PubMed

Environ Pollut. 2023 Nov 17:122949. doi: 10.1016/j.envpol.2023.122949. Online ahead of print.ABSTRACTThe psychotropic drug flunitrazepam (FLZ) is frequently detected in aquatic environments, yet its neurotoxicity to aquatic organisms has not received sufficient attention. In this study, microbiome, metabolome, and genome analyses were conducted to study the effects of FLZ and its metabolite 7-aminoflunitrazepam (7-FLZ) on the zebrafish nervous system and understand their toxic mechanisms. The results demonstrated that drug exposure induced gut dysbiosis, decreased short-chain fatty acids and promoted the production of lipopolysaccharides (LPS). LPS entered the brain and interacted with Toll-like receptors to cause neuroinflammation by upregulating the expression of proinflammatory cytokines TNFα and NF-κB. The increased ratio of S-adenosylmethionine to S-adenosylhomocysteine in brain tissues indicated abnormal expression of Dnmt1 gene. Whole-genome bisulfite sequencing displayed an increase in differentially methylated regions (DMRs) associated-genes and pertinent biological pathways encompassed the MAPK signaling pathway, calcium signaling pathway, and Wnt signaling pathway. Correlation analysis confirmed connections between gut microbiota, their metabolites, inflammatory factors, and DNA methylation-related markers in brain tissue. These findings indicate that while the toxicity is somewhat reduced in metabolized products, both FLZ and 7-FLZ can induce DNA methylation in brain tissue and ultimately affect the biological function of the nervous system by disrupting gut microbiota and their metabolites.PMID:37981184 | DOI:10.1016/j.envpol.2023.122949

Sci Total Environ. 2023 Nov 17:168482. doi: 10.1016/j.scitotenv.2023.168482. Online ahead of print.ABSTRACTNanoplastics, as a new class of environmental pollutants, have been frequently detected in environmental media and organisms. Monopterus albus (M. albus) is an important economic aquatic product with a high dietary consumption. However, the potential biological effects of nanoplastics on M. albus remain unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) at different concentrations (0, 0.5, 1, 5 and 10 mg/L) on M. albus were investigated using an untargeted metabolomics approach. The results showed that 59, 44, 24, and 31 individual differential metabolites and 16, 9, 6, and 2 significant differential metabolic pathways were significantly changed in 0.5, 1, 5, and 10 mg/L respectively, indicating the greater effect of PS-NPs at the relatively low concentrations. After further analysis, there are four same significant differential metabolic pathways for the 0.5 and 1 mg/L groups, i.e., ABC transporters, cAMP signaling pathway, Neuroactive ligand-receptor interaction, and Synaptic vesicle cycle. In addition, there was one mutual differential metabolic pathway (Neuroactive ligand-receptor interaction) among the four groups, indicative of the probably universal nervous influence of nanoplastics on M. albus. In a word, the current work suggests that PS-NPs might affect the nervous systems of M. albus through disturbing their liver metabolism, and nanoplastics at relatively low concentrations may possess a greater effect, which provides significant information for assessing the toxic effect and exposure risk of nanoplastics to organisms in aquatic environment.PMID:37981139 | DOI:10.1016/j.scitotenv.2023.168482

