PubMed

Food Res Int. 2024 Apr;182:114149. doi: 10.1016/j.foodres.2024.114149. Epub 2024 Feb 20.ABSTRACTThe effects of cysteine (Cys), glutathione (GSH) and cystine (GCys) on sulfides and meaty aroma were studied based on concentration monitoring and metabolomics. In multi-component models, Cys and GSH demonstrated a greater capacity to decrease dimethyl trisulfide (DMTS) levels and increase the proportion of 2-methyl-3-furanthiol (MFT), compared with GCys. Moreover, no discernible difference between Cys and GSH in dynamic profiles of volatiles to further analyze the synergistic effect of both. Results of single factor experiment and optimization revealed that the optimal thermal processing was a second-order thermal procedure. Aroma profiles revealed that the addition of Cys and GSH mixture increased the meaty intensity during the optimal thermal processing. Metabolomics based on Encyclopedia of Genes and Genomes pathway annotation confirmed that Cys and GSH significantly affected the degradation of methionine and thiamine in amino acid and protein metabolic pathways, resulting in various amounts of DMTS and MFT. Research on effect and potentially metabolic mechanisms revealed that the combination of Cys and GSH at ratio of 3:7 had higher and more effective control capacity for free radical reaction of sulfides than either one alone during second-order thermal processing, which would lay theoretical foundation for the development of high-quality thermal process products.PMID:38519161 | DOI:10.1016/j.foodres.2024.114149

Lancet Digit Health. 2024 Apr;6(4):e251-e260. doi: 10.1016/S2589-7500(23)00265-0.ABSTRACTBACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners.METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts.FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001).INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways.FUNDING: Pfizer.PMID:38519153 | DOI:10.1016/S2589-7500(23)00265-0

Clin Chim Acta. 2024 Mar 20:117859. doi: 10.1016/j.cca.2024.117859. Online ahead of print.NO ABSTRACTPMID:38518968 | DOI:10.1016/j.cca.2024.117859

J Ethnopharmacol. 2024 Mar 20:118052. doi: 10.1016/j.jep.2024.118052. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cholic acid (CA) is one of the main active ingredients in Calculus Bovis, a traditional Chinese medicine, which helps to regulate the heart and liver meridians, clearing the heart, opening the mouth, cooling the liver and calming the wind. However, the molecular mechanism of its liver protective effect is still unclear.AIM OF THE STUDY: Growing attention has been directed towards traditional Chinese medicine (TCM), particularly Calculus Bovis, as a potential solution for liver protection. Despite this interest, a comprehensive understanding of its hepatoprotective mechanisms remains lacking. This research seeks to explore the potential protective properties of cholic acid (CA) against CCl4-induced acute liver injury (ALI) in mice, while also examining the mechanisms involved.MATERIALS AND METHODS: In the experiment, a mouse model was employed to ALI using CCl4, and the potential therapeutic effects of orally administered CA at varying doses (15, 30, and 60 mg/kg) were assessed. The study employed a multi-faceted approach, integrating liver transcriptomics with serum metabolomics, and conducting thorough analyses of serum biochemical markers and liver histopathological sections.RESULTS: Oral CA administration markedly reduced the organ indices of the liver, spleen, and thymus in comparison with the model group. It also elevated the expression of superoxide dismutase (SOD) in serum while diminishing the concentrations of ALT, AST, MDA, IL-6, and TNF-α. Moreover, CA ameliorated the pathological damage induced by CCl4. Integrated metabolomic and transcriptomic analyses indicated that the hepatoprotective action of CA on ALI is mediated through the modulation of lipid metabolic pathways-specifically, metabolisms of glycerophospholipid, arachidonic acid, as well as linoleic acid-and by altering the expression of genes such as Ptgr1, PLpp1, Tbxas1, and Cyp2c37.CONCLUSIONS: The current investigation offers insights into the hepatoprotective mechanisms by which CA mitigates ALI caused by CCl4 exposure, thus supporting the further evaluation and development of CA-based therapeutics for ALI.PMID:38518967 | DOI:10.1016/j.jep.2024.118052

J Ethnopharmacol. 2024 Mar 20:118050. doi: 10.1016/j.jep.2024.118050. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders.AIM OF THE STUDY: While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques.MATERIALS AND METHODS: 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites.RESULTS: LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels.CONCLUSIONS: This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D.PMID:38518966 | DOI:10.1016/j.jep.2024.118050

