PubMed

Plant Physiol Biochem. 2023 Feb 18;196:807-820. doi: 10.1016/j.plaphy.2023.02.031. Online ahead of print.ABSTRACTSeed germination is crucial for plant productivity, and the biochemical changes during germination affect seedling survival, plant health and yield. While the general metabolism of germination is extensively studied, the role of specialized metabolism is less investigated. We therefore analyzed the metabolism of the defense compound dhurrin during sorghum (Sorghum bicolor) grain germination and early seedling development. Dhurrin is a cyanogenic glucoside, which is catabolized into different bioactive compounds at other stages of plant development, but its fate and role during germination is unknown. We dissected sorghum grain into three different tissues and investigated dhurrin biosynthesis and catabolism at the transcriptomic, metabolomic and biochemical level. We further analyzed transcriptional signature differences of cyanogenic glucoside metabolism between sorghum and barley (Hordeum vulgare), which produces similar specialized metabolites. We found that dhurrin is de novo biosynthesized and catabolized in the growing embryonic axis as well as the scutellum and aleurone layer, two tissues otherwise mainly acknowledged for their involvement in release and transport of general metabolites from the endosperm to the embryonic axis. In contrast, genes encoding cyanogenic glucoside biosynthesis in barley are exclusively expressed in the embryonic axis. Glutathione transferase enzymes (GSTs) are involved in dhurrin catabolism and the tissue-resolved analysis of GST expression identified new pathway candidate genes and conserved GSTs as potentially important in cereal germination. Our study demonstrates a highly dynamic tissue- and species-specific specialized metabolism during cereal grain germination, highlighting the importance of tissue-resolved analyses and identification of specific roles of specialized metabolites in fundamental plant processes.PMID:36863218 | DOI:10.1016/j.plaphy.2023.02.031

Environ Int. 2023 Feb 26;173:107851. doi: 10.1016/j.envint.2023.107851. Online ahead of print.ABSTRACTEmerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid metabolic changes in pregnant rats treated with relatively low dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1-18]. We explored the molecular mechanisms underlying the metabolic perturbation. Oral glucose tolerance test (OGTT) and biochemical tests were performed to assess the glucose homeostasis and serum lipid profiles in pregnant Sprague-Dawley (SD) rats randomly assigned to starch, 0.03 and 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined with non-targeted metabolomic assays were further performed to identify differentially altered genes and metabolites in the liver of maternal rats, and to determine their correlation with the maternal metabolic phenotypes. Results of transcriptome showed that differentially expressed genes at 0.03 and 0.3 mg/kg·bw·d PFOS exposure were related to several metabolic pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic acid metabolism, insulin resistance, cholesterol metabolism, unsaturated fatty acid synthesis, bile acid secretion. The untargeted metabolomics identified 164 and 158 differential metabolites in 0.03 and 0.3 mg/kg·bw·d exposure groups, respectively under negative ion mode of Electrospray Ionization (ESI-), which could be enriched in metabolic pathways such as α-linolenic acid metabolism, glycolysis/gluconeogenesis, glycerolipid metabolism, glucagon signaling pathway, glycine, serine and threonine metabolism. Co-enrichment analysis indicated that PFOS exposure may disturb the metabolism pathways of glycerolipid, glycolysis/gluconeogenesis, linoleic acid, steroid biosynthesis, glycine, serine and threonine. The key involved genes included down-regulated Ppp1r3c and Abcd2, and up-regulated Ogdhland Ppp1r3g, and the key metabolites such as increased glycerol 3-phosphate and lactosylceramide were further identified. Both of them were significantly associated with maternal fasting blood glucose (FBG) level. Our findings may provide mechanistic clues for clarifying metabolic toxicity of PFOS in human, especially for susceptible population such as pregnant women.PMID:36863164 | DOI:10.1016/j.envint.2023.107851

