PubMed

Anim Biosci. 2024 Apr 26. doi: 10.5713/ab.23.0422. Online ahead of print.ABSTRACTOBJECTIVE: Previous research reported that dietary addition with phytosterols improved the energy utilisation of the rumen microbiome, suggesting its potential to alleviate the negative energy balance of perinatal cows. This experiment aimed to explore the effects of feeding phytosterols on the metabolic status of perinatal cows through plasma metabolomics and faecal bacteria metabolism.METHODS: Ten perinatal Holstein cows (multiparous, 2 parities) with a similar calving date were selected four weeks before calving. After 7 days for adaptation, cows were allocated to two groups (n=5), which respectively received the basal rations supplementing commercial phytosterols at 0 and 200 mg/d during a 42-day experiment. The milk yield of each cow was recorded daily after calving. On days 1 and 42, blood and faeces samples were all collected from perinatal cows before morning feeding for analysing plasma biochemicals and metabolome, and faecal bacteria metabolism.RESULTS: Dietary addition with phytosterols at 200 mg/d had no effects on plasma cholesterol and numerically increased milk yield by 1.82 kg/d (p>0.10) but attenuated their negative energy balance in perinatal cows as observed from the significantly decreased plasma level of β-hydroxybutyric acid (p=0.002). Dietary addition with phytosterols significantly altered 12 and 15 metabolites (p<0.05) within the plasma and faeces of perinatal cows, respectively. Of these metabolites, 5 upregulated plasma fatty acids indicated an improved energy status (i.e., C18:1T, C14:0, C17:0, C18:0, and C16:0). Milk yield negatively correlated with plasma concentrations of ketone bodies (p=0.035) and 5-methoxytryptamine (p=0.039). Furthermore, dietary addition with phytosterols at 200 mg/d had no effects on fermentation characteristics and bacterial diversity of cow faeces (p>0.10) but improved potentially beneficial bacteria such as Christensenellaceae family (p<0.05) that positively correlated with feed efficiency.CONCLUSION: Dietary addition with phytosterols at 200 mg/d could effectively improve the energy status in perinatal cows by attenuating their negative energy balance.PMID:38665074 | DOI:10.5713/ab.23.0422

Phytochem Anal. 2024 Apr 25. doi: 10.1002/pca.3359. Online ahead of print.ABSTRACTINTRODUCTION: Artemisia argyi Folium (AAF) is a traditional medicinal herb and edible plant. Analyzing the differential metabolites that affect the efficacy of AAF with different aging years is necessary.OBJECTIVE: The aim of the study was to investigate the changing trend and differential markers of volatile and nonvolatile metabolites of AAF from different aging years, which are necessary for application in clinical medicine.METHODOLOGY: Metabolites were analyzed using a widely targeted metabolomic approach based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS).RESULTS: A total of 153 volatile metabolites and 159 nonvolatile metabolites were identified. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) could clearly distinguish AAF aged for 1 year (AF-1), 3 years (AF-3), and 5 years (AF-5). Seven flavonoids and nine terpenoids were identified as biomarkers for tracking the aging years.CONCLUSIONS: The metabolomic method provided an effective strategy for tracking and identifying biomarkers of AAF from different aging years. This study laid the foundation for analysis of the biological activity of Artemisia argyi with different aging years.PMID:38665054 | DOI:10.1002/pca.3359

Stem Cell Res Ther. 2024 Apr 25;15(1):121. doi: 10.1186/s13287-024-03717-0.ABSTRACTBACKGROUND: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and, despite its adverse effects, chemotherapy is the standard systemic treatment option for TNBC. Since, it is of utmost importance to consider the combination of different agents to achieve greater efficacy and curability potential, MSC secretome is a possible innovative alternative.METHODS: In the present study, we proposed to investigate the anti-tumor effect of the combination of a chemical agent (paclitaxel) with a complex biological product, secretome derived from human Uterine Cervical Stem cells (CM-hUCESC) in TNBC.RESULTS: The combination of paclitaxel and CM-hUCESC decreased cell proliferation and invasiveness of tumor cells and induced apoptosis in vitro (MDA-MB-231 and/or primary tumor cells). The anti-tumor effect was confirmed in a mouse tumor xenograft model showing that the combination of both products has a significant effect in reducing tumor growth. Also, pre-conditioning hUCESC with a sub-lethal dose of paclitaxel enhances the effect of its secretome and in combination with paclitaxel reduced significantly tumor growth and even allows to diminish the dose of paclitaxel in vivo. This effect is in part due to the action of extracellular vesicles (EVs) derived from CM-hUCESC and soluble factors, such as TIMP-1 and - 2.CONCLUSIONS: In conclusion, our data demonstrate the synergistic effect of the combination of CM-hUCESC with paclitaxel on TNBC and opens an opportunity to reduce the dose of the chemotherapeutic agents, which may decrease chemotherapy-related toxicity.PMID:38664697 | DOI:10.1186/s13287-024-03717-0

