PubMed

Arch Gynecol Obstet. 2024 Nov 6. doi: 10.1007/s00404-024-07695-9. Online ahead of print.ABSTRACTPURPOSE: To explore the effects of high-altitude hypoxia on the microenvironment of oocyte development and fertilization potential, we compared the metabolomic patterns of follicular fluid from women living in different altitude areas and traced their oocyte maturation and subsequent development.METHODS: A total of 315 clinical cases were collected and divided into three groups according to their residence altitudes: 138 cases in low-altitude (< 2300 m) group, 100 cases in middle-altitude (2300-2800 m) group and 77 cases in high-altitude (> 2800 m) group. The clinical outcomes were statistically estimated, including hormonal level, oocyte maturation, in vitro fertilization, and embryo development. Meanwhile, a metabolomic analysis was performed on the follicular fluid of women from different groups using ultra-high-performance liquid chromatography and high-resolution mass spectrometry and differential metabolites were analyzed through the KEGG pathway.RESULTS: The clinical data indicated that the physical condition and reproductive hormone secretion were similar among different groups. Although personalized gonadotropin-releasing hormone strategies were applied, the numbers of antral follicles and obtained oocytes were not impacted by the residence altitude change. In in vitro culture, the maturing rate, fertility rate and cleavage rate of high-altitude group were compared with the other groups. However, the rates of high-quality embryo, formative blastocyst, and available blastocyst were gradually decreased with the rise of residence altitude. Metabolome analysis identified 1193 metabolites in female follicular fluid. Differential analysis indicated that metabolic components in follicular fluid were remarkably changed with the elevation of residence altitude. These differential metabolites were closely related with amino acid metabolism, protein digestion and absorption, oocyte meiosis and steroid biosynthesis.CONCLUSION: The residence altitude alters the microenvironment of follicular fluid, which could damage the oocyte developmental potential. This study provides diagnostic basis and therapeutic targets for research on female oocyte and embryo development.PMID:39503772 | DOI:10.1007/s00404-024-07695-9

J Sep Sci. 2024 Nov;47(21):e70019. doi: 10.1002/jssc.70019.ABSTRACTGuyinjian (GYJ) is a classic traditional Chinese medicine formula for the treatment of polycystic ovary syndrome, ovulation disorders, immuno-sterility, oligomenorrhea with kidney deficiency, and so forth. Due to the unclear chemical components of GYJ, the elucidation of the pharmacological mechanism, and the comprehensive development and utilization of GYJ in clinical is being restricted. In this study, ultra-high-performance liquid chromatography with quadrupole time-of-flight-tandem mass spectrometry combined with the Progenesis QI platform and using reference standards, online and self-built databases matching, fragmentation rules analysis of mass spectrometry peaks, a total of 235 compounds were preliminarily characterized, including 69 flavonoids, 65 terpenoids, 34 phenylpropanoids, 22 saccharides, sugar esters, and glycosides, 15 organic acids, and 30 others. These compounds may reflect the chemical properties of GYJ. The method established in this study can systematically, rapidly, and accurately resolve the chemical components in GYJ, which lays the foundation for further establishment of the pharmacodynamic substance basis and quality control.PMID:39503440 | DOI:10.1002/jssc.70019

Mult Scler. 2024 Nov 6:13524585241292974. doi: 10.1177/13524585241292974. Online ahead of print.ABSTRACTThe pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.PMID:39503321 | DOI:10.1177/13524585241292974

