PubMed

Atherosclerosis. 2023 Sep 22:117274. doi: 10.1016/j.atherosclerosis.2023.117274. Online ahead of print.ABSTRACTCardiovascular diseases (CVD) are the leading cause of death worldwide for both men and women, but their prevalence and burden show marked sex differences. The existing knowledge gaps in research, prevention, and treatment for women emphasize the need for understanding the biological mechanisms contributing to the sex differences in CVD. Sex differences in the plasma lipids that are well-known risk factors and predictors of CVD events have been recognized and are believed to contribute to the known disparities in CVD manifestations in men and women. However, the current understanding of sex differences in lipids has mainly come from the studies on routinely measured standard lipids- low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total triglycerides, and total cholesterol, which have been the mainstay of the lipid profiling. Sex differences in individual lipid species, collectively called the lipidome, have until recently been less explored due to the technological challenges and analytic costs. With the technological advancements in the last decade and growing interest in understanding mechanisms of sexual dimorphism in metabolic disorders, many investigators utilized metabolomics and lipidomics based platforms to examine the effect of biological sex on detailed lipidomic profiles and individual lipid species. This review presents an overview of the research on sex differences in the concentrations of circulating lipid species, focusing on findings from the metabolome- and lipidome-wide studies. We also discuss the potential contribution of genetic factors including sex chromosomes and sex-specific physiological factors such as menopause and sex hormones to the sex differences in lipidomic profiles.PMID:37743161 | DOI:10.1016/j.atherosclerosis.2023.117274

J Physiol. 2023 Sep 23. doi: 10.1113/JP285124. Online ahead of print.ABSTRACTMitochondria adapt to increased energy demands during muscle contraction by acutely altering metabolite fluxes and substrate oxidation. With age, an impaired mitochondrial metabolic response may contribute to reduced exercise tolerance and decreased skeletal muscle mass, specific force, increased overall fatty depositions in the skeletal muscle, frailty and depressed energy maintenance. We hypothesized that elevated energy stress in mitochondria with age alters the capacity of mitochondria to utilize different substrates following muscle contraction. To test this hypothesis, we used in vivo electrical stimulation to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise in young (5-7 months) and aged (27-29 months) male and female mice to characterize effects of age and sex on mitochondrial substrate utilization in skeletal muscle following contraction. Mitochondrial respiration using glutamate decreased in aged males following HII and glutamate oxidation was inhibited following HII in both the contracted and non-stimulated muscle of aged female muscle. Analyses of the muscle metabolome of female mice indicated that changes in metabolic pathways induced by HII and LISS contractions in young muscle are absent in aged muscle. To test improved mitochondrial function on substrate utilization following HII, we treated aged females with elamipretide (ELAM), a mitochondrially-targeted peptide shown to improve mitochondrial bioenergetics and restore redox status in aged muscle. ELAM removed inhibition of glutamate oxidation and showed increased metabolic pathway changes following HII, suggesting rescuing redox status and improving bioenergetic function in mitochondria from aged muscle increases glutamate utilization and enhances the metabolic response to muscle contraction in aged muscle. KEY POINTS: Acute local contraction of gastrocnemius can systemically alter mitochondrial respiration in non-stimulated muscle. Age-related changes in mitochondrial respiration using glutamate or palmitoyl carnitine following contraction are sex-dependent. Respiration using glutamate after high-intensity contraction is inhibited in aged female muscle. Metabolite level and pathway changes following muscle contraction decrease with age in female mice. Treatment with the mitochondrially-targeted peptide elamipretide can partially rescue metabolite response to muscle contraction.PMID:37742081 | DOI:10.1113/JP285124

