PubMed

J Appl Toxicol. 2023 May 1. doi: 10.1002/jat.4480. Online ahead of print.ABSTRACTCompound diclofenac sodium chlorphenamine maleate tablets (CDCT) is widely used for the cold in Asia. However, CDCT can cause hematuria symptoms in clinical and the underlying mechanism is unknown. This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites, and further explore the possible mechanisms of CDCT-induced nephrotoxicity. Sprague-Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6 days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolites, such as succinate, leukotriene B4 (LTB4 ) and cardiolipin (CL), are observed in the CDCT-induced nephrotoxicity. Functionally, succinate accumulation leads to mitochondrial damage, as evidence by the imbalance of complex I and complex II and an increase in mitochondrial reactive oxygen species (mito SOX). Meanwhile, LTB4 activated the NF-κB signaling, as shown by increased protein of p65, phosphor-p65, and decreased protein of IκBα and phosphor-IκBα. Eventually, the apoptosis pathway was triggered in response to reduced CL, inflammation and mito SOX, as demonstrated by the expression of cyt c, Bax, Bcl-2, caspase-3 and caspase-9. This study indicated that CDCT-induced metabolic disorders triggered nephrotoxicity and provided a comprehensive information to elucidate the mechanism of CDCT induced nephrotoxicity.PMID:37127545 | DOI:10.1002/jat.4480

J Agric Food Chem. 2023 Apr 26. doi: 10.1021/acs.jafc.3c00771. Online ahead of print.ABSTRACTAmomum tsao-ko is an important spice and medicinal plant that has received extensive attention in recent years for its high content of bioactive constituents with the potential for food additives and drug development. Diarylheptanoids are major and characteristic compounds in A. tsao-ko; however, the biochemical and molecular foundation of diarylheptanoids in fruit is unknown. We performed comparative metabolomics and transcriptomics studies in the ripening stages of A. tsao-ko fruit. The chemical constituents of fruit vary in different harvest periods, and the diarylheptanoids have a trend to decrease or increase with fruit development. GO enrichment analysis revealed that plant hormone signaling pathways including the ethylene-activated signaling pathway, salicylic acid, jasmonic acid, abscisic acid, and response to hydrogen peroxide were associated with fruit ripening. The biosynthetic pathways including phenylpropanoid, flavonoids, and diarylheptanoids biosynthesis were displayed in high enrichment levels in ripening fruit. The molecular networking and phytochemistry investigation of A. tsao-ko fruit has isolated and identified 10 diarylheptanoids including three new compounds. The candidate genes related to diarylheptanoids were obtained by coexpression network analysis and phylogenetic analysis. Two key genes have been verified to biosynthesize linear diarylheptanoids. This integrative approach provides gene regulation and networking associated with the biosynthesis of characteristic diarylheptanoids, which can be used to improve the quality of A. tsao-ko as food and medicine.PMID:37126773 | DOI:10.1021/acs.jafc.3c00771

J Proteome Res. 2023 May 1. doi: 10.1021/acs.jproteome.2c00691. Online ahead of print.ABSTRACTExercise plays a beneficial role in the management of Alzheimer's disease (AD), but its effects on brain metabolism are still far from being understood. Here, we examined behavioral changes of APP/PS1 mice after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) and analyzed metabolomics profiles in the hippocampus, cortex, and hypothalamus by using nuclear magnetic resonance spectroscopy to explore potential metabolic mechanisms. The results demonstrate that both HIIT and MICT alleviated anxiety/depressive-like behaviors as well as learning and memory impairments of AD mice. Metabolomics analysis reveals that energy metabolism, neurotransmitter metabolism, and membrane metabolism were significantly altered in all three brain regions after both types of exercises. Amino acid metabolism was detected to be affected in the cortex and hypothalamus after HIIT and in the hippocampus and hypothalamus after MICT. However, only HIIT significantly altered astrocyte-neuron metabolism in the hippocampus and hypothalamus of AD mice. Therefore, our study suggests that exercise can shape brain metabolism of AD mice in a region- and exercise-specific manner, indicating that the precise modification of brain metabolism by a specific type of exercise might be a novel perspective for the prevention and treatment of AD.PMID:37126732 | DOI:10.1021/acs.jproteome.2c00691

Annu Rev Immunol. 2023 Apr 26;41:317-342. doi: 10.1146/annurev-immunol-101220-031513.ABSTRACTOver the last decade, immunometabolism has emerged as a novel interdisciplinary field of research and yielded significant fundamental insights into the regulation of immune responses. Multiple classical approaches to interrogate immunometabolism, including bulk metabolic profiling and analysis of metabolic regulator expression, paved the way to appreciating the physiological complexity of immunometabolic regulation in vivo. Studying immunometabolism at the systems level raised the need to transition towards the next-generation technology for metabolic profiling and analysis. Spatially resolved metabolic imaging and computational algorithms for multi-modal data integration are new approaches to connecting metabolism and immunity. In this review, we discuss recent studies that highlight the complex physiological interplay between immune responses and metabolism and give an overview of technological developments that bear the promise of capturing this complexity most directly and comprehensively.PMID:37126419 | DOI:10.1146/annurev-immunol-101220-031513

