PubMed

Curr Atheroscler Rep. 2023 Aug 18. doi: 10.1007/s11883-023-01132-z. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: The goal of this article is to characterize the endothelium's role in the development of hypertension and dyslipidemia and to point out promising therapeutic directions.RECENT FINDINGS: Dyslipidemia may facilitate the development of hypertension, whereas the collaboration of these two silent killers potentiates the risk of atherosclerosis. The common pathophysiological denominator for hypertension and dyslipidemia is endothelial cell dysfunction, which manifests as dysregulation of homeostasis, redox balance, vascular tone, inflammation, and thrombosis. Treatment focused on mediators acting in these processes might be groundbreaking. Metabolomic research on hypertension and dyslipidemia has revealed new therapeutic targets. State-of-the-art solutions integrating interview, clinical examination, innovative imaging, and omics profiles along with artificial intelligence have been already shown to improve patients' risk stratification and treatment. Pathomechanisms underlying hypertension and dyslipidemia take place in the endothelium. Novel approaches involving endothelial biomarkers and bioinformatics advances could open new perspectives in patient management.PMID:37594602 | DOI:10.1007/s11883-023-01132-z

Cell Mol Life Sci. 2023 Aug 18;80(9):257. doi: 10.1007/s00018-023-04861-1.ABSTRACTSevere acute pancreatitis (SAP) is a common critical disease of the digestive system, with high mortality and a lack of effective prevention and treatment measures. Despite mesenchymal stromal cell transplantation having the potential to treat SAP, its clinical application prospect is limited, and the mechanism is unclear. Here, we reveal the therapeutic role of exosomes from TNF-α-preconditioned human umbilical cord mesenchymal stromal cells (HUCMSCs) in attenuating SAP and show that it is partly dependent on exosomal metabolites. Bioactive metabolomics analysis showed that 48 metabolites be significantly differentially expressed between the two groups (Exo-Ctrl group versus Exo-TNF-α group). Then, the further functional experiments indicated that 3,4-dihydroxyphenylglycol could be a key molecule mediating the therapeutic effect of TNF-α-preconditioned HUCMSCs. The animal experiments showed that 3,4-dihydroxyphenylglycol reduced inflammation and oxidative stress in the pancreatic tissue and inhibited acinar cell autophagy in a rat model of SAP. Mechanistically, we revealed that 3,4-dihydroxyphenylglycol activated the mTOR pathway to inhibit acinar cell autophagy and alleviate SAP. In summary, our study demonstrated that exosomes from TNF-α-preconditioned HUMSCs inhibit the autophagy of acinar cells of SAP by shuttling 3,4-dihydroxyphenylglycol and inhibiting the mTOR pathway. This study revealed the vital role and therapeutic potential of metabolite-derived exosomes in SAP, providing a new promising method to prevent and therapy SAP.PMID:37594573 | DOI:10.1007/s00018-023-04861-1

Anal Chem. 2023 Aug 18. doi: 10.1021/acs.analchem.3c02888. Online ahead of print.ABSTRACTMetabolomics based on high-resolution mass spectrometry has become a powerful technique in biomedical research. The development of various analytical tools and online libraries has promoted the identification of biomarkers. However, how to make mass spectrometry collect more data information is an important but underestimated research topic. Herein, we combined full-scan and data-dependent acquisition (DDA) modes to develop a new targeted DDA based on the inclusion list of differential and preidentified ions (dpDDA). In this workflow, the MS1 datasets for statistical analysis and metabolite preidentification were first obtained using full-scan, and then, the MS/MS datasets for metabolite identification were obtained using targeted DDA of quality control samples based on the inclusion list. Compared with the current methods (DDA, data-independent acquisition, targeted DDA with time-staggered precursor ion list, and iterative exclusion DDA), dpDDA showed better stability, higher characteristic ion coverage, higher differential metabolites' MS/MS coverage, and higher quality MS/MS spectra. Moreover, the same trend was verified in the analysis of large-scale clinical samples. More surprisingly, dpDDA can distinguish patients with different severities of coronary heart disease (CHD) based on the Canadian Cardiovascular Society angina classification, which we cannot distinguish through conventional metabolomics data collection. Finally, dpDDA was employed to differentiate CHD from healthy control, and targeted metabolomics confirmed that dpDDA could identify a more complete metabolic pathway network. At the same time, four unreported potential CHD biomarkers were identified, and the area under the receiver operating characteristic curve was greater than 0.85. These results showed that dpDDA would expand the discovery of biomarkers based on metabolomics, more comprehensively explore the key metabolites and their association with diseases, and promote the development of precision medicine.PMID:37594469 | DOI:10.1021/acs.analchem.3c02888

