PubMed

Sci Rep. 2023 Nov 9;13(1):19465. doi: 10.1038/s41598-023-46499-w.ABSTRACTPreterm-born children are at risk of long-term pulmonary deficits, including those who developed bronchopulmonary dysplasia (BPD) in infancy, however the underlying mechanisms remain poorly understood. We characterised the exhaled breath condensate (EBC) metabolome from preterm-born children, both with and without BPD. Following spirometry, EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates study, were analysed using Time-of-Flight Mass Spectrometry. Metabolite Set Enrichment Analysis (MSEA) linked significantly altered metabolites to biological processes. Linear regression models examined relationships between metabolites of interest and participant demographics. EBC was analysed from 214 children, 144 were born preterm, including 34 with BPD. 235 metabolites were detected, with 38 above the detection limit in every sample. Alanine and pyroglutamic acid were significantly reduced in the BPD group when compared to preterm controls. MSEA demonstrated a reduction in glutathione metabolism. Reduced quantities of alanine, ornithine and urea in the BPD group were linked with alteration of the urea cycle. Linear regression revealed significant associations with BPD when other characteristics were considered, but not with current lung function parameters. In this exploratory study of the airway metabolome, preterm-born children with a history of BPD had changes consistent with reduced antioxidant mechanisms suggesting oxidative stress.PMID:37945650 | DOI:10.1038/s41598-023-46499-w

Atherosclerosis. 2023 Oct 20:117344. doi: 10.1016/j.atherosclerosis.2023.117344. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Cardiovascular disease (CVD) remains the largest cause of death globally due to various risk factors. One novel potential contributor to CVD might be the metabolism of the essential amino acid tryptophan (Trp), which through many pathways can produce immunomodulatory metabolites such as kynurenine, indole-3-propionate and serotonin. We aim to identify the metabolites with the strongest association with cardiovascular disease, utilizing a substantial and diverse cohort of individuals. In our pursuit of this aim, our primary focus is to validate and reinforce the findings from previous cross-sectional studies.METHODS: We used the community-based EPIC-Norfolk cohort (46.3 % men, age 59.8 ± 9.0) with a median follow-up of 22.1 (17.6-23.3) years to study associations between the relative levels of Trp metabolites measured with untargeted metabolomics and incident development of CVD. Serum from n = 11,972 apparently healthy subjects was analysed, of which 6982 individuals had developed CVD at the end of follow-up. Cox proportional hazard models were used to study associations, adjusted for sex, age, conventional cardiovascular risk factors and CRP. All metabolites were Ln-normalised prior to analysis.RESULTS: Higher levels of Trp were inversely associated with mortality (HR 0.73; CI 0.64-0.83) and fatal CVD (HR 0.76; CI 0.59-0.99). Higher levels of kynurenine (HR 1.33; CI 1.19-1.49) and the [Kynurenine]/[Tryptophan]-ratio (HR 1.24; CI 1.14-1.35) were associated with a higher incident development of CVD. Serotonin was not associated with overall CVD, but we did find associations for myocardial infarction and stroke. Adjustment for CRP did not yield any discernible differences in effect size.CONCLUSIONS: Tryptophan levels were inversely correlated with CVD, while several of its major metabolites (especially kynurenine and serotonin) were positively correlated. These findings indicate that mechanistic studies are required to understand the role of Trp metabolism in CVD with the goal to identify new therapeutic targets.PMID:37945449 | DOI:10.1016/j.atherosclerosis.2023.117344