Microb Cell Fact. 2024 Apr 26;23(1):120. doi: 10.1186/s12934-024-02394-1.ABSTRACTBACKGROUND: The conversion of plant biomass into biochemicals is a promising way to alleviate energy shortage, which depends on efficient microbial saccharification and cellular metabolism. Trichoderma spp. have plentiful CAZymes systems that can utilize all-components of lignocellulose. Acetylation of polysaccharides causes nanostructure densification and hydrophobicity enhancement, which is an obstacle for glycoside hydrolases to hydrolyze glycosidic bonds. The improvement of deacetylation ability can effectively release the potential for polysaccharide degradation.RESULTS: Ammonium sulfate addition facilitated the deacetylation of xylan by inducing the up-regulation of multiple carbohydrate esterases (CE3/CE4/CE15/CE16) of Trichoderma harzianum. Mainly, the pathway of ammonium-sulfate's cellular assimilates inducing up-regulation of the deacetylase gene (Thce3) was revealed. The intracellular metabolite changes were revealed through metabonomic analysis. Whole genome bisulfite sequencing identified a novel differentially methylated region (DMR) that existed in the ThgsfR2 promoter, and the DMR was closely related to lignocellulolytic response. ThGsfR2 was identified as a negative regulatory factor of Thce3, and methylation in ThgsfR2 promoter released the expression of Thce3. The up-regulation of CEs facilitated the substrate deacetylation.CONCLUSION: Ammonium sulfate increased the polysaccharide deacetylation capacity by inducing the up-regulation of multiple carbohydrate esterases of T. harzianum, which removed the spatial barrier of the glycosidic bond and improved hydrophilicity, and ultimately increased the accessibility of glycosidic bond to glycoside hydrolases.PMID:38664812 | DOI:10.1186/s12934-024-02394-1

BMC Cardiovasc Disord. 2024 Apr 25;24(1):226. doi: 10.1186/s12872-024-03798-y.ABSTRACTBACKGROUND: Pathogenesis and diagnostic biomarkers of aortic dissection (AD) can be categorized through the analysis of differential metabolites in serum. Analysis of differential metabolites in serum provides new methods for exploring the early diagnosis and treatment of aortic dissection.OBJECTIVES: This study examined affected metabolic pathways to assess the diagnostic value of metabolomics biomarkers in clients with AD.METHOD: The serum from 30 patients with AD and 30 healthy people was collected. The most diagnostic metabolite markers were determined using metabolomic analysis and related metabolic pathways were explored.RESULTS: In total, 71 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism and four different metabolites considered of most diagnostic value including N2-gamma-glutamylglutamine, PC(phocholines) (20:4(5Z,8Z,11Z,14Z)/15:0), propionyl carnitine, and taurine. These four predictive metabolic biomarkers accurately classified AD patient and healthy control (HC) samples with an area under the curve (AUC) of 0.9875. Based on the value of the four different metabolites, a formula was created to calculate the risk of aortic dissection. Risk score = (N2-gamma-glutamylglutamine × -0.684) + (PC (20:4(5Z,8Z,11Z,14Z)/15:0) × 0.427) + (propionyl carnitine × 0.523) + (taurine × -1.242). An additional metabolic pathways model related to aortic dissection was explored.CONCLUSION: Metabolomics can assist in investigating the metabolic disorders associated with AD and facilitate a more in-depth search for potential metabolic biomarkers.PMID:38664632 | DOI:10.1186/s12872-024-03798-y