PLoS One. 2023 Mar 2;18(3):e0282316. doi: 10.1371/journal.pone.0282316. eCollection 2023.ABSTRACTMedicinal plants contain valuable compounds that have attracted worldwide interest for their use in the production of natural drugs. The presence of compounds such as rosmarinic acid, carnosic acid, and carnosol in Rosmarinus officinalis has made it a plant with unique therapeutic effects. The identification and regulation of the biosynthetic pathways and genes will enable the large-scale production of these compounds. Hence, we studied the correlation between the genes involved in biosynthesis of the secondary metabolites in R. officinalis using proteomics and metabolomics data by WGCNA. We identified three modules as having the highest potential for the metabolite engineering. Moreover, the hub genes highly connected to particular modules, TFs, PKs, and transporters were identified. The TFs of MYB, C3H, HB, and C2H2 were the most likely candidates associated with the target metabolic pathways. The results indicated that the hub genes including Copalyl diphosphate synthase (CDS), Phenylalanine ammonia lyase (PAL), Cineole synthase (CIN), Rosmarinic acid synthase (RAS), Tyrosine aminotransferase (TAT), Cinnamate 4-hydroxylase (C4H), and MYB58 are responsible for biosynthesis of important secondary metabolites. Thus, we confirmed these results using qRT-PCR after treating R. officinalis seedlings with methyl jasmonate. These candidate genes may be employed for genetic and metabolic engineering research to increase R. officinalis metabolite production.PMID:36862714 | DOI:10.1371/journal.pone.0282316

PLoS One. 2023 Mar 2;18(3):e0279335. doi: 10.1371/journal.pone.0279335. eCollection 2023.ABSTRACTWeight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.PMID:36862673 | DOI:10.1371/journal.pone.0279335

PLoS One. 2023 Mar 2;18(3):e0272750. doi: 10.1371/journal.pone.0272750. eCollection 2023.ABSTRACTThe pollution of soil with heavy metals is an increasingly serious worldwide problem, and cadmium (Cd) has attracted attention because of its high toxicity to almost all plants. Since castor tolerates the accumulation of heavy metals, it has the potential for heavy metal soil remediation. We studied the mechanism of the tolerance of castor to Cd stress treatments at three doses: 300 mg/L, 700 mg/L, and 1,000 mg/L. This research provides new ideas for revealing the defense and detoxification mechanisms of Cd-stressed castor. By combining the results of physiology, differential proteomics and comparative metabolomics, we conducted a comprehensive analysis of the networks that regulate the response of castor to Cd stress. The physiological results mainly emphasize the super-sensitive responses of castor plant roots to Cd stress and the effects of Cd stress on plants' antioxidant system, ATP synthesis and ion homeostasis. We confirmed these results at the protein and metabolite levels. In addition, proteomics and metabolomics indicated that under Cd stress, the expressions of proteins involved in defense and detoxification, energy metabolism and other metabolites such as organic acids and flavonoids were significantly up-regulated. At the same time, proteomics and metabolomics also show that castor plants mainly block the root system's absorption of Cd2+ by enhancing the strength of the cell wall, and inducing programmed cell death in response to the three different doses of Cd stress. In addition, the plasma membrane ATPase encoding gene (RcHA4), which was significantly upregulated in our differential proteomics and RT-qPCR studies, was transgenically overexpressed in wild type Arabidopsis thaliana for functional verification. The results indicated that this gene plays an important role in improving plant Cd tolerance.PMID:36862668 | DOI:10.1371/journal.pone.0272750

J Clin Invest. 2023 Mar 2:e167133. doi: 10.1172/JCI167133. Online ahead of print.ABSTRACTCircadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. Todecipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysisperformed on control mice and mice with inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that ~30% RNAs, ~20% proteins and ~20% metabolites are rhythmic in kidneys of control mice. Several key metabolic pathways including NAD+ biosynthesis, fatty acid transport, carnitine shuttle,and b-oxidation displayed impairments in kidneys of cKOt, resulting in a perturbedmitochondrial activity. Carnitine reabsorption from the primary urine was one of the mostimpacted processes with a ~50% reduction in plasma carnitine levels and a parallel systemicdecrease in tissues carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.PMID:36862511 | DOI:10.1172/JCI167133