J Transl Med. 2023 Sep 23;21(1):662. doi: 10.1186/s12967-023-04537-1.ABSTRACTBACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute the gold standard treatment for type 2 diabetes mellitus (T2DM). Among them, empagliflozin (EMPA) has shown beneficial effects against heart failure. Because cardiovascular diseases (mainly diabetic cardiomyopathy) are the leading cause of death in diabetic patients, the use of EMPA could be, simultaneously, cardioprotective and antidiabetic, reducing the risk of death from cardiovascular causes and decreasing the risk of hospitalization for heart failure in T2DM patients. Interestingly, recent studies have shown that EMPA has positive benefits for people with and without diabetes. This finding broadens the scope of EMPA function beyond glucose regulation alone to include a more intricate metabolic process that is, in part, still unknown. Similarly, this significantly increases the number of people with heart diseases who may be eligible for EMPA treatment.METHODS: This study aimed to clarify the metabolic effect of EMPA on the human myocardial cell model by using orthogonal metabolomics, lipidomics, and proteomics approaches. The untargeted and multivariate analysis mimicked the fasting blood sugar level of T2DM patients (hyperglycemia: HG) and in the average blood sugar range (normal glucose: NG), with and without the addition of EMPA.RESULTS: Results highlighted that EMPA was able to modulate and partially restore the levels of multiple metabolites associated with cellular stress, which were dysregulated in the HG conditions, such as nicotinamide mononucleotide, glucose-6-phosphate, lactic acid, FA 22:6 as well as nucleotide sugars and purine/pyrimidines. Additionally, EMPA regulated the levels of several lipid sub-classes, in particular dihydroceramide and triacylglycerols, which tend to accumulate in HG conditions resulting in lipotoxicity. Finally, EMPA counteracted the dysregulation of endoplasmic reticulum-derived proteins involved in cellular stress management.CONCLUSIONS: These results could suggest an effect of EMPA on different metabolic routes, tending to rescue cardiomyocyte metabolic status towards a healthy phenotype.PMID:37742032 | DOI:10.1186/s12967-023-04537-1

Commun Biol. 2023 Sep 23;6(1):977. doi: 10.1038/s42003-023-05366-0.ABSTRACTCancer cachexia is characterized by weight loss and skeletal muscle wasting. Based on the up-regulation of catabolism and down-regulation of anabolism, here we showed genetic mutation-mediated metabolic reprogramming in the progression of cancer cachexia by screening for metabolites and investigating their direct effect on muscle atrophy. Treatment with 93 μM D-2-hydroxyglutarate (D2HG) resulted in reduced myotube width and increased expression of E3 ubiquitin ligases. Isocitrate Dehydrogenase 1 (IDH1) mutant patients had higher D2HG than non-mutant patients. In the in vivo murine cancer cachexia model, mutant IDH1 in CT26 cancer cells accelerated cachexia progression and worsened overall survival. Transcriptomics and metabolomics revealed a distinct D2HG-induced metabolic imbalance. Treatment with the IDH1 inhibitor ivosidenib delayed the progression of cancer cachexia in murine GL261 glioma model and CT26 colorectal carcinoma models. These data demonstrate the contribution of IDH1 mutation mediated D2HG accumulation to the progression of cancer cachexia and highlight the individualized treatment of IDH1 mutation associated cancer cachexia.PMID:37741882 | DOI:10.1038/s42003-023-05366-0

Gut Microbes. 2023 Dec;15(2):2257273. doi: 10.1080/19490976.2023.2257273. Epub 2023 Sep 23.ABSTRACTMaternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.PMID:37741856 | DOI:10.1080/19490976.2023.2257273

Gut Microbes. 2023 Dec;15(2):2256749. doi: 10.1080/19490976.2023.2256749. Epub 2023 Sep 23.ABSTRACTGestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3'-sialyllactose (3'-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3'-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3'-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.PMID:37741825 | DOI:10.1080/19490976.2023.2256749