Plant Cell Environ. 2024 Nov 6. doi: 10.1111/pce.15269. Online ahead of print.ABSTRACTAn autofluorescent inclusion (AFI) specifically accumulated in mesophyll cells (MCs) of non-salt-secretor mangrove was found to be related to salt, but its biosynthesis and spatial distribution characteristics remain unclear. Here, Kandelia obovata served as the experimental material, and the composition of AFI was identified as condensed tannin (CT). Na contents increased in purified AFIs under NaCl treatment, while Na+ efflux in MCs was lower than the control. In vitro, Na+ addition caused aggregations of AFIs. Proteins related to Na+/H+ and vesicle transport were identified in the purified AFIs by liquid chromatography-mass spectrometry. TEM images revealed the structures involved in CT biosynthesis in chloroplasts and CT accretions in vacuoles were more visible under higher salinity. Spatial metabolomics analysis on flavonoid metabolites involving in CT biosynthesis illustrated those flavonoids and three CT monomers were positively related to salt in MCs. Real-time quantitative PCR verified the genes encoding enzymes for CT biosynthesis were upregulated accordingly. Taken together, CT biosynthesis is positively correlated with Na accumulation in leaves. The CTs synthesized in chloroplasts are transported as shuttles to vacuole via cytoplasm, facilitating the sequestration and compartmentalization of excessive Na+ ions into the vacuole, which confers non-salt-secretor mangrove K. obovata a higher salt tolerance.PMID:39503313 | DOI:10.1111/pce.15269

Pediatr Allergy Immunol. 2024 Nov;35(11):e14274. doi: 10.1111/pai.14274.ABSTRACTBACKGROUND: Infants hospitalized for bronchiolitis are at high risk for developing recurrent wheeze in childhood. The role of airway lipids in the link between these two conditions remains unclear. This study aimed to identify the association between airway lipids in infants hospitalized for bronchiolitis and the development of recurrent wheeze, with a focus on immunoglobulin E (IgE) sensitization.METHODS: In a multicenter prospective cohort study of 919 infants (age <1 year) hospitalized for bronchiolitis, we performed lipidomic profiling of nasopharyngeal airway specimens collected at hospitalization. We first identified lipid modules composed of highly correlated lipids by performing weighted correlation network analysis. We then examined the longitudinal association of those lipid modules with the rate of recurrent wheeze by age 3 years after discharge from hospitalization for bronchiolitis. We also examined the associations of lipid modules with IgE non-sensitized (i.e., neither sensitized at admission nor at age 3 years) and IgE-sensitized (i.e., sensitized at admission and/or at age 3 years) recurrent wheeze by age 3 years, respectively.RESULTS: Our analysis identified 15 distinct lipid modules in the nasopharyngeal airway lipidome data. Overall, lipid modules composed of triacylglycerols (hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.26-2.51, FDR < 0.01) and sphingolipids (HR 1.74, 95% CI 1.25-2.44, FDR <0.01) had the strongest associations with recurrent wheeze development. Stratification by IgE sensitization revealed differential associations. For example, the module composed of triacylglycerols was significantly associated with IgE non-sensitized recurrent wheeze, whereas the module composed of sphingolipids was significantly associated with IgE-sensitized recurrent wheeze (both FDR <0.05).CONCLUSION: Distinct nasopharyngeal airway lipid modules are associated with recurrent wheeze development following severe bronchiolitis, with different patterns based on IgE sensitization status.PMID:39503262 | DOI:10.1111/pai.14274

Food Chem. 2024 Oct 18;464(Pt 2):141683. doi: 10.1016/j.foodchem.2024.141683. Online ahead of print.ABSTRACTCoffee is a widely popular beverage worldwide, known for its distinct sensory properties which are greatly affected by geographical origin. Herein, we performed an untargeted metabolomic evaluation of green coffee beans (n = 40) from four different regions in Brazil: Cerrado Mineiro, Sul de Minas, Caparaó, and Mogiana Paulista; by using UHPLC-HRMS (ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry). The most significant metabolites responsible for coffee characterization were theobromine, zeatin, phenylacetaldehyde, 2-acetyl-1-pyrroline, chlorogenic acids, ferulic acid, p-coumaric acid, abscisic acid, and jasmonic acid. Our findings demonstrate that the green coffee cultivated in Cerrado Mineiro, the most valuable among the four samples evaluated, exhibits a unique and typical metabolite profile, setting it apart from the coffee beans grown in other regions. Finally, the findings reported may be relevant for coffee producers in the Cerrado Mineiro area, as they contribute to establishing a certificate of origin for their high-quality product.PMID:39503088 | DOI:10.1016/j.foodchem.2024.141683

