective effect by maintaining NAb level. However, how to maintain Nab level remains elusive. To address this question, we recruited 80 patients with confirmed COVID-19 and collected 480 consecutive blood samples and performed NAb testing six months after their recovery. The NAb level were categorized into two groups: a low-titer NAb group (≤20) and a high-titer NAb group (>20). To achieve a comprehensive understanding of the changes in NAb level, 16 serum samples were randomly selected for an untargeted metabolomic analysis, whereas 9 samples were designated for a label-free proteomic analysis. We successfully identified differentially expressed 751 metabolites and 845 proteins. In both the low and high NAb titer groups, we identified three key differential proteins, phosphoglucose translocase 2(PGM2), UDP-Glc 4-epimerase (GALE), and alcohol dehydrogenase 1B (ADH1B), that play important roles in fluctuating NAb level through the glycogen synthesis, galactose metabolism and ethanol degradation pathways. These three key differential proteins may serve as potential biomarkers for maintaining NAb level and enhancing immune protection in patients recovering from COVID-19.PMID:39464477 | PMC:PMC11500150 | DOI:10.1021/acsomega.4c04047

Front Neurosci. 2024 Oct 11;18:1459141. doi: 10.3389/fnins.2024.1459141. eCollection 2024.ABSTRACTInsomnia and depression are psychiatric disorders linked to substantial health burdens. The gut microbiome and metabolomic pathways are increasingly recognized as key contributors to these conditions' pathophysiology. Suanzaoren Decoction (SZRD), a traditional Chinese herbal formulation, has demonstrated significant therapeutic benefits for both insomnia and depression. This study aims to elucidate the mechanistic effects of SZRD on insomnia and depression by integrating gut microbiome and metabolomic analyses and to assess the differential impacts of SZRD dosages. Using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), we identified 66 chemical constituents within SZRD. Behavioral assays indicated that low-dose SZRD (LSZRD) significantly ameliorated insomnia symptoms in rat models, whereas high-dose SZRD (HSZRD) markedly improved depressive behaviors. 16S rRNA sequencing revealed that SZRD modulated gut microbiome dysbiosis induced by insomnia and depression, characterized by an increased abundance of short-chain fatty acid (SCFA)-producing genera. Metabolomic profiling demonstrated reduced plasma amino acid metabolites and disrupted γ-aminobutyric acid (GABA) and L-glutamic acid metabolism in the hippocampus of affected rats. SZRD administration restored fecal SCFA levels and ameliorated metabolic imbalances in both plasma and hippocampal tissues. These findings underscore the pivotal role of gut microbiome modulation and metabolic regulation in the therapeutic effects of SZRD, providing a scientific basis for its use in treating insomnia and depression.PMID:39464422 | PMC:PMC11502468 | DOI:10.3389/fnins.2024.1459141

Front Microbiol. 2024 Oct 11;15:1433175. doi: 10.3389/fmicb.2024.1433175. eCollection 2024.ABSTRACTINTRODUCTION: Canine protein-losing enteropathy (PLE) is a syndrome characterized by gastrointestinal loss of proteins. While fecal microbiome and metabolome perturbations have been reported in dogs with chronic enteropathy, they have not been widely studied in dogs with PLE. Therefore, the study aims were to investigate gut microbiome and targeted fecal metabolites in dogs with inflammatory PLE (iPLE) and evaluate whether treatment affects these changes at short-term follow-up.METHODS: Thirty-eight dogs with PLE and histopathological evidence of gastrointestinal inflammation and 47 healthy dogs were enrolled. Fecal samples were collected before endoscopy (T0) and after one month of therapy (T1). Microbiome and metabolome alterations were investigated using qPCR assays (dysbiosis index, DI) and gas chromatography/mass spectrometry (long-chain fatty acids, sterols, unconjugated bile acids), respectively.RESULTS: Median (min-max) DI of iPLE dogs was 0.4 (-5.9 to 7.7) and was significantly higher (p < 0.0001) than median DI in healthy dogs [-2.0 (-6.0 to 5.3)]. No significant associations were found between DI and selected clinicopathological variables. DI did not significantly differ between T0 and T1. In iPLE dogs, at T0, myristic, palmitic, linoleic, oleic, cis-vaccenic, stearic, arachidonic, gondoic, docosanoic, erucic, and nervonic acids were significantly higher (p < 0.0001) than healthy dogs. In iPLE dogs, oleic acid (p = 0.044), stearic acid (p = 0.013), erucic acid (p = 0.018) and nervonic acid (p = 0.002) were significantly decreased at T1. At T0, cholesterol and lathosterol (p < 0.0001) were significantly higher in iPLE dogs compared to healthy dogs, while total measured phytosterols were significantly lower (p = 0.001). No significant differences in total sterols, total phytosterols and total zoosterols content were found at T1, compared to T0. At T0, total primary bile acids and total secondary bile acids did not significantly differ between healthy control dogs and iPLE dogs. No significant differences in fecal bile acid content were found at T1.DISCUSSION: Dysbiosis and lipid metabolism perturbations were observed in dogs with iPLE. Different therapeutic protocols lead to an improvement of some but not all metabolome perturbations at short-term follow-up.PMID:39464397 | PMC:PMC11505111 | DOI:10.3389/fmicb.2024.1433175