Anal Chem. 2023 Mar 2. doi: 10.1021/acs.analchem.2c04985. Online ahead of print.ABSTRACTDroplet microfluidics enables high-throughput experimentation and screening by encapsulating chemical and biochemical samples in aqueous droplets segmented by an immiscible fluid. In such experiments, it is critical that each droplet remains chemically distinct. A common approach is to use fluorinated oils with surfactants to stabilize droplets. However, some small molecules have been observed to transport between droplets under these conditions. Attempts to study and mitigate this effect have relied on evaluating crosstalk using fluorescent molecules, which inherently limits the analyte scope and conclusions drawn about the mechanism of the effect. In this work, transport of low molecular weight compounds between droplets was investigated using electrospray ionization mass spectrometry (ESI-MS) for measurement. The use of ESI-MS significantly expands the scope of analytes that can be tested. We tested 36 structurally diverse analytes that were found to exhibit crosstalk ranging from negligible to complete transfer using HFE 7500 as the carrier fluid and 008-fluorosurfactant as a surfactant. Using this data set, we developed a predictive tool showing that high log P and log D values correlate with high crosstalk, and high polar surface area and log S correlate with low crosstalk. We then investigated several carrier fluids, surfactants, and flow conditions. It was discovered that transport is strongly dependent on all of these factors and that experimental design and surfactant tailoring can reduce carryover. We present evidence for mixed crosstalk mechanisms including both micellar and oil partitioning transfer. By understanding the driving mechanisms, surfactant and oil compositions can be designed to better reduce chemical transport for screening workflows.PMID:36862378 | DOI:10.1021/acs.analchem.2c04985

Planta. 2023 Mar 2;257(4):72. doi: 10.1007/s00425-023-04104-4.ABSTRACTWe identified circRNAs in the Cannabis sativa L. genome and examined their association with 28 cannabinoids in three tissues of C. sativa. Nine circRNAs are potentially involved in the biosynthesis of six cannabinoids. Cannabis sativa L. has been widely used in the production of medicine, textiles, and food for over 2500 years. The main bioactive compounds in C. sativa are cannabinoids, which have multiple important pharmacological actions. Circular RNAs (circRNAs) play essential roles in growth and development, stress resistance, and the biosynthesis of secondary metabolites. However, the circRNAs in C. sativa remain unknown. In this study, to explore the role of circRNAs in cannabinoid biosynthesis, we performed RNA-Seq and metabolomics analysis on the leaves, roots, and stems of C. sativa. We identified 741 overlapping circRNAs by three tools, of which 717, 16, and 8 circRNAs were derived from exonic, intronic, and intergenic, respectively. Functional enrichment analysis indicated that the parental genes (PGs) of circRNAs were enriched in many processes related to biological stress responses. We found that most of the circRNAs showed tissue-specific expression and 65 circRNAs were significantly correlated with their PGs (P < 0.05, |r|≥ 0.5). We also determined 28 cannabinoids by High-performance liquid chromatography-ESI-triple quadrupole-linear ion trap mass spectrometry. Ten circRNAs, including ciR0159, ciR0212, ciR0153, ciR0149, ciR0016, ciR0044, ciR0022, ciR0381, ciR0006, and ciR0025 were found to be associated with six cannabinoids by weighted gene co-expression network analysis. Twenty-nine of 53 candidate circRNAs, including 9 cannabinoids related were validated successfully using PCR amplification and Sanger sequencing. Taken together, all these results would help to enhance our acknowledge of the regulation of circRNAs, and lay the foundation for breeding new C. sativa cultivars with high cannabinoids through manipulating circRNAs.PMID:36862222 | DOI:10.1007/s00425-023-04104-4

Physiol Plant. 2023 Mar 2:e13886. doi: 10.1111/ppl.13886. Online ahead of print.ABSTRACTMetabolic profiles in xylem sap are considered a fundamental mechanism for Cd detoxification in plants. However, the metabolic mechanism of Brassica juncea xylem sap in response to Cd is still unclear. Here, we investigated the effects on the metabolomics of B. juncea xylem sap treated with Cd at different times by utilizing a non-targeted LC-MS-based metabolomics method for further elucidating the response mechanism of Cd exposure. The findings indicated that 48 h and 7 d Cd exposure caused significant differences in metabolic profiles of the B. juncea xylem sap. Those differential metabolites are primarily involved in amino acids, organic acids, lipids, and carbohydrates, and most of them were downregulated, which played essential roles in response to Cd stress. Furthermore, B. juncea xylem sap resisted 48 h Cd exposure via regulation of glycerophospholipid metabolism, carbon metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, linoleic acid metabolism, C5-branched dibasic acid metabolism, alpha-linolenic acid metabolism, cyanoamino acid metabolism, ABC transporters, biosynthesis of amino acids, and pyrimidine metabolism; whereas alpha-linolenic acid metabolism, glycerophospholipid metabolism, photosynthesis, and oxidative phosphorylation were regulated for resisting 7 d Cd exposure. This article is protected by copyright. All rights reserved.PMID:36862032 | DOI:10.1111/ppl.13886