Sci Total Environ. 2024 Mar 20:171851. doi: 10.1016/j.scitotenv.2024.171851. Online ahead of print.ABSTRACTUntargeted metabolomics is a non-a priori analysis of biomolecules that characterizes the metabolome variations induced by short- and long-term exposures to stressors. Even if the metabolite annotation remains lacunar due to database gaps, the global metabolomic fingerprint allows for trend analyses of dose-response curves for hundreds of cellular metabolites. Analysis of dose/time-response curve trends (biphasic or monotonic) of untargeted metabolomic features would thus allow the use of all the chemical signals obtained in order to determine stress levels (defense or damage) in organisms. To develop this approach in a context of time-dependent microbial community changes, mature river biofilms were exposed for 1 month to four cobalt (Co) concentrations (from background concentration to 1 × 10-6 M) in an open system of artificial streams. The meta-metabolomic response of biofilms was compared against a multitude of biological parameters (including bioaccumulation, biomass, chlorophyll a content, composition and structure of prokaryotic and eukaryotic communities) monitored at set exposure times (from 1 h to 28 days). Cobalt exposure induced extremely rapid responses of the meta-metabolome, with time range inducing defense responses (TRIDeR) of around 10 s, and time range inducing damage responses (TRIDaR) of several hours. Even in biofilms whose structure had been altered by Co bioaccumulation (reduced biomass, chlorophyll a contents and changes in the composition and diversity of prokaryotic and eukaryotic communities), concentration range inducing defense responses (CRIDeR) with similar initiation thresholds (1.41 ± 0.77 × 10-10 M Co2+ added in the exposure medium) were set up at the meta-metabolome level at every time point. In contrast, the concentration range inducing damage responses (CRIDaR) initiation thresholds increased by 10 times in long-term Co exposed biofilms. The present study demonstrates that defense and damage responses of biofilm meta-metabolome exposed to Co are rapidly and sustainably impacted, even within tolerant and resistant microbial communities.PMID:38518822 | DOI:10.1016/j.scitotenv.2024.171851

Cell Rep Med. 2024 Mar 21:101480. doi: 10.1016/j.xcrm.2024.101480. Online ahead of print.ABSTRACTThe gut microbiome is associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigate the fecal and plasma metabolome of samples obtained from a cohort of 51 extremely premature infants at several time points, using liquid chromatography (LC)-high-resolution mass spectrometry (MS)-based untargeted metabolomics and LC-MS/MS-based targeted analysis for investigating bile acids and amidated bile acid conjugates. The data are integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor, and T cell profiles. We find an early onset of differentiation in neuroactive metabolites between infants with and without brain injury. We detect several bacterially derived bile acid amino acid conjugates in plasma and feces. These results provide insights into the early-life metabolome of extremely premature infants.PMID:38518769 | DOI:10.1016/j.xcrm.2024.101480

Biochem Biophys Res Commun. 2024 Mar 15;708:149770. doi: 10.1016/j.bbrc.2024.149770. Online ahead of print.ABSTRACTBACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury.OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects.METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis.RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels.CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.PMID:38518722 | DOI:10.1016/j.bbrc.2024.149770

Talanta. 2024 Mar 19;273:125924. doi: 10.1016/j.talanta.2024.125924. Online ahead of print.ABSTRACTWildlife conservation is often challenged by a lack of knowledge about the reproduction biology and adaptability of endangered species. Although monitoring steroids and related molecules can increase this knowledge, the applicability of current techniques (e.g. immunoassays) is hampered by species-specific steroid metabolism and the requisite to avoid invasive sampling. This study presents a validated steroidomics method for the (un)targeted screening of a wide range of sex and stress steroids and related molecules in urine using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). In total, 50 steroids (conjugated and non-conjugated androgens, estrogens, progestogens and glucocorticoids) and 6 prostaglandins could be uniquely detected. A total of 45 out of 56 compounds demonstrated a detection limit below 0.01 ng μL-1. Excellent linearity (R2 > 0.99), precision (CV < 20 %), and recovery (80-120 %) were observed for 46, 41, and 39 compounds, respectively. Untargeted screening of pooled giant panda and human samples yielded 9691 and 8366 features with CV < 30 %, from which 84.1 % and 83.0 %, respectively, also demonstrated excellent linearity (R2 > 0.90). The biological validity of the method was investigated on male and female giant panda urine (n = 20), as well as pooled human samples (n = 10). A total of 24 different steroids were detected with clear qualitative and quantitative differences between human and giant panda samples. Furthermore, expected differences were revealed between female giant panda samples from different reproductive phases. In contrast to traditional biomonitoring techniques, the developed steroidomics method was able to screen a wide range of compounds and provide information on the putative identities of metabolites potentially important for reproductive monitoring in giant pandas. These results illustrate the advancements steroidomics brings to the field of wildlife biomonitoring in the pursuit to better understand the biology of endangered species.PMID:38518717 | DOI:10.1016/j.talanta.2024.125924