J Ethnopharmacol. 2023 Nov 17:117437. doi: 10.1016/j.jep.2023.117437. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura & Migo (DEN) is a traditional medicine in China since Han dynasty. Decoction of its stem is often used in the treatment of Type-II diabetes (T2D), which is a typical metabolic disease accompanied with the impaired metabolic function of blood glucose and lipid.AIM OF THE STUDY: Our study aimed to investigate the role of gut microbiota in differentiating DEN from different sources and its related pathway in the alleviation of metabolic syndromes induced by T2D.MATERIALS AND METHODS: The aqueous extracts of four commercially available Dendrobium (DEN-1∼4) were prepared and screened through an in-vitro fermentation system. Based on their alterations in monosaccharide composition and short chain fatty acids (SCFA) formation during fermentation with db/db faecal fluid, one DEN extract was selected for further in vivo verification. The selected Dendrobium (DEN-4) was orally administered to db/db mice for 16 days once daily at the dosage of 200 mg/kg followed by evaluating its effect on blood glucose level, liver function and intestinal microenvironment including alterations of intestinal integrity and gut microbiota composition. In addition, liver metabolomics analysis was employed to reveal the related metabolic pathways.RESULTS: Different extent of SCFA formation and utilization of monosaccharides were observed for the extracts of four DEN from different sources with a negative correlation between SCFA level and the ratio of Utilized glucose/Utilized mannose observed in the in-vitro fermentation system with db/db faecal fluid. DEN-4 with the highest SCFA formation during the in-vitro fermentation was selected and exhibited significantly hypoglycaemic effect in db/db mice with the alleviation of hepatic steatosis and impaired lipid homeostasis. Further mechanistic studies revealed that orally administered DEN-4 could improve the intestinal integrity of db/db mice via elevating their tight junction protein (ZO-1 and Occludin) expression in the colon and improve the diversity of gut microbiota with enhanced formation of SCFA. Moreover, metabolomics and KEGG pathway analysis of liver tissues suggested that the alleviated metabolic syndrome in db/db mice by DEN-4 might possibly be achieved through activation of PPAR pathway.CONCLUSION: Our current study not only revealed the potential of gut microbiota in differentiating DEN from different sources, but also demonstrated that DEN exhibited its beneficial effect on the T2D induced metabolic syndrome possibly through enhancement of intestinal integrity and activation of PPAR pathway via gut-liver axis in db/db mice.PMID:37981116 | DOI:10.1016/j.jep.2023.117437

J Proteomics. 2023 Nov 17:105048. doi: 10.1016/j.jprot.2023.105048. Online ahead of print.ABSTRACTToxin metalloproteinases are the primary components responsible for various toxicities in jellyfish venom, and there is still no effective specific therapy for jellyfish stings. The comprehension of the pathogenic mechanisms underlying toxin metalloproteinases necessitates further refinement. In this study, we conducted a differential analysis of a dermatitis mouse model induced by jellyfish Nemopilema nomurai venom (NnNV) samples with varying levels of metalloproteinase activity. Through skin tissue proteomics and serum metabolomics, the predominant influence of toxin metalloproteinase activity on inflammatory response was revealed, and the signal pathway involved in its regulation was identified. In skin tissues, many membrane proteins were significantly down-regulated, which might cause tissue damage. The expression of pro-inflammatory factors was mainly regulated by PI3K-Akt signaling pathway. In serum, many fatty acid metabolites were significantly down-regulated, which might be the anti-inflammation feedback regulated by NF-κB p65 signaling pathway. These results reveal the dermatitis mechanism of toxin metalloproteinases and provide new therapeutic targets for further studies. SIGNIFICANCE: Omics is an important method to analyze the pathological mechanism and discover the key markers, which can reveal the pathological characteristics of jellyfish stings. Our research first analyzed the impact of toxin metalloproteinases on jellyfish sting dermatitis by skin proteomics and serum metabolomics. The present results suggest that inhibition of toxin metalloproteinases may be an effective treatment strategy, and provide new references for further jellyfish sting studies.PMID:37981009 | DOI:10.1016/j.jprot.2023.105048

Food Chem. 2023 Nov 10;438:137863. doi: 10.1016/j.foodchem.2023.137863. Online ahead of print.ABSTRACTUnripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.PMID:37980871 | DOI:10.1016/j.foodchem.2023.137863

