Specific Metabolites Research Articles

Early Sepsis Metabolic Changes in Kidney and Liver Precede Clinical Evidence of Organ Dysfunction.

Organ-specific metabolic pathways, including those related to mitochondrial metabolism, could provide insight to mechanisms underlying sepsis-induced organ dysfunction. However, it remains unclear if metabolic changes result from or precede clinical organ dysfunction. To determine if blood levels of the mitochondrial metabolites acetylcarnitine and L-carnitine correlate with organ-specific signals of sepsis-induced dysfunction, we performed a series of translational analyses of two cohorts of human sepsis and experiments using a murine model of polymicrobial sepsis. We evaluated the association between mitochondrial metabolites and clinical indices of organ function. In the blood of patients with sepsis or septic shock, we found metabolic signals of dysfunctional mitochondrial b-oxidation that were correlated with clinical measures of renal and liver dysfunction. The relevance of these findings was corroborated in an experimental model that showed distinct patterns of change in organ metabolism that correlated with the blood acetylcarnitine to L-carnitine ratio. In addition, sepsis-induced changes in organ metabolism were distinct in the liver and kidney highlighting the unique energy economies of each organ. Importantly, metabolic changes preceded changes in clinical indices of organ function and histological evidence of cellular apoptosis. Based on these findings, sepsis-induced disruption in blood levels of specific metabolites could serve as more physiologically relevant indicators of early organ dysfunction than those we presently use. These early metabolite signals provide mechanistic insights to altered metabolism that may hold the key to timely identification of impending organ dysfunction. This could lead to strategies directed at the interruption of sepsis-induced organ failure.

Integrated analysis of proteomics and metabolomics in infantile epileptic spasms syndrome

Infantile Epileptic Spasms Syndrome (IESS) is a severe developmental epileptic encephalopathy that manifests in infancy, significantly impacting the health and quality of life of affected children. The treatment of IESS poses a significant challenge, primarily due to the incomplete understanding of its etiology and pathogenesis. Objective: This study aims to investigate the pathogenic mechanisms of IESS, utilizing metabolomics and proteomics analyses to uncover potential biomarkers for the disease, thereby providing new insights for diagnostic and therapeutic strategies. Cerebrospinal fluid samples from 6 IESS patients and 6 control subjects with benign intracranial hypertension were collected and analyzed using metabolomics and proteomics techniques. Significant differential metabolites and proteins were identified and correlated to determine key proteins associated with specific metabolites. The study then expanded the sample size to 10 per group and validated the identified proteins through ELISA analysis. A total of 24 differential metabolites (12 upregulated and 12 downregulated) and 79 differential proteins (18 upregulated and 61 downregulated) were identified. Metabolomic analysis suggests that linoleic acid is a highly noteworthy differential metabolite in the cerebrospinal fluid of IESS patients. The associated differential protein HLA-A and SEZ6L2 proteins were notably downregulated (p < 0.05). Linoleic acid and its metabolism-related proteins HLA-A and SEZ6L2 could serve as potential biomarkers for IESS, providing new insights into the complex pathogenic mechanisms of the disease. Additionally, these findings also assist in identifying new therapeutic targets and developing more effective treatment strategies.

Multi-omic analyses unveil contrasting composition and spatial distribution of specialized metabolites in seeds of Camelina sativa and other Brassicaceae.

Seeds of Brassicaceae produce a large diversity of beneficial and antinutritional specialized metabolites (SMs) that influence their quality and provide resistance to stresses. While SM distribution has been described in leaves and root tissues, limited information is available about their spatiotemporal accumulation in seeds. Camelina sativa (camelina) is an oilseed Brassicaceae cultivated for human and animal nutrition and for industrial uses. While we previously explored SM diversity and plasticity, no information is available about SM distribution and expression of related proteins and genes in camelina seeds. In this study, we used a multi-omic approach, integrating untargeted metabolomics, proteomics, and transcriptomics to investigate the synthesis, modification, and degradation of SMs accumulated in camelina seed tissues (seed coat, endosperm, embryo) at six developmental and two germination stages. Metabolomic results showed distinct patterns of SMs and their related pathways, highlighting significant contrasts in seed composition and spatial distribution for the defense-related and antinutritional glucosinolate (GSL) compounds among camelina, Arabidopsis thaliana, and Brassica napus, three closely related Brassicaceae species. Notably, thanks to metabolomic and proteomic/transcriptomic techniques the variation in GSL spatial distributions was primarily driven by differences in their structure (metabolomics data) and transport (transcriptomic and proteomic data) mechanisms. Long-chain C8-C11 methylsulfinylalkyl GSLs were predominantly accumulated in the seed coat and endosperm, while mid- and short-chain C3-C7 methylsulfinylalkyl GSLs were accumulated in the embryo. Characterizing the spatial dynamics of seed SMs provides valuable insights that can guide the development of crops with optimized distribution of beneficial and toxic metabolites, improving seed nutritional profiles.

