PubMed

Int J Mol Sci. 2024 Oct 17;25(20):11189. doi: 10.3390/ijms252011189.ABSTRACTColorectal cancer (CRC) arises from aberrant mutations in colorectal cells, frequently linked to chronic inflammation. This study integrated human gut metagenome analysis with an azoxymethane and dextran sulfate sodium-induced CRC mouse model to investigate the dynamics of inflammation, gut microbiota, and metabolomic profiles throughout tumorigenesis. The analysis of stool metagenome data from 30 healthy individuals and 40 CRC patients disclosed a significant escalation in both gut microbiota diversity and abundance in CRC patients compared to healthy individuals (p < 0.05). Marked structural disparities were identified between the gut microbiota of healthy individuals and those with CRC (p < 0.05), characterized by elevated levels of clostridia and diminished bifidobacteria in CRC patients (p < 0.05). In the mouse model, CRC mice exhibited distinct gut microbiota structures and metabolite signatures at early and advanced tumor stages, with subtle variations noted during the intermediate phase. Additionally, inflammatory marker levels increased progressively during tumor development in CRC mice, in contrast to their stable levels in healthy counterparts. These findings suggest that persistent inflammation might precipitate gut dysbiosis and altered microbial metabolism. Collectively, this study provides insights into the interplay between inflammation, gut microbiota, and metabolite changes during CRC progression, offering potential biomarkers for diagnosis. While further validation with larger cohorts is warranted, the data obtained support the development of CRC prevention and diagnosis strategies.PMID:39456970 | DOI:10.3390/ijms252011189

J Agric Food Chem. 2024 Oct 25. doi: 10.1021/acs.jafc.4c06094. Online ahead of print.ABSTRACTThe modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.PMID:39454127 | DOI:10.1021/acs.jafc.4c06094

Sci Adv. 2024 Oct 25;10(43):eado5887. doi: 10.1126/sciadv.ado5887. Epub 2024 Oct 25.ABSTRACTCellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA. However, the mechanisms linking DNA damage to senescence remain unclear. Here, we show that DNA damage response (DDR) signaling to mitochondria triggers senescence. A genome-wide small interfering RNA screen implicated the outer mitochondrial transmembrane protein BNIP3 in senescence induction. We found that BNIP3 is phosphorylated by the DDR kinase ataxia telangiectasia mutated (ATM) and contributes to an increase in the number of mitochondrial cristae. Stable isotope labeling metabolomics indicated that the increase in cristae enhances fatty acid oxidation (FAO) to acetyl-coenzyme A (acetyl-CoA). This promotes histone acetylation and expression of the cyclin-dependent kinase inhibitor p16INK4a. Notably, pharmacological activation of FAO alone induced senescence both in vitro and in vivo. Thus, mitochondrial energy metabolism plays a critical role in senescence induction and is a potential intervention target to control senescence.PMID:39454000 | DOI:10.1126/sciadv.ado5887

PLoS One. 2024 Oct 25;19(10):e0310135. doi: 10.1371/journal.pone.0310135. eCollection 2024.ABSTRACTBACKGROUND: Adequate dietary consumption of calcium is crucial in the preservation of bone health and the prevention of osteoporosis. This study investigated the prevalence of insufficient dietary calcium intake among individuals aged ≥50 years in Iran.METHODS: We analyzed data from the Iranian Multicenter Osteoporosis Study (IMOS-2021). Participants aged 50 years and older completed a 168-item food frequency questionnaire. Insufficient dietary calcium intake was characterized as a daily calcium intake of <1000 mg for men aged 50-70 years, and <1200 mg for men over 70 years and women over 50 years and older. Stata v17 statistical software facilitated a survey set analysis to estimate the population's mean and median dietary calcium intake and the prevalence of insufficient dietary calcium intake.RESULTS: The study included 1450 participants with a mean age of 60.7±7.9 years. The estimated mean dietary calcium intake in Iran was 1062.7 mg/day (95% CI: 1029.6-1095.8), with a median intake of 943.5 mg/d (95% CI: 910.5-976.4). The prevalence of insufficient dietary calcium intake in Iran was estimated to be 62.9% (95% CI: 60.0%-65.7%). Notably, the prevalence was higher among women at 75.5% (95% CI: 71.9%-78.8%), compared to men at 47.8% (95% CI: 43.4%-52.3%) with a significant difference (P<0.001). In age-related findings, individuals aged 65 years and older had a higher prevalence of insufficient intake, at 69.0% (95% CI: 63.9%-74.0%), versus those under 65 years, at 60.3% (95% CI: 56.9%-63.8%), with this difference being statistically significant (P = 0.007). Furthermore, a significant inverse relationship was identified between both educational years and socioeconomic status and the prevalence of insufficient dietary calcium intake (Ps for trends<0.001).CONCLUSION: Our findings revealed a significant prevalence of insufficient dietary calcium intake in women and those aged 65 and older. We advocate for targeted public health strategies to ensure sufficient dietary calcium intake across these populations.PMID:39453896 | DOI:10.1371/journal.pone.0310135