Front Plant Sci. 2024 Oct 11;15:1430752. doi: 10.3389/fpls.2024.1430752. eCollection 2024.ABSTRACTDiethyl aminoethyl hexanoate (DA-6) serving as a non-toxic and low-cost plant growth regulator is used for improving plant growth and stress tolerance, but the DA-6-mediated organic metabolites remodeling in relation to drought tolerance is not well documented in crops. The aims of the present study were to evaluate impacts of DA-6 on physiological functions including osmotic adjustment, photochemical efficiency, oxidative damage, and cell membrane stability as well as organic metabolites remodeling in white clover (Trifolium repens) leaves based on the analysis of metabolomics. Plants were foliarly treated with or without DA-6 and subsequently exposed to drought stress for 8 days. Results demonstrated that foliar application of DA-6 (1.5 mM) could significantly ameliorate drought tolerance, which was linked with better leaf water status, photosynthetic performance, and cell membrane stability as well as lower oxidative injury in leaves. Metabolic profiling of organic metabolites identified a total of 59 metabolites including 17 organic acids, 20 sugars, 12 alcohols, and 10 other metabolites. In response to drought stress, the DA-6 induced accumulations of many sugars and sugar alcohols (erythrulose, arabinose, xylose, inosose, galactose, talopyranose, fucose, erythritol, and ribitol), organic acids (propanoic acid, 2,3-dihydroxybutanoic acid, palmitic acid, linolenic acid, and galacturonic acid), and other metabolites (2-oxazoline, silane, and glycine) in white clover. These altered metabolites induced by the DA-6 could perform critical functions in maintenances of osmo-protection, osmotic adjustment, redox homeostasis, cell wall structure and membrane stability when white clover suffered from water deficit. In addition, the campesterol and stigmasterol significantly accumulated in all plants in spite of the DA-6 pretreatment under drought stress, which could be an important adaptive response to water deficit due to beneficial roles of those two metabolites in regulating cell membrane stability and antioxidant defense. Present findings provide new evidence of DA-6-regulated metabolic homeostasis contributing to drought tolerance in leguminous plants.PMID:39464286 | PMC:PMC11502329 | DOI:10.3389/fpls.2024.1430752