J Adv Res. 2023 Sep 21:S2090-1232(23)00259-X. doi: 10.1016/j.jare.2023.09.010. Online ahead of print.ABSTRACTINTRODUCTION: Micro- and nanoplastics (MNPs) are emerging environmental pollutants that have raised serious concerns about their potential impact on ecosystem and organism health. Despite increasing efforts to investigate the impacts of micro- and nanoplastics (MNPs) on biota little is known about their potential impacts on terrestrial organisms, especially insects, at environmental concentrations.OBJECTIVES: To address this gap, we used an insect model, silkworm Bombyx mori to examine the potential long-term impacts of different sizes of polystyrene (PS) MNPs at environmentally realistic concentrations (0.25 to 1.0 μg/mL).METHODS: After exposure to PS-MNPs over most of the larval lifetime (from second to last instar), the endpoints were examined by an integrated physiological (growth and survival) and multiomics approach (metabolomics, 16S rRNA, and transcriptomics).RESULTS: Our results indicated that dietary exposures to PS-MNPs had no lethal effect on survivorship, but interestingly, increased host body weight. Multiomics analysis revealed that PS-MNPs exposure significantly altered multiple pathways, particularly lipid metabolism, leading to enriched energy reserves. Furthermore, the exposure changed the structure and composition of the gut microbiome and increased the abundance of gut bacteria Acinetobacter and Enterococcus. Notably, the predicted functional profiles and metabolite expressions were significantly correlated with bacterial abundance. Importantly, these observed effects were particle size-dependent and were ranked as PS-S (91.92 nm) > PS-M (5.69 µm) > PS-L (9.7 µm).CONCLUSION: Overall, PS-MNPs at environmentally realistic concentrations exerted stimulatory effects on energy metabolism that subsequently enhanced body weight in silkworms, suggesting that chronic PS-MNPs exposure might trigger weight gain in animals and humans by influencing host energy and microbiota homeostasis.PMID:37741508 | DOI:10.1016/j.jare.2023.09.010

J Ethnopharmacol. 2023 Sep 21:117205. doi: 10.1016/j.jep.2023.117205. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Spleen Yang Deficiency Syndrome (SYDS), which is a syndrome commonly treated with Traditional Chinese Medicine (TCM), manifests as overall metabolic dysfunction caused mainly by digestive system disorders. Atractylodes lancea (Thunb.) DC. (AL) is a widely used traditional herb with the efficacy of eliminate dampness and strengthen the spleen, Atractylodes oil (AO) is a medicinal component of AL and can be used to treat various gastrointestinal disorders. However, its effects on SYDS and underlying mechanisms have not been clarified to date.AIM OF THE STUDY: The present study aimed to investigate the efficacy of AO in the improvement of the symptoms of SYDS in rat and the underlying mechanism by integrating transcriptomics, and metabolomics.MATERIALS AND METHODS: The SYDS rats induced by reserpine were treated with AO. The protective effect of AO on SYDS rats was evaluated by serum biochemical detection, histopathological analyses. Enzyme-linked immunosorbent assay (ELISA), colorimetric assay and immunofluorescence (IF) were performed to determine the levels of relevant indicators of mitochondrial function and energy metabolism in the liver. Liver metabolites and transcript levels were assessed by non-targeted metabolomics and transcriptomics to analyze potential molecular mechanisms and targets. The expression of the corresponding proteins was verified using Western blotting.RESULTS: AO not only regulated the digestion, absorption function and oxidative stress status of SYDS rats, but also improved mitochondrial function and alleviated energy metabolism disorders in SYDS rats. Metabolomic and transcriptomic analyses demonstrated that AO regulation is mainly exerted in amino acid metabolism, unsaturated fatty acid metabolism, TCA cycle as well as PPAR and AMPK signaling pathways. In addition, The AMPK signaling pathway was verified and AO promoted AMPK phosphorylation and the expression of SIRT1, PGC-1α, and PPARα in SYDS rats.CONCLUSIONS: The therapeutic effect of AO on SYDS is potentially attributable to activation of the AMPK/SIRT1/PGC-1α signaling pathway, which enhances transport and regulation of energy metabolism.PMID:37741473 | DOI:10.1016/j.jep.2023.117205