Ultrason Sonochem. 2023 Nov 17;101:106698. doi: 10.1016/j.ultsonch.2023.106698. Online ahead of print.ABSTRACTIn this study, an efficient cholesterol-lowering strain of Lactiplantibacillus plantarum 54-1 was screened and its degradation molecular mechanism was investigated. Furthermore, a novel practical MRS medium for screening cholesterol-lowering lactic acid bacteria (LAB) was developed based on ultrasound treatment. L. plantarum 54-1 was found to have the highest ability to eliminate cholesterol (340.69 ± 5.87 µg/mL). According to SEM and the count of viable LAB results, the morphology of LAB in the cholesterol-containing medium developed in this experiment was close to the normal (full and smooth), and it can grow normally. Metabolomics revealed that L. plantarum 54-1 initially converted a portion of cholesterol to 7α-hydroxy-cholesterol and then to the key metabolite taurine, via the phosphotransferase system. These metabolites were further transformed into L-alanine, L-lysine, N6-Acetyl-L-lysine, (R)-b-aminoisobutyric acid, and 2-oxoarginine, through glycine, serine, and threonine metabolism, citrate cycle, D-arginine and D-ornithine metabolism, lysine degradation, and pyruvate metabolism pathways. Prokaryotic reference transcriptomics found that this may be mainly regulated by the bsh, phnE, ptsP, B0667_RS04545, and B0667_RSRS12300 genes, which was further validated by qPCR. Furthermore, molecular docking results demonstrated that 8 differential metabolites might bind to another portion of cholesterol via PI-PI conjugation and hydrophobic interactions and lower cholesterol via co-sedimentation. This study has strategic implications for developing probiotic powder food that lowers cholesterol.PMID:37980826 | DOI:10.1016/j.ultsonch.2023.106698

Poult Sci. 2023 Oct 19;103(1):103217. doi: 10.1016/j.psj.2023.103217. Online ahead of print.ABSTRACTThe concept of competitive exclusion is well established in poultry and different products are used to suppress the multiplication of enteric pathogens in the chicken intestinal tract. While the effect has been repeatedly confirmed, the specific principles of competitive exclusion are less clear. The aim of the study was to compare metabolites in the cecal digesta of differently colonized chickens. Metabolites in the cecal contents of chickens treated with a commercial competitive exclusion product or with an experimental product consisting of 23 gut anaerobes or in control untreated chickens were determined by mass spectrometry. Extensive differences in metabolite composition among the digesta of all 3 groups of chickens were recorded. Out of 1,706 detected compounds, 495 and 279 were differently abundant in the chicks treated with a commercial or experimental competitive exclusion product in comparison to the control group, respectively. Soyasaponins, betaine, carnitine, glutamate, tyramine, phenylacetaldehyde, or 3-methyladenine were more abundant in the digesta of control chicks while 4-oxododecanedioic acid, nucleotides, dipeptides, amino acids (except for glutamate), and vitamins were enriched in the digesta of chickens colonized by competitive exclusion products. Metabolites enriched in the digesta of control chicks can be classified as of plant feed origin released in the digesta by degradative activities of the chicken. Some of these molecules disappeared from the digesta of chicks colonized by complex microbiota due to them being metabolized. Instead, nucleotides, amino acids, and vitamins increased in the digesta of colonized chicks as a consequence of the additional digestive potential brought to the cecum by microbiota from competitive exclusion products. It is therefore possible to affect metabolite profiles in the chicken cecum by its colonization with selected bacterial species.PMID:37980752 | DOI:10.1016/j.psj.2023.103217

