PubMed

Mov Disord. 2024 Nov 12. doi: 10.1002/mds.30054. Online ahead of print.ABSTRACTBACKGROUND: Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality.OBJECTIVES: Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.METHODS: A nested case-control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics.RESULTS: Thirteen microbial metabolites were identified nominally associated with PD risk (P-value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD-associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals.CONCLUSION: Changes in microbial metabolites may represent a pre-diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.PMID:39530417 | DOI:10.1002/mds.30054

Pediatr Allergy Immunol. 2024 Nov;35(11):e14267. doi: 10.1111/pai.14267.ABSTRACTBACKGROUND: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.OBJECTIVE: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.METHODS: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.RESULTS: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.CONCLUSIONS: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.PMID:39530396 | DOI:10.1111/pai.14267

Onco Targets Ther. 2024 Nov 6;17:933-948. doi: 10.2147/OTT.S482767. eCollection 2024.ABSTRACTPURPOSE: Gastric cancer (GC) is a disease with high prevalence and mortality, but we lack convenient and accurate methods to screen for this disease. Thus, we aimed to search for some salivary biomarkers and explore changes in metabolites in patients' saliva after radical gastrectomy.PATIENTS AND METHODS: A total of 152 subjects were divided into three groups (healthy group, GC group, and one-week postoperative group). After simple processing, saliva samples were analyzed by liquid chromatography-mass spectrometry. First, we used total ion chromatography and principal component analysis to determine the metabolite profiles. Next, t-test, partial least squares discriminant analysis, support vector machine, and receiver operating characteristics curve analysis were performed to identify biomarkers. Then, Fisher discriminant analysis and hierarchical clustering analysis were performed to determine the discriminating ability of biomarkers. Finally, we established a generalized linear model to predict GC based on biomarkers, and used bootstrapping for internal validation.RESULTS: Between the healthy and GC groups, we identified four biomarkers: lactic acid, kynurenic acid, 3-hydroxystachydrine, and S-(1,2,2-trichlorovinyl)-L-cysteine. We used stepwise regression to select five metabolites and develop a model with areas under the curve equal to 0.973 in the training dataset and 0.924 in the validation dataset. Between the GC and one-week postoperative groups, we found two differential metabolites: 19-hydroxyprostaglandin E2 and DG (14:0/0:0/18:2n6).CONCLUSION: Differential metabolites were observed among the three groups. GC could be initially diagnosed on the basis of detection of these biomarkers. Moreover, changes in salivary metabolites in postoperative patients could provide important insights for basic studies.PMID:39530041 | PMC:PMC11551007 | DOI:10.2147/OTT.S482767

Arch Endocrinol Metab. 2024 Oct 17;68:e230527. doi: 10.20945/2359-4292-2023-0527. eCollection 2024.ABSTRACTOBJECTIVE: This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk.SUBJECTS AND METHODS: A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system.RESULTS: SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m2 (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications.CONCLUSION: The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility.PMID:39529984 | PMC:PMC11554360 | DOI:10.20945/2359-4292-2023-0527