Adv Med Sci. 2023 Nov 7:S1896-1126(23)00049-4. doi: 10.1016/j.advms.2023.10.009. Online ahead of print.ABSTRACTPURPOSE: Bronchoalveolar lavage (BAL) procedure is a useful tool in the diagnosis of patients with interstitial lung disease (ILD) and is helpful in clinical research of chronic obstructive pulmonary disease (COPD) patients. Still little is known about predictors of poor BAL salvage. The trial aims to find the most efficient way to improve BAL recovery.MATERIAL AND METHODS: Our study is a prospective, multicenter, international, two-arm randomized controlled trial. We aim to obtain BAL samples from a total number of 300 patients: 150 with ILD and 150 with COPD to achieve a statistical power of 80 ​%. Patients with initial BAL salvage <60 ​% will be randomized into the non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) arm. The NIV and CPAP will be set according to the study protocol. The influence on BAL salvage will be assessed in terms of BAL volume and content. Multivariable analysis of the additional test results to determine predictors for low BAL recovery will be conducted. In a study subgroup of approximately 20 patients per specific disease, a metabolomic assessment of exhaled air condensate will be performed. All procedures will be assessed in terms of the patient's safety. The trial was registered on clinicaltrials.gov (ID# NCT05631132). Interested experienced centers are invited to join the research group by writing to the corresponding author.CONCLUSION: The results of our prospective study will address the currently unsolved problem of how to increase BAL salvage in patients with pulmonary diseases without increasing the risk of respiratory failure exacerbation.PMID:37945441 | DOI:10.1016/j.advms.2023.10.009

Pestic Biochem Physiol. 2023 Nov;196:105594. doi: 10.1016/j.pestbp.2023.105594. Epub 2023 Aug 28.ABSTRACTThe toxic effects of neonicotinoid pesticides on honeybees is a global concern, whereas little is known about the effect of stereoisomeric pesticides among honeybee social behavior. In this study, we investigated the effects of stereoisomeric dinotefuran on honeybee social behavior. We found that honeybees exhibit a preference for consuming food containing S-dinotefuran, actively engage in trophallaxis with S-dinotefuran-consuming peers, and consequently acquire higher levels of S-dinotefuran compared with R-dinotefuran. In comparison to R-dinotefuran, S-dinotefuran stimulates honeybees to elevate their body temperature, thereby attracting more peers for trophallaxis. Transcriptome analysis revealed a significant enrichment of thermogenesis pathways due to S-dinotefuran exposure. Additionally, metabolome data indicated that S-dinotefuran may enhance body temperature by promoting lipid synthesis in the lysine degradation pathway. Consequently, body temperature emerges as a key factor influencing honeybee social behavior. Our study is the first to highlight the propensity of S-dinotefuran to raise honeybee body temperature, which prompts honeybee to preferentially engage in trophallaxis with peers exhibiting higher body temperatures. This preference may lead honeybees to collect more dinotefuran-contaminated food in the wild, significantly accelerating dinotefuran transmission within a population. Proactive trophallaxis further amplifies the risk of neonicotinoid pesticide transmission within a population, making honeybees that have consumed S-dinotefuran particularly favored within their colonies. These findings may contribute to our understanding of the higher risk associated with neonicotinoid use compared with other pesticides.PMID:37945244 | DOI:10.1016/j.pestbp.2023.105594

Pestic Biochem Physiol. 2023 Nov;196:105612. doi: 10.1016/j.pestbp.2023.105612. Epub 2023 Sep 9.ABSTRACTRice false smut, caused by the fungus Ustilaginoidea virens, is a destructive grain disease in rice-producing areas worldwide. To reveal the action mechanism of osthole against U. virens, the mycelial morphology, differential genes and metabolites of osthole-treated U. virens were determined using electron microscopy and multi-omics, respectively. The hyphae of osthole-treated U. virens were severely wrinkled and distorted with rough cell walls, uneven thickness, and protoplast aggregation. Calcium fluorescent white staining showed that osthole affected chitin synthesis in U. virens. The differential genes and metabolites in U. virens were significantly enriched in amino sugar and nucleotide sugar metabolism pathway. The expression of the acetylglucosamine phosphate mutase (AGM) gene (UvAGM1) and UDP-N-acetylglucosamine was significantly down regulated. The AGM of osthole-treated U. virens was 133.43 ng/mL, which was significantly lower than that of the control group (205.67 ng/mL). Osthole combined with the amino acid residue THR334 of AGM via hydrogen bonding. These results indicate that UvAGM1 may be a key candidate gene of osthole against U. virens. Overall, the results provide valuable information for the application of osthole to control rice false smut.PMID:37945229 | DOI:10.1016/j.pestbp.2023.105612

