PubMed

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<3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP<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)<0.5, P<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

Microbiol Res. 2024 Feb 17;282:127649. doi: 10.1016/j.micres.2024.127649. Online ahead of print.ABSTRACTBacterial wilt is the leading disease of sesame and alters the bacterial community composition, function, and metabolism of sesame rhizosphere soil. However, its pattern of change is unclear. Here, the purpose of this study was to investigate how these communities respond to three differing severities of bacterial wilt in mature continuously cropped sesame plants by metagenomic and metabolomic techniques, namely, absence (WH), moderate (WD5), and severe (WD9) wilt. The results indicated that bacterial wilt could significantly change the bacterial community structure in the rhizosphere soil of continuously cropped sesame plants. The biomarker species with significant differences will also change with increasing disease severity. In particular, the gene expression levels of Ralstonia solanacearum in the WD9 and WD5 treatments increased by 25.29% and 33.61%, respectively, compared to those in the WH treatment (4.35 log10 copies g-1). The occurrence of bacterial wilt significantly altered the functions of the bacterial community in rhizosphere soil. KEEG and CAZy functional annotations revealed that the number of significantly different functions in WH was greater than that in WD5 and WD9. Bacterial wilt significantly affected the relative content of metabolites, especially acids, in the rhizosphere soil, and compared with those in the rhizosphere soil from WH, 10 acids (including S-adenosylmethionine, N-acetylleucine, and desaminotyrosine, etc.) in the rhizosphere soil from WD5 or WD9 significantly increased. In comparison, the changes in the other 10 acids (including hypotaurine, erucic acid, and 6-hydroxynicotinic acid, etc.) were reversed. The occurrence of bacterial wilt also significantly inhibited metabolic pathways such as ABC transporter and amino acid biosynthesis pathways in rhizosphere soil and had a significant impact on two key enzymes (1.1.1.11 and 2.6.1.44). In conclusion, sesame bacterial wilt significantly alters the rhizosphere soil bacterial community structure, function, and metabolites. This study enhances the understanding of sesame bacterial wilt mechanisms and lays the groundwork for future prevention and control strategies against this disease.PMID:38402727 | DOI:10.1016/j.micres.2024.127649

Stem Cell Reports. 2024 Feb 12:S2213-6711(24)00012-2. doi: 10.1016/j.stemcr.2024.01.009. Online ahead of print.ABSTRACTQuality control of human induced pluripotent stem cells (iPSCs) is critical to ensure reproducibility of research. Recently, KOLF2.1J was characterized and published as a male iPSC reference line to study neurological disorders. Emerging evidence suggests potential negative effects of mtDNA mutations, but its integrity was not analyzed in the original publication. To assess mtDNA integrity, we conducted a targeted mtDNA analysis followed by untargeted metabolomics analysis. We found that KOLF2.1J mtDNA integrity was intact at the time of publication and is still preserved in the commercially distributed cell line. In addition, the basal KOLF2.1J metabolome profile was similar to that of the two commercially available iPSC lines IMR90 and iPSC12, but clearly distinct from an in-house-generated ERCC6R683X/R683X iPSC line modeling Cockayne syndrome. Conclusively, we validate KOLF2.1J as a reference iPSC line, and encourage scientists to conduct mtDNA analysis and unbiased metabolomics whenever feasible.PMID:38402620 | DOI:10.1016/j.stemcr.2024.01.009

Cell Stem Cell. 2024 Feb 19:S1934-5909(24)00041-9. doi: 10.1016/j.stem.2024.01.011. Online ahead of print.ABSTRACTMechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.PMID:38402617 | DOI:10.1016/j.stem.2024.01.011

Neuron. 2024 Feb 13:S0896-6273(24)00050-3. doi: 10.1016/j.neuron.2024.01.024. Online ahead of print.ABSTRACTAlzheimer's disease (AD) and the mechanisms underlying its etiology and progression are complex and multifactorial. The higher AD risk in women may serve as a clue to better understand these complicated processes. In this review, we examine aspects of AD that demonstrate sex-dependent effects and delve into the potential biological mechanisms responsible, compiling findings from advanced technologies such as single-cell RNA sequencing, metabolomics, and multi-omics analyses. We review evidence that sex hormones and sex chromosomes interact with various disease mechanisms during aging, encompassing inflammation, metabolism, and autophagy, leading to unique characteristics in disease progression between men and women.PMID:38402606 | DOI:10.1016/j.neuron.2024.01.024

