PubMed

ACS Meas Sci Au. 2023 Dec 8;4(1):117-126. doi: 10.1021/acsmeasuresciau.3c00055. eCollection 2024 Feb 21.ABSTRACTProstate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits limited specificity and comes with poor predictive value. Prior to PSA, prostatic acid phosphatase (PAP) was used, but it was replaced by PSA because PSA improved the early detection of PCa. Upon revisiting PAP and its glycosylation specifically, it appears to be a promising new biomarker candidate. Namely, previous studies have indicated that PAP glycoforms differ between PCa and non-PCa individuals. However, an in-depth characterization of PAP glycosylation is still lacking. In this study, we established an in-depth glycoproteomic assay for urinary PAP by characterizing both the micro- and macroheterogeneity of the PAP glycoprofile. For this purpose, PAP samples were analyzed by capillary electrophoresis coupled to mass spectrometry after affinity purification from urine and proteolytic digestion. The developed urinary PAP assay was applied on a pooled DRE (digital rectal examination) urine sample from nine individuals. Three glycosylation sites were characterized, namely N94, N220, and N333, via N-glycopeptide analysis. Taking sialic acid linkage isomers into account, a total of 63, 27, and 4 N-glycan structures were identified, respectively. The presented PAP glycoproteomic assay will enable the determination of potential glycomic biomarkers for the early detection and prognosis of PCa in cohort studies.PMID:38404489 | PMC:PMC10885330 | DOI:10.1021/acsmeasuresciau.3c00055

Vet Q. 2024 Dec;44(1):1-11. doi: 10.1080/01652176.2024.2319828. Epub 2024 Feb 25.ABSTRACTChinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p < .05) the concentrations of several saturated fatty acids (SFA, including myristic acid and stearic acid), monounsaturated fatty acids (MUFA, including petroselinic acid, elaidic acid, trans-11-eicosenoic acid, and cis-11-eicosenoic acid), polyunsaturated fatty acids (PUFA, including linolelaidic acid, linoleic acid, γ-linolenic acid, α-linolenic acid, 11c,14c-eicosadienoic acid, eicosatrienoic acid, homo-γ-linolenic acid, arachidonic acid, and docosapentaenoic acid), and fatty acid indexes (total MUFA, n-3 and n-6 PUFA, PUFA/SFA, hypocholesterolemic/hypercholesterolaemic ratio, health promotion index, and desirable fatty acids) in egg yolks. Collectively, these findings suggest that dietary CHF supplementation could improve the nutritional value of fatty acids in egg yolks of aged laying hens, which would be beneficial for the production of healthier eggs to meet consumer demands.PMID:38404134 | DOI:10.1080/01652176.2024.2319828

FEBS Open Bio. 2024 Feb 25. doi: 10.1002/2211-5463.13776. Online ahead of print.ABSTRACTThe precise etiology of inflammatory bowel diseases (IBDs) remains elusive. The Escherichia coli strain LF82 (LF82) is known to be associated with IBD, and we hypothesized that this association may be related to the chuT and shuU genes. Here we constructed a germ-free (GF) honeybee model to investigate the effects of LF82 chuT and shuU genes on the honeybee intestine and their mechanisms. The chuT and shuU gene deletion strains LF82∆chuT and LF82∆shuU were generated by CRISPR-Cas9. These strains, together with nonpathogenic E. coli MG1655 (MG1655) and wildtype LF82, were allowed to colonize the guts of GF honeybees to establish single bacterial colonization models. Intestinal permeability was assessed following the administration of a sterile Brilliant Blue (FCF) solution. Comprehensive transcriptomic and metabolomic analyses of intestinal samples indicated that MG1655 had few disadvantageous effects on honeybees. Conversely, colonization with LF82 and its gene-deletion mutants provoked pronounced activation of genes associated with innate immune pathways, stimulated defensive responses, and induced expression of genes associated with inflammation, oxidative stress, and glycosaminoglycan degradation. Crucially, the LF82∆chuT and LF82∆shuU strains perturbed host heme and iron regulation, as well as tryptophan metabolism. These findings suggest that the deletion of chuT and shuU genes in E. coli LF82 may alleviate intestinal inflammation by partially modulating tryptophan catabolism. Our study proposes that targeting iron uptake mechanisms could be a potential strategy to mitigate the virulence of IBD-associated bacteria.PMID:38403884 | DOI:10.1002/2211-5463.13776