Anal Chem. 2023 Aug 18. doi: 10.1021/acs.analchem.3c01345. Online ahead of print.ABSTRACTProbing the entirety of any species metabolome is an analytical grand challenge, especially on a cellular scale. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a common spatial metabolomics assay, but this technique has limited molecular coverage for several reasons. To expand the application space of spatial metabolomics, we developed an on-tissue chemical derivatization (OTCD) workflow using 4-APEBA for the confident identification of several dozen elusive phytocompounds. Overall, this new OTCD method enabled the annotation of roughly 280 metabolites, with only a 10% overlap in metabolic coverage when compared to analog negative ion mode MALDI-MSI on serial sections. We demonstrate that 4-APEBA outperforms other derivatization agents by providing: (1) broad specificity toward carbonyls, (2) low background, and (3) introduction of bromine isotopes. Notably, the latter two attributes also facilitate more confidence in our bioinformatics for data processing. The workflow detailed here trailblazes a path toward spatial hormonomics within plant samples, enhancing the detection of carboxylates, aldehydes, and plausibly other carbonyls. As such, several phytohormones, which have various roles within stress responses and cellular communication, can now be spatially profiled, as demonstrated in poplar root and soybean root nodule.PMID:37594382 | DOI:10.1021/acs.analchem.3c01345

Biomed Chromatogr. 2023 Aug 18:e5711. doi: 10.1002/bmc.5711. Online ahead of print.ABSTRACTMallotus apelta leaf, recorded in the quality standard of Yao Medicinal Material in Guangxi Zhuang autonomous region, is commonly used in the treatment of liver diseases. Total flavonoids of M. apelta leaf (TFM) had good anti-fibrosis activity, but the anti-fibrosis mechanism of TFM is still unclear. Nuclear magnetic resonance technology was used to study the dynamic changes of urine metabolites in CCl4 -induced liver fibrosis before and after TFM treatment. Ingenuity Path Analysis (IPA) was used to find potential target genes for TFM to improve liver fibrosis and verify the expression of target genes by real-time fluorescent quantitative PCR and Western blotting. TFM can significantly reduce serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) levels, improve liver steatosis and reduce inflammation; in urine metabolomics, a total of seven potential biomarkers were found, mainly involving two metabolic pathways; IPA analysis showed that TNF may be a potential target for TFM to improve liver fibrosis induced by CCl4 in rats. This study found that TNF may be a potential target gene for TFM treatment of liver fibrosis, and shows that the anti-fibrosis mechanism of TFM could improve liver fibrosis by regulating the tricarboxylic acid cycle and subtaurine metabolism.PMID:37593807 | DOI:10.1002/bmc.5711

Biomed Chromatogr. 2023 Aug 18:e5710. doi: 10.1002/bmc.5710. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a common endocrine syndrome, and obesity is the most common clinical manifestation. Acupuncture is effective in treating PCOS, but the differences in the biological mechanisms of acupuncture therapy and Western medicine treatment have not been determined. Thus, the purpose of this study was to find glucose metabolism-related pathways in acupuncture treatment and differentiate them from Western medical treatment. Sixty patients with PCOS-related obesity were randomly distributed into three groups: patients receiving (1) acupuncture treatment alone, (2) conventional Western medicine treatment, and (3) acupuncture combined with Western medicine treatment. A targeted metabolomics approach was used to identify small molecules and metabolites related to glucose metabolism in the serum of each group, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze different metabolic fractions. The results showed acupuncture treatment modulates the activity of citric and succinic acids in the tricarboxylic acid cycle, regulates glycolytic and gluconeogenesis pathways, and improves the levels of sex hormones and energy metabolism. The intervention effects on the metabolic pathways were different between patients receiving combination therapy and patients receiving acupuncture therapy alone, suggesting that the dominant modulatory effect of Western drugs may largely conceal the efficacy of acupuncture intervention.PMID:37593801 | DOI:10.1002/bmc.5710