JAMA Netw Open. 2023 May 1;6(5):e2310909. doi: 10.1001/jamanetworkopen.2023.10909.ABSTRACTIMPORTANCE: Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited.OBJECTIVES: To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis.DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021.EXPOSURES: Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications.MAIN OUTCOMES AND MEASURES: The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)-related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression.RESULTS: Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR], 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure]: HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use]: HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31]; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33]) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52]; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth factor 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16]), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78]; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26]; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79]) had higher odds of CAC progression compared with patients who achieved all 3 target levels.CONCLUSIONS AND RELEVANCE: In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease-mineral and bone disorder among patients undergoing dialysis.PMID:37126347 | DOI:10.1001/jamanetworkopen.2023.10909

Physiol Genomics. 2023 May 1. doi: 10.1152/physiolgenomics.00129.2022. Online ahead of print.ABSTRACTSpinal cord injury (SCI) results in rapid muscle loss. Exogenous molecular interventions to slow muscle atrophy after SCI have been relatively ineffective and requires the search for novel therapeutic targets. Connexin hemichannels (CxHC) allow non-selective passage of small molecules into and out of the cell. Boldine, a CxHC-inhibiting aporphine found in the boldo tree (Peumus boldus), has shown promising pre-clinical results in slowing atrophy during sepsis and restoring muscle function in dysferlinopathy. We administered 50 mg/kg/d of boldine to spinal cord transected mice beginning 3 d post-injury. Tissue was collected 7 and 28 d post-SCI and the gastrocnemius was used for multiomics profiling. Boldine did not prevent body or muscle mass loss but attenuated SCI-induced changes in the abundance of the amino acids proline, phenylalanine, leucine and isoleucine, as well as glucose, 7 d post-SCI. SCI resulted in the differential expression of ~7,700 and ~2,000 genes at 7 and 28 d, respectively, compared to sham controls. Pathway enrichment of these genes highlighted ribosome biogenesis at 7 d and translation and oxidative phosphorylation at both timepoints. Boldine altered the expression of ~150 genes at 7 d and ~110 genes at 28 d post-SCI. Pathway enrichment of these genes indicated a potential role for boldine in suppressing protein ubiquitination and degradation at the 7 d timepoint. Methylation analyses showed minimal differences between groups. Taken together, boldine is not an efficacious therapy to preserve body and muscle mass after complete SCI, though it attenuated some SCI-induced changes across the metabolome and transcriptome.PMID:37125768 | DOI:10.1152/physiolgenomics.00129.2022

Hypertension. 2023 May 1. doi: 10.1161/HYPERTENSIONAHA.123.20921. Online ahead of print.ABSTRACTBACKGROUND: Primary aldosteronism is frequently caused by an adrenocortical aldosterone-producing adenoma (APA) carrying a somatic mutation that drives aldosterone overproduction. APAs with a mutation in KCNJ5 (APA-KCNJ5MUT) are characterized by heterogeneous CYP11B2 (aldosterone synthase) expression, a particular cellular composition and larger tumor diameter than those with wild-type KCNJ5 (APA-KCNJ5WT). We exploited these differences to decipher the roles of transcriptome and metabolome reprogramming in tumor pathogenesis.METHODS: Consecutive adrenal cryosections (7 APAs and 7 paired adjacent adrenal cortex) were analyzed by spatial transcriptomics (10x Genomics platform) and metabolomics (in situ matrix-assisted laser desorption/ionization mass spectrometry imaging) co-integrated with CYP11B2 immunohistochemistry.RESULTS: We identified intratumoral transcriptional heterogeneity that delineated functionally distinct biological pathways. Common transcriptomic signatures were established across all APA specimens which encompassed 2 distinct transcriptional profiles in CYP11B2-immunopositive regions (CYP11B2-type 1 or 2). The CYP11B2-type 1 signature was characterized by zona glomerulosa gene markers and was detected in both APA-KCNJ5MUT and APA-KCNJ5WT. The CYP11B2-type 2 signature displayed markers of the zona fasciculata or reticularis and predominated in APA-KCNJ5MUT. Metabolites that promote oxidative stress and cell death accumulated in APA-KCNJ5WT. In contrast, antioxidant metabolites were abundant in APA-KCNJ5MUT. Finally, APA-like cell subpopulations-negative for CYP11B2 gene expression-were identified in adrenocortical tissue adjacent to APAs suggesting the existence of tumor precursor states.CONCLUSIONS: Our findings provide insight into intra- and intertumoral transcriptional heterogeneity and support a role for prooxidant versus antioxidant systems in APA pathogenesis highlighting genotype-dependent capacities for tumor expansion.PMID:37125608 | DOI:10.1161/HYPERTENSIONAHA.123.20921