Phytomedicine. 2023 Dec 27;128:155291. doi: 10.1016/j.phymed.2023.155291. Online ahead of print.ABSTRACTBACKGROUND: As a traditional Chinese medicinal herb, the lipid-lowing biological potential of Eucommia ulmoides leaves (EL) has been demonstrated. After fermentation, the EL have been made into various products with lipid-lowering effects and antioxidant activity. However, the anti-hyperlipidemic mechanism of fermented Eucommia ulmoides leaves (FEL) is unclear now.PURPOSE: To evaluate the effects of FEL on hyperlipidemia and investigate the mechanism based on regulating gut homeostasis and host metabolism.METHODS: Hyperlipidemia animal model in Wistar rats was established after 8 weeks high-fat diet (HFD) fed. The administered doses of aqueous extract of FEL (FELE) were 128, 256 and 512 mg/kg/d, respectively. Serum biochemical parameters detection, histopathological sections analysis, 16S rDNA sequencing of gut microbiota and untargeted fecal metabolomics analysis, were performed to determine the therapeutic effects and predict related pathways of FELE on hyperlipidemia. The changes of proteins and genes elated to lipid were detected by Immunofluorescence (IF) and quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS: 56 Components in FELE were identified by UPLC-MS, with organic acids, flavonoids and phenolic acids accounting for the majority. The intervention of FELE significantly reduced the body weight, lipid accumulation and the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) in hyperlipidemia rats, while increased the level of High-density lipoprotein-cholesterol (HDL-C). Meanwhile, FELE improved the inflammatory makers and oxidative stress factors, which is tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). These results demonstrated that FETE can effectively reduce blood lipids and alleviate inflammation and oxidative damage caused by hyperlipidemia. Mechanistically, FELE restore the homeostasis of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of probiotics, especially Lactobacillus, Rombousia, Bacteroides, Roseburia, Clostridia_UCG-014_Unclassified, while modulated metabolism through amino acid, bile acid and lipid-related metabolism pathways. In addition, the Pearson correlation analysis found that the upregulated bilirubin, threonine, dopamine and downregulated lipocholic acid, d-sphingosine were key metabolites after FELE intervention. IF and qRT-PCR analysis showed that FELE upregulated the expression of fatty acid oxidation proteins and genes (PPARα, CPT1A), bile acid synthesis and excretion proteins and genes (LXRα, CYP7A1, FXR), and downregulated the expression of adipogenic gene (SREBP-1c) by regulating gut microbiota to improve metabolism and exert a lipid-lowering effect.CONCLUSION: This work filled the lipid-lowering mechanism gap of FEL. FELE can improve HFD-induced hyperlipidemia by regulating the gut microbiota homeostasis and metabolism. Thus, FEL has the potential to develop into the novel raw material of lipid-lowering drugs.PMID:38518640 | DOI:10.1016/j.phymed.2023.155291

Phytomedicine. 2024 Feb 8;128:155411. doi: 10.1016/j.phymed.2024.155411. Online ahead of print.ABSTRACTBACKGROUND: Emodin-8-O-β-D-glucopyranoside (Em8G) is an active ingredient of traditional Chinese medicine Rhei Radix et Rhizoma and Polygonum multiflorum Thunb.. And it caused hepatotoxicity, while the underlying mechanism was not clear yet.PURPOSE: We aimed to explore the detrimental effects of Em8G on the zebrafish liver through the metabolome and transcriptome integrated analysis.STUDY DESIGN AND METHODS: In this study, zebrafish larvae were used in acute toxicity tests to reveal the hepatotoxicity of Em8G. Adult zebrafish were then used to evaluate the gender differences in hepatotoxicity induced by Em8G. Integration of transcriptomic and metabolomic analysis was used further to explore the molecular mechanisms underlying gender differences in hepatotoxicity.RESULTS: Our results showed that under non-lethal concentration exposure conditions, hepatotoxicity was observed in Em8G-treated zebrafish larvae, including changes in liver transmittance, liver area, hepatocyte apoptosis and hepatocyte vacuolation. Male adult zebrafish displayed a higher Em8G-induced hepatotoxicity than female zebrafish, as demonstrated by the higher mortality and histopathological alterations. The results of transcriptomics combined with metabolomics showed that Em8G mainly affected carbohydrate metabolism (such as TCA cycle) in male zebrafish and amino acid metabolism (such as arginine and proline metabolism) in females, suggesting that the difference of energy metabolism disorder may be the potential mechanism of male and female liver toxicity induced by Em8G.CONCLUSIONS: This study provided the direct evidence for the hepatotoxicity of Em8G to zebrafish models in vivo, and brought a new insight into the molecular mechanisms of Em8G hepatotoxicity, which can guide the rational application of this phytotoxin. In addition, our findings revealed gender differences in the hepatotoxicity of Em8G to zebrafish, which is related to energy metabolism and provided a methodological reference for evaluating hepatotoxic drugs with gender differences.PMID:38518638 | DOI:10.1016/j.phymed.2024.155411