Transl Gastroenterol Hepatol. 2024 Aug 9;9:65. doi: 10.21037/tgh-24-14. eCollection 2024.ABSTRACTBACKGROUND: Acute pancreatitis (AP) is a complex inflammatory condition with rising incidence globally. Despite various known causes, early diagnosis remains challenging due to limitations in existing biomarkers. Metabolomics offers a promising avenue for identifying novel biomarkers and elucidating underlying pathophysiological mechanisms. Previous AP metabolomics studies primarily focused on analyzing serum, urine, and pancreatic tissues from patients or animal models. However, systematic metabolomics studies that analyze multiple tissues simultaneously are still lacking. The primary aim of our study is to obtain valuable clues to explore the pathophysiological mechanisms of AP and discover novel biomarkers to enable early detection.METHODS: Using a mouse model of AP induced by cerulein, we conducted gas chromatography-mass spectrometry (GC-MS) metabolomic analysis on serum, pancreas, liver, spleen, colon, and kidney samples. Twelve male C57BL/6J mice were randomly divided into AP and control (CON) groups. Serum and tissue samples were collected, processed, and analyzed using established protocols. Multivariate statistical analysis was employed to identify differential metabolites and impacted metabolic pathways.RESULTS: Distinct metabolic profiles were observed between AP and CON groups across multiple tissues. Elevated levels of ketone bodies, amino acids, citric acid, and lipids were noted, with significant differences in metabolite levels identified. Notably, 3-hydroxybutyric acid (3-HBA), branched-chain amino acids (BCAAs), phenylalanine, and L-lysine showed consistent alterations, suggesting their potential as early diagnostic biomarkers for AP. Pathway analysis revealed perturbations in several metabolic pathways, providing insights into the pathophysiological mechanisms underlying AP.CONCLUSIONS: Our study highlights the utility of metabolomics in identifying potential biomarkers for early diagnosis of AP and elucidating associated metabolic pathways. 3-HBA, BCAAs, phenylalanine and L-lysine emerge as promising biomarkers for further clinical validation. These findings contribute to a better understanding of AP pathophysiology and underscore the potential of metabolomics in precision medicine approaches for AP management.PMID:39503020 | PMC:PMC11535808 | DOI:10.21037/tgh-24-14

Front Nutr. 2024 Oct 22;11:1438740. doi: 10.3389/fnut.2024.1438740. eCollection 2024.ABSTRACTConsumption of plant-based diets, including vegan diets, necessitates attention to the quality of the diet for the prevention and early detection of nutritional deficiencies. Within the VEGANScreener project, a unique brief screening tool for the assessment and monitoring of diet quality among vegans in Europe was developed. To provide a standardized tool for public use, a clinical study will be conducted to evaluate the VEGANScreener against a reference dietary assessment method and nutritional biomarkers. An observational study is set to include 600 participants across five European sites - Belgium, Czech Republic, Germany, Spain, and Switzerland. In total, 400 self-reported vegans (≥2 years on a vegan diet), and 170 self-reported omnivore controls will be examined, aged between 18 and 65 years, with males and females being equally represented in a 1:1 ratio for two age groups (18-35 and 36-65 years). Participants with diseases affecting metabolism and intestinal integrity will be excluded. The clinical assessment will include a structured medical history, along with taking blood pressure and anthropometric measurements. Blood and urine will be sampled and analyzed for a set of dietary biomarkers. Metabolomic analyses will be conducted to explore potential novel biomarkers of vegan diet. Moreover, saliva samples will be collected to assess the metabolome and the microbiome. Participants will receive instructions to complete a nonconsecutive 4-day diet record, along with the VEGANScreener, a socio-demographic survey, a well-being survey, and a FFQ. To evaluate reproducibility, the VEGANScreener will be administered twice over a three-weeks period. Among vegans, the construct validity and criterion validity of the VEGANScreener will be analyzed through associations of the score with nutrient and food group intakes, diet quality scores assessed from the 4-day diet records, and associations with the dietary biomarkers. Secondary outcomes will include analysis of dietary data, metabolomics, and microbiomes in all participants. Major nutrient sources and variations will be assessed in the sample. Exploratory metabolomic analysis will be performed using multivariable statistics and regression analysis to identify novel biomarkers. Standard statistical models will be implemented for cross-sectional comparisons of geographical groups and vegans versus omnivores.PMID:39502879 | PMC:PMC11534613 | DOI:10.3389/fnut.2024.1438740