Environ Pollut. 2023 Nov 7:122894. doi: 10.1016/j.envpol.2023.122894. Online ahead of print.ABSTRACTNanopolystyrene (NP) and diclofenac (DCF) are common environmental contaminants in the aquatic ecosystem; therefore, the present study aimed to investigate the hepatotoxicity of NP and/or DCF exposure on aquatic organisms and the underlying mechanisms. Juvenile Mylopharyngodon piceus were used as a model organism to study the effects of NP and/or DCF exposure at environmentally relevant concentrations for 21 days. Subchronic exposure to NP and/or DCF resulted in liver histological damage. In the NP group, the presence of large lipid droplets was observed, whereas the DCF group exhibited marked hepatic sinusoidal dilatation accompanied by inflammation. Additionally, this exposure induced liver oxidative stress, as evidenced by the changes in several physiological parameters, including catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reactive oxygen species (ROS), and malondialdehyde (MDA). Integrated transcriptomic and metabolomic analysis was performed to further investigate the molecular mechanism underlying hepatotoxicity. Multi-omics analysis demonstrated, for the first time to our knowledge, that NP induced hepatic steatosis mainly through activating the glycerol-3-phosphate pathway and inhibiting VLDL assembly by targeting several key enzyme genes including GPAT, DGAT, ACSL, APOB, and MTTP. Furthermore, NP exposure disrupted arachidonic acid metabolism, which induced the release of inflammatory factors and inhibited the release of anti-inflammatory factors, ultimately causing liver inflammation in M. piceus. In contrast, DCF induced interleukin production and downregulated KLF2, causing hepatic sinusoidal dilatation with inflammation in juvenile M. piceus, which is consistent with the finding of JAK-STAT signaling pathway activation. In addition, the upregulated AMPK signaling pathway in the DCF group suggested perturbation of energy metabolism. Collectively, these findings provide novel insights into the molecular mechanism of the multiple hepatotoxicity endpoints of NP and/or DCF exposure in aquatic organisms.PMID:37944890 | DOI:10.1016/j.envpol.2023.122894

Exp Neurol. 2023 Nov 7:114610. doi: 10.1016/j.expneurol.2023.114610. Online ahead of print.ABSTRACTHampering assessment of treatment outcomes in gene therapy and other clinical trials in patients with childhood dementia is the lack of an objective, non-invasive measure of neurodegeneration. Optical coherence tomography (OCT) is a widely available, rapid, non-invasive, and quantitative method for examining the integrity of the neuroretina. Profound brain and retinal dysfunction occur in patients and animal models of childhood dementia, including Sanfilippo syndrome and we recently revealed a correlation between the age of onset and rate of progression of retinal and brain degeneration in sulfamidase-deficient Sanfilippo mice. The aim of the current study was to use OCT to visualise the discrete changes in retinal structure that occur during disease progression. A progressive decline in retinal thickness was readily observable in Sanfilippo mice using OCT, with differences seen in affected animals from 10-weeks of age. OCT applied to i.v. AAV9-sulfamidase-treated Sanfilippo mice enabled visualisation of improved retinal anatomy in living animals, an outcome confirmed via histology. Importantly, brain disease lesions were also ameliorated in treated Sanfilippo mice. The findings highlight the sensitivity, ease of repetitive use and quantitative capacity of OCT for detection of discrete changes in retinal structure and their prevention with a therapeutic. Combined with the knowledge that retinal and brain degeneration are correlated in Sanfilippo syndrome, OCT provides a window to the brain in this and potentially other childhood dementias.PMID:37944880 | DOI:10.1016/j.expneurol.2023.114610

