1H NMR analysis of metabolites from leaf tissue of resistant and susceptible oil palm breeding materials against Ganoderma boninense.

INTRODUCTION: Breeding for oil palm resistance against basal stem rot caused by Ganoderma boninense is challenging and time-consuming. Advanced oil palm gene pools are very limited, hence it is assumed that parental palms have experienced genetic drift and lost their resistance genes against Ganoderma. High-throughput selection criteria should be developed. Metabolomic analysis using 1H nuclear magnetic resonance (NMR) spectroscopy is easy, and the resulting metabolite can be used as a diagnostic tool for detecting disease in various host-pathogen combinations. OBJECTIVES: The objective of this study was to identify metabolite variations in Dura (D) and Pisifera (P) parental palms with different resistance levels against Ganoderma and moderately resistant DxP using 1H NMR analysis. METHODS: Leaf tissues of seven different oil palm categories consisting of: resistant, moderate, and susceptible Dura (D); moderate and susceptible Pisifera (P); resistant Tenera/Pisifera (T/P) parental palms; and moderately resistant DxP variety progenies, were sampled and their metabolites were determined using NMR spectroscopy. RESULTS: Twenty-nine types of metabolites were identified, and most of the metabolites fall in the monosaccharides, amino acids, and fatty acids compound classes. The PCA, PLS-DA, and heatmap multivariate analysis indicated two identified groups of resistance based on their metabolites. The first group consisted of resistant T/P, moderate P, resistant D, and moderately resistant DxP. In contrast, the second group consisted of susceptible P, moderate D, and susceptible D. Glycerol and ascorbic acid were detected as biomarker candidates by OPLS-DA to differentiate moderately resistant DxP from susceptible D and P. The pathway analysis suggested that glycine, serine, and threonine metabolism and taurine and hypotaurine metabolism were involved in the oil palm defense mechanism against Ganoderma. CONCLUSION: A metabolomic study with 1H NMR was able to describe the metabolite composition that could differentiate the characteristics of oil palm resistance against basal stem rot (BSR) caused by G. boninense. These metabolites revealed in this study have enormous potential to become support tools for breeding new oil palm varieties with higher resistance against BSR.

Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability.

Anacardic acid (AnAc) inhibits the growth of estrogen receptor α (ERα)-positive MCF-7 breast cancer (BC) cells and MDA-MB-231 triple-negative BC (TNBC) cells, without affecting primary breast epithelial cells. RNA sequencing (seq) and network analysis of AnAc-treated MCF-7 and MDA-MB-231 cells suggested that AnAc inhibited lipid biosynthesis and increased endoplasmic reticulum stress. To investigate the impact of AnAc on cellular metabolism, a comprehensive untargeted metabolomics analysis was performed in five independent replicates of control versus AnAc-treated MCF-7 and MDA-MB-231 cells and additional TNBC cell lines: MDA-MB-468, BT-20, and HCC1806. An analysis of the global metabolome identified key metabolic differences between control and AnAc-treated within each BC cell line and between MCF-7 and the TNBC cell lines as well as metabolic diversity among the four TNBC cell lines, reflecting TNBC heterogeneity. AnAc-regulated metabolites were involved in alanine, aspartate, glutamate, and glutathione metabolism; the pentose phosphate pathway; and the citric acid cycle. Integration of the transcriptome and metabolome data for MCF-7 and MDA-MB-231 identified Signal transduction: mTORC1 downstream signaling in both cell lines and additional cell-specific pathways. Together, these data suggest that AnAc treatment differentially alters multiple pools of cellular building blocks, nutrients, and transcripts resulting in reduced BC cell viability.

Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.

Alterations in metabolome and lipidome in patients with in-stent restenosis.

CONTEXT: In-stent restenosis (ISR) can lead to blood flow obstruction, insufficient blood supply to the brain, and may even result in serious complications such as stroke. Endothelial cell hyperproliferation and thrombosis are the primary etiologies, frequently resulting in alterations in intravascular metabolism. However, the metabolic changes related to this process are still undermined. OBJECTIVE: We tried to characterize the serum metabolome of patients with ISR and those with non-restenosis (NR) using metabolomics and lipidomics, exploring the key metabolic pathways of this pathological phenomenon. RESULTS: We observed that the cysteine and methionine pathways, which are associated with cell growth and oxidative homeostasis, showed the greatest increase in the ISR group compared to the NR group. Within this pathway, the levels of N-formyl-l-methionine and L-methionine significantly increased in the ISR group, along with elevated levels of downstream metabolites such as 2-ketobutyric acid, pyruvate, and taurocholate. Additionally, an increase in phosphatidylcholine (PC) and phosphatidylserine (PS), as well as a decrease in triacylglycerol in the ISR group, indicated active lipid metabolism in these patients, which could be a significant factor contributing to the recurrence of blood clots after stent placement. Importantly, phenol sulfate and PS(38:4) were identified as potential biomarkers for distinguishing ISR, with an area under the curve of more than 0.85. CONCLUSIONS: Our study revealed significant metabolic alterations in patients with ISR, particularly in the cysteine and methionine pathways, with phenol sulfate and PS(38:4) showing promise for ISR identification.