Front Immunol. 2023 Aug 1;14:1236812. doi: 10.3389/fimmu.2023.1236812. eCollection 2023.ABSTRACTThe subject of this study was to explore the optimum requirements of loach (Paramisgurnus dabryanus) regarding dietary proteins and lipids and discuss the underlying mechanism. We designed nine diets to determine the effects of different levels of dietary crude protein (CP: 30%, 35%, and 40%) and ether extract (EE: 6%, 10%, and 14%) on the growth performance and metabolism of P. dabryanus. In total, 2160 healthy P. dabryanus (5.19 ± 0.01 g) were divided into nine groups with four replications at 60 fish per barrel stocking density. The trial lasted for eight weeks. Serum and liver samples were gathered for metabolomic and transcriptomic analyses. The results showed that the specific growth rate of P. dabryanus in the CP40EE10 group was the fastest and notably higher than that in other groups (P< 0.05). Analysis of the metabolome results found that the mTOR signaling pathway, glycerophospholipid metabolism, D-arginine and D-ornithine metabolism were significantly enriched pathways in the CP40EE10 group compared with the other groups (P< 0.05). Moreover, the transcriptomic analysis of differentially expressed genes (DEGs) showed that the expression of ARG (arginase) involved in protein synthesis was significantly upregulated in the CP40EE10 group compared to the slowest growing group (P< 0.05). Additionally, the expression of SPLA2 (secretory phospholipase A2) involved in lipid metabolism and FBP (fructose-1,6-bisphosphatase) involved in glucose metabolism were all significantly downregulated in the CP30EE6 group compared with the CP40EE10 group (P< 0.05). Furthermore, the analysis of differentially expressed metabolites (DEMs) and DEGs co-enriched in the KEGG pathway revealed that the significantly enriched pathways were arginine and proline metabolism, glycerophospholipid metabolism, and glycolysis/gluconeogenesis in CP40EE10 compared with other groups (P< 0.05). We conclude that including 40% CP and 10% EE in the P. dabryanus diet could result in a better growth rate. We hypothesized from metabolomic and transcriptomic analyses that the CP40EE10 diet might promote the growth of P. dabryanus by promoting protein synthesis, lipid metabolism, and energy production.PMID:37593743 | PMC:PMC10431964 | DOI:10.3389/fimmu.2023.1236812

EClinicalMedicine. 2023 Aug 3;62:102132. doi: 10.1016/j.eclinm.2023.102132. eCollection 2023 Aug.ABSTRACTBACKGROUND: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs).METHODS: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728).FINDINGS: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs.INTERPRETATION: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond.FUNDING: National Key Research and Development Program of China, the National Natural Science Foundation of China.PMID:37593224 | PMC:PMC10430172 | DOI:10.1016/j.eclinm.2023.102132