Front Plant Sci. 2024 Oct 28;15:1425815. doi: 10.3389/fpls.2024.1425815. eCollection 2024.ABSTRACTINTRODUCTION: Microplastic pollution has emerged as a significant global change factor, with the potential to alter the biological, physicochemical properties of soil and to subsequently affect plant growth. Despite growing recognition of the impacts of microplastic pollution, the mechanisms by which microplastics modify plant leaf chemistry and influence allelopathic interactions among co-existing plant species remain unclear.METHODS: We used the native perennial forb Achyranthes bidentata and the invasive annual forb Amaranthus spinosus as focal species. We grew the two species with and without competition with each other. This setup was further combined with a treatment involving the addition of polyethylene (PE). We then testd the effects of aqueous extract on seed germination and seedling growth for five invasive and five native species. Subsequently, metabolomic analysis was conducted on the aqueous extracts, in which significant allelopathic effects were observed on test species.RESULTS AND DISCUSSION: The presence of PE microplastics enhanced the biomass of both Achyranthes and Amaranthus under competitive and non-competitive growth conditions. Furthermore, PE microplastics were found to induce a negative allelopathic effect for the native plant Achyranthes on co-occurring plants, which appeared to be mediated through changes in leaf chemistry. Bisdemethoxycurcumin, ethylparaben, salicin 6'-sulfate and 5-hydroxy-3',4',7-trimethoxyflavone glucoside were proven important compounds for allelopathic enhancement. Overall, these results suggest that microplastic pollution has the capability to influence the co-existence of invasive and native plants by altering their allelopathic potential. This insight into the interactions between microplastics and plant allelopathy provides a novel perspective on how microplastic pollution could modify plant species interactions and ecosystem dynamics. Future studies could aim to answer how microplastics might affect plant root exudates and whether this process would mediate biological invasion.PMID:39529932 | PMC:PMC11551022 | DOI:10.3389/fpls.2024.1425815

Front Pharmacol. 2024 Oct 28;15:1447077. doi: 10.3389/fphar.2024.1447077. eCollection 2024.ABSTRACTINTRODUCTION: This study aimed to establish a fermentation system based on Lactobacillus casei (LC) and Arctium lappa L. root (AR) to investigate its effects. The objectives included comparing metabolite profiles pre- and post-fermentation using untargeted metabolomics and evaluating the impact of LC-AR in high-fat diet-induced hyperlipidemic mice.METHODS: Untargeted metabolomics was used to analyze differences in metabolites before and after fermentation. In vitro antioxidant activity, liver injury, lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA expression were assessed. 16S rRNA sequencing was conducted to evaluate changes in gut microbiota composition.RESULTS: LC-AR exhibited stronger antioxidant activity and higher metabolite levels than AR. It also improved liver injury as well as better regulation of lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA. 16S rRNA analysis revealed that LC-AR decreased the Firmicutes/Bacteroidetes ratio, which correlated negatively with triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.DISCUSSION: These findings suggest that LC-AR may serve as a promising functional food and drug raw material for improving hyperlipidemia, particularly through its beneficial effects on gut microbiota and lipid regulation.PMID:39529876 | PMC:PMC11551023 | DOI:10.3389/fphar.2024.1447077

Front Microbiol. 2024 Oct 28;15:1478330. doi: 10.3389/fmicb.2024.1478330. eCollection 2024.ABSTRACTBACKGROUND: Tian-ma (Gastrodia elata) is a traditional medicinal herb found in China. It is used in healthy food and to treat various diseases, therefore cultivated extensively in southwest China. However, continuous cropping of this species has led to various obstacles, such as microbial disease and pest infestation, significantly affecting the production and development of valuable medicinal and food resources. As per the growth habit, soil is presumed to be the primary factor contributing to these obstacles, despite the known issues of continuous cropping obstacles in Gastrodia elata, such as microbial disease, there is a lack of comprehensive understanding of the specific soil bacterial communities and metabolites involved in these processes.METHODS: We analyzed soil samples collected during the year of Tian-ma cultivation (0 Year), after the Tian-ma harvest (1 Year), after two years (2 Year), and three years (3 Year) of fallowing post-cultivation using soil 16S rRNA metabarcoding sequencing by illumina platform and metabolomics (GC-MS/MS). Soil sample collected from the uncultivated field was used as the control (CK).RESULTS: Metabarcoding sequencing showed high bacterial alpha diversity during the cultivation of Tian-ma (0 Year) and the period of deterioration of soil bacterial community. (1 Year), with decreased anaerobic bacterial abundance and increased copiotrophic bacterial abundance. Bacteria associated with sulfur metabolism also showed increased abundance during the year of cropping obstacles. Further metabolomics approach identified 4-hydroxy-benzenemethanol as an indicator of Tian-ma continuous cropping obstacles. Besides, metabolites of the carbohydrate class were found to be the most abundant during the occurrence of continuous cropping obstacles of Gastrodia elata, suggesting that regulation of soil microbial diversity may be a critical factor in addressing these obstacles. Finally, the correlation analysis indicated a positive association between the abundance of some metabolite, e.g., carbamic acid, N-(2-butyl)-N-octadecyl-, ethyl ester detected after Tian-ma cultivation and the abundance of bacteria capable of degrading toxic metabolites, such as Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella.CONCLUSION: This study has revealed the specific soil bacteria and metabolic factors related to the continuous cropping obstacles of Gastrodia elata. These findings not only deepen our understanding of the continuous cropping issues but also pave the way for developing effective strategies to overcome them.PMID:39529674 | PMC:PMC11550952 | DOI:10.3389/fmicb.2024.1478330