Front Plant Sci. 2024 Oct 11;15:1478055. doi: 10.3389/fpls.2024.1478055. eCollection 2024.ABSTRACTPeach gummosis, a devastating disease caused by Neofusicoccum parvum, significantly shortens peach tree lifespan and reduces the yield of peach trees. Despite its impact, the molecular mechanism underlying this disease remains largely unexplored. In this study, we used RNA-seq, sugar metabolism measurements, and an integrated transcriptional and metabolomic analysis to uncover the molecular events driving peach gummosis. Our results revealed that N. parvum infection drastically altered the transcripts of cell wall degradation-related genes, the log2Fold change in the transcript level of Prupe.1G088900 encoding xyloglucan endotransglycosylase decreased 2.6-fold, while Prupe.6G075100 encoding expansin increased by 2.58-fold at 12 hpi under N. parvum stress. Additionally, sugar content analysis revealed an increase in maltose, sucrose, L-rhamnose, and inositol levels in the early stages of infection, while D-galactose, D-glucose, D-fructose consistently declined as gummosis progressed. Key genes related to cell wall degradation and starch degradation, as well as UDP-sugar biosynthesis, were significantly upregulated in response to N. parvum. These findings suggest that N. parvum manipulates cell wall degradation and UDP-sugar-related genes to invade peach shoot cells, ultimately triggering gum secretion. Furthermore, weighted gene co-expression network analysis (WGCNA) identified two transcription factors, ERF027 and bZIP9, as central regulators in the downregulated and upregulated modules, respectively. Overall, this study enhances our understanding of the physiological and molecular responses of peach trees to N. parvum infection and provide valuable insights into the mechanisms of peach defense against biotic stresses.PMID:39464283 | PMC:PMC11503026 | DOI:10.3389/fpls.2024.1478055

Front Endocrinol (Lausanne). 2024 Oct 11;15:1426517. doi: 10.3389/fendo.2024.1426517. eCollection 2024.ABSTRACTBACKGROUND: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence.METHODS: A total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential).RESULTS: Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2'-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle.CONCLUSIONS: We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.PMID:39464191 | PMC:PMC11502346 | DOI:10.3389/fendo.2024.1426517

bioRxiv [Preprint]. 2024 Oct 14:2024.10.14.618283. doi: 10.1101/2024.10.14.618283.ABSTRACTCastration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 and UAP1 being downregulated in metastatic CRPC. GNPNAT1 knockdown has been shown to increase cell proliferation and metastasis in CRPC cell lines, though the mechanisms remain unclear. To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of GNPNAT1 in 22Rv1 CRPC cells, analyzing its impact on metabolomic, glycoproteomic, and transcriptomic profiles of cells. We hypothesize that HBP inhibition disrupts the cytoskeleton, altering mitotic progression and promoting uncontrolled growth. GNPNAT1 KO cells showed reduced levels of cytoskeletal filaments, such as actin and microtubules, leading to cell structure disorganization and chromosomal mis-segregation. GNPNAT1 inhibition also activated PI3K/AKT signaling, promoting proliferation, and impaired cell adhesion by mislocalizing EphB6, enhancing migration via the RhoA pathway and promoting epithelial-to-mesenchymal transition. These findings suggest that HBP plays a critical role in regulating CRPC cell behavior, and targeting this pathway could provide a novel therapeutic approach.PMID:39464080 | PMC:PMC11507681 | DOI:10.1101/2024.10.14.618283

bioRxiv [Preprint]. 2024 Oct 18:2024.10.15.618589. doi: 10.1101/2024.10.15.618589.ABSTRACTEnteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion 1 . Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders 2-5 . However, the signals and underlying mechanisms of this microbiota-neuron communication are unknown. We studied the effects of microbiota on the recovery of the enteric nervous system after microbial dysbiosis caused by antibiotics. We found that both enteric neurons and glia are lost after antibiotic exposure, but recover when the pre-treatment microbiota is restored. Using murine gnotobiotic models and fecal metabolomics, we identified neurogenic bacterial species and their derived metabolite succinate as sufficient to rescue enteric neurons and glia. Unbiased single-nuclei RNA-seq analysis uncovered a novel neural precursor-like population marked by the expression of the neuronal gene Nav2. Genetic fate-mapping showed that Plp1+ enteric glia differentiate into neurons following antibiotic exposure. In contrast, Nav2+ neurons expand upon succinate treatment and indicate an alternative mode of neuronal regeneration under recovery conditions. Our findings highlight specific microbial species, metabolites, and the underlying cellular mechanisms involved in neuronal regeneration, with potential therapeutic implications for peripheral neuropathies.PMID:39463929 | PMC:PMC11507891 | DOI:10.1101/2024.10.15.618589