J Ethnopharmacol. 2023 Nov 7:117387. doi: 10.1016/j.jep.2023.117387. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Pluchea indica (L.) Less (family Asteraceae) is popularly consumed as a medicinal vegetable and used in ethnomedicine to treat various diseases including gastrointestinal problems such as dysentery and leucorrhoea, which are due to bacterial, fungal or parasitic infections. There have been numerous studies on the antimicrobial effects of the plant due to these ethnomedicine use.AIM OF THIS REVIEW: This review is comprehensively discussed the information on the anti-infective properties of P. indica and its secondary metabolites, and highlight the potential of the plant as a new source of anti-infective agents.MATERIALS AND METHODS: Scientific databases such as Web of Science, Google Scholar, Science Direct, PubMed, Wiley Online Library, and ACS Publications were used to gather the relevant information on the ability of P. indica to fight infections, with the leaves and roots receiving most of the attention.RESULTS: Anti-bacterial, anti-mycobacterial, anti-malarial, and anti-viral activities have been the most exploited. Most studies were carried out on the crude extracts of the plant and in most studies the bioactive extracts were not standardized or chemically characterized. Several studies have reported the anti-infective activity of several bioactive components of P. indica including caffeoylquinic acids, terpenoid glycosides, thiophenes, and kaempferol.CONCLUSIONS: The strong anti-infective effect and underlying mechanisms of the compounds provide insights into the potential of P. indica as a source of new leads for the development of anti-infective agents for use in food and pharmaceutical industries.PMID:37944874 | DOI:10.1016/j.jep.2023.117387

J Ethnopharmacol. 2023 Nov 7:117348. doi: 10.1016/j.jep.2023.117348. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its notable efficacy in weight management. Historical records indicated that rhubarb initially exhibited robust laxative properties, but extended and consistent usage may lead to an astringent response in the later stages of long-term use. In contrast, steamed pieces of rhubarb (SR), preparing through the process of steaming with wine, have demonstrated a gentle laxative effect with no reported adverse effects.AIM OF THE STUDY: Our study was designed to explore the intricate mechanisms underlying laxative and astringent properties of rhubarb through metabolomics research.MATERIALS AND METHODS: In this investigation, we employed a serum metabolomics approach utilizing the UPLC-Q-Extractive-Orbitrap-MS method to delve into the contrasting laxative and astringent effects of rhubarb, as well as to unravel the mechanisms of underpinning its bidirectional regulatory influence. To commence, we assessed alterations in Evacuation Index (EI) values, intestinal hormone levels, and colon histopathology in mice to gauge rhubarb's laxative and astringent effects. Subsequently, metabolomics methodology was employed for cluster analysis through Principal Component Analysis (PCA) and biomarker identification via Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Then, we delved into the distinctions in characteristic biomarkers, metabolic pathways, their association with pathological changes, and correlation heatmap for biomarkers between raw pieces of rhubarb (RR) and SR to gain insights into the potential mechanisms behind rhubarb's bidirectional regulatory effects.RESULTS: Our findings revealed that RR exhibited a laxative effect in the early stage and transitioned to an astringent effect in the later stage, as indicated by the EI values. In contrast, SR consistently demonstrated a mild laxative effect. Biochemical indexes and histopathological assessments unveiled that RR triggered its astringent effect by inhibiting secretion of motilin (MTL), promoting secretion of vasoactive intestinal peptide (VIP) and epinephrine (EPI), and inducing onset of inflammation. Furthermore, serum metabolomics analysis identified 59 discriminative biomarkers modulated by RR and SR. Through comprehensive analysis, we elucidated the in vivo transformation relationships among multiple endogenous metabolites. Notably, our results underscored the down-regulation of certain phosphatidylcholines (PCs), amino acids, acylcarnitines, and up-regulation of lysophosphatidylcholines (LysoPCs) played pivotal roles in the onset of gut dysfunction, intestinal inflammation, gut barrier damage, and gastrointestinal motility disorder upon prolonged RR administration, ultimately contributing to its astringent effect. Additionally, our correlation analysis elucidated that anthraquinones, stilbenes, and phenylbutanones were the pharmacodynamic material basis responsible for inducing the astringent effect of RR.CONCLUSION: This study provides valuable insights into the bidirectional regulatory effects of rhubarb and sheds light on its underlying mechanisms through a comprehensive metabolomics approach.PMID:37944871 | DOI:10.1016/j.jep.2023.117348