Front Cell Dev Biol. 2024 Oct 28;12:1473616. doi: 10.3389/fcell.2024.1473616. eCollection 2024.ABSTRACTType 2 innate lymphoid cells (ILC2s) have emerged as pivotal regulators in the pathogenesis of diseases, with their roles in inflammation, metabolism, and tissue homeostasis becoming increasingly recognized. This review provides an overview of the current understanding of ILC2s in inflammation and metabolic disorders, including their functional contributions. Moreover, we will discuss how these cells adapt their metabolic processes to support their function and survival and how their metabolic requirements change under different physiological and pathological conditions. Lastly, we will review recent omics studies that have provided insights into the molecular and cellular characteristics of ILC2s. This includes transcriptomic, proteomic, and metabolomic analyses that have elucidated the gene expression profiles, protein interactions, and metabolic networks, respectively, associated with ILC2s. These studies have advanced our understanding of the functional diversity of ILC2s and their involvement in metabolic disease.PMID:39529633 | PMC:PMC11551558 | DOI:10.3389/fcell.2024.1473616

J Anim Sci. 2024 Nov 12:skae350. doi: 10.1093/jas/skae350. Online ahead of print.ABSTRACTThe in-utero environment is key to both fetal and postnatal growth and development. The objective of this study was to determine if administration of an acute low-dose lipopolysaccharide (LPS) to gestating sows during mid to late gestation and post-weaning would alter the offsprings metabolomic profile of the longissimus dorsi (LD) and muscle ultrastructure. Pregnant Camborough sows were randomly assigned to receive LPS (LPS; n= 7) at a dose of 2.5 μg/kg or saline (CON; n = 7) on 78 ± 1.8 d of gestation. At weaning (21 ± 1.3 d of age), barrows (CON n = 17; LPS n = 17) from each treatment were selected to receive a secondary LPS. Barrows were administered the secondary LPS challenge at a dose of 10 μg/kg 7 d post weaning. Twenty-four h after the postnatal LPS dose, barrows (31 ± 1.3 d of age) were euthanized, and each LD was removed. The left LD was utilized for morphometric measurements. Two samples from the medial section of the right LD were preserved for immunohistochemical measurements and metabolomic analyses. Mass spectral data were deconvoluted, aligned, and annotated using MS-DIAL. Univariate and multivariate analyses were conducted using MetaboAnalyst. Pathway analysis was conducted and compared to the Homo sapiens pathway library. Morphometric and immunohistochemical measurements were analyzed using the MIXED procedure of SAS version 9.4. Significance for all analyses was declared at P ≤ 0.05 and tendencies were considered at P ≤ 0.10. Average diameter of myosin heavy chain (MHC) type I and IIB/X fibers was increased (P ≤ 0.048) in LPS offspring compared with CON. Average cross-sectional area was increased (P = 0.030) in MHC IIB/X fibers and tended to be increased (P = 0.080) in MHC I fibers of LPS offspring. There were no differences (P ≥ 0.186) between treatment groups for total nuclei or nuclei positive for MYF5, PAX7, or MYF5 and PAX7 nuclei. Metabolomic analyses identified 14 differentially expressed (P < 0.05) metabolites in the LD between treatment groups. There were 10 metabolites within the LD that tended (P ≤ 0.096) to differ between treatment groups. Thus, this study shows that in-utero immune stimulation using LPS in gestating sows and a subsequent LPS challenge postnatally alters the metabolomic profile and muscle ultrastructure of the LD in weaned pigs.PMID:39529455 | DOI:10.1093/jas/skae350

