PubMed

Environ Int. 2024 Apr 2;186:108620. doi: 10.1016/j.envint.2024.108620. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health.PMID:38579451 | DOI:10.1016/j.envint.2024.108620

Sci Adv. 2024 Apr 5;10(14):eadj7540. doi: 10.1126/sciadv.adj7540. Epub 2024 Apr 5.ABSTRACTFewer than 20% of triple-negative breast cancer patients experience long-term responses to mainstay chemotherapy. Resistant tumor subpopulations use alternative metabolic pathways to escape therapy, survive, and eventually recur. Here, we show in vivo, longitudinal metabolic reprogramming in residual disease and recurrence of triple-negative breast cancer xenografts with varying sensitivities to the chemotherapeutic drug paclitaxel. Optical imaging coupled with metabolomics reported an increase in non-glucose-driven mitochondrial metabolism and an increase in intratumoral metabolic heterogeneity during regression and residual disease in resistant MDA-MB-231 tumors. Conversely, sensitive HCC-1806 tumors were primarily reliant on glucose uptake and minimal changes in metabolism or heterogeneity were observed over the tumors' therapeutic life cycles. Further, day-matched resistant HCC-1806 tumors revealed a higher reliance on mitochondrial metabolism and elevated metabolic heterogeneity compared to sensitive HCC-1806 tumors. Together, metabolic flexibility, increased reliance on mitochondrial metabolism, and increased metabolic heterogeneity are defining characteristics of persistent residual disease, features that will inform the appropriate type and timing of therapies.PMID:38579004 | DOI:10.1126/sciadv.adj7540

Sci Adv. 2024 Apr 5;10(14):eadk8093. doi: 10.1126/sciadv.adk8093. Epub 2024 Apr 5.ABSTRACTTrained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.PMID:38578989 | DOI:10.1126/sciadv.adk8093

J Alzheimers Dis. 2024 Mar 30. doi: 10.3233/JAD-230053. Online ahead of print.ABSTRACTBACKGROUND: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer's disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans.OBJECTIVE: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population.METHODS: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory.RESULTS: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory.CONCLUSIONS: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.PMID:38578885 | DOI:10.3233/JAD-230053

Plant J. 2024 Apr 5. doi: 10.1111/tpj.16734. Online ahead of print.ABSTRACTThe mature seed in legumes consists of an embryo and seed coat. In contrast to knowledge about the embryo, we know relatively little about the seed coat. We analyzed the gene expression during seed development using a panel of cultivated and wild pea genotypes. Gene co-expression analysis identified gene modules related to seed development, dormancy, and domestication. Oxidoreductase genes were found to be important components of developmental and domestication processes. Proteomic and metabolomic analysis revealed that domestication favored proteins involved in photosynthesis and protein metabolism at the expense of seed defense. Seed coats of wild peas were rich in cell wall-bound metabolites and the protective compounds predominated in their seed coats. Altogether, we have shown that domestication altered pea seed development and modified (mostly reduced) the transcripts along with the protein and metabolite composition of the seed coat, especially the content of the compounds involved in defense. We investigated dynamic profiles of selected identified phenolic and flavonoid metabolites across seed development. These compounds usually deteriorated the palatability and processing of the seeds. Our findings further provide resources to study secondary metabolism and strategies for improving the quality of legume seeds which comprise an important part of the human protein diet.PMID:38578789 | DOI:10.1111/tpj.16734

Plant J. 2024 Apr 5. doi: 10.1111/tpj.16745. Online ahead of print.ABSTRACTTuta absoluta ("leafminer"), is a major pest of tomato crops worldwide. Controlling this insect is difficult due to its efficient infestation, rapid proliferation, and resilience to changing weather conditions. Furthermore, chemical pesticides have only a short-term effect due to rapid development of T. absoluta strains. Here, we show that a variety of tomato cultivars, treated with external phenylalanine solutions exhibit high resistance to T. absoluta, under both greenhouse and open field conditions, at different locations. A large-scale metabolomic study revealed that tomato leaves absorb and metabolize externally given Phe efficiently, resulting in a change in their volatile profile, and repellence of T. absoluta moths. The change in the volatile profile is due to an increase in three phenylalanine-derived benzenoid phenylpropanoid volatiles (BPVs), benzaldehyde, phenylacetaldehyde, and 2-phenylethanol. This treatment had no effect on terpenes and green leaf volatiles, known to contribute to the fight against insects. Phe-treated plants also increased the resistance of neighboring non-treated plants. RNAseq analysis of the neighboring non-treated plants revealed an exclusive upregulation of genes, with enrichment of genes related to the plant immune response system. Exposure of tomato plants to either benzaldehyde, phenylacetaldehyde, or 2-phenylethanol, resulted in induction of genes related to the plant immune system that were also induced due to neighboring Phe-treated plants. We suggest a novel role of phenylalanine-derived BPVs as mediators of plant-insect interactions, acting as inducers of the plant defense mechanisms.PMID:38578218 | DOI:10.1111/tpj.16745