FASEB J. 2024 Oct 31;38(20):e70134. doi: 10.1096/fj.202401565RR.ABSTRACTAcute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.PMID:39453737 | DOI:10.1096/fj.202401565RR

J Agric Food Chem. 2024 Oct 25. doi: 10.1021/acs.jafc.4c06507. Online ahead of print.ABSTRACTSalinization is recognized as a global problem, restricting agricultural production and sustainability. Targeting the salinity-induced oxidative stress, antioxidant treatment represents a protective strategy to improve plant salt tolerance. Herein, we report a V4C3 MXene nanozyme (MXenzyme), which exhibits good biocompatibility and excellent reactive oxygen species scavenging activity to ameliorate the salt stress-induced inhibition of seed germination. V4C3 MXenzyme treatment can significantly relieve salinity-induced oxidative stress and restore the antioxidant system in pea seeds, thus improving the phenotypic traits during germination. The molecular mechanism by which antioxidant V4C3 MXenzymes augment salt tolerances is revealed through transcriptomics and metabolomics. V4C3 MXenzymes significantly regulate the gene expression of antioxidant enzymes and molecule biosynthesis that correlate closely with hormone signal transduction genes and energy metabolism genes. With correlation and the combined analysis, redox homeostasis targeted by antioxidant V4C3 MXenzymes plays a critical role in promoting plant growth under salt stress.PMID:39453732 | DOI:10.1021/acs.jafc.4c06507

Plant J. 2024 Oct 25. doi: 10.1111/tpj.17097. Online ahead of print.ABSTRACTFlavonoids represent a diverse group of plant specialised metabolites which are also discussed in the context of dietary health and inflammatory response. Numerous studies have revealed that flavonoids play a central role in plant acclimation to abiotic factors like low temperature or high light, but their structural and functional diversity frequently prevents a detailed mechanistic understanding. Further complexity in analysing flavonoid metabolism arises from the different subcellular compartments which are involved in biosynthesis and storage. In the present study, non-aqueous fractionation of Arabidopsis leaf tissue was combined with metabolomics and proteomics analysis to reveal the effects of flavonoid deficiencies on subcellular metabolism during cold acclimation. During the first 3 days of a 2-week cold acclimation period, flavonoid deficiency was observed to affect pyruvate, citrate and glutamate metabolism which indicated a role in stabilising C/N metabolism and photosynthesis. Also, tetrahydrofolate metabolism was found to be affected, which had significant effects on the proteome of the photorespiratory pathway. In the late stage of cold acclimation, flavonoid deficiency was found to affect protein stability, folding and proteasomal degradation, which resulted in a significant decrease in total protein amounts in both mutants. In summary, these findings suggest that flavonoid metabolism plays different roles in the early and late stages of plant cold acclimation and significantly contributes to establishing a new protein homeostasis in a changing environment.PMID:39453687 | DOI:10.1111/tpj.17097