STAR Protoc. 2023 Feb 27;4(1):102137. doi: 10.1016/j.xpro.2023.102137. Online ahead of print.ABSTRACTLiquid-chromatography-mass-spectrometry-based metabolomics is widely used in prospective case-control studies for disease prediction. Given the large amount of clinical and metabolomics data involved, data integration and analyses are crucial to provide an accurate understanding of the disease. We provide a comprehensive analysis approach to explore associations among clinical risk factors, metabolites, and disease. We describe steps for performing Spearman correlation, conditional logistic regression, casual mediation, and variance partitioning to investigate the potential effects of metabolites on disease. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1.PMID:36861827 | DOI:10.1016/j.xpro.2023.102137

Singapore Med J. 2023 Feb 15. doi: 10.4103/singaporemedj.SMJ-2021-154. Online ahead of print.NO ABSTRACTPMID:36861624 | DOI:10.4103/singaporemedj.SMJ-2021-154

Indian J Med Res. 2023 Feb 27. doi: 10.4103/ijmr.ijmr_3475_21. Online ahead of print.ABSTRACTBACKGROUND & OBJECTIVE: COVID-19 has been a global pandemic since early 2020. It has diverse clinical manifestations, but consistent immunological and metabolic correlates of disease severity and protection are not clear. This study was undertaken to compare seropositivity rate, antibody levels against nucleocapsid and spike proteins, virus neutralization and metabolites between adult and child COVID-19 patients.METHODS: Plasma samples from naïve control (n=14) and reverse transcription (RT)-PCR positive COVID-19 participants (n=132) were tested for reactivity with nucleocapsid and spike proteins by ELISA, neutralization of SARS-CoV-2 infectivity in Vero cells and metabolites by 1H nuclear magnetic resonance (NMR) spectroscopy.RESULTS: An ELISA platform was developed using nucleocapsid and spike proteins for COVID-19 serosurvey. The participants showed greater seropositivity for nucleocapsid (72%) than spike (55.3%), and males showed higher seropositivity than females for both the proteins. Antibody levels to both the proteins were higher in intensive care unit (ICU) than ward patients. Children showed lower seropositivity and antibody levels than adults. In contrast to ICU adults (81.3%), ICU children (33.3%) showed lower seropositivity for spike. Notably, the neutralization efficiency correlated with levels of anti-nucleocapsid antibodies. The levels of plasma metabolites were perturbed differentially in COVID-19 patients as compared with the naive controls.INTERPRETATION & CONCLUSIONS: Our results reflect the complexity of human immune response and metabolome to SARS-CoV-2 infection. While innate and cellular immune responses are likely to be a major determinant of disease severity and protection, antibodies to multiple viral proteins likely affect COVID-19 pathogenesis. In children, not adults, lower seropositivity rate for spike was associated with disease severity.PMID:36861542 | DOI:10.4103/ijmr.ijmr_3475_21

Int J Syst Evol Microbiol. 2022 Oct;72(10). doi: 10.1099/ijsem.0.005581.ABSTRACTThree strains (H4-D09T, S2-D11 and S9-F39) of a member of the genus Paracoccus attributed to a novel species were isolated from topsoil of temperate grasslands. The genome sequence of the type strain H4-D09T exhibited a complete set of genes required for denitrification as well as methylotrophy. The genome of H4-D09T included genes for two alternative pathways of formaldehyde oxidation. Besides the genes for the canonical glutathione (GSH)-dependent formaldehyde oxidation pathway, all genes for the tetrahydrofolate-formaldehyde oxidation pathway were identified. The strain has the potential to utilize methanol and/or methylamine as a single carbon source as evidenced by the presence of methanol dehydrogenase (mxaFI) and methylamine dehydrogenase (mau) genes. Apart from dissimilatory denitrification genes (narA, nirS, norBC and nosZ), genes for assimilatory nitrate (nasA) and nitrite reductases (nirBD) were also identified. The results of phylogenetic analysis based on 16S rRNA genes coupled with riboprinting revealed that all three strains represented the same species of genus Paracoccus. Core genome phylogeny of the type strain H4-D09T indicated that Paracoccus thiocyanatus and Paracoccus denitrificans are the closest phylogenetic neighbours. The average nucleotide index (ANI) and digital DNA-DNA hybridization (dDDH) with the closest phylogenetic neighbours revealed genetic differences at the species level, which were further substantiated by differences in several physiological characteristics. The major respiratory quinone is Q-10, and the predominant cellular fatty acids are C18 : 1ω7c, C19 : 0cyclo ω7c, and C16 : 0, which correspond to those detected in other members of the genus. The polar lipid profile consists of a diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), aminolipid (AL), glycolipid (GL) and an unidentified lipid (L).On the basis of our results, we concluded that the investigated isolates represent a novel species of the genus Paracoccus, for which the name Paracoccus methylovorus sp. nov. (type strain H4-D09T=LMG 31941T= DSM 111585T) is proposed.PMID:36861375 | DOI:10.1099/ijsem.0.005581