J Ren Nutr. 2023 Nov 7:S1051-2276(23)00190-5. doi: 10.1053/j.jrn.2023.10.007. Online ahead of print.ABSTRACTOBJECTIVE: There is inconsistent evidence on the efficacy of a low-protein diet for CKD patients and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression.METHODS: Non-targeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, non-drug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates.RESULTS: 127 (26%) children experienced CKD progression during 5 years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n=1, dairy: n=7, red and processed meat: n=2, nuts and beans: n=1), including one amino acid, one cofactor and vitamin, four lipids, two nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression.CONCLUSION: Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.PMID:37944769 | DOI:10.1053/j.jrn.2023.10.007

Plant Sci. 2023 Nov 7:111917. doi: 10.1016/j.plantsci.2023.111917. Online ahead of print.ABSTRACTAcer truncatum is a horticultural tree species with individuals that display either yellow or red leaves in autumn, giving it high ornamental and economic value. 'Lihong' of A. truncatum is an excellent cultivar due to its characteristic of having autumn leaves that turn a bright and beautiful shade of red, while its closely related cultivar 'Bunge' does not. However, the molecular mechanism underlying the color change in the cultivar 'Lihong' is still unclear. Here, we assembled a high-quality genome sequence of Acer truncatum 'Lihong' (genome size = 688Mb, scaffold N50 = 9.14Mb) with 28,438 protein-coding genes predicted. Through comparative genomic analysis, we found that 'Lihong' had experienced more tandem duplication events although it's a high degree of collinearity with 'Bunge'. Especially, the expansion of key enzymes in the anthocyanin synthesis pathway was significantly uneven between the two varieties, with 'Lihong' genome containing a significantly higher number of tandem/dispersed duplication key genes. Further transcriptomic, metabolomic, and molecular functional analyses demonstrated that several UFGT genes, mainly resulting from tandem/dispersed duplication, followed by the promoter sequence variation, may contribute greatly to the leaf color phenotype, which provides new insights into the mechanism of divergent anthocyanin accumulation process in the 'Lihong' and 'Bunge' with yellow leaves in autumn. Further, constitutive expression of two UFGT genes, which showed higher expression in 'Lihong', elevated the anthocyanin content. We proposed that the small-scale duplication events could contribute to phenotype innovation.PMID:37944703 | DOI:10.1016/j.plantsci.2023.111917

Ecotoxicol Environ Saf. 2023 Nov 7;267:115637. doi: 10.1016/j.ecoenv.2023.115637. Online ahead of print.ABSTRACTA variety of microplastics (MPs) have become ubiquitous environmental pollutants, leading to inevitable human contact and health impacts. Most previous research has explored the toxic effects of a single type of MPs exposure. However, the effects of co-exposure to both common types of MPs, polyvinyl chloride (PVC) and polystyrene (PS) MPs on mammals have not been explored. Here, adult mice were exposed to PS-PVC (1.0 µm PS and 2.0 µm PVC both at the concentration of 0.5 mg/day) for 60 days. The results showed that PS-PVC co-exposure-induced hepatotoxicity was evidenced by liver histopathological changes, the release of inflammatory cytokines, and the activation of oxidative stress. Moreover, the intestinal mucosal barrier was damaged after PS-PVC treatment. The results of 16S rRNA gene sequencing reported there was a marked shift in the gut microbial structure accompanied by decreased relative abundances of probiotics, such as Clostridium, Lachnospiraceae_UCG-006, Desulfovibrio, Clostridiales_unclassified and Ruminococcaceae_unclassified and increased the conditional pathogen abundances, such as Erysipelatoclostridium. Furthermore, the triglyceride (TG) and total cholesterol (TCH) expression levels in the serum and liver were increased after PS-PVC co-exposure. Serum metabolomics analysis showed that there were 717 differential expression metabolites found in the positive- and negative-ion modes, including 476 up-regulated and 241 down-regulated, mainly enriched in butyrate metabolism, thiamine metabolism, and phenylacetate metabolism. In addition, remarked changes in the gut microbiota and serum metabolic profiles were closely related to hepatic and intestinal injuries after PS-PVC co-exposure. These results have provided new insights into the toxic effects of PS and PVC MPs co-exposure through the gut-liver axis and the health risks of PS and PVC MPs should be paid more attention to humans.PMID:37944461 | DOI:10.1016/j.ecoenv.2023.115637