Metabolomics. 2024 Oct 25;20(6):120. doi: 10.1007/s11306-024-02187-y.ABSTRACTINTRODUCTION AND OBJECTIVES: The application of untargeted metabolomics assays using ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) to study metabolism in biological systems including humans is rapidly increasing. In some of these studies there is a requirement to collect and analyse low sample volumes of biofluids (e.g. tear fluid) or low cell and tissue mass samples (e.g. tissue needle biopsies). The application of microflow, capillary or nano liquid chromatography (≤ 1.0 mm column internal diameter (i.d.)) theoretically should accomplish a higher assay sensitivity compared to analytical liquid chromatography (2.1-5.0 mm column internal diameter). To date, there has been limited research into microflow UHPLC-MS assays that can be applied to study samples of low volume or mass.METHODS: This paper presents three complementary UHPLC-MS assays (aqueous C18 reversed-phase, lipidomics C18 reversed-phase and Hydrophilic Interaction Liquid Chromatography (HILIC)) applying 1.0 mm internal diameter columns for untargeted metabolomics. Human plasma and urine samples were applied for the method development, with porcine plasma, urine and tear fluid used for method assessment. Data were collected and compared for columns of the same length, stationary phase and stationary phase particle size but with two different column internal diameters (2.1 mm and 1.0 mm).RESULTS AND CONCLUSIONS: All three assays showed an increase in peak areas and peak widths when applying the 1.0 mm i.d. assays. HILIC assays provide an advantage at lower sample dilutions whereas for reversed phase (RP) assays there was no benefit added. This can be seen in the validation study where a much higher number of compounds were detected in the HILIC assay. RP assays were still appropriate for small volume samples with hundreds of compounds being detected. In summary, the 1.0 mm i.d. column assays are applicable for small volume samples where dilution is required during sample preparation.PMID:39453548 | DOI:10.1007/s11306-024-02187-y

Toxins (Basel). 2024 Oct 1;16(10):424. doi: 10.3390/toxins16100424.ABSTRACTAmong the widespread trichothecene mycotoxins, T-2 toxin is considered the most toxic congener. In the present study, we utilized high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), coupled to the zebrafish (Danio rerio) embryo model, as a toxicometabolomics approach to elucidate the cellular, molecular and biochemical pathways associated with T-2 toxicity. Aligned with previous studies in the zebrafish embryo model, exposure to T-2 toxin was lethal in the high parts-per-billion (ppb) range, with a median lethal concentration (LC50) of 105 ppb. Exposure to the toxins was, furthermore, associated with system-specific alterations in the production of reactive oxygen species (ROS), including decreased ROS production in the liver and increased ROS in the brain region, in the exposed embryos. Moreover, metabolic profiling based on HRMAS NMR revealed the modulation of numerous, interrelated metabolites, specifically including those associated with (1) phase I and II detoxification, and antioxidant pathways; (2) disruption of the phosphocholine lipids of cell membranes; (3) mitochondrial energy metabolism, including apparent disruption of the tricarboxylic acid (TCA) cycle, and the electron transport chain of oxidative phosphorylation, as well as "upstream" effects on carbohydrate, i.e., glucose metabolism; and (4) several compensatory catabolic pathways. Taken together, these observations enabled development of an integrated, system-level model of T-2 toxicity in relation to human and animal health.PMID:39453200 | DOI:10.3390/toxins16100424

Metabolites. 2024 Oct 21;14(10):568. doi: 10.3390/metabo14100568.ABSTRACTBACKGROUND: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety.METHODS AND RESULTS: To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval Portunus trituberculatus, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval P. trituberculatus displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups.CONCLUSIONS: Our results demonstrate the possible existence of anxiety-like behavior in the larvae of P. trituberculatus from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of P. trituberculatus offer a convenient model for studying the mechanisms of anxiety in crustaceans.PMID:39452949 | DOI:10.3390/metabo14100568

Metabolites. 2024 Oct 21;14(10):566. doi: 10.3390/metabo14100566.ABSTRACTBackground and aims: Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. Methods: We conducted a pilot case-control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. Results: The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4-10.8), total cholesterol (OR 14 CI 3.2-62), esterified cholesterol (OR 3.3 CI 1.9-5.8), and sphingomyelin (OR 2.6 CI 1.2-5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1-6.6). Conclusions: Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids.PMID:39452946 | DOI:10.3390/metabo14100566