Front Neurol. 2024 Oct 11;15:1460852. doi: 10.3389/fneur.2024.1460852. eCollection 2024.ABSTRACTPURPOSE: This research employed Mendelian randomization (MR) methods to explore whether metabolites are causally associated with embolic stroke of undetermined source (ESUS).METHODS: Genome-Wide Association Study (GWAS) data regarding metabolites and ESUS were downloaded from the database. Metabolites were employed as exposure factors, ESUS served as the outcome variable, and single nucleotide polymorphisms (SNPs) exhibiting significant association with ESUS were chosen as instrumental variables. The causal association between exposure factor metabolites and the outcome variable ESUS was assessed using two methods: MR-Egger regression and inverse variance-weighted (IVW) analysis.RESULTS: A causal relationship was observed between X-11593--O-methylascorbate* and ESUS, indicating a protective factor. Moreover, a causal relationship was identified between cholesterol esters in large very-low-density lipoprotein (VLDL), cholesterol esters in medium low-density lipoprotein (LDL), concentration of medium LDL particles, phospholipids in medium LDL, phenylalanine, total cholesterol in small LDL, total lipids in medium LDL and ESUS, representing risk factor. Funnel plots exhibited a symmetrical distribution of SNPs, while pleiotropic tests (p > 0.05) and leave-one-out tests indicated that the results were relatively stable.CONCLUSION: Metabolites are causally associated with ESUS. LDL and VLDL-related metabolites are identified as risk factors for ESUS.PMID:39463788 | PMC:PMC11502368 | DOI:10.3389/fneur.2024.1460852

Plant Biotechnol (Tokyo). 2024 Jun 25;41(2):165-168. doi: 10.5511/plantbiotechnology.24.0421a.ABSTRACTPapaya (Carica papaya L.) is a herbaceous plant belonging to the family Caricaceae in the order Brassicales. The shape of papaya fruit was linked to sex, and the fruit of female plants is round, whereas that of hermaphrodites is pyriform. Although fruit shape preferences vary by region, differences in their functionalities have not been investigated. Since unripe fruit, also called green papaya, is known for its nutritional and therapeutic benefits, we performed a metabolome analysis of unripe papaya using liquid chromatography coupled with quadrupole/time of flight mass spectrometry. We first focused on capraine derivatives, major piperidine alkaloids, and bioactive compounds with significant antiplasmodial activity. Interestingly, carpaine derivatives tended to be altered in the peel and pulp but not in the seed. Multivariate analyses indicated little difference or minor differences to the extent that they can be caused by individual differences in metabolite profiling between the two sexes. Conversely, total polyphenol content and proteolytic activity were also investigated, but there were no differences between females and hermaphrodites for total polyphenol content and proteolytic activity. In conclusion, the metabolome and major functionalities were similar between hermaphrodites and female unripe fruit. However, it would be worth considering the sex of the material fruit, especially when focusing on the functional properties of carpaine derivatives.PMID:39463775 | PMC:PMC11500600 | DOI:10.5511/plantbiotechnology.24.0421a

J Dairy Res. 2024 Oct 28:1-9. doi: 10.1017/S0022029924000487. Online ahead of print.ABSTRACTOne of the major challenges in lameness management is prompt detection, especially before visible gait disturbance. This scoping review describes the potential biomarkers for lameness in dairy cows reported in the literature, their relevance in lameness diagnosis, identifying cows at risk of developing claw lesions and monitoring recovery after treatment. Using specific keywords, a comprehensive literature search was performed in three databases: PubMed, Google Scholar and ScienceDirect to retrieve relevant articles published between 2010 and 2022. A total of 31 articles fulfilling the inclusion criteria were analysed. The categories of potential markers for lameness reported in the literature included acute phase proteins (APPs), nociceptive neuropeptides, stress hormones, proteomes, inflammatory cytokines and metabolites in serum, urine and milk. Cortisol, APPs (serum amyloid A and haptoglobin) and serum, urinary and milk metabolites were the most studied biomarkers for lameness in dairy cows. While APPs, nociceptive neuropeptides and blood cortisol analyses assisted in elucidating the pain and stress experienced by lame cows during diagnosis and after treatment, evidence-based data are lacking to support their use in identifying susceptible animals. Meanwhile, metabolomic techniques revealed promising results in assessing metabolic alterations occurring before, during and after lameness onset. Several metabolites in serum, urinary and milk were reported that could be used to identify susceptible cows even before the onset of clinical signs. Nevertheless, further research is required employing metabolomic techniques to advance our knowledge of claw horn lesions and the discovery of novel biomarkers for identifying susceptible cows. The applicability of these biomarkers is challenging, particularly in the field, as they often require invasive procedures.PMID:39463263 | DOI:10.1017/S0022029924000487