BMC Plant Biol. 2024 Apr 25;24(1):335. doi: 10.1186/s12870-024-05016-5.ABSTRACTBACKGROUND: The vivid red, purple, and blue hues that are observed in a variety of plant fruits, flowers, and leaves are produced by anthocyanins, which are naturally occurring pigments produced by a series of biochemical processes occurring inside the plant cells. The purple-stalked Chinese kale, a popular vegetable that contains anthocyanins, has many health benefits but needs to be investigated further to identify the genes involved in the anthocyanin biosynthesis and translocation in this vegetable.RESULTS: In this study, the purple- and green-stalked Chinese kale were examined using integrative transcriptome and metabolome analyses. The content of anthocyanins such as cyanidin-3-O-(6″-O-feruloyl) sophoroside-5-O-glucoside, cyanidin-3,5-O-diglucoside (cyanin), and cyanidin-3-O-(6″-O-p-hydroxybenzoyl) sophoroside-5-O-glucoside were considerably higher in purple-stalked Chinese kale than in its green-stalked relative. RNA-seq analysis indicated that 23 important anthocyanin biosynthesis genes, including 3 PAL, 2 C4H, 3 4CL, 3 CHS, 1 CHI, 1 F3H, 2 FLS, 2 F3'H, 1 DFR, 3 ANS, and 2 UFGT, along with the transcription factor BoMYB114, were significantly differentially expressed between the purple- and green-stalked varieties. Results of analyzing the expression levels of 11 genes involved in anthocyanin production using qRT-PCR further supported our findings. Association analysis between genes and metabolites revealed a strong correlation between BoGSTF12 and anthocyanin. We overexpressed BoGSTF12 in Arabidopsis thaliana tt19, an anthocyanin transport mutant, and this rescued the anthocyanin-loss phenotype in the stem and rosette leaves, indicating BoGSTF12 encodes an anthocyanin transporter that affects the accumulation of anthocyanins.CONCLUSION: This work represents a key step forward in our understanding of the molecular processes underlying anthocyanin production in Chinese kale. Our comprehensive metabolomic and transcriptome analyses provide important insights into the regulatory system that controls anthocyanin production and transport, while providing a foundation for further research to elucidate the physiological importance of the metabolites found in this nutritionally significant vegetable.PMID:38664614 | DOI:10.1186/s12870-024-05016-5

EMBO J. 2024 Apr 25. doi: 10.1038/s44318-024-00098-1. Online ahead of print.NO ABSTRACTPMID:38664540 | DOI:10.1038/s44318-024-00098-1

Sci Rep. 2024 Apr 25;14(1):9555. doi: 10.1038/s41598-024-60217-0.ABSTRACTSystemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.PMID:38664528 | DOI:10.1038/s41598-024-60217-0

Sci Rep. 2024 Apr 25;14(1):9519. doi: 10.1038/s41598-024-60167-7.ABSTRACTFemale and latent genital tuberculosis (FGTB and LGTB) in young women may lead to infertility by damaging ovarian reserve function, but the regulatory mechanisms remain unclear. In this study, we investigated the effects of FGTB and LGTB on ovarian reserve function and potential regulatory mechanisms by untargeted metabolomics of follicular fluid, aiming to provide insights for the clinical management and treatment approaches for afflicted women. We recruited 19 patients with FGTB, 16 patients with LGTB, and 16 healthy women as a control group. Clinical data analysis revealed that both the FGTB and LGTB groups had significantly lower ovarian reserve marker levels compared to the control group, including lower anti-Müllerian hormone levels (FGTB: 0.82 [0.6, 1.1] μg/L; LGTB: 1.57 [1.3, 1.8] μg/L vs. control: 3.29 [2.9, 3.5] μg/L), reduced antral follicular counts (FGTB: 6 [5.5, 9.5]; LGTB: 10.5 [7, 12.3] vs. control: 17 [14.5, 18]), and fewer retrieved oocytes (FGTB: 3 [2, 5]; LGTB: 8 [4, 8.3] vs. control: 14.5 [11.5, 15.3]). Conversely, these groups exhibited higher ovarian response marker levels, such as longer gonadotropin treatment days (FGTB: 12 [10.5, 12.5]; LGTB: 11 [10.8, 11.3] vs. control: 10 [8.8, 10]) and increased gonadotropin dosage requirements (FGTB: 3300 [3075, 3637.5] U; LGTB: 3037.5 [2700, 3225] U vs. control: 2531.25 [2337.5, 2943.8] U). All comparisons were statistically significant at P < 0.05. The results suggested that FGTB and LGTB have adverse effects on ovarian reserve and response. Untargeted metabolomic analysis identified 92 and 80 differential metabolites in the control vs. FGTB and control vs. LGTB groups, respectively. Pathway enrichment analysis revealed significant alterations in metabolic pathways in the FGTB and LGTB groups compared to the control group (P < 0.05), with specific changes noted in galactose metabolism, biotin metabolism, steroid hormone biosynthesis, and nicotinate and nicotinamide metabolism in the FGTB group, and caffeine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerophospholipid metabolism in the LGTB group. The analysis of metabolic levels has revealed the potential mechanisms by which FGTB and LGTB affect ovarian reserve function, namely through alterations in metabolic pathways. The study emphasizes the importance of comprehending the metabolic alterations associated with FGTB and LGTB, which is of considerable relevance for the clinical management and therapeutic approaches in afflicted women.PMID:38664479 | DOI:10.1038/s41598-024-60167-7