J Transl Med. 2024 Feb 25;22(1):202. doi: 10.1186/s12967-024-05004-1.ABSTRACTBACKGROUND: The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored.METHODS: In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites.RESULTS: Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces.CONCLUSIONS: Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.PMID:38403655 | DOI:10.1186/s12967-024-05004-1

J Sep Sci. 2024 Feb;47(4):e2300836. doi: 10.1002/jssc.202300836.ABSTRACTPhellodendri Amurensis Cortex (PAC) is a medicinal herb that has been generally used to treat diarrhea and jaundice. In order to comprehensively evaluate the PAC in the main production areas quality, a qualitative and quantitative method with highly effective, sensitive, and reliable was developed. The chemical compositions of PAC were analyzed, and fingerprints were established by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). Then, the determination of berberine, canthin-6-one, dictamnine, γ-fagarine, and magnoflorine from PAC samples was simultaneously performed using UPLC-QQQ-MS. Furthermore, the chemical components of PAC from different regions were compared and analyzed by combining hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. A total of 58 compounds were identified, including 36 alkaloids, four phenylpropanoids, seven terpenoids, four flavonoids and their glycosides, an organic acid compound, and six other components. The fingerprint results show that samples have good similarity. Meanwhile, the content of the five ingredients in different habitats is quite different. By multivariate statistical analysis, 18 batches of PAC could be divided into three categories, and 20 components were identified as differential markers of various origins. A comprehensive method of PAC quality evaluation and chemical composition difference analysis was established, which provided the scientific basis for quality evaluation and further pharmacological mechanism research.PMID:38403444 | DOI:10.1002/jssc.202300836

Biotechnol J. 2024 Feb;19(2):e2300566. doi: 10.1002/biot.202300566.ABSTRACTVinegar and related bioproducts containing acetic acid as the main component are among the most appreciated fermented foodstuffs in numerous European and Asian countries because of their exceptional organoleptic and bio-healthy properties. Regarding the acetification process and obtaining of final products, there is still a lack of knowledge on fundamental aspects, especially those related to the study of biodiversity and metabolism of the present microbiota. In this context, omic technologies currently allow for the massive analysis of macromolecules and metabolites for the identification and characterization of these microorganisms working in their natural media without the need for isolation. This review approaches comprehensive research on the application of omic tools for the identification of vinegar microbiota, mainly acetic acid bacteria, with subsequent emphasis on the study of the microbial diversity, behavior, and key molecular strategies used by the predominant groups throughout acetification. The current omics tools are enabling both the finding of new vinegar microbiota members and exploring underlying strategies during the elaboration process. The species Komagataeibacter europaeus may be a model organism for present and future research in this industry; moreover, the development of integrated meta-omic analysis may facilitate the achievement of numerous of the proposed milestones. This work might provide useful guidance for the vinegar industry establishing the first steps towards the improvement of the acetification conditions and the development of new products with sensory and bio-healthy profiles adapted to the agri-food market.PMID:38403443 | DOI:10.1002/biot.202300566

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2024 Feb 20;42(2):152-155. doi: 10.3760/cma.j.cn121094-20230703-00227.ABSTRACTForest encephalitis is a natural focal disease transmitted through the bite of hard ticks, and its pathogen is the tick-borne encephalitis virus from the Flaviviridae family. The mortality rate of forest encephalitis is relatively high, making laboratory testing significant in diagnosing this disease. This article elaborates on the etiological diagnostic methods and recent research progress in forest encephalitis. Laboratory tests for forest encephalitis mainly include routine examinations, serological tests, virus isolation, and molecular biological testing. The detection of serum-specific IgM antibodies against the forest encephalitis virus is of great importance for early diagnosis, and specific IgG antibodies serve as a "gold standard" for differentiation from other diseases. Techniques such as enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay for detecting specific IgM antibodies in serum and/or cerebrospinal fluid, the serum hemagglutination inhibition test or serum complement fixation test, and the double serum hemagglutination inhibition test or complement fixation test all contribute to the early diagnosis. The development of molecular testing methods is rapid, and techniques such as metabolomics, digital PCR, and matrix metalloproteinases are also applied in the early diagnosis of forest encephalitis.PMID:38403427 | DOI:10.3760/cma.j.cn121094-20230703-00227