Poult Sci. 2023 Oct 20;103(1):103220. doi: 10.1016/j.psj.2023.103220. Online ahead of print.ABSTRACTThe eggshell color of avian species is an important trait that is predominantly determined by the pigments biliverdin and protoporphyrin. Various factors affect eggshell pigment deposition and coloration; however, the underlying mechanisms remain unclear. We analyzed the hepatic transcriptomes and metabolomes of Changshun green-shell hens laying dark green and light green eggs to investigate the potential role of the liver in regulating the intensity of the green eggshell color. In total, 350 differentially expressed genes and 211 differentially altered metabolites were identified. Gene set enrichment analysis revealed that the enriched pathways and Gene Ontology (GO) terms were mainly associated with energy, immunity, and nutrient metabolism. Metabolite set enrichment analysis revealed that the enriched pathways were mainly associated with amino acid, vitamin, bile acid, and lipid metabolism. Moreover, gene-metabolite interaction network analysis revealed 1 subnetwork. Most genes and metabolites in this subnetwork were determined to be related to melanin metabolism and transport. In conclusion, our results suggest that hepatic melanin metabolism and transport are critical for eggshell coloration. Six candidate genes (CDKN2B, DDC, PYCR1, ABCG5, SLC3A1, and P2RX2) and 7 candidate metabolites (serotonin, 5-hydroxyindoleacetic acid, ornithine, acetylcholine, L-tryptophan, D-ornithine, and ADP) were suggested to play important roles in this process. Meanwhile, this study suggests that changes in hepatic energy metabolism, immune status, antioxidation activity, nutrient availability, and bile acid synthesis can impair eggshell coloration.PMID:37980748 | DOI:10.1016/j.psj.2023.103220

J Alzheimers Dis. 2023 Nov 13. doi: 10.3233/JAD-230706. Online ahead of print.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease.OBJECTIVE: To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs.METHODS: High resolution 1H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the "preclinical" period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control.RESULTS: Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups.CONCLUSIONS: We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans.PMID:37980669 | DOI:10.3233/JAD-230706

Insights Imaging. 2023 Nov 19;14(1):197. doi: 10.1186/s13244-023-01530-6.ABSTRACTPURPOSE: To investigate the clinical value of radiomic analysis on [18F]FDG and [18F]FLT PET on the differentiation of [18F]FDG-avid benign and malignant pulmonary nodules (PNs).METHODS: Data of 113 patients with inconclusive PNs based on preoperative [18F]FDG PET/CT who underwent additional [18F]FLT PET/CT scans within a week were retrospectively analyzed in the present study. Three methods of analysis including visual analysis, radiomic analysis based on [18F]FDG PET/CT images alone, and radiomic analysis based on dual-tracer PET/CT images were evaluated for differential diagnostic value of benign and malignant PNs.RESULTS: A total of 678 radiomic features were extracted from volumes of interest (VOIs) of 123 PNs. Fourteen valuable features were thereafter selected. Based on a visual analysis of [18F]FDG PET/CT images, the diagnostic accuracy, sensitivity, and specificity were 61.6%, 90%, and 28.8%, respectively. For the test set, the area under the curve (AUC), sensitivity, and specificity of the radiomic models based on [18F]FDG PET/CT plus [18F]FLT signature were equal or better than radiomics based on [18F]FDG PET/CT only (0.838 vs 0.810, 0.778 vs 0.778, 0.750 vs 0.688, respectively).CONCLUSION: Radiomic analysis based on dual-tracer PET/CT images is clinically promising and feasible for the differentiation between benign and malignant PNs.CLINICAL RELEVANCE STATEMENT: Radiomic analysis will add differential diagnostic value of benign and malignant pulmonary nodules: a hybrid imaging study based on [18F]FDG and [18F]FLT PET/CT.KEY POINTS: • Radiomics brings new insights into the differentiation of benign and malignant pulmonary nodules beyond the naked eyes. • Dual-tracer imaging shows the biological behaviors of cancerous cells from different aspects. • Radiomics helps us get to the histological view in a non-invasive approach.PMID:37980611 | DOI:10.1186/s13244-023-01530-6

Cell Rep. 2023 Nov 18;42(12):113481. doi: 10.1016/j.celrep.2023.113481. Online ahead of print.ABSTRACTHydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H2S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer Escherichia coli to titrate H2S across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip is engineered to maintain H2S gas tension and enables visualization of co-culture in real time with confocal microscopy. Engineered strains colonize the chip and are metabolically active for 2 days, during which they produce H2S across a 16-fold range and induce changes in host gene expression and metabolism in an H2S-concentration-dependent manner. These results validate a platform for studying the mechanisms underlying microbe-host interactions by enabling experiments that are infeasible with current animal and in vitro models.PMID:37980564 | DOI:10.1016/j.celrep.2023.113481