Trends Endocrinol Metab. 2024 Apr 24:S1043-2760(24)00093-6. doi: 10.1016/j.tem.2024.04.010. Online ahead of print.ABSTRACTLiver-targeted acetyl-coenzyme A (CoA) carboxylase (ACC) inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD) trials reveal notable secondary effects: hypertriglyceridemia and altered glucose metabolism, paradoxically with reduced hepatic steatosis. In their study, Deja et al. explored how hepatic ACC influences metabolism using different pharmacological and genetic methods, coupled with targeted metabolomics and stable isotope-based tracing techniques.PMID:38664153 | DOI:10.1016/j.tem.2024.04.010

Life Sci Alliance. 2024 Apr 25;7(7):e202302498. doi: 10.26508/lsa.202302498. Print 2024 Jul.ABSTRACTMitochondrial transcription factor A, TFAM, is essential for mitochondrial function. We examined the effects of overexpressing the TFAM gene in mice. Two types of transgenic mice were created: TFAM heterozygous (TFAM Tg) and homozygous (TFAM Tg/Tg) mice. TFAM Tg/Tg mice were smaller and leaner notably with longer lifespans. In skeletal muscle, TFAM overexpression changed gene and protein expression in mitochondrial respiratory chain complexes, with down-regulation in complexes 1, 3, and 4 and up-regulation in complexes 2 and 5. The iMPAQT analysis combined with metabolomics was able to clearly separate the metabolomic features of the three types of mice, with increased degradation of fatty acids and branched-chain amino acids and decreased glycolysis in homozygotes. Consistent with these observations, comprehensive gene expression analysis revealed signs of mitochondrial stress, with elevation of genes associated with the integrated and mitochondrial stress responses, including Atf4, Fgf21, and Gdf15. These found that mitohormesis develops and metabolic shifts in skeletal muscle occur as an adaptive strategy.PMID:38664021 | DOI:10.26508/lsa.202302498

Insect Biochem Mol Biol. 2024 Apr 23:104126. doi: 10.1016/j.ibmb.2024.104126. Online ahead of print.ABSTRACTInsect wax accumulates on the surface of insect cuticle, which acts as an important protective barrier against rain, ultraviolet light radiation, pathogens, etc. The waxing behavior, wax composition and molecular mechanism underling wax biosynthesis are unclear in dustywings. Herein, the current study determined the vital developmental stage for waxing behavior in dustywings, examined the components of waxy secretions, and identified key regulatory genes for wax biosynthesis. The wax glands were mainly located on the thorax and abdomen of dustywing adults. The adults spread the waxy secretions over their entire body surface. The metabolomics analysis identified 32 lipids and lipid-like molecules, 15 organic acids and derivatives, 7 benzenoids, etc. as the main components of waxy secretions. The fatty acids represented the largest proportion of the category of lipid and lipid-like molecules. The conjoint analysis of metabolomics and transcriptomics identified two crucial genes fatty acyl-CoA reductase (CsFAR) and calmodulin (CsCaM) for wax biosynthesis. The down-regulation of these genes via nanocarrier-mediated RNA interference technology significantly reduced the amount of wax particles. Notably, the RNAi of CsCaM apparently suppressed the expression of most genes in fatty acid biosynthesis pathway, indicating the CsCaM might act as a main upstream regulator of fatty acid biosynthesis pathway.PMID:38663758 | DOI:10.1016/j.ibmb.2024.104126