J Diabetes. 2024 Oct;16(10):e70021. doi: 10.1111/1753-0407.70021.ABSTRACTBACKGROUND: The composition and function of gut microbiota, lipids, and metabolites in patients with type 1 diabetes (T1D) or its association with glycemic control remains unknown. We aimed to use multi-omics sequencing technology and machine learning (ML) approaches to investigate potential function and relationships among the gut microbiota, lipids, and metabolites in T1D patients at varied glycemic levels.METHODS: We conducted a multi-omics analysis of the gut microbiome from fecal samples, metabolites, and lipids obtained from serum samples, collected from a cohort of 72 T1D patients. The patients were divided into two groups based on their hemoglobin A1c (HbA1c) levels. 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in composition and function of gut microbiota, metabolites, and lipids.RESULTS: The linear discriminant analysis, Shapley additive explanations (SHAP) algorithm, and ML algorithms revealed the enrichment of Bacteroides_nordii, Bacteroides_cellulosilyticus in the glycemic control (GC) group, while Bacteroides_coprocola and Sutterella_wadsworthensis were enriched in the poor glycemic control (PGC) group. Several metabolic enrichment sets like fatty acid biosynthesis and glycerol phosphate shuttle metabolism were different between two groups. Bacteroides_nordii exhibited a negative association with D-fructose, a component involved in the starch and sucrose metabolism pathway, as well as with monoglycerides (16:0) involved in the glycerolipid metabolism pathway.CONCLUSIONS: We identified distinct characteristics of gut microbiota, metabolites, and lipids in T1D patients exhibiting different levels of glycemic control. Through comprehensive analysis, microbiota (Bacteroides_nordii, Bacteroides_coprocola), metabolites (D-fructose), and lipids (Monoglycerides) may serve as potential mediators that communicated the interaction between the gut, circulatory systems, and glucose fluctuations in T1D patients.PMID:39463013 | DOI:10.1111/1753-0407.70021

Essays Biochem. 2024 Oct 28:EBC20240002. doi: 10.1042/EBC20240002. Online ahead of print.ABSTRACTIt is increasingly clear that cellular metabolic function varies not just between cells of different tissues, but also within tissues and cell types. In this essay, we envision how differences in central carbon metabolism arise from multiple sources, including the cell cycle, circadian rhythms, intrinsic metabolic cycles, and others. We also discuss and compare methods that enable such variation to be detected, including single-cell metabolomics and RNA-sequencing. We pay particular attention to biosensors for AMPK and central carbon metabolites, which when used in combination with metabolic perturbations, provide clear evidence of cellular variance in metabolic function.PMID:39462995 | DOI:10.1042/EBC20240002

Chem Biodivers. 2024 Oct 27:e202402000. doi: 10.1002/cbdv.202402000. Online ahead of print.ABSTRACTPlatycladus orientalis leaves are widely used in traditional medicine to treat different ailments. In the present study, the volatile constituents were obtained by n-hexane extraction and hydrodistillation. Comprehensive metabolomic profiling was performed using GC-MS analysis. Furthermore, in vitro antioxidant potential and enzyme-inhibitory activity were assessed and supported by in silico profiling. Results revealed the predominance of monoterpene hydrocarbons in the hydrodistilled volatile oil (42.30%) followed by oxygenated sesquiterpenes (32.10%); with cedrol as the main component. Diterpenoids (49.70%) and sesquiterpene hydrocarbons (13.43%) were the major components of the n-hexane extract; with vulgarol A, a diterpene alcohol, as the major constituent. The volatile oil demonstrated significantly higher antioxidant potential across all assays, including ABTS and DDPH scavenging activity, CUPRAC, and FRAP assays. However, the n-hexane extract demonstrated broad inhibitory effects against butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase enzymes, supported by molecular docking study and predictive ADME profiling. Therefore, it may be concluded that the n-hexane extract is a viable option for treating dysregulated enzyme conditions. In addition, the potential use of volatile oil in the pharmaceutical industries and management of oxidative stress can be inferred. These results warrant further studies to validate the therapeutic potential of the volatile oil and the n-hexane extract.PMID:39462973 | DOI:10.1002/cbdv.202402000