Potential mechanism associated with post-heart transplantation diabetes mellitus in Chinese patients.

Post-transplantation diabetes mellitus (PTDM) is a common metabolic complication following heart transplantation, which not only leads to elevated microvascular morbidity, but also seriously affects graft function and recipient survival. However, the specific metabolites and underlying mechanisms are not yet fully understood. A total of 106 adult heart transplant recipients (56 PTDM and 50 non-PTDM) who followed for more than one year were enrolled in the study. The untargeted metabolomics was performed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The demographic, clinical data and drug information were collected at the time of sample collection. PTDM patients were older (p=0.003), with higher BMI (p=0.010), higher triglyceride levels (TG, p=0.007), and a higher prevalence of hypertension (p=0.001) than non-PTDM. A total of 1174 metabolites were detected, of which 99 metabolites showed significantly differentially abundant (VIP>1, p<0.05, FC>1.5 or <0.67). KEGG functional enrichment analysis showed these differently expressed metabolites could be further enriched in ABC transporter, carbon metabolism, retrograde endocannabinoid signaling, phospholipase D signaling pathway. Compared with non-PTDM group, glutamate, diacylglycerol (DAG) and D-sorbitol were significantly changed in PTDM through metabolomics. These findings may provide a novel understanding of the pathological mechanism of PTDM and could be utilized to predict the development and progression of PTDM.

Maternal organophosphate esters and sex steroid hormones in mid-pregnancy.

/Aims: Organophosphate esters (OPEs) are synthetic chemicals used in consumer products as flame retardants and plasticizers. OPEs are potential endocrine disruptors, but little is known regarding gestational OPE exposure and maternal sex steroid hormones in human pregnancy. Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort participants (n=265) provided biospecimens and completed questionnaires in each trimester. In second trimester samples, we measured urinary OPE metabolite concentrations using HPLC-MS/MS. In second and third trimester serum samples, we measured sex steroids (total testosterone [TT], free testosterone, estrone [E1], estradiol [E2], and estriol [E3]) using LC-MS/MS. We fitted linear regression and linear mixed models examining each log-transformed, specific gravity-adjusted OPE metabolite in relation to sex steroid concentrations, adjusting for covariates. Three OPEs with >70% detection were considered continuously; six less prevalent metabolites were dichotomized (above vs below lower limit of detection). Secondary models were fit for male and female fetuses, separately. Results are shown as % difference in hormone levels. Percent detection of OPEs ranged from 26% to 100%. Diphenyl phosphate (DPHP) had the highest concentration (median 0.9ng/mL). Across trimesters 2 and 3, a log-unit increase in dibutyl phosphate/di-isobutyl phosphate (DBUP/DIBP) was associated with lower TT (%Δ= -6.6, 95%CI: -11.5, -1.5), E1 (%Δ= -5.6, 95%CI: -10.8, -0.1), and E2 (%Δ= -5.3, 95%CI: -8.2, -2.3). Compared to those with non-detectable levels, participants with detectable bis(methylphenyl) phosphate (BMPP) had lower E3 (%Δ= -45.9, 95%CI: -67.9, -8.9) and participants with detectable bis(2-chloroethyl) phosphate (BCETP) had lower E2 (%Δ= -1.4, 95%CI: -2.4, -0.4). Numerous associations were observed in trimesters 2 and 3, individually. We observed several differences by fetal sex that varied in magnitude and direction. OPEs may act as endocrine disruptors by altering maternal sex steroid hormones during pregnancy, with some differences by fetal sex. Further research is needed to understand implications for maternal and child health.

Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n= 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n= 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy invivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.

Different performance of tea plants to shade based on key metabolites and transcriptome profiles: case study of cultivars Longjing 43 and Yabukita.

Shading is widely used in tea cultivation to improve quality by modulating various metabolic pathways in tea plants. However, the differential sensitivity of specific metabolites and the cultivar-dependent responses to shading are not yet fully understood. This study examined the impact of shading on the chemical composition and transcriptional profiles of cv. Longjing 43 and cv. Yabukita. Among the main quality-related compounds, flavonol glycosides were highly responsive to shading, while catechins displayed distinct cultivar-specific responses. KEGG enrichment analysis revealed that flavonoid biosynthesis was the key secondary metabolic difference between cv. Longjing and cv. Yabukita plants under the sunlight, and shading regulated flavonoid biosynthetic pathways in both cultivars. The genes such as ANTHOCYANIDIN REDUCTASE (CsANR) and ANTHOCYANIDIN SYNTHASE (CsANS) were less sensitive to shade in cv. Longjing 43 than cv. Yabukita, leading to relatively higher levels of epi-type catechins in the shade-treated cv. Longjing 43 sample. Additionally, the UVR8-mediated light signaling pathway demonstrated cultivar-specific expression patterns, although the functional roles of key signaling proteins were conserved across both cultivars. The insights into the chemical and molecular responses of tea plants to shading deepen our understanding of the mechanisms driving the cultivar-dependent behaviors of flavonoids, which offers valuable applications for maintaining consistent matcha quality and informing breeding programs of matcha.

Impact of Exogenous Sugars on the Potency of Selected Secondary Metabolites in Non-Starchy Amaranth (Amaranthus hybridus L.)

The biosynthesis of secondary metabolites plays a significant role in determining the value of medicinal herbs, with sugar metabolism frequently influencing overall metabolic processes. To investigate the regulatory mechanisms, exogenous sugars (sucrose, glucose, and fructose) were applied to the leaves of Amaranthus hybridus L., a highly valued and multifunctional vegetable plant, both individually and in combination (sucrose + glucose + fructose), along with a control (water). Our findings revealed that exogenous sugars enhanced the accumulation of starch and soluble sugars, while also increasing enzyme activities associated with carbohydrate assimilation. Additionally, plant biomass was significantly boosted by combined exogenous sugars, sucrose alone enhanced the photosynthetic rate, and the combined sugars accelerated the accumulation of phenols and flavonoids. Metabolomic analysis further confirmed that exogenous sugars increased the levels of phenolic and flavonoid compounds. The levels of UDP-glucose pyrophosphorylase (UGP) and hexokinase (HKX) were elevated by exogenous sugars and showed a strong correlation with their metabolic activities, which in turn stimulated the synthesis of specific secondary metabolites. These results provide valuable insights into the key factors contributing to the value formation of A. hybridus and suggest a potential approach to enhancing its quality.

Evolution and diversification of the momilactone biosynthetic gene cluster in the genus Oryza.

Plants are master chemists and collectively are able to produce hundreds of thousands of different organic compounds. The genes underlying the biosynthesis of many specialized metabolites are organized in biosynthetic gene clusters (BGCs), which is hypothesized to ensure their faithful coinheritance and to facilitate their coordinated expression. In rice (Oryza sativa), momilactones are diterpenoids that act in plant defence and various organismic interactions. Many of the genes essential for momilactone biosynthesis are grouped in a BGC. We applied comparative genomics of diploid and allotetraploid Oryza species to reconstruct the species-specific architecture, evolutionary trajectory, and sub-functionalisation of the momilactone biosynthetic gene cluster (MBGC) in the Oryza genus. Our data show that the evolution of the MBGC is marked by lineage-specific rearrangements and gene copy number variation, as well as by occasional cluster loss. We identified a distinct cluster architecture in Oryza coarctata, which represents the first instance of an alternative architecture of the MBGC in Oryza and strengthens the idea of a common origin of the cluster in Oryza and the distantly related genus Echinochloa. Our research illustrates the evolutionary and functional dynamics of a biosynthetic gene cluster within a plant genus.