Chemosphere. 2023 Sep 21:140246. doi: 10.1016/j.chemosphere.2023.140246. Online ahead of print.ABSTRACTSuperworm (larve of Zophobas atratus) could consume foams of expanded polystyrene plastics. However, there is no sufficient understanding of the impact of microplastics on superworms and the degradation pathways of polystyrene. Herein, we explored the weight and survival change of superworms while fed with polystyrene microplastics, and found that survival rate and mean weight would reduce. In terms of gut microbial community structure of surperworms, significant shifts were detected with the relative abundance of Hafnia-Obesumbacterium sp. increasing. In addition, we domesticated two microbiota from the gut of superworms, and confirmed their ability to degrade PS in vitro. The last but most important, 1291 metabolites were identified by HPLC-TOF-MS/MS, and six metabolites related to polystyrene degradation were identified through comparative metabolomic analysis. According to the content and pathways of these metabolites, three metabolic pathways of polystyrene were (a) styrene-phenylacetyl-CoA-L-2-aminoadipic acid; (b) styrene-phenylacetyl-CoA-benzaldehyde; (c) styrene-2-hydroxyacetophenone. These results would help to further screen bacteria of PS degradation and investigate PS metabolic pathways in invertebrates.PMID:37741374 | DOI:10.1016/j.chemosphere.2023.140246

Chemosphere. 2023 Sep 21:140219. doi: 10.1016/j.chemosphere.2023.140219. Online ahead of print.ABSTRACTRhizosphere phosphatases can exhibit hormetic effects in response to cadmium (Cd) ion stimulation. However, understanding the mechanisms underlying hormesis effects on soil ecosystems is challenging as studies on hormesis are usually specific to an organism, cell, or organ. To comprehensively investigate the mechanism of phosphatase hormesis, this study utilized in situ zymography and metabolomics to analyze the rhizosphere of Trifolium repens L. (white clover). Zymograms showed that rhizosphere phosphatase displayed a hormetic effect in 10 mg kg-1 Cd contaminated soil, with a hotspot area 1.8 times larger than non-Cd contaminated soil and a slight increase in enzyme activity. Nevertheless, the phosphatase activity was substantially suppressed upon elevating the Cd concentration in the soil to 50 mg kg-1. Differential metabolite identification and KEEG pathway enrichment analysis revealed that both rhizosphere organic acids and amino acid compounds positively affected phosphatase activity, and both were able to stabilize complexation with Cd ions via carboxyl groups. Besides, molecular docking models suggested that Cd ions act as cofactors to induce the formation of hydrogen bonds between amino acids/organic acids and phosphatase residues to form a triplet complex with a more stable structure, thereby improving phosphatase activity. The results indicated that amino acids and organic acids are heavily enriched in the rhizosphere of white clover and form a particular structure with soil Cd ions and phosphatase, which is essential for inducing the phosphatase hormesis as a detoxification mechanism in the rhizosphere micro-ecosystem.PMID:37741368 | DOI:10.1016/j.chemosphere.2023.140219

J Nutr Biochem. 2023 Sep 21:109448. doi: 10.1016/j.jnutbio.2023.109448. Online ahead of print.ABSTRACTMultiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequence to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.PMID:37741298 | DOI:10.1016/j.jnutbio.2023.109448

Biomed Pharmacother. 2023 Sep 21;167:115531. doi: 10.1016/j.biopha.2023.115531. Online ahead of print.ABSTRACTBACKGROUND: Acute kidney injury (AKI) is a known complication of cisplatin administration; currently, there are no effective ways to prevent it. Therefore, it largely limited the use of cisplatin in chemotherapy in the clinic. In this study, we reported that Limonin, a triterpenoid compound extracted from citrus, alleviated cisplatin-induced AKI through metabolic reprogramming in the diseased kidneys.METHODS: Cisplatin was employed to induce AKI in mice. Three groups were set up: Sham, cisplatin + vehicle, and cisplatin + Limonin. Using UHPLC-TOF/MS, we conducted metabolomics to profile the kidneys' endogenous metabolites and metabolic pathways. A network pharmacological method was performed to identify the targets of Limonin on AKI. The human proximal tubular epithelial cell line (HK-2) was applied for in vitro studies.RESULTS: Limonin preserved serum creatinine and blood urea nitrogen levels after cisplatin-induced AKI. Employing metabolomics, we identified 33 endogenous differentially expressed metabolites and 7 significantly disturbed metabolic pathways in the diseased kidneys within three groups. After AKI, Limonin significantly reduced linoleic acid and its downstream product, arachidonic acid, thus exerting a protective effect on the kidney. The network pharmacological method identified CYP3A4 as a key target of Limonin in treating AKI, while CYP3A4 also serve as a mediator of arachidonic acid metabolism. In vitro, Limonin markedly reduced the level of arachidonic acid and HK-2 cell apoptosis triggered by cisplatin, mainly related to the targeted inhibition of CYP3A4-mediated arachidonic acid metabolism.CONCLUSION: Limonin ameliorates cisplatin-induced AKI by inhibiting CYP3A4 activity to regulate arachidonic acid metabolism, ultimately preserving kidney function.PMID:37741252 | DOI:10.1016/j.biopha.2023.115531