Cell Rep. 2023 Nov 18;42(12):113434. doi: 10.1016/j.celrep.2023.113434. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) exhibits distinct molecular subtypes: classical/progenitor and basal-like/squamous. Our study aimed to identify genes contributing to the development of the basal-like/squamous subtype, known for its aggressiveness. Transcriptome analyses revealed consistent upregulation of SERPINB3 in basal-like/squamous PDAC, correlating with reduced patient survival. SERPINB3 transgene expression in PDAC cells enhanced in vitro invasion and promoted lung metastasis in a mouse PDAC xenograft model. Metabolome analyses unveiled a metabolic signature linked to both SERPINB3 and the basal-like/squamous subtype, characterized by heightened carnitine/acylcarnitine and amino acid metabolism, associated with poor prognosis in patients with PDAC and elevated cellular invasiveness. Further analysis uncovered that SERPINB3 inhibited the cysteine protease calpain, a key enzyme in the MYC degradation pathway, and drove basal-like/squamous subtype and associated metabolic reprogramming through MYC activation. Our findings indicate that the SERPINB3-MYC axis induces the basal-like/squamous subtype, proposing SERPINB3 as a potential diagnostic and therapeutic target for this variant.PMID:37980563 | DOI:10.1016/j.celrep.2023.113434

BMC Microbiol. 2023 Nov 18;23(1):355. doi: 10.1186/s12866-023-03092-5.ABSTRACTBACKGROUND: Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae), followed by antimicrobial screening against various bacterial and fungal strains.RESULTS: Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium, Fusarium, and Aspergillus. The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1-16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans.CONCLUSION: These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production of undiscovered compounds different from the antibiotics classes.PMID:37980505 | DOI:10.1186/s12866-023-03092-5

J Orthop Surg Res. 2023 Nov 18;18(1):876. doi: 10.1186/s13018-023-04335-x.ABSTRACTBACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) are a major source of osteoblast precursor cells and are directly involved in osteoporosis (OP) progression. Bromodomain-containing protein 4 (BRD4) is an important regulator for osteogenic differentiation. Therefore, its role and mechanism in osteogenic differentiation process deserve further investigation.METHODS: hBMSCs osteogenic differentiation was evaluated by flow cytometry, alkaline phosphatase assay and alizarin red staining. Western blot was used to test osteogenic differentiation-related proteins, BRD4 protein, WNT family members-4 (WNT4)/NF-κB-related proteins, and glycolysis-related proteins. Metabolomics techniques were used to detect metabolite changes and metabolic pathways. BRD4 and WNT4 mRNA levels were determined using quantitative real-time PCR. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect BRD4 and WNT4 interaction. Glycolysis ability was assessed by testing glucose uptake, lactic acid production, and ATP levels.RESULTS: After successful induction of osteogenic differentiation, the expression of BRD4 was increased significantly. BRD4 knockdown inhibited hBMSCs osteogenic differentiation. Metabolomics analysis showed that BRD4 expression was related to glucose metabolism in osteogenic differentiation. Moreover, BRD4 could directly bind to the promoter of the WNT4 gene. Further experiments confirmed that recombinant WNT4 reversed the inhibition effect of BRD4 knockdown on glycolysis, and NF-κB inhibitors (Bardoxolone Methyl) overturned the suppressive effect of BRD4 knockdown on hBMSCs osteogenic differentiation.CONCLUSION: BRD4 promoted hBMSCs osteogenic differentiation by inhibiting NF-κB pathway via enhancing WNT4 expression.PMID:37980502 | DOI:10.1186/s13018-023-04335-x