Phytomedicine. 2024 Feb 7;128:155425. doi: 10.1016/j.phymed.2024.155425. Online ahead of print.ABSTRACTBACKGROUND: Intestinal barrier dysfunction caused by the disrupted balance of group 3 innate lymphoid cells (ILC3)/group 1 innate lymphoid cells (ILC1) is a significant feature in the pathogenesis of inflammatory bowel disease (IBD). Activation of aryl hydrocarbon receptor (AhR) signaling contributes to the maintenance of ILC3/ILC1 balance. Wogonin, a natural flavonoid from Scutellaria baicalensis Georgi, can repair intestinal mucosal damage of IBD. However, it remains unclear if wogonin can exert a therapeutic effect by activating the AhR pathway to regulate the plasticity of ILC3/ILC1.PURPOSE: In this study, we investigated the immunomodulatory effects of wogonin on IBD and its potential mechanisms in vitro and in vivo.STUDY DESIGN AND METHODS: Chronic colitis was induced by four cycles of 2 % DSS treatment in mice. 20 mg kg-1/day wogonin was administrated by oral gavage and mice were treated intraperitoneally with 10 mg kg-1/2 days CH223191 to block the AhR pathway. Colon tissues were processed for histopathological examination and evaluation of the epithelial barrier function by immunohistochemistry. The activation of the AhR pathway and the plasticity of ILC3/ILC1 were determined by western blot and flow cytometry. Then, we also detected the intestinal microflora and their metabolites by 16 s sequencing and non-targeted Metabolomics analysis. Furthermore, an in vitro culture system consisting of MNK3 cells and NCM460 cells, and a CETSA assay were performed to confirm the molecular mechanism.RESULTS: Wogonin ameliorated histological severity of the colon, decreased the secretion of inflammatory factors, and increased tight junction proteins in colitis mice. These effects are associated with the tendency of conversion from ILC3 to ILC1 prevented by wogonin, which was offset by AhR antagonist CH223191. In addition, wogonin exerted the curative effect by altering gut microbiota to produce metabolites such as Kynurenic acid, and 1H-Indole-3-carboxaldehyde as AhR endogenous ligands. In vitro data further verified that wogonin as an exogenous ligand directly binds to the structural domain of AhR by CETSA. Also, the supernatant of MNK-3 cells stimulated with wogonin enhanced expression of Occludin and Claudin1 in NCM460 cells induced by LPS.CONCLUSION: Cumulatively, our study illustrated that wogonin improved the outcomes of DSS-induced chronic colitis via regulating the plasticity of ILC3/ILC1. Its specific mechanism is to binding to AhR directly, and to activate the AhR pathway indirectly by altering the tryptophan metabolisms of gut microbiota.PMID:38518634 | DOI:10.1016/j.phymed.2024.155425