Food Chem. 2023 Sep 7;434:137372. doi: 10.1016/j.foodchem.2023.137372. Online ahead of print.ABSTRACTThe effect of steaming treatment on salmon quality was explored by different multi-omics and electronic sensory system in this study. A comparison between conventional steaming (CS) and anaerobic steaming (AS) was conducted in organoleptic quality of salmon. Twelve key volatile compounds were identified, which contributed to the flavor difference. The concentrations of hexanal, (E)-2-octen-1-al, and decanal in AS salmon were significantly lower than in CS salmon, which account for 68.9-80.5 % of the latter. During steaming, the fatty acids and diacylglycerols decreased significantly by 37.4 % and 57.9 %, respectively. Anaerobic steaming limited the degradation of some oxidized lipids, further reduced some volatile secondary oxidation products. Nucleotides and derivatives, succinic acid, glutamic acid, hydroxyproline and betaine contributed to the saltness, umami, richness of steamed salmon. Metabolomics data revealed that the higher creatinine, Ala-Ala and Ala-Leu provided more umami and less bitterness to AS salmon.PMID:37741235 | DOI:10.1016/j.foodchem.2023.137372

Virology. 2023 Aug 19;587:109866. doi: 10.1016/j.virol.2023.109866. Online ahead of print.ABSTRACTWe previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression. Surprisingly, ORF4 protein was determined to be the only JCV protein specifically targeting the promyelocytic leukemia nuclear bodies (PML-NBs) and inducing their reorganization in nucleus. Although ORF4 protein has a modest effect on JCV replication, it is implicated to play major roles during the JCV life cycle, perhaps by regulating the antiviral response of PML-NBs against JCV infections and thus facilitating the progression of the JCV-induced disease in infected individuals.PMID:37741199 | DOI:10.1016/j.virol.2023.109866

J Plant Physiol. 2023 Sep 16;289:154095. doi: 10.1016/j.jplph.2023.154095. Online ahead of print.ABSTRACTFew studies have been conducted to investigate the impact of pesticides on the secondary metabolism of traditional Chinese medicine and strategies to mitigate the toxicity of pesticide-induced oxidative stress. The current study focuses on evaluating the potential impacts of nano selenium (NSe) and imidacloprid (IMI) on the quality, physiological biochemistry, and secondary metabolites in Perilla frutescens (L.) Britt. (P. frutescens). The study utilized metabolome analysis to explore the toxicity mechanism of IMI. The study noted that IMI-induced stress could emerge with detrimental effects by targeting the destruction of the phenylpropanoid biosynthesis pathway. IMI-induced phenylpropanoid metabolism disorder resulted in an 8%, 17%, 25%, 10%, 65%, and 29% reduction in phenylalanine, coniferyl aldehyde, ferulic acid, cafestol, p-coumaraldehyde, and p-coumaric acid levels, respectively. Under the treatment of exogenous NSe, the levels of these metabolites were increased by 16%, 32%, 22%, 22%, 92%, and 29%, respectively. The application of exogenous NSe increased the levels of these metabolites and improved the biochemical disorder and quality of P. frutescens leaves by optimizing the phenylpropanoid metabolic pathway and enhancing the antioxidant system. Overall, the results suggest that foliar application of NSe could alleviate the oxidative stress toxicity induced by IMI and improve the quality of P. frutescens.PMID:37741053 | DOI:10.1016/j.jplph.2023.154095