J Chin Med Assoc. 2024 Apr 5. doi: 10.1097/JCMA.0000000000001094. Online ahead of print.ABSTRACTBACKGROUND: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone (CS) patients, pigmented gallstone (PS) patients, and controls.METHODS: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics.RESULT: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium, Prevotella 9 and Bacteroides plebeius DSM 17135. The CS group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the PS group had more abundant Escherichia-Shigella. In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group (p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences, but was correlated to the serum cholesterol level and bacterial richness and evenness.CONCLUSION: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.PMID:38578093 | DOI:10.1097/JCMA.0000000000001094

Nanotheranostics. 2024 Feb 25;8(3):270-284. doi: 10.7150/ntno.94071. eCollection 2024.ABSTRACTThough there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.PMID:38577320 | PMC:PMC10988213 | DOI:10.7150/ntno.94071

Heliyon. 2024 Mar 27;10(7):e28636. doi: 10.1016/j.heliyon.2024.e28636. eCollection 2024 Apr 15.ABSTRACTThe root of Angelica sinensis is utilized in Traditional Chinese medicine to enhance blood replenishment and facilitate blood circulation. The early bolting and flowering (EBF) of A. sinensis, however, compromises the quality of the roots and restricts the yield of medicinal substances. The study was conducted to compare the transcriptomic and metabolomic profiles between EBF plants and normal plants of two cultivars of A. sinensis, followed by validation of the transcriptome results using qRT-PCR. There were 3677 DEGs in EBF plants compared to normal plants of cultivar 2 (Mingui No.2), and cultivar 4 (Mingui No.4) was 3354. The main differential metabolites in the EBF and normal plants were phenolic acids, flavonoids, lignans, and coumarins. The analysis of 5 EBF-related pathways revealed 28 genes exhibiting differential expression and 5 metabolites showing differential accumulation. The expression of the Lhcb5, Lhcb2, Lhcb6, Lhcb1, Lhca4, ATPG1, EGLC, CELB, AMY, glgA, CYCD3, SnRK2, PYL, AHK2, AUX1, BSK, FabI/K, ACACA and FabV decreased and the expression of the PsbR, PsbA, LHY, FT, CO, malQ, HK, GPI and DELLA increased in EBF plants. In addition, the Abscisic acid, d-Glucose-6P, α-d-Glucose-1P, NADP+, and ADP were more significantly enriched in EBF plants. The findings offer novel perspectives on the EBF mechanisms in A. sinensis and other medicinal plants of the Apiaceae family.PMID:38576577 | PMC:PMC10990851 | DOI:10.1016/j.heliyon.2024.e28636

Heliyon. 2024 Mar 29;10(7):e28807. doi: 10.1016/j.heliyon.2024.e28807. eCollection 2024 Apr 15.ABSTRACTCurcumin and exercise have been reported to show good anti-tumour effects. However, relevant research on the combined effects of physical exercise and curcumin supplementation on cancer and the underlying mechanisms is still lacking. The current study aimed to construct an anti-breast tumour mouse model using the combined effects of curcumin treatment and swimming exercise. Transcriptomic and metabolomic techniques were used to screen for differentially expressed genes and metabolites, evaluate the anticancer effects, and analyse the molecular regulatory mechanisms related to metabolism. Observation of the mouse phenotypes, including tumour appearance, in-vivo tumour imaging, and HE staining results of pathological sections, suggested a more obvious inhibitory effect of the combination of curcumin administration and exercise intervention on breast cancer than that of a single treatment. The combination treatment group had a total of 445 differentially expressed (154 upregulated and 291 downregulated) genes. Functional enrichment analysis showed the calcium signalling pathway, Wnt signalling pathway, PI3K Akt signalling pathway, and IL-17 signalling pathway to significantly participate in the anti-breast cancer process of curcumin-exercise combination treatment. Results of the intergroup differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways, namely the amino sugar and nucleotide sugar metabolism, which includes chitosan, d-glucosamine 6-phosphate, l-fucose, and N-acetyl beta-mannosamine, and the amino acid biosynthesis, which includes dl-isoleucine, dl-tyrosine, and homocysteine. Collectively, the top-ranked genes and metabolites with the highest degree of associations were further revealed by O2PLS analysis. Overall, the study helped reveal the mechanism of action of curcumin-exercise combination treatment on breast cancer at multi-omics level.PMID:38576560 | PMC:PMC10990956 | DOI:10.1016/j.heliyon.2024.e28807