Rapid Commun Mass Spectrom. 2023 May 1:e9529. doi: 10.1002/rcm.9529. Online ahead of print.ABSTRACTRATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problem, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma.METHODS: Metabolic profiling of sera from thymoma and thymic hyperplasia patients was performed using UPLC-HRMS in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental MS/MS spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence.RESULTS: A total of 47 differential metabolites were identified in thymoma. Significant higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significant lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG (-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma.CONCLUSION: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.PMID:37125446 | DOI:10.1002/rcm.9529

Toxicol Res (Camb). 2023 Mar 25;12(2):282-295. doi: 10.1093/toxres/tfad020. eCollection 2023 Apr.ABSTRACTBACKGROUND: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent.METHODS AND RESULTS: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline.CONCLUSION: This work provides a meaningful insight for the mechanism of AAΙ renal injury.PMID:37125334 | PMC:PMC10141773 | DOI:10.1093/toxres/tfad020

Toxicol Res (Camb). 2023 Feb 14;12(2):201-215. doi: 10.1093/toxres/tfad008. eCollection 2023 Apr.ABSTRACTINTRODUCTION: Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions.METHODS: Subjects with Qi deficiency and non-Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology.RESULTS: QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non-Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non-Qi deficiency subjects. The "herbs-compounds-pathways" diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways.CONCLUSION: Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory.PMID:37125330 | PMC:PMC10141780 | DOI:10.1093/toxres/tfad008

Front Microbiol. 2023 Apr 13;14:1155438. doi: 10.3389/fmicb.2023.1155438. eCollection 2023.ABSTRACTExamining how host cells affect metabolic behaviors of probiotics is pivotal to better understand the mechanisms underlying the probiotic efficacy in vivo. However, studies to elucidate the interaction between probiotics and host cells, such as intestinal epithelial cells, remain limited. Therefore, in this study, we performed a comprehensive metabolome analysis of a co-culture containing Bifidobacterium breve MCC1274 and induced pluripotent stem cells (iPS)-derived small intestinal-like cells. In the co-culture, we observed a significant increase in several amino acid metabolites, including indole-3-lactic acid (ILA) and phenyllactic acid (PLA). In accordance with the metabolic shift, the expression of genes involved in ILA synthesis, such as transaminase and tryptophan synthesis-related genes, was also elevated in B. breve MCC1274 cells. ILA production was enhanced in the presence of purines, which were possibly produced by intestinal epithelial cells (IECs). These findings suggest a synergistic action of probiotics and IECs, which may represent a molecular basis of host-probiotic interaction in vivo.PMID:37125172 | PMC:PMC10133457 | DOI:10.3389/fmicb.2023.1155438

Front Nutr. 2023 Apr 14;10:1166393. doi: 10.3389/fnut.2023.1166393. eCollection 2023.ABSTRACTBACKGROUND: To investigate the mechanism of plant protein components on nutritional value, growth performance, flesh quality, flavor, and proliferation of myocytes of yellow catfish (Pelteobagrus fulvidraco).METHODS: A total of 540 yellow catfish were randomly allotted into six experimental groups with three replicates and fed six different diets for 8 weeks.RESULTS AND CONCLUSIONS: The replacement of fish meal with cottonseed meal (CM), sesame meal (SEM), and corn gluten meal (CGM) in the diet significantly reduced growth performance, crude protein, and crude lipid, but the flesh texture (hardness and chewiness) was observably increased. Moreover, the flavor-related amino acid (glutamic acid, glycine, and proline) contents in the CM, SEM, and CGM groups of yellow catfish muscle were significantly increased compared with the fish meal group. The results of metabolomics showed that soybean meal (SBM), peanut meal (PM), CM, SEM, and CGM mainly regulated muscle protein biosynthesis by the variations in the content of vitamin B6, proline, glutamic acid, phenylalanine, and tyrosine in muscle, respectively. In addition, Pearson correlation analysis suggested that the increased glutamic acid content and the decreased tyrosine content were significantly correlated with the inhibition of myocyte proliferation genes. This study provides necessary insights into the mechanism of plant proteins on the dynamic changes of muscle protein, flesh quality, and myocyte proliferation in yellow catfish.PMID:37125039 | PMC:PMC10140373 | DOI:10.3389/fnut.2023.1166393

