PubMed

Front Plant Sci. 2022 Dec 16;13:1075231. doi: 10.3389/fpls.2022.1075231. eCollection 2022.ABSTRACTThe present study aims to evaluate the response of the three Mediterranean local grapevines 'Garnacha Blanca', 'Garnacha Tinta', and 'Macabeo' to treatments with biocontrol products, namely a botanical extract (Akivi, Dittrichia viscosa extract) and a beneficial microorganism (Bacillus UdG, Bacillus velezensis). A combination of transcriptomics and metabolomics approaches were chosen in order to study grapevine gene expression and to identify gene marker candidates, as well as, to determine differentially concentrated grapevine metabolites in response to biocontrol product treatments. Grapevine plants were cultivated in greenhouse under controlled conditions and submitted to the treatments. Thereafter, leaves were sampled 24h after treatment to carry out the gene expression study by RT-qPCR for the three cultivars and by RNA-sequencing for 'Garnacha Blanca'. Differentially expressed genes (DEGs) were investigated for both treatments and highly influenced DEGs were selected to be tested in the three cultivars as treatment gene markers. In addition, the extraction of leaf components was performed to quantify metabolites, such as phytohormones, organic acids, and phenols. Considering the upregulated and downregulated genes and the enhanced metabolites concentrations, the treatments had an effect on jasmonic acid, ethylene, and phenylpropanoids defense pathways. In addition, several DEG markers were identified presenting a stable overexpression after the treatments in the three grapevine cultivars. These gene markers could be used to monitor the activity of the products in field treatments. Further research will be necessary to confirm these primary results under field conditions.PMID:36589113 | PMC:PMC9803176 | DOI:10.3389/fpls.2022.1075231

Front Plant Sci. 2022 Dec 14;13:1014396. doi: 10.3389/fpls.2022.1014396. eCollection 2022.ABSTRACTUniconazole, a triazole plant growth regulator, is widely used to regulate plant height and prevent the overgrowth of seedlings. However, the underlying molecular mechanism of uniconazole in inhibiting the hypocotyl elongation of seedlings is still largely unclear, and there has been little research on the integration of transcriptomic and metabolomic data to investigate the mechanisms of hypocotyl elonga-tion. Herein we observed that the hypocotyl elongation of flowering Chinese cabbage seedings was significantly inhibited by uniconazole. Interestingly, based on combined transcriptome and metabolome analyses, we found that the "phenylpropanoid biosynthesis" pathway was significantly affected by uniconazole. In this pathway, only one member of the portal enzyme gene family, named BrPAL4, was remarkably downregulated, which was related to lignin biosynthesis. Furthermore, the yeast one-hybrid and dual-luciferase assays showed that BrbZIP39 could directly bind to the promoter region of BrPAL4 and activate its transcript. The virus-induced gene silencing system further demonstrated that BrbZIP39 could positively regulate hypocotyl elongation and the lignin biosynthesis of hypocotyl. Our findings provide a novel insight into the molecular regulatory mechanism of uniconazole inhibiting hypocotyl elongation in flowering Chinese cabbage and confirm, for the first time, that uniconazole decreases lignin content through repressing the BrbZIP39-BrPAL4 module-mediated phenylpropanoid biosynthesis, which leads to the hypocotyl dwarfing of flowering Chinese cabbage seedlings.PMID:36589099 | PMC:PMC9794620 | DOI:10.3389/fpls.2022.1014396