Microbiol Res. 2024 Mar 20;283:127700. doi: 10.1016/j.micres.2024.127700. Online ahead of print.ABSTRACTAs the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various aspects of gut health. These bacteria are renowned for their involvement in immunomodulation and their remarkable capacity to break down complex carbohydrates and fibers. However, the human gut microbiota is known to produce many metabolites that ultimately mediate important microbe-host and microbe-microbe interactions. To gain further insights into the metabolites produced by the gut commensal strains of this order, we examined the metabolite composition of their bacterial cell cultures in the stationary phase. Based on their abundance in the gastrointestinal tract and their relevance in health and disease, we selected a total of six bacterial strains from the relevant genera Bacteroides, Phocaeicola, Parabacteroides, and Segatella. We grew these strains in modified Gifu anaerobic medium (mGAM) supplemented with mucin, which resembles the gut microbiota's natural environment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolite profiling revealed 179 annotated metabolites that had significantly differential abundances between the studied bacterial strains and the control growth medium. Most of them belonged to classes such as amino acids and derivatives, organic acids, and nucleot(s)ides. Of particular interest, Segatella copri DSM 18205 (previously referred to as Prevotella copri) produced substantial quantities of the bioactive metabolites phenylethylamine, tyramine, tryptamine, and ornithine. Parabacteroides merdae CL03T12C32 stood out due to its ability to produce cadaverine, histamine, acetylputrescine, and deoxycarnitine. In addition, we found that strains of the genera Bacteroides, Phocaeicola, and Parabacteroides accumulated considerable amounts of proline-hydroxyproline, a collagen-derived bioactive dipeptide. Collectively, these findings offer a more detailed comprehension of the metabolic potential of these Bacteroidales strains, contributing to a better understanding of their role within the human gut microbiome in health and disease.PMID:38518452 | DOI:10.1016/j.micres.2024.127700

Food Chem. 2024 Mar 20;448:139085. doi: 10.1016/j.foodchem.2024.139085. Online ahead of print.ABSTRACTThe effects and underlying molecular mechanisms of binary probiotics (Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953 and Lacticaseibacillus casei CGMCC 1.5956) on the quality of wolfberry fermented beverages (WFB) were investigated. The results indicated that binary probiotics increased the number of probiotics, anthocyanin (89.92 ± 1.64 mg/L), polyphenol content (283.04 ± 3.81 µg/mL), and odor score (24.19) in WFB. Metabolomics found that they could enhance signal exchange (cyclic AMP) between binary probiotics and improve the utilization of citrulline, d-proline, d-glucose, and d-galactose through galactose metabolism and amino acid biosynthesis pathway to promote probiotics growth. Furthermore, HS-SPME-GC-MS and GS-IMS revealed that the improvement in flavor was mainly due to an increase in the content of the aromatic flavor substances 3-heptanol, glutaraldehyde, and 2-heptanone, and a decrease in the content of the off-flavor substances methyl isobutyl ketone-D and 2-undecanone. This is strategically important for the development of WFB with high probiotic content and unique flavor.PMID:38518444 | DOI:10.1016/j.foodchem.2024.139085

J Agric Food Chem. 2024 Mar 22. doi: 10.1021/acs.jafc.3c08454. Online ahead of print.ABSTRACTMicroplastics derived from plastic waste have emerged as a pervasive environmental pollutant with potential transfer and accumulation through the food chain, thus posing risks to both ecosystems and human health. The gut microbiota, tightly intertwined with metabolic processes, exert substantial influences on host physiology by utilizing dietary compounds and generating bacterial metabolites such as tryptophan and bile acid. Our previous studies have demonstrated that exposure to microplastic polystyrene (PS) disrupts the gut microbiota and induces colonic inflammation. Meanwhile, intervention with cyanidin-3-O-glucoside (C3G), a natural anthocyanin derived from red bayberry, could mitigate colonic inflammation by reshaping the gut bacterial composition. Despite these findings, the specific influence of gut bacteria and their metabolites on alleviating colonic inflammation through C3G intervention remains incompletely elucidated. Therefore, employing a C57BL/6 mouse model, this study aims to investigate the mechanisms underlying how C3G modulates gut bacteria and their metabolites to alleviate colonic inflammation. Notably, our findings demonstrated the efficacy of C3G in reversing the elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and the upregulation of mRNA expression (Il-6, Il-1β, and Tnf-α) induced by PS exposure. Meanwhile, C3G effectively inhibited the reduction in levels (IL-22, IL-10, and IL-4) and the downregulation of mRNA expression (Il-22, Il-10, and Il-4) of anti-inflammatory cytokines induced by PS exposure. Moreover, PS-induced phosphorylation of the transcription factor NF-κB in the nucleus, as well as the increased level of protein expression of iNOS and COX-2 in the colon, were inhibited by C3G. Metabolisms of gut bacterial tryptophan and bile acids have been extensively implicated in the regulation of inflammatory processes. The 16S rRNA high-throughput sequencing disclosed that PS treatment significantly increased the abundance of pro-inflammatory bacteria (Desulfovibrio, norank_f_Oscillospiraceae, Helicobacter, and Lachnoclostridium) while decreasing the abundance of anti-inflammatory bacteria (Dubosiella, Akkermansia, and Alistipes). Intriguingly, C3G intervention reversed these pro-inflammatory changes in bacterial abundances and augmented the enrichment of bacterial genes involved in tryptophan and bile acid metabolism pathways. Furthermore, untargeted metabolomic analysis revealed the notable upregulation of metabolites associated with tryptophan metabolism (shikimate, l-tryptophan, indole-3-lactic acid, and N-acetylserotonin) and bile acid metabolism (3b-hydroxy-5-cholenoic acid, chenodeoxycholate, taurine, and lithocholic acid) following C3G administration. Collectively, these findings shed new light on the protective effects of dietary C3G against PS exposure and underscore the involvement of specific gut bacterial metabolites in the amelioration of colonic inflammation.PMID:38518253 | DOI:10.1021/acs.jafc.3c08454