Feruloyl-amides as natural antimicrobials for crop and food protection

BackgroundPlants have developed multiple chemical defence responses against pathogen attacks. The main mechanism of defence is based on a rapid transcriptional reprogramming of genes encoding biosynthetic enzymes that synthesize specific secondary metabolites. Increasing evidence indicates phenylamides (PAs) as an important group of bioactive compounds in food plants.ResultsWe synthesized a small collection of ferulic acid-derived phenylamides by chemoenzymatic approaches. The compounds were tested against fungal and bacterial pathogens to assess their antimicrobial potential. The treatment with the synthesized phenylamides showed modest inhibition of the fungal growth (up to 25%) and had no significant influence on spore germination, whereas some of the compounds gave a considerable inhibition of Pyricularia oryzae appressorium formation, up to 94%. They also exhibited in vitro antibacterial activity against six foodborne bacterial pathogens. Monitoring of six growth parameters (taking into account growth rate, time and absorbance) measured during 24 h incubation showed that the synthesized molecules, assayed at four concentrations between 12.5 and 100 mg/L, produced a stronger average antimicrobial effect against Gram-positive pathogenic strains than against Gram-negative ones.ConclusionsThe obtained results evidenced that the effect of this class of compounds is mainly related to blocking fungal virulence mechanisms, mediated by a significant effect on appressorium maturation, rather than to mycelium growth inhibition. Together with the observed in vitro antibacterial activity against foodborne bacterial pathogens, we conclude that PAs are promising candidates for future developments in the agri-food sector.Graphical

Non-targeted metabolomics reveals fatty acid and associated pathways driving resistance to whitefly and tomato leafminer in wild tomato accessions.

Wild tomato species exhibit natural insect resistance, yet the specific secondary metabolites and underlying mechanisms governing the resistance remain unclear. Moreover, defense expression dynamically adapts to insect herbivory, causing significant metabolic changes and species-specific secondary metabolite accumulation. The present study aims to identify the resistance-related metabolites in wild tomato accessions that influence the defense mechanism against whitefly (Bemisia tabaci Asia II 7) and leafminer (Phthorimaea absoluta). In this study, LC-HRMS-based non-targeted metabolomics of resistant wild (Solanum cheesmaniae and Solanum galapagense) and susceptible cultivated (Solanum lycopersicum) accessions following 6- and 12-h post-infestation (hpi) by B. tabaci Asia II 7 and P. absoluta revealed distinct sets of resistance-related constitutive (RRC) and induced (RRI) metabolites. The key resistance-related metabolites were those involved in the fatty acid and associated biosynthesis pathways (e.g., triacontane, di-heptanoic acid, dodecanoic acid, undecanoic acid, N-hexadecanoic acid, pentacosane, monogalactosyldiacylglycerols, sphinganine, and 12-hydroxyjasmonic acid), which are recognized for their direct or indirect role in mediating plant defense against insects. Additionally, the differential accumulation of metabolites was evident through partial least squares-discriminant analysis (PLS-DA), highlighting differences in metabolite profiles between resistant and susceptible accessions at 6 and 12 hpi of B. tabaci and P. absoluta. Volcano plot analysis revealed a higher number of significantly upregulated metabolites in wild accessions following herbivory. Moreover, wild tomato accessions responded uniquely to B. tabaci and P. absoluta, highlighting species-specific metabolic responses of tomato accessions to the two feeding guilds. This study uncovered biochemical mechanisms governing resistance in wild tomato accessions, elucidated the influence of dual herbivory on the plant metabolome, and offered well-characterized parent materials and candidate metabolites for breeding insect-resistant varieties.