Front Plant Sci. 2022 Dec 16;13:1065049. doi: 10.3389/fpls.2022.1065049. eCollection 2022.ABSTRACTPeanut testa (seed coat) contains large amounts of flavonoids that significantly influence seed color, taste, and nutritional qualities. There are various colors of peanut testa, however, their precise flavonoid components and regulatory mechanism of pigmentation remain unclear. In this study, a total of 133 flavonoids were identified and absolutely quantified in the seed coat of four peanut cultivars with different testa color using a widely targeted metabolomic approach. Black peanut skin had more types and substantial higher levels of cyanidin-based anthocyanins, which possibly contribute to its testa coloration. Procyanidins and flavan-3-ols were the major co-pigmented flavonoids in the red, spot and black peanuts, while flavanols were the most abundant constitutes in white cultivar. Although the concentrations as well as composition characteristics varied, the content ratios of procyanidins to flavan-3-ols were similar in all samples except for white peanut. Furthermore, MYB-like transcription factors, anthocyanidin reductases (ANR), and UDP-glycosyltransferases (UGT) were found to be candidate genes involved in testa pigmentation via RNA-seq and weighted gene co-expression network analysis. It is proposed that UGTs and ANR compete for the substrate cyanidin and the prevalence of UGTs activities over ANR one will determine the color pattern of peanut testa. Our results provide a comprehensive report examining the absolute abundance of flavonoid profiles in peanut seed coat, and the finding are expected to be useful for further understanding of regulation mechanisms of seed coat pigmentation in peanut and other crops.PMID:36589085 | PMC:PMC9800836 | DOI:10.3389/fpls.2022.1065049

Front Plant Sci. 2022 Dec 15;13:1101199. doi: 10.3389/fpls.2022.1101199. eCollection 2022.ABSTRACTAs a stem variety of lettuce, the fleshy stem is the main product organ of stem lettuce. The molecular mechanism of fleshy stem expansion in stem lettuce is a complex biological process. In the study, the material accumulation, gene expression, and morphogenesis during fleshy stem expansion process were analyzed by the comparative analysis of metabolome, transcriptome and the anatomical studies. The anatomical studies showed that the occurrence and activity of vascular cambium mainly led to the development of fleshy stems; and the volume of pith cells gradually increased and arranged tightly during the expansion process. A total of 822 differential metabolites and 9,383 differentially expressed genes (DEGs) were identified by the metabolomics and transcriptomics analyses, respectively. These changes significantly enriched in sugar synthesis, glycolysis, and plant hormone anabolism. The expression profiles of genes in the sugar metabolic pathway gradually increased in fleshy stem expansion process. But the sucrose content was the highest in the early stage of fleshy stem expansion, other sugars such as fructose and glucose content increased during fleshy stem expansion process. Plant hormones, including IAA, GA, CTK, and JA, depicted important roles at different stem expansion stages. A total of 1,805 DEGs were identified as transcription factors, such as MYB, bHLH, and bZIP, indicating that these transcription factor families might regulate the fleshy stems expansion in lettuce. In addition, the expression patterns identified by qRT-PCR were consistent with the expression abundance identified by the transcriptome data. The important genes and metabolites identified in the lettuce fleshy stem expansion process will provide important information for the further molecular mechanism study of lettuce fleshy stem growth and development.PMID:36589074 | PMC:PMC9798005 | DOI:10.3389/fpls.2022.1101199

Front Pharmacol. 2022 Dec 14;13:1040544. doi: 10.3389/fphar.2022.1040544. eCollection 2022.ABSTRACTThe alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, including testicular protection. The current study looked into the protective effects of ICA in preventing CP-induced spermatogenesis dysfunction. The current study looked into the role of ICA in preventing testicular dysfunction caused by CP. For 5 days, healthy adult mice were given saline or a single dose of CP (50 mg/kg) intraperitoneally (i.p). For the next 30 days, mice were given ICA (80 mg/kg) by gavage. Animals were euthanized 12 h after receiving ICA, and testes were removed for biochemical, histopathological, sperm evaluation, and transmission electron microscope analysis (TEM). We also investigated the potential biological effects of ICA on CP-induced spermatogenesis dysfunction in mice using an integrated proteomic and metabolomic approach. The levels of 8309 proteins and 600 metabolites were measured. The majority of the differential proteins and metabolites were found to be enriched in a variety of metabolic pathways, including the PI3K-Akt signaling pathway, necroptosis, the mTOR signaling pathway, glycerophospholipid metabolism, and ABC transporters, implying that ICA may have molecular mechanisms that contribute to CP-induced spermatogenesis dysfunction in the testis. Taken together, these findings show that ICA effectively reduces testis injury, implying that ICA may have a role in male infertility preservation.PMID:36588705 | PMC:PMC9794755 | DOI:10.3389/fphar.2022.1040544