Diabetes Obes Metab. 2024 Nov 11. doi: 10.1111/dom.16053. Online ahead of print.ABSTRACTAIMS: Obesity always leads to profound perturbation of metabolome. Metabolome studies enrich the knowledge on associations between endogenous metabolites and obesity, potentially providing innovative strategies for the development of novel anti-obesity pharmacotherapy. This study aims to identify an endogenous metabolite that regulates energy expenditure and to explore its application for obesity treatment.MATERIALS AND METHODS: C57BL/6 mice were fed with a high-fat and high-cholesterol (HFC) diet, comprising 60% fat and 1.2% cholesterol, for 12 weeks to induce obesity. Significant metabolites were identified in the livers of both health and obese mice through comparative hepatic metabolomics analysis. Correlation between serum or adipose L-aspartate level and body weight in obese mice, as well as human body mass index (BMI), was evaluated. In addition, saline or 200 mg/kg L-aspartate was orally administrated to HFC diet mice and HFC diet-induced obese mice for 6-7 weeks. Body weight, adipose tissue weight, glucose tolerance and liver damage were assessed to evaluate the effect on obesity prevention and treatment. Comprehensive lab animal monitoring system (CLAMS) and seahorse assay were employed to investigate the regulatory effect of L-aspartate on energy metabolism in vivo and in vitro, respectively. 3T3-L1 preadipocytes and murine white adipose tissue (WAT) were utilized to examine the impact of L-aspartate on adipocyte adipogenesis and lipogenesis and cellular signalling pathway in vitro and in vivo.RESULTS: L-aspartate, an approved drug for liver injury and chronic fatigue, was identified as an endogenous inducer of energy expenditure. Serum or adipose L-aspartate levels were found to be negatively correlated with the severity of obesity in both humans and mice. Administration of L-aspartate to HFC diet mice led to a significant reduction in body weight, with decreases of 14.5% in HFC diet mice and 8.5% in HFC diet-induced obese mice, respectively. In addition, the treatment improved related metabolic syndrome (Figure 2 and Figure S3). These therapeutics were associated with enhancements in whole-body energy expenditure and suppression of adipocyte adipogenesis along with activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway.CONCLUSION: L-aspartate may serve as a novel endogenous inducer of energy expenditure and suppressor of adipogenesis and lipogenesis along with activation of AMPK, thereby offering a promising therapeutic strategy for obesity prevention and treatment.PMID:39529440 | DOI:10.1111/dom.16053

Gut Microbes. 2024 Jan-Dec;16(1):2426623. doi: 10.1080/19490976.2024.2426623. Epub 2024 Nov 11.ABSTRACTGut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.PMID:39529240 | DOI:10.1080/19490976.2024.2426623

Int J Biol Macromol. 2024 Nov 9;282(Pt 6):137429. doi: 10.1016/j.ijbiomac.2024.137429. Online ahead of print.ABSTRACTRapid postharvest senescence and quality deterioration severely limit logistics of cowpeas. Melatonin (MEL) is a pivotal bioactive molecule that can modulate multiple physiological attributes in plants. In this study, physiological, transcriptomic and metabolomic analyses were conducted to explore the effects of exogenous MEL on cowpea senescence and its underlying mechanisms. Physiological results showed that 100 μM MEL treatment maintained sensory quality (greeness, firmness and soluble solids content), reduced weight loss as well as inhibited the degradation of chlorophyll (Chl) and protopectin. Preservation of color and firmness in cowpeas was greatly attributed to inhibition of expression of genes related to Chl and cell wall metabolism, which was based on a transcriptomic analysis. Integrated transcriptomic and metabolomic analyses revealed that MEL promoted transcription of genes associated with amino acid and carbohydrate metabolism, resulting in the accumulation of amino acid and sugar metabolites. Additionally, by integrating transcription factor-binding site analysis with cis-acting element analysis, we constructed a regulatory network of transcription factors underlying MEL-mediated antisenescence. The present study found a series of potential candidate genes and metabolites involved in regulating senescence process and provided an insight into improving postharvest quality of cowpeas.PMID:39528182 | DOI:10.1016/j.ijbiomac.2024.137429