Biotechnol J. 2024 Feb;19(2):e2300495. doi: 10.1002/biot.202300495.ABSTRACTThe optimization of bioprocess for CHO cell culture involves careful consideration of factors such as nutrient consumption, metabolic byproduct accumulation, cell growth, and monoclonal antibody (mAb) production. Valuable insights can be obtained by understanding cellular physiology to ensure robust and efficient bioprocess. This study aims to improve our understanding of the CHO-K1 cell metabolism using 1 H NMR-based metabolomics. Initially, the variations in culture performance and metabolic profiles under varied aeration conditions and copper supplementations were thoroughly examined. Furthermore, a comprehensive metabolic pathway analysis was performed to assess the impact of these conditions on the implicated pathways. The results revealed substantial alterations in the pyruvate metabolism, histidine metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis, which were especially evident in cultures subjected to copper deficiency conditions. Conclusively, significant metabolites governing cell growth and mAb titer were identified through orthogonal partial least square-discriminant analysis (OPLS-DA). Metabolites, including glycerol, alanine, formate, glutamate, phenylalanine, and valine, exhibited strong associations with distinct cell growth phases. Additionally, glycerol, acetate, lactate, formate, glycine, histidine, and aspartate emerged as metabolites influencing cell productivity. This study demonstrates the potential of employing 1 H NMR-based metabolomics technology in bioprocess research. It provides valuable guidance for feed medium development, feeding strategy design, bioprocess parameter adjustments, and ultimately the enhancement of cell proliferation and mAb yield.PMID:38403407 | DOI:10.1002/biot.202300495

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(1):232-242. doi: 10.19540/j.cnki.cjcmm.20230914.706.ABSTRACTThis study aimed at investigating the mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus(GX) in treating cardiovascular diseases in rats with the syndrome of combined phlegm and stasis. The rat model was established by a high-fat diet, ice-water bath combined with subcutaneous injection of adrenalin hydrochloride, and the syndrome score was determined. The serum samples of rats in the control, model, and GX groups were collected. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to analyze the metabolic profiles of the serum samples. The differential metabolites were screened and identified by partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The intervention targets of GX-regulated metabolites and their metabolic pathways were searched against MetaboAnalyst. Gene Ontology enrichment was carried out to predict the biological pathways associated with the intervention targets of metabolic pathways. A total of 129 potential biomarkers were detected in the rat model with the syndrome of combined phlegm and stasis via metabolomics, and GX regulated 54 metabolites in several metabolic pathways such as linoleic acid metabolism, sphingolipid metabolism, and tricarboxylic acid cycle. The further screening against MetaboAnalyst showed that GX recovered the levels of nine metabolites associated with cardiovascular diseases with the syndrome of combined phlegm and stasis, which involved 69 targets in the pathways regarding cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism. The above-mentioned results suggested that GX can alleviate the symptoms of the rat model of cardiovascular diseases with the syndrome of combined phlegm and stasis by regulating the metabolism of linoleic acid, sphingosine, docosahexaenoic acid, rosemary acid, succinic acid, adenine, L-phenylalanine, L-valine and modulating the biological pathways such as cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism.PMID:38403356 | DOI:10.19540/j.cnki.cjcmm.20230914.706

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(1):224-231. doi: 10.19540/j.cnki.cjcmm.20230808.402.ABSTRACTThis study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1β, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.PMID:38403355 | DOI:10.19540/j.cnki.cjcmm.20230808.402