Food Chem (Oxf). 2022 Dec 13;6:100157. doi: 10.1016/j.fochms.2022.100157. eCollection 2023 Jul 30.ABSTRACTThe objective of this study was to characterize the microbiota biodiversity of Uruçú-Amarela honey through metagenomics. Furthermore, the impact of maturation temperatures (20 and 30 °C) and time (0-180 days) on the physicochemical and antioxidant properties was investigated. 1H NMR was performed to verify metabolites formed during maturation. Uruçú-Amarela honey was mainly composed by lactic acid bacteria and osmophilic yeasts of genus Zygosaccharomyces. Maturation at 30 °C led to a higher fermentation activity, resulting in greater carbohydrate consumption, ethanol formation (0.0-0.6 %) and increased acidity (34.78-45.74 meq/kg) over the 180 days. It also resulted in honey with higher brown color (a* 0.7 to 3.89, b* 17.50-25.29) and antioxidant capacity, corroborating that the maturation is a suitable preservation technique for stingless bee honey, because it does not cause negative changes as it extends the shelf life of the stingless bee honey.PMID:36588603 | PMC:PMC9794890 | DOI:10.1016/j.fochms.2022.100157

J Anim Sci. 2023 Jan 2:skac427. doi: 10.1093/jas/skac427. Online ahead of print.ABSTRACTLiver abscesses in feedlot cattle are a polymicrobial infection with Fusobacterium necrophorum and Trueperella pyogenes as the primary and secondary etiologic agents, respectively. Cattle with liver abscesses do not exhibit clinical signs and the abscesses are detected only at slaughter. The objective was to conduct metabolomics analysis of purulent materials of liver abscesses to identify biochemicals. Liver abscesses from crossbred cattle (n=24) and Holstein steers (n=24), each fed high-grain finishing diet with tylosin (n=12) or no tylosin (n=12) were included in the study. Abscess purulent materials were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy. A total of 759 biochemicals were identified and were broadly categorized into carbohydrates, energy metabolism pathways intermediates, peptides, amino acids and their metabolites, lipids and their metabolites, nucleotides, vitamins and cofactors, xenobiotics, and partially characterized molecules. The top 50 biochemicals identified included amino acids, lipids, nucleotides, xenobiotics, peptides and carbohydrates and their metabolites. Among the 15 amino acid metabolites in the top-50 biochemicals, four were tryptophan metabolites, indoleacrylate, indolepropionate, tryptamine, and anthranilate. The 3-phenylpropionate, a product of phenylalanine metabolism, was the predominant metabolite in purulent materials. Between the four treatment groups, a two-way ANOVA analysis identified biochemicals that exhibited significant main effects for cattle type and in-feed tylosin use and their interactions. A total of 59 and 85 biochemicals were different (P < 0.05) between the cattle type (crossbred vs. Holstein steers) and in-feed tylosin use (tylosin vs. no tylosin), respectively. Succinate, an intermediate of lactate fermentation by some bacterial species, was one of the top 30 biochemicals that differentiated the four treatment groups. A number of lysophospholipids, indicative of bacterial and host cell membrane lyses, were identified in the purulent materials. In conclusion, to our knowledge this is the first report on the metabolome of liver abscess purulent materials and several biochemicals identified were related to metabolic activities of the bacterial community, particularly F. necrophorum and T. pyogenes. Biochemicals unique to liver abscesses that appear in the blood may serve as biomarkers and be of diagnostic value to detect liver abscesses of cattle before slaughter.PMID:36588460 | DOI:10.1093/jas/skac427