Aquac Nutr. 2023 Jan 5;2023:5422035. doi: 10.1155/2023/5422035. eCollection 2023.ABSTRACTSteatosis and inflammation have been common gut symptoms in Atlantic salmon fed plant rich diets. Choline has recently been identified as essential for salmon in seawater, and β-glucan and nucleotides are frequently used to prevent inflammation. The study is aimed at documenting whether increased fishmeal (FM) levels (8 levels from 0 to 40%) and supplementation (Suppl) with a mixture of choline (3.0 g/kg), β-glucan (0.5 g/kg), and nucleotides (0.5 g/kg) might reduce the symptoms. Salmon (186 g) were fed for 62 days in 16 saltwater tanks before samples were taken from 12 fish per tank for observation of biochemical, molecular, metabolome, and microbiome indicators of function and health. Steatosis but no inflammation was observed. Lipid digestibility increased and steatosis decreased with increasing FM levels and supplementation, seemingly related to choline level. Blood metabolites confirmed this picture. Genes in intestinal tissue affected by FM levels are mainly involved in metabolic and structural functions. Only a few are immune genes. The supplement reduced these FM effects. In gut digesta, increasing FM levels increased microbial richness and diversity, and changed the composition, but only for unsupplemented diets. An average choline requirement of 3.5 g/kg was indicated for Atlantic salmon at the present life stage and under the present condition.PMID:36860972 | PMC:PMC9973201 | DOI:10.1155/2023/5422035

Front Plant Sci. 2023 Feb 13;14:1112264. doi: 10.3389/fpls.2023.1112264. eCollection 2023.ABSTRACTPotassium ions (K+) are important for plant growth and crop yield. However, the effects of K+ deficiency on the biomass of coconut seedlings and the mechanism by which K+ deficiency regulates plant growth remain largely unknown. Therefore, in this study, we compared the physiological, transcriptome, and metabolite profiles of coconut seedling leaves under K+-deficient and K+-sufficient conditions using pot hydroponic experiments, RNA-sequencing, and metabolomics technologies. K+ deficiency stress significantly reduced the plant height, biomass, and soil and plant analyzer development value, as well as K content, soluble protein, crude fat, and soluble sugar contents of coconut seedlings. Under K+ deficiency, the leaf malondialdehyde content of coconut seedlings were significantly increased, whereas the proline (Pro) content was significantly reduced. Superoxide dismutase, peroxidase, and catalase activities were significantly reduced. The contents of endogenous hormones such as auxin, gibberellin, and zeatin were significantly decreased, whereas abscisic acid content was significantly increased. RNA-sequencing revealed that compared to the control, there were 1003 differentially expressed genes (DEGs) in the leaves of coconut seedlings under K+ deficiency. Gene Ontology analysis revealed that these DEGs were mainly related to "integral component of membrane," "plasma membrane," "nucleus", "transcription factor activity," "sequence-specific DNA binding," and "protein kinase activity." Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the DEGs were mainly involved in "MAPK signaling pathway-plant," "plant hormone signal transduction," "starch and sucrose metabolism," "plant-pathogen interaction," "ABC transporters," and "glycerophospholipid metabolism." Metabolomic analysis showed that metabolites related to fatty acids, lipidol, amines, organic acids, amino acids, and flavonoids were generally down-regulated in coconut seedlings under K+ deficiency, whereas metabolites related to phenolic acids, nucleic acids, sugars, and alkaloids were mostly up-regulated. Therefore, coconut seedlings respond to K+ deficiency stress by regulating signal transduction pathways, primary and secondary metabolism, and plant-pathogen interaction. These results confirm the importance of K+ for coconut production, and provide a more in-depth understanding of the response of coconut seedlings to K+ deficiency and a basis for improving K+ utilization efficiency in coconut trees.PMID:36860901 | PMC:PMC9968814 | DOI:10.3389/fpls.2023.1112264