Fitoterapia. 2024 Apr 23:105974. doi: 10.1016/j.fitote.2024.105974. Online ahead of print.ABSTRACTAlhagi honey is derived from the secretory granules of Alhagi pseudoalhagi Desv., a leguminous plant commonly known as camelthorn. Modern medical research has demonstrated that the extract of Alhagi honey possesses regulatory properties for the gastrointestinal tract and immune system, as well as exerts anti-tumor, anti-oxidative, anti-inflammatory, anti-bacterial, and hepatoprotective effects. The aim of this study was to isolate and purify oligosaccharide monomers (referred to as Mel) from camelthorn and elucidate their structural characteristics. Subsequently, the impact of Mel on liver injury induced by carbon tetrachloride (CCl4) in mice was investigated. The analysis identified the isolated oligosaccharide monomer (α-D-Glcp-(1 → 3)-β-D-Fruf-(2 → 1)-α-D-Glcp), with the molecular formula C18H32O16. In a mouse model of CCl4-induced liver fibrosis, Mel demonstrated significant therapeutic effects by attenuating the development of fibrosis. Moreover, it enhanced anti-oxidant enzyme activity (glutathione peroxidase and superoxide dismutase) in liver tissues, thereby reducing oxidative stress markers (malondialdehyde and reactive oxygen species). Mel also improved serum albumin levels, lowered liver enzyme activities (aspartate aminotransferase and alanine aminotransferase), and decreased inflammatory factors (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Immunohistochemistry, immunofluorescence, and western blotting analyses confirmed the ability of Mel to downregulate hepatic stellate cell-specific markers (collagen type I alpha 1 chain, alpha-smooth muscle actin, transforming growth factor-beta 1. Non-targeted metabolomics analysis revealed the influence of Mel on metabolic pathways related to glutathione, niacin, pyrimidine, butyric acid, and amino acids. In conclusion, the results of our study highlight the promising potential of Mel, derived from Alhagi honey, as a viable candidate drug for treating liver fibrosis. This discovery offers a potentially advantageous option for individuals seeking natural and effective means to promote liver health.PMID:38663563 | DOI:10.1016/j.fitote.2024.105974

Clin Chim Acta. 2024 Apr 23:119687. doi: 10.1016/j.cca.2024.119687. Online ahead of print.ABSTRACTOvarian cancers (OC) are the most common, lethal, and stage-dependent cancers at the global level, specifically in female patients. Targeted therapies involve the administration of drugs that specifically target the alterations in tumour cells responsible for their growth, proliferation, and metastasis, with the aim of treating particular patients. Presently, within the realm of gynaecological malignancies, specifically in breast and OCs, there exist various prospective therapeutic targets encompassing tumour-intrinsic signalling pathways, angiogenesis, homologous-recombination deficit, hormone receptors, and immunologic components. Breast cancers are often detected in advanced stages, primarily due to the lack of a reliable screening method. However, various tumour markers have been extensively researched and employed to evaluate the condition, progression, and effectiveness of medication treatments for this ailment. The emergence of recent technological advancements in the domains of bioinformatics, genomics, proteomics, and metabolomics has facilitated the exploration and identification of hitherto unknown biomarkers. The primary objective of this comprehensive review is to meticulously investigate and analyze both established and emerging methodologies employed in the identification of tumour markers associated with OC.PMID:38663473 | DOI:10.1016/j.cca.2024.119687

Respiration. 2024 Apr 25. doi: 10.1159/000538911. Online ahead of print.ABSTRACTINTRODUCTION: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD.METHODS: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients.RESULTS: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin-treatment group than in the COPD group.CONCLUSION: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.PMID:38663359 | DOI:10.1159/000538911

J Hazard Mater. 2024 Apr 19;471:134360. doi: 10.1016/j.jhazmat.2024.134360. Online ahead of print.ABSTRACTLead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.PMID:38663295 | DOI:10.1016/j.jhazmat.2024.134360