Mol Plant. 2022 Dec 31:S1674-2052(22)00476-2. doi: 10.1016/j.molp.2022.12.022. Online ahead of print.ABSTRACTKiwifruit is a recently domesticated horticultural fruit crop with substantial economic and nutritional value, especially for the high content of vitamin C in fruit. Here, we de novo assembled two telomere-to-telomere kiwifruit genomes of A. chinensis var 'Donghong' (DH) and A. latifolia (KY), with total lengths of 608,327,852 bp and 640,561,626 bp for 29 chromosomes respectively. With burst of structural variants involving inversion, translocations and duplications within 8.39 million years, metabolite content of DH and KY exhibited differences including saccharides, lignans and vitamins. A regulatory ERF098 transcription factor family has expanded in KY and Actinidia. eriantha, both with ultra-high vitamin C content. With each assembly been phased into two complete haplotypes, we identified allelic variations between two sets of haplotypes, leading to protein sequence variations of 26,494 and 27,773 gene loci and allele specific expression (ASE) of 4,687 and 12,238 homozygous gene pairs. Synchronized metabolome and transcriptome changes during DH fruit development indicated the same dynamic patterns in expression and metabolite content levels, including free fatty acids and flavonols accumulated in the early stages, while sugar substances and amino acids in the late stages. An allele dominance AcSWEET9b gene was identified to positively correlate with high sucrose content in fruit. Compared to wild varieties and other Actinidia species, AcSWEET9b promoters were selected in red-flesh kiwifruits, facilitating the boost of fruit sucrose content, which probably explained why red-flesh kiwifruits are sweeter. These two gap-free kiwifruit genomes provide a valuable genetic basis for investigating mechanisms of domestication, opening up genome-based breeding era for kiwifruit.PMID:36588343 | DOI:10.1016/j.molp.2022.12.022

RNA Biol. 2023 Jan;20(1):186-197. doi: 10.1080/15476286.2023.2204586.ABSTRACTHere, we provide an in-depth analysis of the usefulness of single-sample metabolite/RNA extraction for multi-'omics readout. Using pulverized frozen livers of mice injected with lymphocytic choriomeningitis virus (LCMV) or vehicle (Veh), we isolated RNA prior (RNA) or following metabolite extraction (MetRNA). RNA sequencing (RNAseq) data were evaluated for differential expression analysis and dispersion, and differential metabolite abundance was determined. Both RNA and MetRNA clustered together by principal component analysis, indicating that inter-individual differences were the largest source of variance. Over 85% of LCMV versus Veh differentially expressed genes were shared between extraction methods, with the remaining 15% evenly and randomly divided between groups. Differentially expressed genes unique to the extraction method were attributed to randomness around the 0.05 FDR cut-off and stochastic changes in variance and mean expression. In addition, analysis using the mean absolute difference showed no difference in the dispersion of transcripts between extraction methods. Altogether, our data show that prior metabolite extraction preserves RNAseq data quality, which enables us to confidently perform integrated pathway enrichment analysis on metabolomics and RNAseq data from a single sample. This analysis revealed pyrimidine metabolism as the most LCMV-impacted pathway. Combined analysis of genes and metabolites in the pathway exposed a pattern in the degradation of pyrimidine nucleotides leading to uracil generation. In support of this, uracil was among the most differentially abundant metabolites in serum upon LCMV infection. Our data suggest that hepatic uracil export is a novel phenotypic feature of acute infection and highlight the usefulness of our integrated single-sample multi-'omics approach.PMID:37095747 | DOI:10.1080/15476286.2023.2204586

Best Pract Res Clin Gastroenterol. 2023 Feb-Mar;62-63:101830. doi: 10.1016/j.bpg.2023.101830. Epub 2023 Mar 16.ABSTRACTLifestyle modification is the primary intervention to control NAFLD progression, but despite evidence-based effectiveness it is difficult to distinguish the benefits of nutrition from physical activity and the optimal diet composition is not established. Macronutrients as saturated fatty acids, sugars and animal proteins are harmful in NAFLD and the Mediterranean Diet reducing sugar, red meat and refined carbohydrates and increasing unsaturated-fatty-acids was reported to be beneficial. However one size cannot fit all since NAFLD is a multifaceted syndrome encompassing many diseases of unknown etiologies, different clinical severity and outcomes. Studies of the intestinal metagenome, provided new insights into the physio-pathological interplay between intestinal microbiota and NAFLD. How much the microbiota heterogeneity can influence response to diet remains unknown. New knowledge indicates that AI guided personalized nutrition based on clinic-pathologic and genetic data combined with pre/post nutritional intervention gut metagenomics/metabolomics will be part of the future management of NAFLD.PMID:37094914 | DOI:10.1016/j.bpg.2023.101830