J Sci Food Agric. 2024 Oct 27. doi: 10.1002/jsfa.13986. Online ahead of print.ABSTRACTBACKGROUND: Radix Astragali, commonly known as Astragalus, is a traditional medicinal and edible plant valued for its Qi-tonifying properties. The dosage form of Radix Astragali processed with honey, known as honey-processed Astragalus (HPA), shows improved Qi-tonifying efficacy as compared to the raw product. Polysaccharides are the main bioactive ingredients in its aqueous extract. This study used a multiomics approach integrating microbiomics and metabolomics to elucidate the Qi-tonifying mechanisms of honey-processed Astragalus polysaccharides (HAPS).RESULTS: HAPS-treated mice showed improved symptom scores, spleen and thymus indices, serum cytokines (tumor necrosis factor α, interleukin 1β) and intestinal mucosa secretory immunoglobulin A (SIgA) compared to the mice with spleen Qi deficiency. The analysis of gut microbiota indicated that HAPS regulated the relative abundance of Bacteroidetes, Bacteroides, Proteobacteria and Helicobacter, thereby improving intestinal flora dysbiosis in mice with spleen Qi deficiency. Eleven biomarkers in fecal metabolomics analysis were screened and identified, primarily associated with linoleic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Furthermore, comprehensive analyses demonstrated that HAPS regulates palmitic acid and sphingolipid metabolism by modulating the abundance of Bacteroidetes, which in turn increased the levels of intestinal mucosal SIgA and restored intestinal mucosal immune function in mice with spleen Qi deficiency.CONCLUSION: Our findings revealed that HAPS is an essential active ingredient of HPA, and its Qi-tonifying mechanism is closely related to the improvement of intestinal immune function. These findings lay the foundation for the application of HAPS as an immunomodulatory agent in health and dietary foods. © 2024 Society of Chemical Industry.PMID:39462888 | DOI:10.1002/jsfa.13986

Tumori. 2024 Oct 27:3008916241291301. doi: 10.1177/03008916241291301. Online ahead of print.ABSTRACTINTRODUCTION: Individuals with Familial Adenomatous Polyposis (FAP) or APC-associated polyposis, an autosomal dominant inherited condition, develop multiple adenomatous polyps and have an increased colorectal cancer (CRC) risk. A change in diet can help reduce cancer risk, and several dietary components have an antitumor effect. We aimed to evaluate the potential of the anti-inflammatory and anticancer substances quercetin (QER), epigallocatechin gallate (EGG) and fisetin (FIS) in decreasing the risk of CRC by reducing the growth of polyps in an organoid model.METHODS: Patient-derived organoid (PDO) lines were generated from polyps obtained from patients with FAP undergoing prophylactic colectomy. PDOs were treated with QER, EGG, or FIS to determine their effect on cell growth. Changes in caspase 3/7 activity and expression of inflammation and apoptosis mediators were assessed by luminescent and colorimetric assays.RESULTS: Three PDO lines with different inactivating pathogenic variants in the APC gene were developed using a combinatorial approach. FIS was the most active of the three substances tested, presenting the lowest IC50 in all PDO lines (range: 42.6-9.2 uM). The IC50 was defined as the concentration required to halve the number of cells after 72 hours. All molecules tested induced apoptosis through activation of caspases 3/7.CONCLUSIONS: QER, EGG, and FIS can be easily taken from foods or dietary supplements, show toxicity on PDOs derived from adenomatous polyps, while they are known to be harmless on normal cells. Diets enriched with these substances could be potential supplemental treatments to reduce the risk of CRC in individuals with FAP.PMID:39462833 | DOI:10.1177/03008916241291301