Metabolites. 2024 Oct 20;14(10):563. doi: 10.3390/metabo14100563.ABSTRACTBackground/Objectives:Meconopsis has long been used in traditional Tibetan medicine to treat various inflammatory and pain-related conditions. However, blue-flowered Meconopsis (M. betonicifolia) is becoming increasingly scarce due to overharvesting. As a potential alternative, yellow-flowered Meconopsis (M. integrifolia) shows promise but requires comprehensive characterization. This study aimed to evaluate and compare the anti-inflammatory potential of yellow- and blue-flowered Meconopsis species. Methods: Liquid chromatography-mass spectrometry (LC-MS) techniques were used to analyze the chemical profiles of yellow- and blue-flowered Meconopsis. Putative targets of shared constituents were subjected to GO and disease enrichment analysis. The LPS-induced RAW264.7 macrophage model was employed to assess anti-inflammatory effects. Metabolomics was applied to gain mechanistic insights. Results: LC-MS revealed over 70% chemical similarity between species. Enrichment analysis associated targets with inflammation-related pathways. In macrophage assays, both species demonstrated dose-dependent antioxidative and anti-inflammatory activities, with yellow Meconopsis exhibiting superior efficacy. Metabolomics showed modulation of key inflammatory metabolic pathways. Conclusions: This integrative study validated yellow-flowered Meconopsis as a credible alternative to its blue-flowered counterpart for anti-inflammatory applications. Metabolic profiling provided initial clues regarding their multi-targeted modes of action, highlighting their potential for sustainable utilization and biodiversity conservation.PMID:39452944 | DOI:10.3390/metabo14100563

Metabolites. 2024 Oct 17;14(10):558. doi: 10.3390/metabo14100558.ABSTRACTPorcine models are increasingly recognized for their similarities to humans and have been utilized in disease modeling and organ grafting research. While extensive metabolomics studies have been conducted in swine, primarily focusing on conventional cohorts or specific animal models, the composition and functions of fecal metabolites in pigs across different age groups-particularly in the elderly-remain inadequately understood. In this study, an untargeted metabolomics approach was employed to analyze the fecal metabolomes of pigs at three distinct age stages: young (one year), middle-aged (four years), and elderly (eight years). The objective was to elucidate age-associated changes in metabolite composition and functionality under standardized rearing conditions. The untargeted metabolomic analysis revealed a diverse array of age-related metabolites. Notably, L-methionine sulfoxide levels were found to increase with age, whereas cytidine-5-monophosphate levels exhibited a gradual decline throughout the aging process. These metabolites demonstrated alterations across various biological pathways, including energy metabolism, pyrimidine metabolism, lipid metabolism, and amino acid metabolism. Collectively, the identified key metabolites, such as L-methionine sulfoxide and Cholecalciferol, may serve as potential biomarkers of senescence, providing valuable insights into the mechanistic understanding of aging in pigs.PMID:39452939 | DOI:10.3390/metabo14100558

Metabolites. 2024 Oct 17;14(10):557. doi: 10.3390/metabo14100557.ABSTRACTBACKGROUND: The increasing prevalence of autism spectrum disorder (ASD) highlights the need for objective diagnostic markers and a better understanding of its pathogenesis. Metabolic differences have been observed between individuals with and without ASD, but their causal relevance remains unclear.METHODS: Bidirectional two-sample Mendelian randomization (MR) was used to assess causal associations between circulating plasma metabolites and ASD using large-scale genome-wide association study (GWAS) datasets-comprising 1091 metabolites, 309 ratios, and 179 lipids-and three European autism datasets (PGC 2015: n = 10,610 and 10,263; 2017: n = 46,351). Inverse-variance weighted (IVW) and weighted median methods were employed, along with robust sensitivity and power analyses followed by independent cohort validation.RESULTS: Higher genetically predicted levels of sphingomyelin (SM) (d17:1/16:0) (OR, 1.129; 95% CI, 1.024-1.245; p = 0.015) were causally linked to increased ASD risk. Additionally, ASD children had higher plasma creatine/carnitine ratios. These MR findings were validated in an independent US autism cohort using machine learning analysis.CONCLUSION: Utilizing large datasets, two MR approaches, robust sensitivity analyses, and independent validation, our novel findings provide evidence for the potential roles of metabolomics and circulating metabolites in ASD diagnosis and etiology.PMID:39452938 | DOI:10.3390/metabo14100557

Metabolites. 2024 Oct 16;14(10):552. doi: 10.3390/metabo14100552.ABSTRACTBackground/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention.PMID:39452933 | DOI:10.3390/metabo14100552

Metabolites. 2024 Oct 13;14(10):546. doi: 10.3390/metabo14100546.ABSTRACTBACKGROUND: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70-80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model.METHODS: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers.RESULTS: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity.CONCLUSIONS: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study's capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise.PMID:39452927 | DOI:10.3390/metabo14100546