Med Pharm Rep. 2024 Oct;97(4):467-476. doi: 10.15386/mpr-2780. Epub 2024 Oct 30.ABSTRACTBACKGROUND AND AIM: Tacrolimus (TAC) has significantly improved kidney graft survival following transplantation, though it is associated with adverse side effects. The most prevalent complication resulting from excessive TAC exposure is the onset of de novo diabetes mellitus (DM), a condition that can negatively impact both renal graft function and patient outcomes. De novo DM is linked to an increased risk of chronic transplant dysfunction, as well as cardiovascular morbidity and mortality. Although the underlying mechanisms remain unclear, emerging research in the field of omics shows promise. The aim of this study was to investigate the metabolomic profile of kidney transplant patients who developed de novo DM, in comparison to those who did not, following TAC exposure, using untargeted metabolomic analysis through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and machine learning algorithms.METHODS: A cohort of 34 kidney transplant patients on a Tacrolimus regimen for at least 6 months was enrolled in the study, with serum samples collected from each patient. Comprehensive profiling of serum metabolites was performed, enabling the classification of patients into de novo diabetes mellitus and non diabetes groups. The metabolomic analysis of serum was conducted using UHPLC-MS.RESULTS: Of the 34 patients, 16 were diagnosed with TAC-induced diabetes. A total of 334 metabolites were identified in the serum samples, of which 10 demonstrated a significant correlation with the de novo diabetes mellitus group. Most of these metabolites were linked to alterations in lipid metabolism.CONCLUSION: The application of metabolomics in kidney transplant patients undergoing a Tacrolimus regimen is both feasible and effective in identifying metabolites associated with de novo diabetes mellitus. This approach may provide valuable insights into the metabolic alterations underlying TAC-induced diabetes.PMID:39502769 | PMC:PMC11534379 | DOI:10.15386/mpr-2780

Int J Microbiol. 2024 Oct 28;2024:1763495. doi: 10.1155/2024/1763495. eCollection 2024.ABSTRACTToxigenic fungi are capable of producing toxic metabolites, called mycotoxins. But the presence of silent and lowly expressed genes represents the main challenge for the discovery of novel mycotoxins, especially their lesser-known forms, commonly referred to as "emerging mycotoxins." Epigenetic modifiers (EMs) are compounds that are able to alter the production of metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of the well-known toxigenic fungal species, Fusarium verticillioides. Four EMs, 5-azacytidine, sodium butyrate, nicotinamide (NIC), and sodium valproate (SV), were used. Following their addition to Fusarium verticillioides cultures, the metabolic profiles were analyzed by using UHPLC-HRMS/MS under targeted and untargeted metabolomics approaches. Metabolites were putatively annotated through the use of MS-DIAL and MS-FINDER. Our results show that the treatment with SV induced the most important alteration of the secondary metabolic profile of F. verticillioides, by promoting the expression of cryptic genes. Among the 50 most discriminating metabolites across five culture conditions, 12 were fusarins or fusarin analogs. In contrast, SB and NIC had little impact on these metabolites. The study highlights SV's ability to alter gene expression by inhibiting DNA deacetylation in fungal strains. This research could have significant implications for agriculture and food industry, especially in regions facing major mycotoxin challenges.PMID:39502514 | PMC:PMC11535422 | DOI:10.1155/2024/1763495