Biomed Pharmacother. 2023 Nov 7;169:115775. doi: 10.1016/j.biopha.2023.115775. Online ahead of print.ABSTRACTPsychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is needed when considering the development of future novel therapeutic approaches. Both metabolic and metabolomics studies may help for these purposes. On one hand, metabolic studies aim to determine the main metabolites of the drug. On the other hand, the application of metabolomics in human psychedelics studies can help to further understand the biological processes underlying the psychedelic state and the mechanisms of action underlying their therapeutic potential. This review presents the state of the art of metabolic and metabolomic studies after lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT) and β-carboline alkaloids (ayahuasca brew), 5-methoxy-DMT and psilocybin administrations in humans. We first describe the characteristics of the published research. Afterward, we reviewed the main results obtained by both metabolic and metabolomics (if available) studies in classical psychedelics and we found out that metabolic and metabolomics studies in psychedelics progress at two different speeds. Thus, whereas the main metabolites for classical psychedelics have been robustly established, the main metabolic alterations induced by psychedelics need to be explored. The integration of metabolomics and pharmacokinetics for investigating the molecular interaction between psychedelics and multiple targets may open new avenues in understanding the therapeutic role of psychedelics.PMID:37944438 | DOI:10.1016/j.biopha.2023.115775

J Biol Chem. 2023 Nov 7;299(12):105422. doi: 10.1016/j.jbc.2023.105422. Online ahead of print.NO ABSTRACTPMID:37944340 | DOI:10.1016/j.jbc.2023.105422

Aquat Toxicol. 2023 Nov 3;265:106745. doi: 10.1016/j.aquatox.2023.106745. Online ahead of print.ABSTRACTDespite growing interest in conventional microplastics (CMPs) and their toxicological effects on aquatic species, little is known about biodegradable microplastics (BMPs) and their corresponding implications for aquatic life. Here, tilapia (Oreochromis mossambicus) were semi-statically exposed for 14 days to the bio-based plastic polylactic acid (PLA, 100 μg/L, 2.52 ± 0.46 μm) and the petroleum-based plastic polyvinyl chloride (PVC, 100 μg/L, 1.58 ± 0.36 μm). The results showed that ingesting the above two types of microplastics (MPs) led to oxidative stress in the fish gut, and damage to gut tissues and organelles, and PLA resulted in more obvious gut tissue edema than PVC. Furthermore, PLA caused increased levels of gut microbiota dysbiosis and a decrease in the abundance of the genus Cetobacterium, which is linked to vitamin B-12 synthesis, whereas an opposite relationship was observed on PVC. Metabolomic analysis indicated that PVC caused a significant down-regulation of orotic acid, co-metabolite of folic acid with vitamin B-12, while PLA did not affect orotic acid, which may lead to the accumulation of folic acid in fish. The joint analysis found that MPs disturbed gut metabolism homeostasis, implying that abnormal gut microbiota metabolites may be a key mechanism for MPs to induce tissue damage and oxidative stress in the gut. Overall, this study systematically illustrates the differential toxic effects of BMPs and CMPs on tilapia through gut microbiota and metabolite interactions, which will contribute to assessing the risks of BMPs to organismal health.PMID:37944327 | DOI:10.1016/j.aquatox.2023.106745

J Plant Physiol. 2023 Oct 28;291:154124. doi: 10.1016/j.jplph.2023.154124. Online ahead of print.ABSTRACTHalophytes are potential future crops with a valuable nutritional profile. Produced in indoor farming, they are considered to contribute to sustainable and resilient food systems. Indoor farms operate using artificial light. In this context narrowband and low dose UVB radiation can be used to increase plant secondary metabolites, such as carotenoids, and provide an improved nutritional profile for a human diet. UVB radiation can cause eustress or distress in the plant depending on the lighting situation. The aim of this study was to identify the doses of UVB that lead to either eustress or distress and to analyze these responses in Salicornia europaea. Therefore, S. europaea plants were exposed to different UVB radiation levels, low, medium and high, and analyzed for reactive oxygen species (ROS), plant hormones, amino acids, and photosynthetic pigments. High UVB treatment was found to affect phenotype and growth, and the metabolite profile was affected in a UVB dose-dependent manner. Specifically, medium UVB radiation resulted in an increase in carotenoids, whereas high UVB resulted in a decrease. We also observed an altered oxidative stress status and increased SA and decreased ABA contents in response to UVB treatment. This was supported by the results of menadione treatment that induces oxidative stress in plants, which also indicated an altered oxidative stress status in combination with altered carotenoid content. Thus, we show that a moderate dose of UVB can increase the carotenoid content of S. europaea. Furthermore, the UVB stress-dependent response led to a better understanding of carotenoid accumulation upon UVB exposure, which can be used to improve lighting systems and in turn the nutritional profile of future crops in indoor farming.PMID:37944241 | DOI:10.1016/j.jplph.2023.154124