Metabolites. 2024 Oct 13;14(10):545. doi: 10.3390/metabo14100545.ABSTRACTMultiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in the pathogenesis of these two latter courses is still unclear. The underlying mechanisms of MS are yet to be elucidated, and the treatment relies on immune-modifying agents. Recently, lipidomics and metabolomics studies using human biofluids, mainly plasma and cerebrospinal fluid (CSF), have suggested an important role of lipids and metabolites in the pathophysiology of MS. In this review, the results from studies on metabolomics and lipidomics analyses performed on biological samples of MS patients and MS-like animal models are presented and analyzed. Based on the collected findings, the biochemical pathways in human and animal cohorts involved were investigated and biological mechanisms and the potential role they have in MS are discussed. Limitations and challenges of metabolomics and lipidomics approaches are presented while concluding that metabolomics and lipidomics may provide a more holistic approach and provide biomarkers for early diagnosis of MS disease.PMID:39452926 | DOI:10.3390/metabo14100545

Metabolites. 2024 Oct 11;14(10):543. doi: 10.3390/metabo14100543.ABSTRACTBACKGROUND: The dramatic temperature fluctuations spurred by global warming and the accompanying extreme weather events inhibit mango growth and threaten mango productivity. Particularly, mango flowering is highly sensitive to temperature changes. The mango fruit setting rate was significantly positively correlated with pollen activity, and pollen activity was regulated by different metabolites.METHODS: In this study, the in vitro pollen of two mango varieties ('Renong No.1' and 'Jinhuang'), in which sensitivity to temperature differed significantly, were subjected to different temperature stresses (15 °C, 25 °C and 35 °C), and their metabolomics were analyzed.RESULTS: The present results showed that 775 differential metabolites were screened by liquid chromatography-mass spectrometry and divided into 12 categories. The two varieties had significant differences in metabolite expression under different temperature stresses and the effect of low temperature on 'Renong No.1' mainly focused on amino acid metabolism, while the effect on 'Jinhuang' was mainly related to glycolysis. However, under the 35 °C temperature stress, 'Renong No.1' responded by redistributing riboflavin and betaine in vivo and the most obvious metabolic pathway of 'Jinhuang' enrichment was pyrimidine metabolism, which had undergone complex main body formation and extensive regulatory processes. The changes of metabolites of different varieties under low temperature and high temperature stress were different. Among them, flavonoids or flavonoid derivatives were included in class A (216 metabolites), C (163 metabolites) and D (233 metabolites) metabolites, indicating that flavonoid metabolites had an obvious regulatory effect on mango pollen metabolism under different temperature stress.CONCLUSIONS: The present results provide valuable information for reproductive biology studies and breeding in mango, in particular, the selection and breeding of the most suitable varieties for different production areas.PMID:39452924 | DOI:10.3390/metabo14100543

Metabolites. 2024 Oct 11;14(10):542. doi: 10.3390/metabo14100542.ABSTRACTBACKGROUND/OBJECTIVES: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach.METHODS: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as "acupuncture" and "metabolites" to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle-Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies.RESULTS: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism.CONCLUSIONS: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture's effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms.PMID:39452923 | DOI:10.3390/metabo14100542

Metabolites. 2024 Oct 9;14(10):539. doi: 10.3390/metabo14100539.ABSTRACTBackground: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and kidneys. Adipose tissue, as an active endocrine organ, plays an important role in maintaining the normal physiological function of cells. However, the metabolic mechanism that causes pentosidine to induce toxicity in adipose tissue remains unclear. Methods: In the study, thirty male Sprague-Dawley rats were divided into a normal diet group, low dose group, and high dose group. A non-targeted metabolomics approach was used to compare the metabolic profiles of adipose tissue between the pentosidine and normal diet groups. Furthermore, histopathological observation and body weight change analysis were performed to test the results of the metabolomics analysis. Results: A total of forty-two differential metabolites were identified. Pentosidine mainly disturbed twelve metabolic pathways, such as ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, sulfur metabolism, pyruvate metabolism, etc. Additionally, pyruvic acid was identified as a possible key upregulated metabolite involved in thirty-four metabolic pathways. α-Ketoglutaric acid was named as a probable key downregulated metabolite involved in nineteen metabolic pathways based on enrichment network analysis. In addition, histopathological analysis and body weight changes confirmed the results of the metabolomics analysis. Conclusions: These results provided a new perspective for the molecular mechanisms of adipose tissue toxicity induced by pentosidine.PMID:39452920 | DOI:10.3390/metabo14100539