J Pharm Pharmacol. 2024 Mar 22:rgae025. doi: 10.1093/jpp/rgae025. Online ahead of print.ABSTRACTOBJECTIVES: This study was designed to investigate the pharmacological activity and therapeutic mechanism of Mahuang Xixin Fuzi decoction (MXFD) on migraine.METHODS: Migraine model rats induced by nitroglycerin were established, and then orally administered with MXFD for 7 days. Blood and urine samples were collected to identify differential metabolites with metabolomics. To integrate the findings from network pharmacology and metabolomics analysis, the metabolites and targets related to MXFD therapy for migraine were filtered.KEY FINDINGS: MXFD was found to alleviate the symptoms of migraines in rats. After treatment with MXFD, nine metabolites were found to be regulated and returned to normal levels. MXFD acted directly on nine key targets including MAOB, MAOA, ADRB1, ADRB2, ADRB3, ADORA2A, ADORA2B, DRD5, and HTR4 and regulated two out of nine metabolites, namely deoxycholic acid and 5-methoxyindoleacetate.CONCLUSIONS: The study found that MXFD can alleviate migraines through multitarget and multicomponent interaction networks.PMID:38517943 | DOI:10.1093/jpp/rgae025

PLoS One. 2024 Mar 22;19(3):e0300593. doi: 10.1371/journal.pone.0300593. eCollection 2024.ABSTRACTBACKGROUND: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles.METHODS: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy.RESULTS: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline.CONCLUSION: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.PMID:38517904 | DOI:10.1371/journal.pone.0300593

PLoS One. 2024 Mar 22;19(3):e0300472. doi: 10.1371/journal.pone.0300472. eCollection 2024.ABSTRACTGilthead seabream (Sparus aurata) is an important species in Mediterranean aquaculture. Rapid intensification of its production and sub-optimal husbandry practices can cause stress, impairing overall fish performance and raising issues related to sustainability, animal welfare, and food safety. The advent of next-generation sequencing technologies has greatly revolutionized the study of fish stress biology, allowing a deeper understanding of the molecular stress responses. Here, we characterized for the first time, using RNA-seq, the different hepatic transcriptome responses of gilthead seabream to common aquaculture challenges, namely overcrowding, net handling, and hypoxia, further integrating them with the liver proteome and metabolome responses. After reference-guided transcriptome assembly, annotation, and differential gene expression analysis, 7, 343, and 654 genes were differentially expressed (adjusted p-value < 0.01, log2|fold-change| >1) in the fish from the overcrowding, net handling, and hypoxia challenged groups, respectively. Gene set enrichment analysis (FDR < 0.05) suggested a scenario of challenge-specific responses, that is, net handling induced ribosomal assembly stress, whereas hypoxia induced DNA replication stress in gilthead seabream hepatocytes, consistent with proteomics and metabolomics' results. However, both responses converged upon the downregulation of insulin growth factor signalling and induction of endoplasmic reticulum stress. These results demonstrate the high phenotypic plasticity of this species and its differential responses to distinct challenging environments at the transcriptomic level. Furthermore, it provides significant resources for characterizing and identifying potentially novel genes that are important for gilthead seabream resilience and aquaculture production efficiency with regard to fish welfare.PMID:38517901 | DOI:10.1371/journal.pone.0300472

Elife. 2024 Mar 22;12:RP90579. doi: 10.7554/eLife.90579.ABSTRACTPartial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems and warrant further investigation into adapting these approaches for in vivo age reversal.PMID:38517750 | DOI:10.7554/eLife.90579

J Pharm Pharmacol. 2024 Mar 22:rgae026. doi: 10.1093/jpp/rgae026. Online ahead of print.ABSTRACTOBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear.METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated.RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment.CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.PMID:38517742 | DOI:10.1093/jpp/rgae026