Acta Neuropsychiatr. 2023 Aug 18:1-36. doi: 10.1017/neu.2023.37. Online ahead of print.ABSTRACTOBJECTIVE: Early-life adversity is one of the strongest predictors of childhood depression, that may be exacerbated by a genetic predisposition to develop depression. We therefore investigated the bio-behavioural effects of an early-life stressor in an accepted rodent model of depression.METHODS: The Flinders sensitive (FSL) and resistant (FRL) line rats were subjected to an early-life stressor, whereafter their bio-behavioural response during pubertal onset was evaluated. Male and female pups were maternally separated for 3 h per day from postnatal day 02 (PND02) to 17, when they were also weaned. Control animals were left undisturbed, until weaning on PND21. Depressive-like behaviour was analysed on PND21 and reassessed on PND36. Hippocampal monoamine levels, markers of oxidative stress and metabolic markers implicating mitochondrial function were also measured.RESULTS: On PND21, the non-maternal separation and early weaning (non-MSEW) FSL rats spent 10% more time mobile than their FRL controls in the tail suspension test (TST) yet displayed increased depressive-like behaviour in the forced swim test (FST) on PND36. The depressive-like behaviour coincided with increased hippocampal norepinephrine levels, serotonin turnover and a dysfunctional redox state. Maternal separation and early weaning (MSEW) appeared to initially reduce early-life (PND21) depressive-like behaviour in the TST but then induced depressive-like behaviour on PND36, and increased norepinephrine levels more profoundly in the FRL rats.CONCLUSION: These findings highlight the need to further investigate the stress response pathway in these animals and that the absence or presence of genetic susceptibility may influence the presentation of early-life adversity effects.PMID:37592838 | DOI:10.1017/neu.2023.37

Reprod Domest Anim. 2023 Aug 17. doi: 10.1111/rda.14453. Online ahead of print.ABSTRACTThe present study evaluated the seminal plasma metabolome of Bos indicus Guzerá bulls with good (n = 4) and poor (n = 5) sperm freezability. Animals were raised in natural pasture of a 'Caatinga' ecosystem, in the semi-arid region of Brazil. Seminal plasma samples were subjected to gas chromatography coupled to mass spectrometry and data, analysed using bioinformatics tools (Cytoscape with the MetScape plug-in). Sixty-two metabolites were identified in the bovine seminal plasma. Fatty acids and conjugates and organic compounds were the predominant seminal fluid metabolites, followed by carboxylic acids and derivatives, amino acids, benzenes and steroids and derivatives, carbohydrates and carbohydrate conjugates and prenol lipids. Multivariate analysis indicated a distinct separation of seminal plasma metabolomes from bulls with contrasting sperm freezability. Abundances of propanoic acid, d-ribose and glycine were greater in the seminal plasma of bulls with good sperm freezability. Heptadecanoic acid and undecanoic acid were the predominant in bulls of poor sperm freezability. Propanoic acid is an energy source for spermatozoa and may act as an antimicrobial component in semen. Glycine acts against oxidizing and denaturing reactions. d-ribose is also an energy source and reduces apoptosis and oxidative stress. Undecanoic acid may protect sperm against fungal damage. This study provides fundamental information approximately the seminal plasma metabolome of tropically adapted bulls and its association with sperm freezability. However, further studies with larger groups of animals are needed to validate those metabolites as markers of sperm freezability. This strategy could support the selection of sires with superior sperm cryoresistance.PMID:37592767 | DOI:10.1111/rda.14453

Phytochem Anal. 2023 Aug 17. doi: 10.1002/pca.3277. Online ahead of print.ABSTRACTINTRODUCTION: We developed Data Base similarity (DBsimilarity), a user-friendly tool designed to organize structure databases into similarity networks, with the goal of facilitating the visualization of information primarily for natural product chemists who may not have coding experience.METHOD: DBsimilarity, written in Jupyter Notebooks, converts Structure Data File (SDF) files into Comma-Separated Values (CSV) files, adds chemoinformatics data, constructs an MZMine custom database file and an NMRfilter candidate list of compounds for rapid dereplication of MS and 2D NMR data, calculates similarities between compounds, and constructs CSV files formatted into similarity networks for Cytoscape.RESULTS: The Lotus database was used as a source for Ginkgo biloba compounds, and DBsimilarity was used to create similarity networks including NPClassifier classification to indicate biosynthesis pathways. Subsequently, a database of validated antibiotics from natural products was combined with the G. biloba compounds to identify promising compounds. The presence of 11 compounds in both datasets points to possible antibiotic properties of G. biloba, and 122 compounds similar to these known antibiotics were highlighted. Next, DBsimilarity was used to filter the NPAtlas database (selecting only those with MIBiG reference) to identify potential antibacterial compounds using the ChEMBL database as a reference. It was possible to promptly identify five compounds found in both databases and 167 others worthy of further investigation.CONCLUSION: Chemical and biological properties are determined by molecular structures. DBsimilarity enables the creation of interactive similarity networks using Cytoscape. It is also in line with a recent review that highlights poor biological plausibility and unrealistic chromatographic behaviors as significant sources of errors in compound identification.PMID:37592443 | DOI:10.1002/pca.3277