Methods Enzymol. 2023;683:153-170. doi: 10.1016/bs.mie.2022.08.039. Epub 2022 Nov 11.ABSTRACTMulti-omics has gained momentum over the past few years especially in plant single cell-type analysis as they aim to understand cellular molecular networks across different levels of genetic information flow. For multi-omics sample preparation, molecular extractions performed non-simultaneously create rooms for variation, inaccurate data, waste of limited samples, resources and labor. Here we optimized a protocol for 3-in-1 simultaneous extraction of RNA, metabolites, and proteins from the same single cell-type sample. We adapted a commercially available RNA kit with a few modifications to obtain high quality starting materials for sequencing and LC-MS/MS-based metabolomics and proteomics. RNAs are bound to the column, metabolites were extracted in a polar solvent and proteins are precipitated using acetone. This creates an all-in-one workflow using a standard RNA kit. Little training is required to carry out this protocol as it is simple and easy to use. It may be used with a wide range of plant species and different amounts of starting materials, including single cells.PMID:37087185 | DOI:10.1016/bs.mie.2022.08.039

Clin Transl Med. 2023 Jan;13(1):e1152. doi: 10.1002/ctm2.1152.ABSTRACTBACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide.METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed.RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point.CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.PMID:36588088 | DOI:10.1002/ctm2.1152

Fish Shellfish Immunol. 2022 Dec 29:108512. doi: 10.1016/j.fsi.2022.108512. Online ahead of print.ABSTRACTAs a pathogen of cultured teleosts, Pseudomonas plecoglossicida has caused significant economic losses. flgC plays an important role in encoding flagellar basal-body rod proteins. Our previous studies revealed the high expression of P. plecoglossicida flgC in infected Epinephelus coioides. To explore the role of flgC in the virulence of P. plecoglossicida and the immune response of E. coioides to the infection of P. plecoglossicida, flgC gene of P. plecoglossicida was knocked down by RNA interference (RNAi). The results showed that the flgC gene in all four mutants of P. plecoglossicida was significantly knocked down, and the mutant with the best knockdown efficiency of 94.3% was selected for subsequent studies. Compared with the NZBD9 strain of P. plecoglossicida, the flgC-RNAi strain showed a significantly decrease in chemotaxis, motility, adhesion, and biofilm formation. Furthermore, compared with the E. coioides infected with the NZBD9 strain, the infection of flgC-RNAi strain resulted in the infected E. coioides a 1.5-day delay in the time of first death and an 80% increase in survival rate, far fewer white nodules upon the spleen surfaces, and lower pathogen load in the spleens. RNAi of flgC significantly influenced the metabolome and transcriptome of the spleen in infected E. coioides. KEGG enrichment analysis exhibited that the Toll-like receptor signaling pathway was the most enriched immune pathway; the most significantly enriched metabolic pathways were associated with Linoleic acid metabolism, Choline metabolism in cancer, and Glycerophospholipid metabolism. Further combined analysis of transcriptome and metabolome indicated significant correlations among pantothenate and CoA biosynthesis, beta-alanine metabolism, lysosome metabolites, and related genes. These results suggested that flgC was a pathogenic gene of P. plecoglossicida; flgC was associated with the regulation of chemotaxis, motility, biofilm formation, and adhesion; flgC influenced the immune response of E. coioides to the infection of P. plecoglossicida.PMID:36587883 | DOI:10.1016/j.fsi.2022.108512

J Ethnopharmacol. 2022 Dec 29:116109. doi: 10.1016/j.jep.2022.116109. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Qifu decoction (QFD) is a famous traditional Chinese medicine (TCM) composed of Astragali Radix (HuangQi) and Aconiti Lateralis Radix Praeparaia (Fuzi), which can alleviate doxorubicin (DOX)-induced cardiotoxicity (DIC). However, its protective mechanism remains obscured.AIM OF THE STUDY: The present study aimed to uncover the cardioprotective mechanism and the synergistic effect of QFD against DIC in mice.MATERIALS AND METHODS: The cardioprotective activity of QFD against DIC was assessed by electrocardiogram, serum biochemical assays and histopathology. Mass spectrometry-based metabolomic approach was conducted to elucidate the preventive mechanisms of QFD, HuangQi decoction (HQD), and Fuzi decoction (FZD) against DIC. QFD, HQD, FZD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of QFD by computational systems analysis. Quantitative real-time PCR (qRT-PCR) was further employed to validate the key metabolic pathways at the level of the gene.RESULTS: The electrocardiogram combined with the biochemical analysis and histopathology showed that the protection effects were sorted as QFD > HQD ≈ FZD. A total of 41 metabolites contributing to DIC were identified in the mice serum, among which 32, 12 and 10 metabolites were significantly reverted by QFD, HQD and FZD, respectively. Metabolic pathway analysis revealed that DOX perturbed 12 metabolic pathways, and QFD, HQD, and FZD-treated groups could significantly reverse 12, 7 and 6 metabolic pathways of these 12 metabolic pathways. Metabolic pathway and qRT-PCR revealed that QFD could protect DIC mainly by regulating energy metabolism, amino acids metabolism, arachidonic acid metabolism and glycerophospholipid metabolism, and HQD and FZD mutually reinforced each other.CONCLUSION: These evidences revealed that QFD was a promising drug candidate for DIC by maintaining metabolic homeostasis. Meanwhile, this work provided a useful approach for evaluating the efficacy and the synergistic effects of TCMs against cardiomyopathy.PMID:36587877 | DOI:10.1016/j.jep.2022.116109