Int Immunopharmacol. 2023 Nov 7;125(Pt A):111170. doi: 10.1016/j.intimp.2023.111170. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Neuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model.METHODS: Male SD rats (180-220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed.RESULTS: Mechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats.CONCLUSION: Emodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.PMID:37944218 | DOI:10.1016/j.intimp.2023.111170

J Clin Oncol. 2023 Nov 9:JCO2202754. doi: 10.1200/JCO.22.02754. Online ahead of print.ABSTRACTPURPOSE: To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology.METHODS: We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context.RESULTS: Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods.CONCLUSION: Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.PMID:37944067 | DOI:10.1200/JCO.22.02754

PLoS Pathog. 2023 Nov 9;19(11):e1011787. doi: 10.1371/journal.ppat.1011787. Online ahead of print.ABSTRACTPlasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display concentration trends that scale with disease severity and might serve as prognostic markers for fatal events. Metabolomics evidence is then used as input data for a sex-specific multi-organ metabolic model. This reconstruction provides a comprehensive view of the impact of COVID-19 on the entire human metabolism. The human (male and female) metabolic network is strongly impacted by the disease to an extent dictated by its severity. A marked metabolic reprogramming at the level of many organs indicates an increase in the generic energetic demand of the organism following infection. Sex-specific modulation of immune response is also suggested.PMID:37943960 | DOI:10.1371/journal.ppat.1011787

PLoS One. 2023 Nov 9;18(11):e0289077. doi: 10.1371/journal.pone.0289077. eCollection 2023.ABSTRACTBACKGROUND: Physical activity (PA) is associated with various health benefits, especially in improving chronic health conditions. However, the metabolic changes in host metabolism in response to PA remain unclear, especially in racially/ethnically diverse populations.OBJECTIVE: This study is to assess the metabolic profiles associated with the frequency of PA in White and African American (AA) men.METHODS: Using the untargeted metabolomics data collected from 698 White and AA participants (mean age: 38.0±8.0, age range: 20-50) from the Louisiana Osteoporosis Study (LOS), we conducted linear regression models to examine metabolites that are associated with PA levels (assessed by self-reported regular exercise frequency levels: 0, 1-2, and ≥3 times per week) in White and AA men, respectively, as well as in the pooled sample. Covariates considered for statistical adjustments included race (only for the pooled sample), age, BMI, waist circumstance, smoking status, and alcohol drinking.RESULTS: Of the 1133 untargeted compounds, we identified 7 metabolites associated with PA levels in the pooled sample after covariate adjustment with a false discovery rate of 0.15. Specifically, compared to participants who did not exercise, those who exercised at a frequency ≥3 times/week showed higher abundances in uracil, orotate, 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) (GPE), threonate, and glycerate, but lower abundances in salicyluric glucuronide and adenine in the pooled sample. However, in Whites, salicyluric glucuronide and orotate were not significant. Adenine, GPE, and threonate were not significant in AAs. In addition, the seven metabolites were not significantly different between participants who exercised ≥3 times/week and 1-2 times/week, nor significantly different between participants with 1-2 times/week and 0/week in the pooled sample and respective White and AA groups.CONCLUSIONS: Metabolite responses to PA are dose sensitive and may differ between White and AA populations. The identified metabolites may help advance our knowledge of guiding precision PA interventions. Studies with rigorous study designs are warranted to elucidate the relationship between PA and metabolites.PMID:37943870 | DOI:10.1371/journal.pone.0289077