J Cachexia Sarcopenia Muscle. 2023 Aug 17. doi: 10.1002/jcsm.13313. Online ahead of print.ABSTRACTBACKGROUND: The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear.METHODS: To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model.RESULTS: The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass.CONCLUSIONS: The results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.PMID:37591518 | DOI:10.1002/jcsm.13313

Biomed Chromatogr. 2023 Aug 17:e5721. doi: 10.1002/bmc.5721. Online ahead of print.ABSTRACTHuangqi Jianzhong Tang (HQJZ) is effective for treating chronic atrophic gastritis (CAG). The present study was carried out to reveal the mechanism of HQJZ in CAG rats. The metabolism and microbial composition of the cecal contents in CAG rats were analyzed through the integration of an untargeted metabolomic approach using ultra-high-performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing, respectively. Finally, MetOrigin analyses were performed to explore the relationship between differential metabolites and intestinal flora. The results showed that HQJZ could significantly regulate metabolic disorders, especially conjugated acid metabolites. 16S rRNA gene sequencing analysis illustrated that HQJZ decreased the abundance of Acetobacter, Desulfovibrio, Escherichia, and Shigella. MetOrigin metabolite traceability analysis showed that the six bile acids associated with HQJZ efficacy included three bacteria-host cometabolites, which were involved in the primary bile acid biosynthesis pathway. Research presented here confirmed that conjugated bile acid metabolism was key to the treatment of CAG by HQJZ and correlates strongly with Bacteroides acidifaciens and Prevotella copri. These findings provide new insights into the mechanisms to explain the efficacy of HQJZ.PMID:37591498 | DOI:10.1002/bmc.5721

Funct Plant Biol. 2023 Aug 18. doi: 10.1071/FP23023. Online ahead of print.ABSTRACTSoil salinisation is a growing threat to global agriculture, reducing crop yields. Brassicaceae crops are vital vegetables and cash crops. Salt stress significantly affects the growth and development of Brassicaceae crops. A better understanding of the molecular and physiological mechanisms of salt tolerance is of theoretical and practical importance to improve Brassicaceae crop's salt tolerance and crop quality. Combined with previous research results, we discuss recent advances in research on salt stress response and salt tolerance in Brassicaceae crops. We summarised recent research progress on the physiological and molecular mechanisms of ionic homeostasis, antioxidant regulation, hormonal regulation and accumulation of osmotic-adjustment substances. We also discussed the molecular mechanism of Brassicaceae crop salt tolerant varieties from the perspective of differentially expressed genes, differentially expressed proteins and metabolites through transcriptome, proteome and metabonomic analysis methods. This paper summarises the molecular mechanisms in the perspective of differentially expressed genes, differentially expressed proteins, and metabolites through transcriptomic, proteome and metabolomics analysis. The review provides abundant data for accelerating the breeding of salt-tolerant Brassicaceae and laid a foundation for understanding the mechanism of salt tolerance of Brassicaceae crops and breeding salt-tolerance varieties.PMID:37591489 | DOI:10.1071/FP23023