Heliyon. 2024 Oct 9;10(21):e39126. doi: 10.1016/j.heliyon.2024.e39126. eCollection 2024 Nov 15.ABSTRACTBACKGROUND: Guillain-Barre syndrome (GBS), an autoimmune disease of the peripheral nervous system, is hallmarked by demyelination and immune cellular infiltration. Experimental autoimmune neuritis (EAN), considered a GBS prototype model, has been studied for its potential therapeutic benefits from lactobacilli. This study evaluated the protective role of Lactobacillus rhamnosus GG (GG) for treatment in EAN. T cell ratio, inflammation factors, sciatic nerve pathology, intestinal permeability, and gut inflammation were assessed on day 19 post-immunization to evaluate GG's effect on EAN. Fecal metabolomics and 16s rRNA microbiome analysis were conducted to elucidate its mechanism.RESULTS: GG dynamically balanced CD4+/CD8+T cell ratio, reduced serum IL-1β and TNF-α expression, improved sciatic nerve demyelination and inflammation, and enhanced neurological scores during peak disease period. Intestinal mucosal damage was evident in EAN rats, with downregulated Occludin and ZO-1 and upregulated IL-1β, TNF-α, and Reg3γ. GG treatment restored intestinal mucosal integrity, upregulated Occludin and ZO-1, and downregulated IL-1, TNF-α, and Reg3γ. GG partially rectified the gut microbiota and metabolite imbalance in EAN rats.CONCLUSION: GG mitigates EAN through immune response modulation and inflammation reduction via the gut microbiota and metabolites.PMID:39524841 | PMC:PMC11550083 | DOI:10.1016/j.heliyon.2024.e39126

Heliyon. 2024 Sep 27;10(21):e38650. doi: 10.1016/j.heliyon.2024.e38650. eCollection 2024 Nov 15.ABSTRACTThe assessment of medication toxicity and safety is pivotal during pregnancy. Curdione, a sesquiterpene compound extracted from Curcumae Radix, displays beneficial properties in terms of anti-inflammatory, tumor growth suppression, and anti-coagulative effects. However, its reproductive toxicity and precise mechanism remain unclear. This study aims to explore the mechanism of curdione-induced toxicity damage in HTR-8/SVneo cells through the epigenetics, proteomics, and metabolomics, and experimental verification. The results showed that curdione elicited alterations in m6A modification, gene expression, protein levels, and cellular metabolism of HTR-8/SVneo cells. Additionally, curdione induces oxidative stress, mitochondrial and DNA damage, while also downregulating the expression of Wnt6, β-catenin, ZO-1, and CLDN1 proteins. Curdione has the potential to modulate oxidative stress, mitochondrial dysfunction, and disruption of tight junctions via the Wnt/β-catenin signaling pathway, which contributes to cellular damage in HTR-8/SVneo cells.PMID:39524727 | PMC:PMC11550733 | DOI:10.1016/j.heliyon.2024.e38650

Eco Environ Health. 2024 May 9;3(4):407-411. doi: 10.1016/j.eehl.2024.05.001. eCollection 2024 Dec.ABSTRACTImage 1.PMID:39524475 | PMC:PMC11541422 | DOI:10.1016/j.eehl.2024.05.001