Aromatic Amino Acids: Exploring Microalgae as a Potential Biofactory

In recent times, microalgae have emerged as powerful hosts for biotechnological applications, ranging from the production of lipids and specialized metabolites (SMs) of pharmaceutical interest to biofuels, nutraceutical supplements, and more. SM synthesis through bioengineered pathways relies on the availability of aromatic amino acids (AAAs) as an essential precursor. AAAs, phenylalanine, tyrosine, and tryptophan are also the building blocks of proteins, maintaining the structural and functional integrity of cells. Hence, they are crucial intermediates linking the primary and specialized metabolism. The biosynthesis pathway of AAAs in microbes and plants has been studied for decades, but not much is known about microalgae. The allosteric control present in this pathway has been targeted for metabolic engineering in microbes. This review focuses on the biosynthesis of AAAs in eukaryotic microalgae and engineering techniques for enhanced production. All the putative genes involved in AAA pathways in the model microalgae Chlamydomonas reinhardtii and Phaeodactylum tricornutum are listed in this review.

Immune cells: Mediators in the metabolites and Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that predominantly affects elderly individuals across the globe. While genetic, environmental, and lifestyle factors are known to influence the onset of AD, the underlying mechanisms remain unclear. To elucidate the intricate interplay between metabolites and immune cell activation in the ethology of AD, and to determine their collective impact on AD risk. We conducted a comprehensive analysis of genome-wide association studies data to examine the relationships between metabolites, immune cell phenotypes, and the risk of AD. Our study encompassed a comprehensive examination involving 731 distinct immune cell types, 1400 metabolites, and a large cohort comprising10,520 AD cases with 401,661 controls. We employed univariate Mendelian randomization to assess bidirectional relationships between metabolites and AD, metabolites and immune cells, as well as immune cells and AD. Subsequently, multivariate Mendelian randomization was then applied to evaluate the potential mediating role of immune cells on the relationship between metabolites and AD. Specific metabolites, the histidine/pyruvate ratio and homoarginine, were positively associated with the risk of AD, mediated by immune cells. Conversely, 4-hydroxycoumarin and glycolithocholate sulfate showed protective associations against AD. Immune cell markers, CD64 on monocytes and HLA DR on CD14+ CD16- monocytes were linked to higher AD risk, while CD33dim HLA DR+ CD11b- myeloid cells and HLA DR on CD8+ T cells were protective. This study highlights the critical role of immune cells in the pathogenesis of AD, demonstrating how their interaction with specific metabolites influences disease risk.

Alterations in fecal bacteriome virome interplay and microbiota-derived dysfunction in patients with schizophrenia

Rising studies have consistently reported gut bacteriome alterations in schizophrenia (SCZ). However, little is known about the role of the gut virome on shaping the gut bacteriome in SCZ. Here in, we sequenced the fecal virome, bacteriome, and host peripheral metabolome in 49 SCZ patients and 49 health controls (HCs). We compared the gut bacterial community composition and specific abundant bacteria in SCZ patients and HCs. Specific gut viruses and host peripheral metabolites co-occurring with differential bacteria were identified using Multiple Co-inertia Analysis (MCIA). Additionally, we construct a latent serial mediation model (SMM) to investigate the effect of the gut virome on SCZ through the bacteriome and host metabolic profile. SCZ patients exhibited a decreased gut bacterial β-diversity compared to HCs, with seven differentially abundant bacteria, including Coprobacillaceae, Enterococcaceae etc. Gut viruses including Suoliviridae and Rountreeviridae, co-occur with these SCZ-related bacteria. We found that the viral-bacterial transkingdom correlations observed in HCs were dramatically lost in SCZ. The altered correlations profile observed in SCZ may impact microbiota-derived peripheral metabolites enriched in the bile acids pathway, eicosanoids pathway, and others, contributing to host immune dysfunction and inflammation. The SMM model suggested potential causal chains between gut viruses and SCZ, indicating that the effect of gut virome on SCZ is significantly mediated by bacteriome and metabolites. In conclusion, these findings provide a comprehensive perspective on the role of gut microbiota in the pathogenesis of SCZ. They reveal that patients with schizophrenia harbor an abnormal virome-bacteriome ecology, shedding light on the potential development of microbial therapeutics.