Int J Biol Macromol. 2023 Aug 15:126365. doi: 10.1016/j.ijbiomac.2023.126365. Online ahead of print.ABSTRACTGrain shape and plumpness affect barley yield. Despite numerous studies on shrunken endosperm mutants in barley, their molecular mechanism and application potential in the food industry are largely unknown. Here, map-based cloning, co-segregation analyses, and allelic variant validation revealed that the loss of HORVU6Hr1G037950 encoding an ADP-glucose transporter caused the shrunken endosperm in sex1. Haplotype analysis suggested that hap4 in the promoter sequence was positively related to the hundred-grain weight showing a breeding potential. A pair of near-isogenic lines targeting HORVU6Hr1G037950 was produced and characterized to investigate molecular mechanisms that SEX1 regulates endosperm development. Results presented that the absence of the SEX1 gene led to the decrease of starch content and A-type granules size, the increase of β-glucan, protein, gelatinization temperature, soluble sugar content, amylopectin A chains, and B1 chains. Enzymatic activity, transcriptome and metabolome analyses revealed the loss of SEX1 results in an impaired ADP-glucose-to-starch conversion process, consequently leading to higher soluble sugar contents and lower starch accumulation, thereby inducing a shrunken-endosperm phenotype in sex1. Taken together, this study provides new insights into barley grain development, and the elevated protein and β-glucan contents of the whole meal in sex1 imply its promising application in the food industry.PMID:37591421 | DOI:10.1016/j.ijbiomac.2023.126365

Environ Pollut. 2023 Aug 15:122387. doi: 10.1016/j.envpol.2023.122387. Online ahead of print.ABSTRACTPersistent organic pollutants (POPs) accumulated in the adipose tissue can affect the fatty acid and lipid metabolism in the body. Gas chromatography-mass spectrometry (GC-MS) metabolomics analysis was carried out to study the metabolic changes induced by internal exposure to the POPs in mouse skeletal muscle (soleus, plantaris, and gastrocnemius), kidney, heart, and lungs. Male donor mice were injected with a mixture of 10 POPs at concentrations of 0 × and 5 × lowest-observed-adverse-effect level (LOAEL). Their adipose tissue (AT) containing the POP was then grafted onto the host mice and the metabolic change of the host mice was monitored for 3 or 21 days. The metabolites related to fatty acid and lipid metabolism were studied. For the host mice engrafted with POP-containing fat pad, there was dysregulation of the fatty acids and glycerides observed in all the organs studied 3 days after the graft. However, there was no longer a significant change in the metabolites 21 days after the graft. The difference in significant values and metabolite regulation in each of the skeletal muscles showed that the POP mixture affects different types of skeletal muscle in a heterogeneous manner. Fold change analysis showed that certain metabolites in the kidney of host mice exposed to POPs for 3 days were greatly affected. Using multivariate analysis, apart from the plantaris, most treated groups exposed to POPs for 3 days are well distinguished from the control groups. However, for host mice exposed to POPs for 21 days, apart from the kidney and heart, groups are not well-distinguished from the control group. This study helps bring new insight into the effects of the pollutants mixture released from AT on fatty acid and lipid metabolism at different periods and how the dysregulation of metabolites might result in diseases associated with the organs.PMID:37591324 | DOI:10.1016/j.envpol.2023.122387

J Hazard Mater. 2023 Aug 14;459:132280. doi: 10.1016/j.jhazmat.2023.132280. Online ahead of print.ABSTRACTCadmium (Cd) contamination poses serious risks to soil ecosystems and human health. Herein, the effect of two drunken horse grasses (Achnatherum inebrians) including endophytes Epichloë gansuensis infected (E+ ) and uninfected (E-) on the phytoremediation of Cd-contaminated soils were analyzed by coupling high-throughput sequencing and soil metabolomics. The results showed that the high-risk soil Cd decreased and the medium- and low-risk Cd fraction increased to varying degrees after planting E+ and E- plants in the soil. Meanwhile, total Cd content decreased by 19.7 % and 35.1 % in E+ and E- A. inebrians-planted soils, respectively. Principal coordinate analysis revealed a significant impact of E+ and E- plants on the soil microbial community. Most stress-tolerant and gram-positive functional bacterial taxa were enriched to stabilize Cd(II) in E+ planted soil. Several beneficial fungal groups related to saprotroph and symbiotroph were enriched to absorb Cd(II) in E- soil. Soil metabolomic analysis showed that the introduction of A. inebrians could weaken the threat of CdCl2 to soil microbe metabolism and improve soil quality, which in turn promoted plant growth and improved phytoremediation efficiency in Cd-contaminated soil. In conclusion, A. inebrians plants alleviate soil Cd pollution by regulating soil microbial metabolism and microbial community structure. These results provide valuable information for an in-depth understanding of the phytoremediation mechanisms of A. inebrians.PMID:37591168 | DOI:10.1016/j.jhazmat.2023.132280