J Ethnopharmacol. 2022 Dec 29:116092. doi: 10.1016/j.jep.2022.116092. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated.AIM OF THE STUDY: To investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology.MATERIALS AND METHODS: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds.RESULTS: In MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3-O-glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment.CONCLUSION: DZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis.PMID:36587875 | DOI:10.1016/j.jep.2022.116092

Sci Total Environ. 2022 Dec 29:161272. doi: 10.1016/j.scitotenv.2022.161272. Online ahead of print.ABSTRACTBlood pressure medications are used to treat hypertension. However, low concentrations of beta-blockers in water systems can negatively impact aquatic wildlife. Here, we conducted a metabolic and behavioral study investigating atenolol, a beta-blocker frequently detected in global wastewater systems. The objectives were to determine the effects of low-level atenolol exposure on early stages of zebrafish. We measured survival, deformities, heartbeat, mitochondrial function, lipid and amino acid profiles, and locomotor activity to discern mechanisms of metabolic disruption. We hypothesized that atenolol disrupts lipid metabolism, which would negatively impact locomotor activity. Atenolol showed no overt toxicity to larval zebrafish up to 10 μg/L and deformities were infrequent (<5 %), and included cardiac edema and larvae with kinked tails. A hatch delay was observed at 2-day post-fertilization (dpf) for fish exposed to >5 μg/L atenolol. Heart rates were reduced in 2 and 3 dpf in fish treated with >500 ng/L atenolol. There was no change in oxygen consumption rates (basal and maximum respiration) of embryos when exposed to a range of atenolol concentrations, suggesting mitochondrial respiration was intact. Oil red staining for lipid content in larvae showed a global reduction in lipids with 10 μg/L exposure, prompting deeper investigation into the lipid profiles. Lipidomics quantified 86 lipids and revealed reduced abundance in Ceramide 18: 1 16:0 (Cer_NS d18:1_16:0), Ether linked Phosphatidylethanolamine 16:0 22:6 (EtherPE 16:0e_22:6), and Ether linked Phosphatidylcholine 16:0 22:6 (EtherPC 16:0e_22:6). We also quantified 12 amino acids and observed a subtle dose-dependent reduction in the levels of L-Histidine. Exposure to atenolol did not impact larval locomotor activity based on a Visual Motor Response test. Taken together, atenolol at environmentally relevant levels decreased heart rate of developing zebrafish and altered lipid content. As such, exposure to beta-blockers like atenolol may have negative consequences for developmental trajectories and growth of aquatic species.PMID:36587689 | DOI:10.1016/j.scitotenv.2022.161272