Scand J Clin Lab Invest. 2024 Feb 25:1-9. doi: 10.1080/00365513.2024.2317763. Online ahead of print.ABSTRACTMetabolomics is a relatively novel omics tool to provide potential biomarkers for early diagnosis of the diseases and to insight the pathophysiology not having discussed ever before. In the present study, an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to the plasma samples of Group T1: Patients with ectopic pregnancy diagnosed using ultrasound, and followed-up with beta-hCG level (n = 40), Group T2: Patients with ectopic pregnancy diagnosed using ultrasound, underwent surgical treatment and confirmed using histopathology (n = 40), Group P: Healthy pregnant women (n = 40) in the first prenatal visit of pregnancy, Group C: Healthy volunteers (n = 40) scheduling a routine gynecological examination. Metabolite extraction was performed using 3 kDa pores - Amicon® Ultra 0.5 mL Centrifugal Filters. A gradient elution program (mobile phase composition was water and acetonitrile consisting of 0.1% formic acid) was applied using a C18 column (Agilent Zorbax 1.8 μM, 100 x 2.1 mm). Total analysis time was 25 min when the flow rate was 0.2 mL/min. The raw data was processed through XCMS - R program language edition where the optimum parameters detected using Isotopologue Parameter Optimization (IPO). The potential metabolites were identified using MetaboAnalyst 5.0 and finally 27 metabolites were evaluated to be proposed as potential biomarkers to be used for the diagnosis of ectopic pregnancy.PMID:38402583 | DOI:10.1080/00365513.2024.2317763

Bioinformatics. 2024 Feb 24:btae084. doi: 10.1093/bioinformatics/btae084. Online ahead of print.ABSTRACTMOTIVATION: Liquid chromatography retention times prediction can assist in metabolite identification, which is a critical task and challenge in non-targeted metabolomics. However, different chromatographic conditions may result in different retention times for the same metabolite. Current retention time prediction methods lack sufficient scalability to transfer from one specific chromatographic method to another.RESULTS: Therefore, we present RT-Transformer, a novel deep neural network model coupled with graph attention network and 1D-Transformer, which can predict retention times under any chromatographic methods. First, we obtain a pre-trained model by training RT-Transformer on the large small molecule retention time dataset containing 80038 molecules, and then transfer the resulting model to different chromatographic methods based on transfer learning. When tested on the small molecule retention time dataset, as other authors did, the average absolute error reached 27.30 after removing not retained molecules. Still, it reached 33.41 when no samples were removed. The pre-trained RT-Transformer was further transferred to 5 datasets corresponding to different chromatographic conditions and fine-tuned. According to the experimental results, RT-Transformer achieves competitive performance compared to state-of-the-art methods. In addition, RT-Transformer was applied to 41 external molecular retention time datasets. Extensive evaluations indicate that RT-Transformer has excellent scalability in predicting retention times for liquid chromatography and improves the accuracy of metabolite identification.AVAILABILITY AND IMPLEMENTATION: The source code for the model is available at https://github.com/01dadada/RT-Transformer.The web server is available at https://huggingface.co/spaces/Xue-Jun/RT-Transformer.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:38402516 | DOI:10.1093/bioinformatics/btae084

Metabolomics. 2024 Feb 25;20(2):26. doi: 10.1007/s11306-024-02093-3.ABSTRACTINTRODUCTION: Soursop (Annona muricata L.) is a crop with medicinal properties and numerous bioactive compounds. Ripening is a complex process that regulates fruit quality and changes in metabolite content, such as flavonoids, polyphenols, and organic acids.OBJECTIVES: This study aimed to analyze the phenolic profiling of soursop fruit ripening.METHODS: The metabolic changes in different days of storage of soursop fruits were investigated using a semi-metabolomic approach based on ultra-performance liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry (UPLC-ESI-QTOF-MS). Further, multivariate analysis such as supervised partial least squares discriminant analysis (PLS-DA) was conducted to identify differential metabolites.RESULTS: A total of 68 metabolites were identified in soursop fruit during postharvest storage. A higher number of metabolites were identified in the Day zero (D0) compared to the Day one (D1), Day three (D3), and Day five (D5), belonging to flavonoids, other polyphenols, phenolic acids, and organic acids. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of flavone and flavonol biosynthesis, flavonoid biosynthesis, and biosynthesis of secondary metabolites were mostly enriched. Additionally, we included all the compounds and their postharvest storage in the public Phenolics profile database.CONCLUSIONS: Here, we show that the stage of ripening has a significant effect on the phenolic content, highlighting the point of cut (D0) and the onset of senescence (D5). The findings of this study provide new insights into the soursop fruit quality and may contribute to the identification of metabolic markers for its storage.PMID:38402513 | DOI:10.1007/s11306-024-02093-3

J Transl Med. 2024 Feb 24;22(1):200. doi: 10.1186/s12967-024-04883-8.ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE.METHODS: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68).CONCLUSIONS: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.PMID:38402378 | DOI:10.1186/s12967-024-04883-8