aBIOTECH. 2024 Mar 21;5(1):29-45. doi: 10.1007/s42994-023-00110-y. eCollection 2024 Mar.ABSTRACTBitter melon fruit is susceptible to yellowing, softening, and rotting under room-temperature storage conditions, resulting in reduced commercial value. Nitric oxide (NO) is an important signaling molecule and plays a crucial role in regulating the fruit postharvest quality. In this study, we investigated the effects of NO treatment on changes in sensory and firmness of bitter melon fruit during postharvest storage. Moreover, transcriptomic, metabolomic, and proteomic analyses were performed to elucidate the regulatory mechanisms through which NO treatment delays the ripening and senescence of bitter melon fruit. Our results show that differentially expressed genes (DEGs) were involved in fruit texture (CSLE, β-Gal, and PME), plant hormone signal transduction (ACS, JAR4, and AUX28), and fruit flavor and aroma (SUS2, LOX, and GDH2). In addition, proteins differentially abundant were associated with fruit texture (PLY, PME, and PGA) and plant hormone signal transduction (PBL15, JAR1, and PYL9). Moreover, NO significantly increased the abundance of key enzymes involved in the phenylpropanoid biosynthetic pathway, thus enhancing the disease resistance and alleviating softening of bitter melon fruit. Finally, differential metabolites mainly included phenolic acids, terpenoids, and flavonoids. These results provide a theoretical basis for further studies on the physiological changes associated with postharvest ripening and senescence of bitter melon fruit.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42994-023-00110-y.PMID:38576434 | PMC:PMC10987440 | DOI:10.1007/s42994-023-00110-y

Sci Total Environ. 2024 Apr 2:172165. doi: 10.1016/j.scitotenv.2024.172165. Online ahead of print.ABSTRACT8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.PMID:38575024 | DOI:10.1016/j.scitotenv.2024.172165

Sci Total Environ. 2024 Apr 2:172037. doi: 10.1016/j.scitotenv.2024.172037. Online ahead of print.ABSTRACTDespite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.PMID:38575003 | DOI:10.1016/j.scitotenv.2024.172037

J Ethnopharmacol. 2024 Apr 2:118147. doi: 10.1016/j.jep.2024.118147. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown.AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways.MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota.RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway.CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.PMID:38574779 | DOI:10.1016/j.jep.2024.118147

Cell. 2024 Mar 27:S0092-8674(24)00238-1. doi: 10.1016/j.cell.2024.02.035. Online ahead of print.ABSTRACTThis study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.PMID:38574728 | DOI:10.1016/j.cell.2024.02.035

J Hazard Mater. 2024 Mar 28;470:134165. doi: 10.1016/j.jhazmat.2024.134165. Online ahead of print.ABSTRACTIt has been reported that N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), a derivative of the tire antioxidant, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), exhibits acute toxicity towards organisms. However, the possible reproductive toxicity of 6PPD-Q in mammals has rarely been reported. In this study, the effects of 6PPD-Q on the reproductive toxicity of C57Bl/6 male mice were assessed after exposure to 6PPD-Q for 40 days at 4 mg/kg body weight (bw). Exposure to 6PPD-Q not only led to a decrease in testosterone levels but also adversely affected semen quality and in vitro fertilization (IVF) outcomes, thereby indicating impaired male fertility resulting from 6PPD-Q exposure. Additionally, transcriptomic and metabolomic analyses revealed that 6PPD-Q elicited differential expression of genes and metabolites primarily enriched in spermatogenesis, apoptosis, arginine biosynthesis, and sphingolipid metabolism in the testes of mice. In conclusion, our study reveals the toxicity of 6PPD-Q on the reproductive capacity concerning baseline endocrine disorders, sperm quality, germ cell apoptosis, and the sphingolipid signaling pathway in mice. These findings contribute to an enhanced understanding of the health hazards posed by 6PPD-Q to mammals, thereby facilitating the development of more robust safety regulations governing the utilization and disposal of rubber products.PMID:38574660 | DOI:10.1016/j.jhazmat.2024.134165