Sci Total Environ. 2022 Dec 29:161261. doi: 10.1016/j.scitotenv.2022.161261. Online ahead of print.ABSTRACTPerfluorobutanesulfonate (PFBS), an alternative to perfluorooctanesulfonate (PFOS), has raised many health concerns. However, PFBS toxicity in the mammalian gut remains unclear. C57BL/6 mice were exposed to 10 μg/L and 500 μg/L PFBS or 500 μg/L PFOS in their water supply for 28 days. PFBS toxicity in the ileum and colon was explored and compared to that of PFOS. Biochemical analysis showed that and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels increased in the ileum exposed to 10 μg/L PFBS, whereas no significant changes were observed in those levels in the colon. Catalase (CAT) activity, malondialdehyde (MDA), TNF-α, and IL-1β levels increased and glutathione (GSH) levels decreased in the ileum of the 500 μg/L-PFBS group, whereas only MDA levels increased in the colon of the 500 μg/L-PFBS group. The results showed that more severe damage occurred in the ileum than in the colon after PFBS exposure, and these align with the 500 μg/L-PFOS group exposure as well. Furthermore, metabolomic analysis revealed glutathione metabolism as a vital factor in inducing PFBS and PFOS toxicities in the ileum. Steroid hormone and amino acid metabolisms were other important factors involved in PFBS and PFOS toxicities, respectively. In the colon, GSH, pyrimidine, and glucose (especially galactose) metabolism was the main contributor to PFBS toxicity, and sulfur amino acid metabolism was the main pathway for PFOS toxicity. This study provides more evidence of the health hazards due to low-dose PFBS exposure in the mammalian gut.PMID:36587682 | DOI:10.1016/j.scitotenv.2022.161261

J Hazard Mater. 2022 Dec 23;446:130659. doi: 10.1016/j.jhazmat.2022.130659. Online ahead of print.ABSTRACTThis study aimed to investigate the relationship among chronic exposure to a low concentration of organochlorine pesticides (OCPs), high-fat diet (HFD)-induced obesity, and caloric restriction in type 2 diabetes (T2D). Thus, female zebrafish were divided into four groups and treated for 12 weeks as follows: (i) negative control, (ii) HFD (obesity) control, (iii) obesity + a mixture of OCPs (OP), and (iv) obesity + a mixture of OCPs + caloric restriction (OPR). We then assessed T2D-related effects via hematological analysis, histopathology, mitochondrial evaluation, and multiomics analyses. The OP group showed a significant increase in glucose levels, whereas the OPR group maintained glucose at nonsignificant levels. Multiomics analyses revealed that the exacerbated metabolic effects in the OP group were associated with molecular alterations in oxidative stress, inflammation, nucleotide metabolism, and glucose/lipid homeostasis. These alterations were histologically verified by the increased numbers of hypertrophic adipocytes and inflammatory cells observed. Caloric restriction activated pathways related to antioxidant response, mitochondrial fatty acid oxidation, and energy metabolism in zebrafish, leading to preserved glucose homeostasis. In conclusion, this study identified molecular mechanisms underlying the synergistic effect of concurrent exposure to a mixture of OCPs and HFD as well as shed light on the beneficial effect of regular caloric restriction in T2D development.PMID:36587596 | DOI:10.1016/j.jhazmat.2022.130659

Nutr Res. 2022 Dec 8;109:58-70. doi: 10.1016/j.nutres.2022.12.002. Online ahead of print.ABSTRACTIntake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.PMID:36587538 | DOI:10.1016/j.nutres.2022.12.002

Mar Pollut Bull. 2022 Dec 30;187:114534. doi: 10.1016/j.marpolbul.2022.114534. Online ahead of print.ABSTRACTAnalyses of the transcriptome and metabolome were conducted to clarify alterations of key genes and metabolites in pearl oysters following exposure to short-term hypoxic treatment. We totally detected 209 DEGs between the control and hypoxia groups. Enrichment analysis indicated the enrichment of GO terms including "oxidation-reduction process", "ECM organization", "chaperone cofactor-dependent protein refolding", and "ECM-receptor interaction" KEGG pathway by the DEGs. In addition, between the two groups, a total of 28 SDMs were identified, which were implicated in 13 metabolic pathways, such as "phenylalanine metabolism", "D-amino acid metabolism", and "aminoacyl-tRNA biosynthesis". Results suggest that pearl oysters are exposed to oxidative stress and apoptosis under short-term hypoxia. Also, pearl oysters might adapt to short-term hypoxic treatment by increasing antioxidant activity, modulating immune and biomineralization activities, maintaining protein homeostasis, and reorganizing the cytoskeleton. The results of our study help unveil the mechanisms by which pearl oysters respond adaptively to short-term hypoxia.PMID:36587532 | DOI:10.1016/j.marpolbul.2022.114534