Antitumor Activity of Warbugia ugandensis: Methanolic Extracts and Gene Regulation in Colorectal Cancer

A promising approach to accelerating the development of innovative anti-cancer therapies involves the evaluation of natural plant compounds. In this study, we focused on examining the effects of Warbugia ugandensis (W. ugandensis) methanolic root and stem infusions on the activity of five target genes—COX-2, CASPS-9, Bcl-xL, Bcl2, and 5-LOX—using colorectal cancer (CRC) cell lines (Caco-2). The plant extracts were prepared for testing by dissolving them in dimethyl sulfoxide (DMSO) after undergoing a step-by-step extraction process. Caco-2 cells were then treated with different concentrations of the extracts, and RNA was extracted and purified for analysis. Our results demonstrated a dose-dependent relationship between the phytoconstituents of W. ugandensis and the overexpression of CASP9, along with the downregulation of COX-2, 5-LOX, Bcl-xL, and Bcl2 genes. This suggests that W. ugandensis acts as a potent natural inhibitor of CRC progression. Given the potential clinical benefits, we propose the use of W. ugandensis methanolic root and stem extracts as promising organic inhibitors for CRC tumorigenesis, with more in vitro studies warranted to validate and expand on our findings. Additionally, we recommend further studies to identify and characterize the specific metabolites in W. ugandensis that contribute to the modulation of pathways responsible for inhibiting CRC growth.

Interspecies interactions mediated by arginine metabolism enhance the stress tolerance of Fusobacterium nucleatum against Bifidobacterium animalis.

Colorectal cancer (CRC) is a common cancer accompanied by microbiome dysbiosis. Exploration of probiotics against oncogenic microorganisms is promising for CRC treatment. Here, differential microorganisms between CRC and healthy control were analyzed. Antibacterial experiments, whole-genome sequencing, and metabolic network reconstruction were combined to reveal the anti-Fusobacterium nucleatum mechanism, which was verified by co-culture assay and mendelian randomization analysis. Sequencing results showed that F. nucleatum was enriched in CRC, yet Bifidobacterium animalis decreased gradually from healthy to CRC. Additionally, F. nucleatum could be inhibited by B. animalis. Whole-genome sequencing of B. animalis showed high phylogenetic similarity with known probiotic strains and highlighted its functions for amino acid and carbohydrate metabolism. Metabolic network reconstruction demonstrated that cross-feeding and specific metabolites (acidic molecules, arginine) had a great influence on the coexistence relationship. Finally, the arginine supplement enhanced the competitive ability of F. nucleatum against B. animalis, and the mendelian randomization and metagenomic sequencing analysis confirmed the positive relationship among F. nucleatum, arginine metabolism, and CRC. Thus, whole-genome sequencing and metabolic network reconstruction are valuable for probiotic mining and patient dietary guidance.IMPORTANCEUsing probiotics to inhibit oncogenic microorganisms (Fusobacterium nucleatum) is promising for colorectal cancer (CRC) treatment. In this study, whole-genome sequencing and metabolic network reconstruction were combined to reveal the anti-F. nucleatum mechanism of Bifidobacterium animalis, which was verified by co-culture assay and mendelian randomization analysis. The result indicated that the arginine supplement enhanced the competitive ability of F. nucleatum, which may be harmful to F. nucleatum-infected CRC patients. B. animalis is a potential probiotic to relieve this dilemma. Thus, using in silico simulation methods based on flux balance analysis, such as genome-scale metabolic reconstruction, provides valuable insights for probiotic mining and dietary guidance for cancer patients.

Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration.

Maternal urinary levels of PAH metabolites, umbilical cord blood telomere length and anthropometric indices in newborns.