Int J Endocrinol. 2024 Oct 28;2024:5540062. doi: 10.1155/2024/5540062. eCollection 2024.ABSTRACTBackground: Type 2 diabetes mellitus (T2DM) has emerged as a global epidemic issue, with high rates of disability and fatality. Traditional diagnostic biomarkers are typically detected once a metabolic imbalance has already occurred, thus the development of early diagnostic biomarkers is crucial for T2DM. Metabolomics studies have identified several predictive biomarkers for T2DM, including miR-320. Our previous research found that miR-320b was significantly downregulated in T2DM patients, but the underlying mechanism remains unclear. Therefore, this study was designed to investigate the significance of miR-320b for T2DM diagnosis and to explore the involved molecular mechanism. Methods: A total of 50 patients with T2DM and 80 sex- and age-matched healthy subjects were selected. The plasma miR-320b of all participations was detected by qRT-PCR and its correlations with other biomarkers of T2DM were analyzed. Besides, the expression of miR-320b in HepG2 cells was suppressed by miRNA inhibitors. Then the glucose consumption of HepG2 cells was measured. The target gene of miR-320b was predicted by four bioinformatics tools and intersected these prediction results by Venny method. The T2DM relevant target genes were identified by the GeneCards database. To ensure disease relevance, these T2DM relevant target genes were subsequently intersected with the target genes of miR-320b. Protein-protein analysis (PPI) was used to screening the gene with the most connections in these target genes. Finally, the target gene of miR-320b specific to T2DM was confirmed directly by luciferase reporter assay. The expression of target gene in HepG2 cell culture supernatant and plasma of all participations was detected. Results: Our results showed that the expression level of miR-320b was significantly lower in T2DM patients compared to the healthy controls. It was negatively correlated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment of insulin resistance (HOMA-IR), but positively with HOMA-β. The glucose consumption of HepG2 cells in the miR-320b inhibitor group was significantly lower compared to inhibitor-NC and blank control group. We predicted and confirmed that phosphatase and tensin homolog (PTEN) was the direct target gene of miR-320b using Bioinformation tools and luciferase reporter assay. Moreover, the concentration of PTEN was significantly higher in the HepG2 cell culture supernatant and plasma of T2DM patients. Conclusions: Our research demonstrated a negative correlation between miR-320b and FPG, HbA1C, and HOMA-IR, while exhibiting a positive correlation with HOMA-β. Suppressing miR-320b expression would impair glucose consumption of HepG2 cells through PI3K pathway by targeting PTEN. These results suggest that miR-320b may be a potential biomarker for diagnosing T2DM and a promising target for therapeutic intervention.PMID:39502509 | PMC:PMC11535181 | DOI:10.1155/2024/5540062