Redox Biol. 2023 Sep 19;67:102889. doi: 10.1016/j.redox.2023.102889. Online ahead of print.ABSTRACTMaternal diets during pregnancy and lactation are key determinants that regulate the development of metabolic syndrome (MetS) in offspring. l-malic acid (MA) was previously reported to improve antioxidant capacity and aerobic metabolism. However, the effects of maternal MA consumption on the metabolic features of offspring remain largely unexplored. Herein, through pig models consuming MA-enriched diets during late pregnancy and lactation, we found that maternal MA consumption potentiated the anti-inflammatory and antioxidant capacity of sows, thereby improving their reproductive performance and the growth performance of piglets. Maternal MA consumption also induced a transition of slow-twitch to fast-twitch fibers in the early life of offspring. Along with muscle growth and fiber-type transition, insulin sensitivity and glucose metabolism, including aerobic metabolism and glycolysis, were improved in the skeletal muscle of offspring. An untargeted metabolomic analysis further revealed the contribution of modified amino acid metabolism to the improved aerobic metabolism. Mechanistically, maternal MA consumption remodeled colonic microbiota of their offspring. Briefly, the abundance of Colidextribacter, Romboutsia, and Family_XIII_AD3011_group increased, which were positively associated with the antioxidant capacity and glucose metabolism of skeletal muscles. A decreased abundance of Prevotella, Blautia, Prevotellaceae_NK3B31_group, and Collinsella was also detected, which were involved in less insulin sensitivity. Notably, milk metabolites, such as ascorbic acid (AA) and granisetron (GS), were found as key effectors regulating the gut microbiota composition of piglets. The properties of AA and GS in alleviating insulin resistance, inflammation, and oxidative stress were further verified through mice treated with high-fat diets. Overall, this study revealed that maternal MA consumption could modulate the inflammatory response, antioxidant capacity, and glucose metabolism by regulating the gut microbiota of offspring through the vertical transmission of milk metabolites. These findings suggest the potential of MA in the prevention and treatment of MetS in early life.PMID:37741046 | DOI:10.1016/j.redox.2023.102889

Environ Int. 2023 Sep 16;180:108215. doi: 10.1016/j.envint.2023.108215. Online ahead of print.ABSTRACTRhizoremediation is a promising remediation technology for the removal of soil persistent organic pollutants (POPs), especially benzo[a]pyrene (BaP). However, our understanding of the associations among rhizospheric soil metabolites, functional microorganisms, and POPs degradation in different plant growth stages is limited. We combined stable-isotope probing (SIP), high-throughput sequencing, and metabolomics to analyze changes in rhizospheric soil metabolites, functional microbes, and BaP biodegradation in the early growth stages (tillering, jointing) and later stage (booting) of ryegrass. Microbial community structures differed significantly among growth stages. Metabolisms such as benzenoids and carboxylic acids tended to be enriched in the early growth stage, while lipids and organic heterocyclic compounds dominated in the later stage. From SIP, eight BaP-degrading microbes were identified, and most of which such as Ilumatobacter and Singulisphaera were first linked with BaP biodegradation. Notably, the relationship between the differential metabolites and BaP degradation efficiency further suggested that BaP-degrading microbes might metabolize BaP directly to produce benzenoid metabolites (3-hydroxybenzo[a]pyrene), or utilize benzenoids (phyllodulcin) to stimulate the co-metabolism of BaP in early growth stage; some lipids and organic acids, e.g. 1-aminocyclopropane-1-carboxylic acid, might provide nutrients for the degraders to promote BaP metabolism in later stage. Accordingly, we determined that certain rhizospheric metabolites might regulate the rhizospheric microbial communities at different growth stages, and shift the composition and diversity of BaP-degrading bacteria, thereby enhancing in situ BaP degradation. Our study sheds light on POPs rhizoremediation mechanisms in petroleum-contaminated soils.PMID:37741005 | DOI:10.1016/j.envint.2023.108215