Transl Pediatr. 2024 Oct 1;13(10):1777-1788. doi: 10.21037/tp-24-288. Epub 2024 Oct 28.ABSTRACTBACKGROUND: Pectus excavatum (PE) is the most common chest wall deformity, characterized by an insidious onset, gradual progression, and challenges in early diagnosis. It is often accompanied by emaciation and distinctive metabolic traits, which may provide valuable insights into its internal physiological and biochemical mechanisms. Our study attempted to screen out biomarkers by identifying the metabolic characteristics of PE, and the results provide a scientific basis for the early diagnosis of PE.METHODS: Untargeted metabolomic and lipidomic analyses using liquid chromatography-mass spectrometry was conducted on serum samples obtained from 20 patients diagnosed with PE and 30 healthy case-controls. Principal component analysis and partial least squares discriminant analysis were employed to assess the quality of the metabolic profiling and delineate the metabolic differences between the PE and healthy cohorts. Receiver operating characteristic analysis was conducted to evaluate the predictive accuracy of the selected biomarkers. Pathway analysis of the dysregulated metabolites was utilized to elucidate the underlying pathological pathways.RESULTS: Fourteen metabolites and seven lipids were found to be differentially expressed between patients with PE and healthy controls. Indole-3-acetaldehyde showed potential as a biomarker for PE, with an area under the curve value of 0.94, making it effective in distinguishing patients with PE. Pathway analysis revealed enrichment of several pathological pathways, such as valine, leucine, and isoleucine biosynthesis; sphingolipid metabolism; glycine, serine, and threonine metabolism; and glycerophospholipid metabolism.CONCLUSIONS: In our study, we employed a multiomics approach to comprehensively examine dysregulated serological molecules in PE patients, and the analyses revealed potential biomarkers for early diagnosis and provided information for pathological studies.PMID:39524383 | PMC:PMC11543133 | DOI:10.21037/tp-24-288

iScience. 2024 Oct 16;27(11):111184. doi: 10.1016/j.isci.2024.111184. eCollection 2024 Nov 15.ABSTRACTIntracranial aneurysms (IAs) are benign cerebrovascular maladies characterized by wall dilatation in the intracranial arteries. Nevertheless, spontaneous aneurysmal rupture can cause a life-threatening spontaneous subarachnoid hemorrhage (SAH). Emerging evidence indicates potential associations between gut dysbiosis and IAs pathogenesis, though the relationship with IA rupture remains unclear. This research analyzed 124 fecal samples for microbiomics and 160 for metabolomics, with the discovery and validation sets established for cross-validation. We identified differential gut microbiota and metabolites associated with ruptured intracranial aneurysms (RIAs) and developed a superior risk assessment model. Subsequent integrative analyses and validation revealed a significant link between disrupted unsaturated fatty acid and essential amino acid metabolic pathways and IA rupture, driven by alterations in gut microbiota. This study underscores the potential association between the gut-brain axis and IA rupture, while also highlighting gut microbiota dysbiosis as a potential risk factor for IA rupture and providing biomarkers for assessment.PMID:39524364 | PMC:PMC11550638 | DOI:10.1016/j.isci.2024.111184

iScience. 2024 Oct 12;27(11):111159. doi: 10.1016/j.isci.2024.111159. eCollection 2024 Nov 15.ABSTRACTLow birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil's potential to mitigate LBW-associated risks.PMID:39524353 | PMC:PMC11546680 | DOI:10.1016/j.isci.2024.111159

Cancers (Basel). 2024 Oct 30;16(21):3671. doi: 10.3390/cancers16213671.ABSTRACTThe gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy.PMID:39518108 | DOI:10.3390/cancers16213671

BMC Musculoskelet Disord. 2024 Nov 6;25(1):883. doi: 10.1186/s12891-024-08010-y.ABSTRACTBACKGROUND: Adult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency.METHODS: Thirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels.RESULTS: Adult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD.CONCLUSION: Adult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.PMID:39508246 | DOI:10.1186/s12891-024-08010-y