Front Oral Health. 2024 Oct 22;5:1475361. doi: 10.3389/froh.2024.1475361. eCollection 2024.ABSTRACTINTRODUCTION: During development of dental caries, oral biofilms undergo changes in microbial composition and phenotypical traits. The aim of this study was to compare the acid tolerance (AT) of plaque from two groups of children: one with severe caries (CA) and one with no caries experience (CF) and to correlate this to the microbial composition and metabolic profile of the biofilms.METHODS: Dental plaque samples from 20 children (2-5 years) in each group were studied. The AT was analyzed by viability assessment after exposure to an acid challenge (pH 3.5), using LIVE/DEAD® BacLight™ stain and confocal microscopy. Levels of acid tolerance (AT) were evaluated using a scoring system ranging from 1 (no/low AT), to 5 (high/all AT). Metabolic profiles were investigated following a 20 mM glucose pulse for one hour through Nuclear Magnetic Resonance (NMR). Microbial composition was characterized by 16S rRNA Illumina sequencing.RESULTS: The mean AT score of the CA group (4.1) was significantly higher than that of the CF group (2.6, p < 0.05). When comparing the end-products of glucose metabolism detected after a glucose-pulse, the CA samples showed a significantly higher lactate to acetate, lactate to formate, lactate to succinate and lactate to ethanol ratio than the CF samples (p < 0.05). The bacterial characterization of the samples revealed 25 species significantly more abundant in the CA samples, including species of Streptococcus, Prevotella, Leptotrichia and Veillonella (p < 0.05).DISCUSSION: Our results show that AT in pooled plaque from the oral cavity of children with severe caries is increased compared to that in healthy subjects and that this can be related to differences in the metabolic activity and microbial composition of the biofilms. Thus, the overall phenotype of dental plaque appears to be a promising indicator of the caries status of individuals. However, longitudinal studies investigating how the AT changes over time in relation to caries development are needed before plaque AT could be considered as a prediction method for the development of dental caries.PMID:39502319 | PMC:PMC11534697 | DOI:10.3389/froh.2024.1475361

J Sci Food Agric. 2024 Nov 6. doi: 10.1002/jsfa.13996. Online ahead of print.ABSTRACTBACKGROUND: Brassica juncea L. (family Brassicaceae) or Indian mustard is a fast-growing oilseed crop. Climate changes mean that it is very important to evaluate the effects of salinity stress on B. juncea. The aim of this study was therefore to show the metabolic effect of salinity stress on shoots and roots using two cultivation models - hydroponic and microplot - in different cultivars, including RH-725 and RH-761. Salinity levels of 5, 7.5, and 10 dS m⁻¹ were investigated, and compared with a control of 0 dS m⁻¹, using untargeted metabolomics with gas chromatography-mass spectrometry (GC-MS) post-silylation, focusing on metabolic markers such as proline and glycine-betaine.RESULTS: A total of 56 metabolites were identified, with the most prevalent classes belonging to sugars (8), followed by organic acids (13), amino acids (11), and fatty acids/esters (11). Shoots were found to have a higher sugar content than roots. Increases in unsaturated fatty acids were also associated with salinity stress, compared with a decrease in saturated fatty acids. Absolute levels of proline and glycine-betaine correlated with salinity stress, with the largest increases detected in shoots grown under hydroponic conditions, particularly for the RH-761 cultivar. Multivariate data analyses revealed that roots were more affected than shoots, regardless of cultivation model.CONCLUSION: These findings might explain the different metabolic behavior of B. juncea's roots and shoots under various levels of salinity, associated with higher levels of free sugars in shoots and lipids in roots. © 2024 Society of Chemical Industry.PMID:39502065 | DOI:10.1002/jsfa.13996

Curr Neuropharmacol. 2024 Nov 4. doi: 10.2174/1570159X23666241101093436. Online ahead of print.ABSTRACTBACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy.CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.PMID:39501955 | DOI:10.2174/1570159X23666241101093436

J Agric Food Chem. 2024 Nov 6. doi: 10.1021/acs.jafc.4c07140. Online ahead of print.ABSTRACTCasein hydrolysates have been proven to exert varying sleep-enhancing and anxiolytic effects due to their distinct release of potential peptides. However, their underlying sleep-enhancing mechanisms at the metabolic level remain unclear. This study aims to investigate the potential sleep-enhancing mechanism of casein hydrolysates through an integrated approach of untargeted and targeted metabolomics in CUMS-induced anxiety mice for the first time. The results showed seven potential biomarkers were identified and screened using orthogonal partial least-squares discriminant analysis, random forest model, and pathway analysis, including ornithine, l-proline, l-prolinamide, inhibitory neurotransmitters gamma-aminobutyric acid, 5-HIAA, fumaric acid, and 4-oxoglutaramate. Moreover, casein hydrolysates exerted sleep-enhancing effects through multiple metabolic pathways, mainly including the GABAergic system, tryptophan metabolism, and cAMP response signaling pathway, which was validated by targeted metabolomics and vital protein expressions. It was interesting that casein hydrolysates with diverse representative peptide compositions exhibited varying activity, which could be attributed to distinct alterations in metabolites via different pathways.PMID:39501924 | DOI:10.1021/acs.jafc.4c07140