The existing evidence indicating that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with a range of adverse outcomes, including alterations in anthropometric indices, underscores the need for further investigation into the underlying mechanisms. This study aims to examine the effects of prenatal PAH exposure on anthropometric indices and telomere length (TL), as well as to explore whether changes in TL can serve as a predictor of alterations in anthropometric measures. The study was conducted in Shenyang, China, with 2460 pregnant women participating between 2022 and 2023. Maternal urine samples were analyzed for eleven PAH metabolites, and neonatal outcomes, such as birth weight (BW), birth length (BL), and head circumference (HC), were extracted from medical records as anthropometric indices. We employed multiple linear regression (MLR), generalized quantile g-computation (g-comp), Bayesian Kernel Machine Regression (BKMR), and mediation analysis to comprehensively assess the associations between PAH exposure and umbilical TL and neonatal outcomes. Notably, significant negative associations were found between several PAH metabolites and umbilical telomere length (TL). These metabolites included 2-hydroxy naphthalene (2-OH Nap), 1-hydroxy pyrene (1-OH Pyr), 6-hydroxy chrysene (6-OH Chr), 9-hydroxy benzo(a)pyrene (9-OH Bap), and the sum of hydroxylated PAHs (Σ-OH PAHs). Additionally, negative correlations were identified between specific PAH metabolites and HC, although no significant associations were found for BW. Birth weight showed a significant inverse relationship with metabolites such as 1-hydroxy phenanthrene (1-OH Phe), 9-hydroxy phenanthrene (9-OH Phe), and 1-hydroxy naphthalene(1-OH Nap). Results from g-comp analysis and BKMR indicated significant mixture effects of PAHs on umbilical TL and HC, with more heterogeneous effects on BW and BL. Mediation analysis indicated that alterations in umbilical TL partially mediated the associations between PAH exposure and BW and HC. Notably, metabolites such as 2-OH Nap and the Σ-OH PAHs demonstrated substantial mediation effects. Overall, our findings suggest that changes in umbilical TL partially mediate the associations between prenatal PAH exposure and HC and BW, highlighting the complex pathways through which PAH metabolites may influence neonatal development.

An overview of the phytochemistry of medicinal bark (trunk, stem or root) from the most popular southern African species

Abstract The ten countries that make up southern Africa are collectively a hot-spot of medicinal plant knowledge, with a unique preference for the utilization of bark over leaves from possibly hundreds of species. The most popular 86 medicinal bark species were identified in an earlier survey of various muthi markets around Johannesburg, and are listed in the current review, out of which chemical data was found for 63 and tabulated. The chemistry of medicinal bark species is, however, incomplete, since many scholars focused their research on metabolites of interest to their research groups, such as essential oils, lipophilic compounds, alkaloids or saponins, to the exclusion of other specialized metabolites present in the respective biota. From the current phytochemical analysis, the medicinal potential of bark relative to leaves is not obvious, as it is dependent on factors such as quantity of specialized metabolites (potency), their identities and anecdotal accounts from traditional healers. Nevertheless, the preference for bark may be due to empirical outcomes in therapy. Southern African medicinal bark species demonstrate an extremely diverse pool of unique/new or relatively unheard of natural products, such as calondendrolide from C. capense, combretastatin from C. caffrum, capensin from C. capense, crotohalimaneic acid from C. sylvaticus, ekebergins from E. capensis, entandrophragmin from E. caudatum, lysisteisoflavone from E. lysistemon, kigelinone from K. africana, holstinones from O. holstii, piptadeniaoside from P. africanum, rauvolfianoids from R. caffra, tetrapterosides from T. tetraptera, voacangine from V. thouarsii, warburganal from W. salutaris and mucronine from Z. mucronata. The review concludes by briefly commenting on pharmacokinetic aspects associated with ingestion or topical application of bark metabolites.

Non-targeted metabolomics-based molecular networking enables the chemical characterization of Rumex sanguineus, a wild edible plant

Introduction and ObjectiveRumex sanguineus, a traditional medicinal plant of the Polygonaceae family, is gaining popularity as an edible resource. However, despite its historical and nutritional significance, its chemical composition remains poorly understood. To deepen the understanding of the of Rumex sanguineus composition, an in-depth analysis using non-targeted, mass spectrometry-based metabolomics was performed. MethodsRumex roots, stems and leaves samples were analyzed by UHPLC-HRMS and subsequently subjected to feature-based molecular networking.Results and ConclusionOverall, 347 primary and specialized metabolites grouped into 8 biochemical classes were annotated. Most of these metabolites (60%) belong to the polyphenols and anthraquinones classes. To investigate potential’ toxicity due to the presence of anthraquinones, the amount of emodin was quantified with analytical standard, revealing higher accumulation in leaves compared to stems and roots. This highlights the need for thorough metabolomic studies to understand both beneficial and harmful compounds, especially in plants with historical medicinal use transitioning to modern culinary use.