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(2):550-558. doi: 10.19540/j.cnki.cjcmm.20231010.501.ABSTRACTThis study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula. Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8). Both groups received routine chemical medicine treatment. In addition, the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks. The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, with the ethical approval No. 2017-023-01, and all the patients signed the informed consent form. The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP), 24 h urinary microalbumin(24hmAlb), urine albumin-to-creatinine ratio(UACR), and estimated glomerular filtration rate(eGFR) of the patients with 24hUP&lt;3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP&lt;3.5 g and subgroup B with 24hUP≥3.5 g). The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients. Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups, and their correlations with clinical indicators were analyzed. Zicuiyin lowered the levels of phenylalanine, pseudouridine, and adenosine [fold change(FC)&lt;0.5, P&lt;0.05] in subgroup A. The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels, and its targets were involved in phenylalanine metabolism and nucleoside metabolism.PMID:38403329 | DOI:10.19540/j.cnki.cjcmm.20231010.501

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(2):461-470. doi: 10.19540/j.cnki.cjcmm.20231013.702.ABSTRACTThis study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 μg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.PMID:38403322 | DOI:10.19540/j.cnki.cjcmm.20231013.702

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(2):453-460. doi: 10.19540/j.cnki.cjcmm.20230914.705.ABSTRACTThis study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.PMID:38403321 | DOI:10.19540/j.cnki.cjcmm.20230914.705

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(2):443-452. doi: 10.19540/j.cnki.cjcmm.20231008.401.ABSTRACTChinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.PMID:38403320 | DOI:10.19540/j.cnki.cjcmm.20231008.401

Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(2):389-402. doi: 10.19540/j.cnki.cjcmm.20231030.302.ABSTRACTUltra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1β(IL-1β), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1β, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.PMID:38403315 | DOI:10.19540/j.cnki.cjcmm.20231030.302

Am J Clin Nutr. 2024 Feb 23:S0002-9165(24)00157-6. doi: 10.1016/j.ajcnut.2024.02.012. Online ahead of print.ABSTRACTBACKGROUND: Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers.AIMS: To investigate metabolite biomarkers of meat intake and their associations with T2D risk.METHODS: Fasting plasma samples were collected from a case-control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed and unprocessed red meat, and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n=4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts.RESULTS: In total, 15 metabolites were associated with at least one meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake (r>0.22, FDR<0.001 for VIP and r>0.05, FDR <0.001 for SMCC) were consistently associated with higher T2D risk in both datasets. Conversely, lysophosphatidylcholine (LPC) 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < -0.12, FDR <0.023 for VIP and r < -0.05, FDR<0.001 for SMCC) and with lower T2D risk in both datasets, except for PC 15:0/18:2 which was significant only in VIP. All associations were attenuated after adjustment for BMI.CONCLUSION: Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.PMID:38403167 | DOI:10.1016/j.ajcnut.2024.02.012

Am J Pathol. 2024 Feb 23:S0002-9440(24)00073-7. doi: 10.1016/j.ajpath.2024.02.004. Online ahead of print.ABSTRACTChanges in the anterior segment due to type 2 diabetes mellitus (T2DM) are not well characterized, in part due to the lack of a reliable animal model. This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites and ciliary body vasculature, in a rat model of type 2 diabetes mellitus (T2DM) compared with human eyes. Sprague-Dawley male rats were fed a high fat diet (HFD, 45% fat) or normal diet, and HFD rats were injected intraperitoneally with streptozotocin (STZ) to create a model of T2DM. Microscopic analysis was performed to determine cataract formation and corneal endothelial cell density. Metabolomics of rat aqueous humor was performed to determine diabetes-related aqueous alterations. Transmission electron microscopy was used to assess qualitative ultrastructural changes of diabetic rat and human ciliary process microvessels at the site of aqueous formation. Diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. Results support use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.PMID:38403162 | DOI:10.1016/j.ajpath.2024.02.004