Physiol Plant. 2024 Nov-Dec;176(6):e14598. doi: 10.1111/ppl.14598.ABSTRACTSaffron stigma, derived from Crocus sativus L., has long been revered in global traditional medicine and continues to hold significant market value. However, despite the extensive focus on saffron stigma, the therapeutic potential of other floral components remains underexplored, primarily due to limited insights into their complex molecular architectures and chemical diversity. To address this gap, we performed a comprehensive metabolomic analysis of various floral organs utilizing advanced analytical platforms, including GC-MS and UPLC-MS/MS. This in-depth profiling revealed a diverse array of 248 metabolites, encompassing amino acids, sugar derivatives, fatty acids, flavonoids, vitamins, polyamines, organic acids, and a broad spectrum of secondary metabolites. Distinct correlation patterns among these metabolites were identified through PCA and PLS-DA, highlighting unique metabolomic signatures inherent to each floral organ. We further integrated these metabolomic findings with our transcriptomic data, enabling a detailed understanding of the molecular and metabolic variations across different floral organs. The pronounced abundance of differentially expressed genes and metabolites in the stamen (424), leaf (345), tepal (196), stigma (177), and corm (133) underscores the intricate regulatory networks governing source-to-sink partitioning and dynamic metabolic processes. Notably, our study identified several bioactive compounds, including crocin, picrocrocin, crocetin, safranal, cannabielsoin, quercetin, prenylnaringenin, isorhamnetin, pelargonidin, kaempferol, and gallic acid, all of which exhibit potential therapeutic properties. In conclusion, this comprehensive analysis significantly enhances our understanding of the molecular mechanisms driving the biosynthesis of apocarotenoids, cannabinoids, anthocyanins, and flavonoids in saffron, thereby providing valuable insights and paving the way for future research in this area.PMID:39501843 | DOI:10.1111/ppl.14598

Aging Cell. 2024 Nov 5:e14395. doi: 10.1111/acel.14395. Online ahead of print.ABSTRACTA new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline. We hypothesized that timing of menopause, a marker of ovarian aging, predicts brain age decades later. We used 2086 subjects with multiple "omics" measurements from post-mortem brain samples. Age at menopause (AAM) is positively correlated with cognitive function and negatively correlated with pre-frontal cortex aging acceleration (calculated as estimated biological age from DNA methylation minus chronological age). Genetic correlations showed that at least part of these associations is derived from shared heritability. To dissect the mechanism linking AAM to cognitive decline, we turned to transcriptomic data which confirmed that later AAM was associated with gene expression in pre-frontal cortex consistent with better cognition, and among those who reached menopause naturally, decreased gene expression of pathways implicated in aging. Those with surgical menopause displayed different molecular changes, including perturbed nicotinamide adenine dinucleotide (NAD+) activity, validated by metabolomics. Bile acid metabolism was perturbed in both groups, although different bile acid ratios were associated with AAM in each. Together, our data suggest that AAM is predictive of brain aging and cognition, with potential mediation by the gut, although through different mechanisms depending on the type of menopause.PMID:39501567 | DOI:10.1111/acel.14395