The impact of surgical treatment for deep endometriosis: metabolic profile, quality of life and psychological aspects.

Objective: To evaluate the effects of surgical treatment of deep endometriosis on the metabolic profile, quality of life and psychological aspects. Methods: Prospective observational study, carried out with women of reproductive age diagnosed with deep endometriosis, treated in a specialized outpatient clinic, from October/2020 to September/2022, at a University Hospital in Fortaleza - Brazil. Standardized questionnaires were applied to collect data on quality of life and mental health, in addition to laboratory tests to evaluate dyslipidemia and dysglycemia, at two moments, preoperatively and six months after surgery. The results were presented using tables, averages and percentages. Results: Thirty women with an average age of 38.5 years were evaluated. Seven quality of life domains showed improved scores: pain, control and impotence, well-being, social support, self-image, work life and sexual relations after surgery (ES ≥ 0.80). There was an improvement in mental health status with a significant reduction in anxiety and depression postoperatively. With the metabolic profile, all average levels were lower after surgery: total cholesterol 8.2% lower, LDL 12.8% lower, triglycerides 10.9% lower, and fasting blood glucose 7.3% lower (p < 0.001). Conclusion: Surgical treatment of deep endometriosis improved the quality of life and psychological aspects of patients. The lipid profile of patients after laparoscopy was favorable when compared to the preoperative lipid profile.

Multi-Omics Analyses of Lettuce (Lactuca sativa) Reveals Primary Metabolism Reorganization Supporting Distinct Features of Secondary Metabolism Induced by Supplementing UV-A Radiation.

UV can serve as an effective light spectrum for regulating plant secondary metabolites, while relevant studies on UV-A are much less extensive than those on UV-B. A comprehensive understanding of the selective effects of UV-A on different secondary metabolites and the specific features of primary metabolism that drive these effects is still lacking. To address this knowledge gap, we conducted a study to analyze the dynamic changes in the metabolome and transcriptome of lettuce leaves irradiated with red plus UV-A light (monochromatic red light as control). Generally, UV-A promoted the synthesis of most phenylpropanoids and terpenoids originating from the shikimate and methylerythritol phosphate (MEP) pathway in plastids but sacrificed the synthesis of terpenoids derived from the mevalonate (MVA) pathway, particularly sesquiterpenes. Increased precursors supply for the shikimate and MEP pathway under UV-A was directly supported by the activation of the Calvin-Benson cycle and phosphoenolpyruvate transport. Whereas, along with phosphoenolpyruvate transport, the TCA cycle was restrained, causing deprivation of the MVA pathway precursor. In addition, UV-A also activated the plastidic oxidative branch of the pentose phosphate pathway, photorespiration, and malate shuttle, to ensure a sufficient supply of nitrogen, circulation homeostasis of the Calvin-Benson cycle, and energy balance, thus indirectly supporting UV-A-induced specific secondary metabolic output. This study provides a comprehensive framework for understanding the flexible primary-secondary metabolism interactions that are able to produce specific metabolites favorable for adaptation to environmental stimuli.

Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses.

BACKGROUND: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. METHODS: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. RESULTS: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. CONCLUSION: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

Deciphering the Interplay: Thieno[2,3-b]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines.

Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f+, and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (p < 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound 1 resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (p < 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (p < 0.001).

13C Tracer Analysis and Metabolomics in Dormant Cancer Cells.

Over the last two decades, major advances in the field of tumor dormancy have been made. Yet, it is not completely understood how dormant disseminated tumor cells survive and transition to a proliferative state to generate a metastatic lesion. On the other hand, metabolic rewiring has been shown to influence metastasis development through the modulation of both intracellular signaling and the crosstalk between metastatic cells and their microenvironment. Thus, studying the metabolic features of dormant disseminated tumor cells has gained importance in understanding the dormancy process. Here, we describe a method to perform metabolomics and 13C tracer analysis in 3D cultures of dormant breast cancer cells.

Plant Tissue Culture and Metabolite Profiling for High-Value Natural Product Synthesis.

The engineering of plant cell cultures to produce high-value natural products is suggested to be a safe, low-cost, and environmentally friendly route to produce a wide range of chemicals. Given that the expression of heterologous biosynthetic pathways in plant tissue culture is limited by a lack of detailed protocols, the biosynthesis of high-value metabolites in plant cell culture is constrained compared with that in microbes. However, both Arabidopsis thaliana and Nicotiana benthamiana can be efficiently transformed with multigene constructs to produce high-value natural products in stable plant cell cultures. This chapter provides a detailed protocol as to how to engineer the plant cell culture as bio-factories for metabolite biosynthesis.

Metabolomic and lipidomic fingerprints in inflammatory skin diseases - Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis.

Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.

A diverse proteome is present and enzymatically active in metabolite extracts.

Metabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types. By combining post-resuspension stable isotope addition and enzyme inhibitors, we demonstrate in-extract metabolite interconversions due to residual transaminase activity. We extend these findings with untargeted metabolomics where we observe extensive protein-mediated metabolite changes, including in-extract formation of glutamate dipeptide and depletion of total glutathione. Finally, we present a simple extraction workflow that integrates 3 kDa filtration for protein removal as a superior method for polar metabolomics. In this work, we uncover a previously unrecognized, protein-mediated source of observer effects in metabolomics experiments with broad-reaching implications across all research fields using metabolomics and molecular metabolism.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Metabolomics-based search for lung cancer markers among patients with different smoking status.

Tobacco smoking is the main etiological factor of lung cancer (LC), which can also cause metabolome disruption. This study aimed to investigate whether the observed metabolic shift in LC patients was also associated with their smoking status. Untargeted metabolomics profiling was applied for the initial screening of changes in serum metabolic profile between LC and chronic obstructive pulmonary disease (COPD) patients, selected as a non-cancer group. Differences in metabolite profiles between current and former smokers were also tested. Then, targeted metabolomics methods were applied to verify and validate the proposed LC biomarkers. For untargeted metabolomics, a single extraction-dual separation workflow was applied. The samples were analyzed using a liquid chromatograph-high resolution quadrupole time-of-flight mass spectrometer. Next, the selected metabolites were quantified using liquid chromatography-triple-quadrupole mass spectrometry. The acquired data confirmed that patients' stratification based on smoking status impacted the discriminating ability of the identified LC marker candidates. Analyzing a validation set of samples enabled us to determine if the putative LC markers were truly robust. It demonstrated significant differences in the case of four metabolites: allantoin, glutamic acid, succinic acid, and sphingosine-1-phosphate. Our research showed that studying the influence of strong environmental factors, such as tobacco smoking, should be considered in cancer marker research since it reduces the risk of false positives and improves understanding of the metabolite shifts in cancer patients.

Integrative proteome and metabolome unveil the central role of IAA alteration in axillary bud development following topping in tobacco.

Axillary bud is an important aspect of plant morphology, contributing to the final tobacco yield. However, the mechanisms of axillary bud development in tobacco remain largely unknown. To investigate this aspect of tobacco biology, the metabolome and proteome of the axillary buds before and after topping were compared. A total of 569 metabolites were differentially abundant before and 1, 3, and 5 days after topping. KEGG analyses further revealed that the axillary bud was characterized by a striking enrichment of metabolites involved in flavonoid metabolism, suggesting a strong flavonoid biosynthesis activity in the tobacco axillary bud after topping. Additionally, 9035 differentially expressed proteins (DEPs) were identified before and 1, 3, and 5 days after topping. Subsequent GO and KEGG analyses revealed that the DEPs in the axillary bud were enriched in oxidative stress, hormone signal transduction, MAPK signaling pathway, and starch and sucrose metabolism. The integrated proteome and metabolome analysis revealed that the indole-3-acetic acid (IAA) alteration in buds control dormancy release and sustained growth of axillary bud by regulating proteins involved in carbohydrate metabolism, amino acid metabolism, and lipid metabolism. Notably, the proteins related to reactive oxygen species (ROS) scavenging and flavonoid biosynthesis were strongly negatively correlated with IAA content. These findings shed light on a critical role of IAA alteration in regulating axillary bud outgrowth, and implied a potential crosstalk among IAA alteration, ROS homeostasis, and flavonoid biosynthesis in tobacco axillary bud under topping stress, which could improve our understanding of the IAA alteration in axillary bud as an important regulator of axillary bud development.

Biochemical indicators, cell apoptosis, and metabolomic analyses of the low-temperature stress response and cold tolerance mechanisms in Litopenaeus vannamei.

The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p < 0.05). Metabolomic analysis displayed significant increases in metabolites such as LysoPC (P-16:0), 11beta-Hydroxy-3,20-dioxopregn-4-en-21-oic acid, and Pirbuterol, while metabolites such as 4-Hydroxystachydrine, Oxolan-3-one, and 3-Methyldioxyindole were significantly decreased in Lv-T compared to Lv-C. The differentially regulated metabolites were mainly enriched in pathways such as Protein digestion and absorption, Central carbon metabolism in cancer and ABC transporters. Our study indicate that low temperature induces damage to the hepatopancreatic duct of shrimp, thereby affecting its metabolic function. The cold resistance mechanism of Lv-T L. vannamei may be due to the enhancement of antioxidant enzymes and lipid metabolism.

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS-based untargeted metabonomics.

Background: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. Methods: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. Results: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". Conclusion: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort.

BACKGROUND: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. METHODS: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. RESULTS: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e - 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. CONCLUSIONS: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Gut microbiota and metabolic changes in children with idiopathic short stature.

BACKGROUND: Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown. METHODS: We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites. RESULTS: We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis. CONCLUSION: Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children's growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.