ISME J. 2023 Nov 18. doi: 10.1038/s41396-023-01549-z. Online ahead of print.ABSTRACTVector-borne pathogens frequently modify traits of their primary hosts and vectors in ways that influence disease transmission. Such effects can themselves be altered by the presence of other microbial symbionts, yet we currently have limited understanding of these interactions. Here we show that effects of pea enation mosaic virus (PEMV) on interactions between host plants and aphid vectors are modulated by the presence of different aphid endosymbionts. In a series of laboratory assays, we found strong interactive effects of virus infection and endosymbionts on aphid metabolomic profiles, population growth, behavior, and virus transmission during aphid feeding. Furthermore, the strongest effects-and those predicted to favor virus transmission-were most apparent in aphid lines harboring particular endosymbionts. These findings show that virus effects on host-vector interactions can be strongly influenced by other microbial symbionts and suggest a potentially important role for such interactions in disease ecology and evolution.PMID:37980433 | DOI:10.1038/s41396-023-01549-z

Nat Commun. 2023 Nov 18;14(1):7495. doi: 10.1038/s41467-023-43298-9.ABSTRACTTrapped ion mobility spectrometry (TIMS) adds an additional separation dimension to mass spectrometry (MS) imaging, however, the lack of fragmentation spectra (MS2) impedes confident compound annotation in spatial metabolomics. Here, we describe spatial ion mobility-scheduled exhaustive fragmentation (SIMSEF), a dataset-dependent acquisition strategy that augments TIMS-MS imaging datasets with MS2 spectra. The fragmentation experiments are systematically distributed across the sample and scheduled for multiple collision energies per precursor ion. Extendable data processing and evaluation workflows are implemented into the open source software MZmine. The workflow and annotation capabilities are demonstrated on rat brain tissue thin sections, measured by matrix-assisted laser desorption/ionisation (MALDI)-TIMS-MS, where SIMSEF enables on-tissue compound annotation through spectral library matching and rule-based lipid annotation within MZmine and maps the (un)known chemical space by molecular networking. The SIMSEF algorithm and data analysis pipelines are open source and modular to provide a community resource.PMID:37980348 | DOI:10.1038/s41467-023-43298-9

J Environ Sci (China). 2024 Mar;137:604-614. doi: 10.1016/j.jes.2023.02.018. Epub 2023 Feb 21.ABSTRACTMicroplastics (MPs) have become a significant concern for their potential toxicity. However, the correlation between the size of plastic particles and their toxicity remains inconclusive. Here, we investigate the toxic effects of different sizes (80 nm, 800 nm, 8 µm and 80 µm) polystyrene MPs (PS-MPs) on the model organism Nile tilapia (Oreochromis niloticus). The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body. H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group. EdU labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group. The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group. The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group. In conclusion, this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity. All the above lay the foundation for further study on the pathological damage of MPs to other organisms.PMID:37980043 | DOI:10.1016/j.jes.2023.02.018

J Environ Sci (China). 2024 Mar;137:120-130. doi: 10.1016/j.jes.2023.02.011. Epub 2023 Feb 15.ABSTRACTSeveral studies have confirmed that the health status of the paternal affects the health of the offspring, however, it remains unknown whether paternal exposure to pesticides affect the offspring health. Here, we used untargeted metabolomics and 16S rRNA sequencing technology, combined with tail suspension test and RT-qPCR to explore the effects of paternal exposure to nitenpyram on the neurotoxicity of offspring. Our results found that the paternal exposure to nitenpyram led to the offspring's depressive-like behaviors, accompanied by the reduction of tryptophan content and the disorder of microbial abundance in the gut of the offspring. Further, we determined the expression of tryptophan metabolism-related genes tryptophanase (tnaA) and tryptophan hydroxylase 1 (TpH1) in gut bacteria and colonic tissues. We found that tryptophan is metabolized to indoles rather than being absorbed into colonocytes, which coursed the reduce of tryptophan availability after nitenpyram exposure. In conclusion, our study deepens our understanding of the intergenerational toxic effects of pesticides.PMID:37980001 | DOI:10.1016/j.jes.2023.02.011