J Pharm Biomed Anal. 2024 Apr 22;245:116167. doi: 10.1016/j.jpba.2024.116167. Online ahead of print.ABSTRACTWilson disease (WD) is an autosomal recessive disorder characterized by abnormal copper metabolism. The accumulation of copper in the liver can progress to liver fibrosis and, ultimately, cirrhosis, which is a primary cause of death in WD patients. Metabonomic technology offers an effective approach to investigate the traditional Chinese medicine (TCM) syndrome types of WD-related liver fibrosis by monitoring the alterations in small molecule metabolites within the body. In this study, we employed 1H-Nuclear Magnetic Resonance (1H NMR) metabonomics to assess the metabolic profiles associated with five TCM syndrome types of WD-related liver fibrosis and analyzed the diagnostic and predictive capabilities of various metabolites. The study found a variety of metabolites, each with varying levels of diagnostic and predictive capabilities. Furthermore, the discerned differential metabolic pathways were primarily associated with various pathways involving carbohydrate metabolism, amino acid metabolism, and lipid metabolism. This study has identified various characteristic metabolic markers and pathways associated with different TCM syndromes of liver fibrosis in WD, providing a substantial foundation for investigating the mechanisms underlying these TCM syndromes.PMID:38663257 | DOI:10.1016/j.jpba.2024.116167

Food Chem. 2024 Feb 15;451:138767. doi: 10.1016/j.foodchem.2024.138767. Online ahead of print.ABSTRACTBy collecting real samples throughout the entire production process and employing chemometrics, metabolomics, and modern separation omic techniques, it unveiled the patterns of pesticide transfer during solid-state fermentation. The results indicated that 12 types of pesticide residues were prevalent during baijiu production, with organochlorine and carbamate pesticides being the most abundant in raw materials. After fermentation, organochlorine pesticides and pyrethroid pesticides exhibited higher content, while carbamate pesticides dominated in the final product. The pathways for pesticide input and elimination were identified, and the intricate mechanisms underlying these changes were further elucidated. Additionally, key control points were defined to facilitate targeted monitoring. The results indicated that pesticide residue primarily originates from raw materials and Daqu, whereas both solid-state fermentation and distillation processes were effective in reducing pesticide residues. The study offers valuable guidance for establishing pesticide residue standards in the context of baijiu production.PMID:38663241 | DOI:10.1016/j.foodchem.2024.138767

Biomater Adv. 2024 Apr 15;160:213861. doi: 10.1016/j.bioadv.2024.213861. Online ahead of print.ABSTRACTNovel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted cellular responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, biochemical molecule embedding, force-tuneable materials, and artificial extracellular matrices are helping understand cellular mechanotransduction. Collectively, these strategies manipulate cellular sensing and regulate signalling cascades including focal adhesions, YAP-TAZ transcription factors, and multiple osteogenic pathways. In this minireview, we are providing a summary of the influence that these materials, particularly titanium-based orthopaedic materials, have on cells. We also highlight recent complementary methodological developments including, but not limited to, the use of metabolomics for identification of active biomolecules that drive cellular differentiation.PMID:38663159 | DOI:10.1016/j.bioadv.2024.213861

Biochem Biophys Res Commun. 2024 Apr 22;714:149977. doi: 10.1016/j.bbrc.2024.149977. Online ahead of print.ABSTRACTMalignant tumors are characterized by a hypoxic microenvironment, and metabolic reprogramming is necessary to ensure energy production and oxidative stress resistance. Although the microenvironmental properties of tumors vary under acute and chronic hypoxia, studies on chronic hypoxia-induced metabolic changes are limited. In the present study, we performed a comprehensive metabolic analysis in a chronic hypoxia model using colorectal cancer (CRC) organoids, and identified an amino acid supply system through the γ-glutamyl cycle, a glutathione recycling pathway. We analyzed the metabolic changes caused by hypoxia over time and observed that chronic hypoxia resulted in an increase in 5-oxoproline and a decrease in oxidized glutathione (GSSG) compared to acute hypoxia. These findings suggest that chronic hypoxia induces metabolic changes in the γ-glutamyl cycle. Moreover, inhibition of the γ-glutamyl cycle via γ-glutamyl cyclotransferase (GGCT) and γ-glutamyl transferase 1 (GGT1) knockdown significantly reversed chronic hypoxia-induced upregulation of 5-oxoproline and several amino acids. Notably, GGT1 knockdown downregulated the intracellular levels of γ-glutamyl amino acids. Conclusively, these results indicate that the γ-glutamyl cycle serves as an amino acid supply system in CRC under chronic hypoxia, which provides fresh insight into cancer metabolism under chronic hypoxia.PMID:38663093 | DOI:10.1016/j.bbrc.2024.149977