Ecotoxicol Environ Saf. 2024 Apr 3;276:116270. doi: 10.1016/j.ecoenv.2024.116270. Online ahead of print.ABSTRACTMycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.PMID:38574645 | DOI:10.1016/j.ecoenv.2024.116270

Insect Sci. 2024 Apr 4. doi: 10.1111/1744-7917.13360. Online ahead of print.ABSTRACTSwarming and pairing behaviors are significant to population dispersal of termites. Tandem running is a key process in pairing behavior of dealates to find a mate. Succinylation can lead to significant changes in protein structure and function, which is widely involved in metabolism and behavior regulation in many organisms. However, whether succinylation modification regulates termites' tandem running is currently unknown. In this research, we performed quantitative modified proteomics of the subterranean termite Reticulitermes chinensis Snyder before and after alate swarming. The succinylation levels of accessory gland protein (ACP) were significantly altered after alate swarming. We found that ACP is enriched in male accessory gland and female oocytes of termites. The acetylation and succinylation sites of ACP affected tandem running of dealates. The transcriptome and metabolome analyses of alates injected with ACP and its mutant proteins showed that β-alanine metabolism pathway was the major downstream pathway of ACP. Silencing the significantly differentially expressed genes in the β-alanine metabolic pathway (acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyisobutyrate dehydrogenase, methylmalonate-semialdehyde dehydrogenase) suppressed tandem running and altered oviposition of paired dealates. These findings demonstrate that protein translation modification is an important regulator of tandem running behavior of termites, which implies that the succinylation and acetylation modification sites of ACP could be potential targets for insecticide action. Our research offers a potential approach for developing novel dispersal inhibitors against social insect pests.PMID:38576063 | DOI:10.1111/1744-7917.13360

Nutr Metab (Lond). 2024 Apr 4;21(1):18. doi: 10.1186/s12986-024-00787-y.ABSTRACTBACKGROUND: Age-related dysbiosis of the microbiota has been linked to various negative health outcomes. This study aims to investigate the effects of a newly discovered dietary fiber compound (DFC) on aging, intestinal microbiota, and related metabolic processes. The DFC was identified through in vitro fermentation screening experiments, and its dosage and composition were determined based on a longevity dietary pattern.METHODS: Aged SPF C57BL/6 J mice (65 weeks old) and young mice (8 weeks old) were divided into three groups: a subgroup without dietary fiber (NDF), a low DFC dose subgroup (LDF, 10% DFC), and a high DFC dose subgroup (HDF, 20% DFC). The total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity in liver and serum samples of the mice were measured according to the manufacturer's protocol. The expression levels of characteristic bacterial genera and fecal metabolite concentrations in mice were determined using quantitative real-time PCR (qPCR) and nuclear magnetic resonance hydrogen spectroscopy (1H NMR). Metabolomics analysis was further conducted to identify biological functions and potential pathways related to aging.RESULTS: After an 8-weeks dietary intervention, DFC supplementation significantly attenuated age-related weight loss, organ degeneration, and oxidative stress. And promoted the growth of Lactobacillus and Bifidobacterium and inhibited the growth of Escherichia coli (E. coli) and Bacteroides (p < 0.05) in the intestinal tracts of aged mice. Metabolomic analysis identified glycolipid and amino acid metabolic pathway biomarkers associated with aging that were differentially regulated by DFC consumption. Correlation analysis between the identified microbial flora and the biomarkers revealed potential mechanistic links between altered microbial composition and metabolic activity with aging markers.CONCLUSIONS: In conclusion, this study revealed an important mechanism by which DFC consumption impacts healthspan and longevity, shedding light on optimizing dietary fiber or developing fiber-based interventions to improve human health.PMID:38575955 | DOI:10.1186/s12986-024-00787-y

BMC Plant Biol. 2024 Apr 5;24(1):245. doi: 10.1186/s12870-024-04918-8.ABSTRACTSeed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.PMID:38575879 | DOI:10.1186/s12870-024-04918-8