Free Radic Biol Med. 2023 Nov 16:S0891-5849(23)01101-2. doi: 10.1016/j.freeradbiomed.2023.11.008. Online ahead of print.ABSTRACTOBJECTIVE: Pulmonary hypertension (PH) is a progressive disease with vascular remodeling as a critical structural alteration. We have previously shown that metabolic reprogramming is an early initiating mechanism in animal models of PH. This metabolic dysregulation has been linked to remodeling the mitochondrial network to favor fission. However, whether the mitochondrial fission/fusion balance underlies the metabolic reprogramming found early in PH development is unknown.METHODS: Utilizing a rat early model of PH, in conjunction with cultured pulmonary endothelial cells (PECs), we utilized metabolic flux assays, Seahorse Bioassays, measurements of electron transport chain (ETC) complex activity, fluorescent microscopy, and molecular approaches to investigate the link between the disruption of mitochondrial dynamics and the early metabolic changes that occur in PH.RESULTS: We observed increased fusion mediators, including Mfn1, Mfn2, and Opa1, and unchanged fission mediators, including Drp1 and Fis1, in a two-week monocrotaline-induced PH animal model (early-stage PH). We were able to establish a connection between increases in fusion mediator Mfn1 and metabolic reprogramming. Using an adenoviral expression system to enhance Mfn1 levels in pulmonary endothelial cells and utilizing 13C-glucose labeled substrate, we found increased production of 13C lactate and decreased TCA cycle metabolites, revealing a Warburg phenotype. The use of a 13C5-glutamine substrate showed evidence that hyperfusion also induces oxidative carboxylation. The increase in glycolysis was linked to increased hypoxia-inducible factor 1α (HIF-1α) protein levels secondary to the disruption of cellular bioenergetics and higher levels of mitochondrial reactive oxygen species (mt-ROS). The elevation in mt-ROS correlated with attenuated ETC complexes I and III activities. Utilizing a mitochondrial-targeted antioxidant to suppress mt-ROS, limited HIF-1α protein levels, which reduced cellular glycolysis and reestablished mitochondrial membrane potential.CONCLUSIONS: Our data connects mitochondrial fusion-mediated mt-ROS to the Warburg phenotype in early-stage PH development.PMID:37979892 | DOI:10.1016/j.freeradbiomed.2023.11.008

Life Sci. 2023 Nov 16:122274. doi: 10.1016/j.lfs.2023.122274. Online ahead of print.ABSTRACTAIMS: Extra virgin olive oil (EVOO) is the highest quality olive oil available and has been shown to regulate postprandial blood glucose in patients with type 1 diabetes (T1D). However, it remains uncertain whether EVOO can prevent the onset of T1D. In this study, we investigated the potential preventive effect of orally administered EVOO on T1D in non-obese diabetic (NOD) mice.MAIN METHODS: We analyzed changes in fecal microbes using 16 s rDNA sequencing and serum metabolites using Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Mass Spectrometry (Q-TOF-MS).KEY FINDINGS: Our findings showed that EVOO supplementation in NOD mice slowed gastric emptying, reduced insulitis, and delayed T1D onset. Moreover, EVOO altered the composition of fecal microbes, increasing the Bacteroidetes/Firmicutes ratio, and promoting the growth of short-chain fatty acids (SCFAs)-producing bacteria, such as Lachnoclostridium and Ruminococcaceae_UCG-005. Moreover, it also increased beneficial serum metabolites, including unsaturated fatty acid and triterpenoid, which positively correlated with the increased SCFA-producing bacteria and negatively correlated with the disease indicators. Conversely, most decreased serum lipid metabolites, such as Oleamide, showed the opposite trend.SIGNIFICANCE: Our study demonstrates that EVOO may ameliorate pancreas inflammation and prevent T1D onset in NOD mice by modulating gut microbiota and serum metabolites.PMID:37979832 | DOI:10.1016/j.lfs.2023.122274