Plant Cell Environ. 2024 Nov 5. doi: 10.1111/pce.15261. Online ahead of print.ABSTRACTPigeon pea, vital for farmers in semi-arid regions, suffers yield losses from Fusarium wilt caused by Fusarium udum. This study demonstrates that introducing the rice oxalate oxidase 4 (Osoxo4) gene significantly boosts wilt resistance. Enhanced resistance in transgenic lines was confirmed through gene expression analysis, enzyme activity assays, biochemical assessments, histochemical staining and in vitro and in vivo bioassays, including spore germination tests. We performed proteomics and metabolomics analyses to investigate mechanisms of enhanced resistance. LC-MS/MS-based label-free proteomics of wilt-infected transgenic and wild-type pigeon pea leaves identified 2386 proteins, with 1048 showing significant abundance changes-738 upregulated and 310 downregulated-in transgenic plants. Notably, proteins such as HMG1/2-like protein, Putative nucleosome assembly protein C364.06, DEAD-box ATP-dependent RNA helicase 3, Lipoxygenase 1, Annexin D1 and Annexin-like protein RJ4 were significantly upregulated, indicating their potential role in developing wilt-resistant cultivars. Metabolomic analysis showed elevated levels of amino acids, sugars, oxalic acid, sugar alcohols and myo-inositol in transgenic pigeon pea, with upregulated pathways in Sugar and Starch Metabolism and Inositol Phosphate Metabolism, indicating enhanced resilience to wilt stress. This study highlights unique regulatory proteins and metabolites, offering insights into stress adaptation and guiding genetic interventions for breeding disease-resistant pigeon pea varieties.PMID:39501468 | DOI:10.1111/pce.15261

J Anim Physiol Anim Nutr (Berl). 2024 Nov;108(6):1650-1664. doi: 10.1111/jpn.14008. Epub 2024 Jun 21.ABSTRACTThe world's increasing need for protein faces challenges in aquaculture production. New applications and tools will need to be added at every stage of the manufacturing line to attain this expansion sustainably, safely, and effectively. Utilizing experimental methods to increase aquatic animal production has become more common as aquatic biotechnology has advanced. High-throughput omics technologies have been introduced to address these issues, including transcriptomic, metabolomic, proteomic, and genomes. But it also faces many difficulties, like other food manufacturing industries. One of the best and most durable approaches to address these issues is probably to understand nutritional requirements and modify diet based on need. Molecular approaches are a subset of multiomics technology. Previously, most of the published work was devoted to the biochemical aspects of protein-lipid interactions in biological systems. In this review, we explore this idea and highlight various works that fall under the umbrella of nutrigenomics, with a particular emphasis on protein utilization and its interactions with carbohydrates and lipids.PMID:39501455 | DOI:10.1111/jpn.14008

Virol J. 2024 Nov 6;21(1):278. doi: 10.1186/s12985-024-02553-1.ABSTRACTBACKGROUND: Researchers gradually focus on the relationship between phage and cancer.OBJECTIVE: To summarize the research hotspots and trends in the field of bacteriophage and cancer.METHODS: The downloaded articles were searched from the Web of Science Core Collection database from January 2008 to June 2023. Bibliometric analysis was carried out through CiteSpace, including the analysis of cooperative networks (country/region, institution, and author), co-citations of references, and key words.Visual analysis of three topics, including gut phage, phage and bacteria, and phage and tumor, was conducted.RESULTS: Overall, the United States and China have the most phage-related research. In terms of gut phage, the future research directions are "gut microbiome", "database" and "microbiota". The bursting citations explored the phage-dominated viral genome to discover its diversity and individual specificity and investigated associations among bacteriome, metabolome, and virome. In terms of phage and bacteria, "lipopolysaccharide" and "microbiota" are future research directions. Future research hotspots should mainly concentrate on the further exploration and application of phage properties. As for phages and tumors, the future research directions should be "colorectal cancer", "protein" and "phage therapy". Future directions are likely to focus on the research on phages in cancer mechanisms, cancer diagnosis, and cancer treatment combined with genetic engineering techniques.CONCLUSION: Phage therapy would become a hot spot and research direction of tumor and phage research, and the relationship between phage and tumor, especially colorectal cancer (CRC), is expected to be further explored.PMID:39501333 | DOI:10.1186/s12985-024-02553-1