Clin Chim Acta. 2024 Feb 23:117845. doi: 10.1016/j.cca.2024.117845. Online ahead of print.ABSTRACTBACKGROUND: Prostate cancer (PCa) lacks convenient and highly specific diagnostic markers. Although the value of extracellular vesicles (EV) in oncology is widely recognized, the diagnostic value of EV metabolites requires further exploration. This study aimed to explore the diagnostic value of urine EV (u-EV) metabolomics in PCa.METHODS: We first detected metabolites in paired tissues cells (cells), tissue EV (t-EVs), u-EVs, and urine samples in cohort 1 (8 PCa vs. 5 benign prostatic hypertrophy, BPH) to prob the feasibility of EV metabolites as diagnostic markers. We then analyzed the value of u-EVs as markers for PCa diagnosis and typing in the expanded sample cohort (60 PCa vs. 40 BPH).RESULTS: U-EV metabolites were more consistent with those in tissue-derived samples (cells and t-EVs) than those in urine, and more differential metabolites between BPH and PCa were identified in u-EV. Subsequently, we used a random forest model to construct a panel of six metabolites for PCa, which showed an area under the curve (AUC) of 0.833 in training cohort and 0.844 in validation cohort. We also found significantly differentially expressed metabolites between PCa subtypes (Gleason ≤ 7 vs. Gleason > 7 and localized vs. metastasis), demonstrating the value of EV metabolites in PCa typing and prognostic assessment.CONCLUSION: Metabolomic analysis of u-EVs is a promising source of noninvasive markers for PCa diagnosis.PMID:38403146 | DOI:10.1016/j.cca.2024.117845

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Feb 23:109865. doi: 10.1016/j.cbpc.2024.109865. Online ahead of print.ABSTRACTThe emergence of graphene quantum dots (GQDs) expands the use of graphene derivatives in nanomedicine for its direct therapeutic applications in treating neurodegeneration, inflammation, metabolic dysfunction, and among others. Nevertheless, the biosafety assessment of GQDs remains deficient mostly because of the diverse surface characteristics of the nanoparticles. Our prior work demonstrated that GQDs can induce strong thigmotactic effects in zebrafish larvae over a wide range of concentrations, yet the underlying metabolic mechanisms remain largely unknown. In this study, we conducted a further exploration about graphene oxide quantum dots (GOQDs) for its potential neurotoxic effect on the behaviors of zebrafish larvae by combining neurotransmitter-targeted metabolomics with locomotion analysis. After continuous exposure to a concentration gradient of GOQDs (12.5 - 25 - 50 - 100 - 200 μg/mL) for 7 days, the thigmotactic activities of zebrafish larvae were observed across all exposure concentrations relative to the control group, while the basal locomotor activities, including distance moved and average velocity, were significantly changed by low concentrations of GOQDs. Targeted metabolomics was performed using zebrafish larvae at 7 days post-fertilization (dpf) that were exposed to 12.5 and 200 μg/mL, both of which were found to perturb the kynurenine pathway by regulating the levels of kynurenine, 3-hydroxyanthranilic acid (3-HAA), and quinolinic acid (QA). Furthermore, the thigmotaxis of larval fish induced by GOQDs during exposure could be counteracted by supplementing Ro-61-8048, an agonist acting on kynurenine 3-monooxygenase (KMO). In conclusion, our study establishes the involvement of the kynurenine pathway in GOQDs-induced thigmotaxis, which is independent of the transcriptional modulation of glutamate receptor families.PMID:38403007 | DOI:10.1016/j.cbpc.2024.109865

Food Chem. 2024 Feb 20;446:138827. doi: 10.1016/j.foodchem.2024.138827. Online ahead of print.ABSTRACTAs the final processing step, drying temperature between 90 and 140 ℃ is usually applied to terminate enzymatic activities and improve sensory characteristics of black tea. Liquid chromatography tandem mass spectrometry (LC-MS) based non-targeted and targeted metabolomics analyses combined in vitro biological assays were adopted to investigate the chemical and biological variations after drying. Fifty-nine differentially expressed metabolites including several hydroxycinnamic acid derivatives and pyroglutamic acid-glucose Amadori rearrangement products (ARPs) were identified, the latter of which was correspondingly accumulated with increasing temperature. The levels of theaflavins (TFs), thearubigins (TRs), monosaccharides and free amino acids gradually decreased with increasing temperature. Furthermore, the bioassays of black tea showed that drying under 110 ℃ provided the highest antioxidant capacities, but the inhibitory effects on α-glucosidase and α-amylase were decreasing along with increasing drying temperature. These results are valuable for optimizing drying process to obtain superior sensory properties and preserve bioactivities of black tea.PMID:38402772 | DOI:10.1016/j.foodchem.2024.138827