Front Plant Sci. 2023 Feb 13;14:1150900. doi: 10.3389/fpls.2023.1150900. eCollection 2023.NO ABSTRACTPMID:36860900 | PMC:PMC9969354 | DOI:10.3389/fpls.2023.1150900

Front Microbiol. 2023 Feb 13;14:1128271. doi: 10.3389/fmicb.2023.1128271. eCollection 2023.ABSTRACTThis study evaluated the effects of inoculation with adult goat ruminal fluid on growth, health, gut microbiota and serum metabolism in lambs during the first 15 days of life. Twenty four Youzhou dark newborn lambs were selected and randomly distributed across 3 treatments (n = 8/group): autoclaved goat milk inoculated with 20 mL sterilized normal saline (CON), autoclaved goat milk inoculated with 20 mL fresh ruminal fluid (RF) and autoclaved goat milk inoculated with 20 mL autoclaved ruminal fluid (ARF). Results showed that RF inoculation was more effective at promoting recovery of body weight. Compared with CON, greater serum concentrations of ALP, CHOL, HDL and LAC in the RF group suggested a better health status in lambs. The relative abundance of Akkermansia and Escherichia-Shigella in gut was lower in the RF group, whereas the relative abundance of Rikenellaceae_RC9_gut_group tended to increase. Metabolomics analysis shown that RF stimulated the metabolism of bile acids, small peptides, fatty acids and Trimethylamine-N-Oxide, which were found the correlation relationship with gut microorganisms. Overall, our study demonstrated that ruminal fluid inoculation with active microorganisms had a beneficial impact on growth, health and overall metabolism partly through modulating the gut microbial community.PMID:36860489 | PMC:PMC9969556 | DOI:10.3389/fmicb.2023.1128271

Front Pharmacol. 2023 Feb 13;14:1111007. doi: 10.3389/fphar.2023.1111007. eCollection 2023.ABSTRACTBackground: Qiweiqiangxin І granules (QWQX І) is a traditional Chinese medicine preparation based on the basic theory of traditional Chinese medicine, which produces a good curative effect in treating chronic heart failure (CHF). However, its pharmacological effect and potential mechanism for CHF remain unknown. Aim of the study: The purpose of this study is to clarify the efficacy of QWQX І and its possible mechanisms. Materials and methods: A total of 66 patients with CHF were recruited and randomly assigned to the control or QWQX І groups. The primary endpoint was the effect of left ventricular ejection fraction (LVEF) after 4 weeks of treatment. The LAD artery of rats was occluded to establish the model of CHF. Echocardiography, HE and Masson staining were performed to evaluate the pharmacological effect of QWQX І against CHF. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) untargeted metabolomics was to screen endogenous metabolites in rat plasma and heart and elucidate the mechanism of QWQX І against CHF. Results: In the clinical study, a total of 63 heart failure patients completed the 4-week follow-up, including 32 in the control group and 31 in QWQX І group. After 4 weeks of treatment, LVEF was significantly improved in QWQX І group compared with the control group. In addition, the patients in QWQX І group had better quality of life than the control group. In animal studies, QWQX І significantly improved cardiac function, decreased B-type natriuretic peptide (BNP) levels, reduced inflammatory cell infiltration, and inhibited collagen fibril rate. Untargeted metabolomic analysis revealed that 23 and 34 differential metabolites were screened in the plasma and heart of chronic heart failure rats, respectively. 17 and 32 differential metabolites appeared in plasma and heart tissue after QWQX І treatment, which were enriched to taurine and hypotaurine metabolism, glycerophospholipid metabolism and linolenic acid metabolism by KEGG analysis. LysoPC (16:1 (9Z)) is a common differential metabolite in plasma and heart, which is produced by lipoprotein-associated phospholipase A2 (Lp-PLA2), hydrolyzes oxidized linoleic acid to produce pro-inflammatory substances. QWQX І regulates the level of LysoPC (16:1 (9Z)) and Lp-PLA2 to normal. Conclusion: QWQX І combined with western medicine can improve the cardiac function of patients with CHF. QWQX І can effectively improve the cardiac function of LAD-induced CHF rats through regulating glycerophospholipid metabolism and linolenic acid metabolism-mediated inflammatory response. Thus, QWQX I might provide a potential strategy for CHF therapy.PMID:36860302 | PMC:PMC9968974 | DOI:10.3389/fphar.2023.1111007