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Aug 11;47:101117. doi: 10.1016/j.cbd.2023.101117. Online ahead of print.ABSTRACTThe sea cucumber Holothuria leucospilota, a nutritive and commercial marine species, has a high protein and low lipid content. To date, the mechanisms underlying gender determination and differentiation in sea cucumbers remain unclear. Identifying gender-specific molecular markers is an effective method of revealing the genetic basis of gender determination and differentiation. The inability to distinguish between male and female individuals causes reproductive efficiency to decline in aquaculture. In this study, we used the gonads of the sea cucumber H. leucospilota as samples to conduct the experiment. The differentially abundant metabolites (DAMs) detected by liquid chromatography-mass spectrometry were enriched in pathways associated with prolactin metabolism, insulin metabolism, hypoxia-inducible factor-1 signaling, and calcium signaling. At the transcriptome level, Illumina sequencing was performed on H. leucospilota, demonstrating that gender-specific expression genes were enriched in the retinoic acid-inducible gene I-like receptor signaling pathway, C-type lectin receptor signaling pathway, alpha-linolenic acid metabolism, and ether lipid metabolism by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. By analyzing the common pathways between DAMs and differentially expressed genes, we found that gender-related genes of H. leucospilota were mostly enriched in the necroptosis pathway and the cysteine and methionine metabolism pathways. According to the common pathways, uch-sc1 and uch-sc2 are male-specific expression genes, and uch-sc3 and bhmt are female-specific expression genes at the mRNA level. These results provide information on gender differences in H. leucospilota.PMID:37591053 | DOI:10.1016/j.cbd.2023.101117

Chin Med. 2023 Aug 17;18(1):102. doi: 10.1186/s13020-023-00793-x.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use.AIM OF THE STUDY: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers.MATERIALS AND METHODS: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively.RESULTS: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9).CONCLUSIONS: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.PMID:37592331 | DOI:10.1186/s13020-023-00793-x

J Transl Med. 2023 Aug 18;21(1):554. doi: 10.1186/s12967-023-04392-0.ABSTRACTBACKGROUND & AIMS: Intestinal fibrosis is a common and severe complication of inflammatory bowel disease without clear pathogenesis. Abnormal expression of host genes and metabolic perturbations might associate with the onset of intestinal fibrosis. In this study, we aimed to investigate the relationship between the development of intestinal fibrosis and the dynamic alterations in both fecal metabolites and host gene expression.METHODS: We induced intestinal fibrosis in a murine model using 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS-treated or control mice were sacrificed after 4 and 6 weeks of intervention; alterations in colonic genes and fecal metabolites were determined by transcriptomics and metabolomics, respectively. Differential, tendency, enrichment, and correlation analyses were performed to assess the relationship between host genes and fecal metabolites.RESULTS: RNA-sequencing analysis revealed that 679 differential genes with enduring changes were mainly enriched in immune response-related signaling pathways and metabolism-related biological processes. Among them, 15 lipid metabolism-related genes were closely related to the development of intestinal fibrosis. Moreover, the fecal metabolic profile was significantly altered during intestinal fibrosis development, especially the lipid metabolites. Particularly, dynamic perturbations in lipids were strongly associated with alterations in lipid metabolism-related genes expression. Additionally, six dynamically altered metabolites might serve as biomarkers to identify colitis-related intestinal fibrosis in the murine model.CONCLUSIONS: Intestinal fibrosis in colitis mice might be related to dynamic changes in gene expression and metabolites. These findings could provide new insights into the pathogenesis of intestinal fibrosis.PMID:37592304 | DOI:10.1186/s12967-023-04392-0