J Sci Food Agric. 2023 Sep 23. doi: 10.1002/jsfa.13002. Online ahead of print.ABSTRACTBACKGROUND: Lianhua-Qingwen (LHQW) capsule is a Traditional Chinese Medicine (TCM) formula having anti-viral and anti-inflammatory activities. During the capsule production, huge byproducts will be yielded and disposed as waste by burying. Resourceful utilization of this kind of TCM byproducts as feed additives through stage-based co-fermentation using enzyme and probiotics could reduce environmental stress and resource shortage. The in vitro characterization and the supplementary effects of the fermented TCM byproducts (FTCM) for weaned piglets (initial body weight, 7.23 ± 0.33 kg; dose: basal diet + 300 mg/kg FTCM) were investigated.RESULTS: Higher reducing sugar content, total flavonoid content, flavonoid compounds (e.g. tectoridin, tricetin, flavone, apigenin, naringenin), and total antioxidant activity were determined in the FTCM compared to the spontaneously fermented and unfermented materials. Supplementation of the FTCM to piglets did not significantly affect the feed intake, body weight gain, and feed/gain ratio, but significantly decreased a pro-inflammatory cytokine IL-8 and increased intestinal total antioxidant activity (TAC) and superoxide dismutase (SOD) activity. Moreover, FTCM supplementation increased α-diversity of the colonic microbiota accompanied with increased abundance of Prevotella genus and Treponema berlinense species. Correlation analysis indicates T. berlinense is responsible for the decreased IL-8 level and enhanced intestinal TAC and SOD activities which might be mediated by a homoserine lactone molecule (3-oxo-C14).CONCLUSION: Overall, the stepwise co-fermentation enriched bioactive compounds within the TCM byproducts and its dietary supplementation did not generate any side effect on growth performance but displayed beneficial effects on enrichment of potential probiotic T. berlinense and relevant functions. This article is protected by copyright. All rights reserved.PMID:37740928 | DOI:10.1002/jsfa.13002

Eur Radiol. 2023 Sep 23. doi: 10.1007/s00330-023-10138-9. Online ahead of print.ABSTRACTOBJECTIVES: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups.METHODS: Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared.RESULTS: The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838).CONCLUSION: Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria.CLINICAL RELEVANCE STATEMENT: The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy.KEY POINTS: • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.PMID:37740778 | DOI:10.1007/s00330-023-10138-9

Metabolomics. 2023 Sep 23;19(10):85. doi: 10.1007/s11306-023-02047-1.ABSTRACTINTRODUCTION: Modern comprehensive instrumentations provide an unprecedented coverage of complex matrices in the form of high-dimensional, information rich data sets.OBJECTIVES: In addition to the usual biomarker research that focuses on the detection of the studied condition, we aimed to define a proper strategy to conduct a correlation analysis on an untargeted colorectal cancer case study with a data set of 102 variables corresponding to metabolites obtained from serum samples analyzed with comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). Indeed, the strength of association existing between the metabolites contains potentially valuable information about the molecular mechanisms involved and the underlying metabolic network associated to a global perturbation, at no additional analytical effort.METHODS: Following Anscombe's quartet, we took particular attention to four main aspects. First, the presence of non-linear relationships through the comparison of parametric and non-parametric correlation coefficients: Pearson's r, Spearman's rho, Kendall's tau and Goodman-Kruskal's gamma. Second, the visual control of the detected associations through scatterplots and their associated regressions and angles. Third, the effect and handling of atypical samples and values. Fourth, the role of the precision of the data on the attribution of the ranks through the presence of ties.RESULTS: Kendall's tau was found the method of choice for the data set at hand. Its application highlighted 17 correlations significantly altered in the active state of colorectal cancer (CRC) in comparison to matched healthy controls (HC), from which 10 were specific to this state in comparison to the remission one (R-CRC) investigated on distinct patients. 15 metabolites involved in the correlations of interest, on the 25 unique ones obtained, were annotated (Metabolomics Standards Initiative level 2).CONCLUSIONS: The metabolites highlighted could be used to better understand the pathology. The systematic investigation of the methodological aspects that we expose allows to implement correlation analysis to various fields and many specific cases.PMID:37740774 | DOI:10.1007/s11306-023-02047-1