Front Pharmacol. 2023 Feb 10;14:1116260. doi: 10.3389/fphar.2023.1116260. eCollection 2023.ABSTRACTThe management of skin wound healing problems is a public health issue in which traditional herbal medicines could play a determining role. Kampo medicine, with three traditionally used ointments, provides interesting solutions for these dermatological issues. These ointments named Shiunkō, Chuōkō, and Shinsen taitsukō all have in common a lipophilic base of sesame oil and beeswax from which herbal crude drugs are extracted according to several possible manufacturing protocols. This review article brings together existing data on metabolites involved in the complex wound healing process. Among them are representatives of the botanical genera Angelica, Lithospermum, Curcuma, Phellodendron, Paeonia, Rheum, Rehmannia, Scrophularia, or Cinnamomum. Kampo provides numerous metabolites of interest, whose content in crude drugs is very sensitive to different biotic and abiotic factors and to the different extraction protocols used for these ointments. If Kampo medicine is known for its singular standardization, ointments are not well known, and research on these lipophilic formulas has not been developed due to the analytical difficulties encountered in biological and metabolomic analysis. Further research considering the complexities of these unique herbal ointments could contribute to a rationalization of Kampo's therapeutic uses for wound healing.PMID:36860294 | PMC:PMC9969195 | DOI:10.3389/fphar.2023.1116260

J Hazard Mater. 2023 Apr 15;448:130904. doi: 10.1016/j.jhazmat.2023.130904. Epub 2023 Feb 2.ABSTRACTThe accumulation and persistence of Bt toxins in soils from Bt plants and Bt biopesticides may result in environmental hazards such as adverse impacts on soil microorganisms. However, the dynamic relationships among exogenous Bt toxins, soil characteristics, and soil microorganisms are not well understood. Cry1Ab is one of the most commonly used Bt toxins and was added to soils in this study to evaluate subsequent changes in soil physiochemical properties, microbial taxa, microbial functional genes, and metabolites profiles via 16S rRNA gene pyrosequencing, high-throughput qPCR, metagenomic shotgun sequencing, and untargeted metabolomics. Higher additions of Bt toxins led to higher concentrations of soil organic matter (SOM), ammonium (NH+4-N), and nitrite (NO2--N) compared against controls without addition after 100 days of soil incubation. High-throughput qPCR analysis and shotgun metagenomic sequencing analysis revealed that the 500 ng/g Bt toxin addition significantly affected profiles of soil microbial functional genes involved in soil carbon (C), nitrogen (N), and phosphorus (P) cycling after 100 days of incubation. Furthermore, combined metagenomic and metabolomic analyses indicated that the 500 ng/g Bt toxin addition significantly altered low molecular weight metabolite profiles of soils. Importantly, some of these altered metabolites are involved in soil nutrient cycling, and robust associations were identified among differentially abundant metabolites and microorganisms due to Bt toxin addition treatments. Taken together, these results suggest that higher levels of Bt toxin addition can alter soil nutrients, probably by affecting the activities of Bt toxin-degrading microorganisms. These dynamics would then activate other microorganisms involved in nutrient cycling, finally leading to broad changes in metabolite profiles. Notably, the addition of Bt toxins did not cause the accumulation of potential microbial pathogens in soils, nor did it adversely affect the diversity and stability of microbial communities. This study provides new insights into the putative mechanistic associations among Bt toxins, soil characteristics, and microorganisms, providing new understanding into the ecological impacts of Bt toxins on soil ecosystems.PMID:36860032 | DOI:10.1016/j.jhazmat.2023.130904