Front Nutr. 2023 Mar 23;10:1104685. doi: 10.3389/fnut.2023.1104685. eCollection 2023.ABSTRACTBACKGROUND: Many studies show that the intake of raspberries is beneficial to immune-metabolic health, but the responses of individuals are heterogeneous and not fully understood.METHODS: In a two-arm parallel-group, randomized, controlled trial, immune-metabolic outcomes and plasma metabolite levels were analyzed before and after an 8-week red raspberry consumption. Based on partial least squares discriminant analysis (PLS-DA) on plasma xenobiotic levels, adherence to the intervention was first evaluated. A second PLS-DA followed by hierarchical clustering was used to classify individuals into response subgroups. Clinical immune and metabolic outcomes, including insulin resistance (HOMA-IR) and sensitivity (Matsuda, QUICKI) indices, during the intervention were assessed and compared between response subgroups.RESULTS: Two subgroups of participants, type 1 responders (n = 17) and type 2 responders (n = 5), were identified based on plasma metabolite levels measured during the intervention. Type 1 responders showed neutral to negative effects on immune-metabolic clinical parameters after raspberry consumption, and type 2 responders showed positive effects on the same parameters. Changes in waist circumference, waist-to-hip ratio, fasting plasma apolipoprotein B, C-reactive protein and insulin levels as well as Matsuda, HOMA-IR and QUICKI were significantly different between the two response subgroups. A deleterious effect of two carotenoid metabolites was also observed in type 1 responders but these variables were significantly associated with beneficial changes in the QUICKI index and in fasting insulin levels in type 2 responders. Increased 3-ureidopropionate levels were associated with a decrease in the Matsuda index in type 2 responders, suggesting that this metabolite is associated with a decrease in insulin sensitivity for those subjects, whereas the opposite was observed for type 1 responders.CONCLUSION: The beneficial effects associated with red raspberry consumption are subject to inter-individual variability. Metabolomics-based clustering appears to be an effective way to assess adherence to a nutritional intervention and to classify individuals according to their immune-metabolic responsiveness to the intervention. This approach may be replicated in future studies to provide a better understanding of how interindividual variability impacts the effects of nutritional interventions on immune-metabolic health.PMID:37125033 | PMC:PMC10130762 | DOI:10.3389/fnut.2023.1104685

Front Endocrinol (Lausanne). 2023 Apr 14;14:1139725. doi: 10.3389/fendo.2023.1139725. eCollection 2023.ABSTRACTINTRODUCTION: Flaxseed oil (FO) and vitamin E (VE) both have antioxidant effects on sperm. The present study investigated the effects of dietary supplementation with FO and/or VE on semen quality.METHODS: 16 fertile Simmental bulls were selected and randomly divided into 4 groups (n = 4): the control group (control diet), FO group (control diet containing 24 g/kg FO), VE group (control diet containing 150 mg/kg VE) and FOVE group (control diet containing 150 mg/kg VE and 24 g/kg FO), and the trial lasted 10 weeks.RESULTS: The results showed that the addition of FO independently can increase sperm motion parameters, the levels of catalase (CAT), glutathione peroxidase (GSH-Px), testosterone (T) and estradiol (E2), while reduce oxidative stress in seminal plasma (P < 0.05). Supplement of VE independently can increased the motility, motility parameters, CAT and superoxide dismutase (SOD) levels, and reduce oxidative stress in seminal plasma (P < 0.05). There was an interaction effect of FO × VE on motility and reactive oxygen species (ROS), while GSH-Px and ROS were affected by week × VE 2-way interaction, levels of T and E2 were also affected by the dietary FO × week interaction (P < 0.05). The triple interaction effects of FO, VE and week were significant for malondialdehyde (MDA) (P < 0.05). Compared with the control group, sperm from the FOVE group had a significantly higher in vitro fertilization (IVF) rate, and subsequent embryos had increased developmental ability with reduced ROS levels at the eight-cell stage, then increased adenosine triphosphate (ATP) content and gene expression levels of CAT, CDX2, Nanog, and SOD at the blastocyst stage (P < 0.05). Metabolomic and transcriptomic results indicated that dietary supplementation of FO and VE increased the expression of the metabolite aconitic acid, as well as the expression of ABAT and AHDHA genes.CONCLUSION: With in-silico analysis, it can be concluded that the effects of dietary FO and VE on improving semen quality and embryo development may be related to increased aconitic acid via the ABAT and AHDHA genes involved in the propionic acid metabolism pathway.PMID:37124753 | PMC:PMC10140321 | DOI:10.3389/fendo.2023.1139725

Front Endocrinol (Lausanne). 2023 Apr 12;14:1095550. doi: 10.3389/fendo.2023.1095550. eCollection 2023.ABSTRACTOBJECTIVES: This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender.MATERIAL AND METHODS: We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed.RESULTS: We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant.CONCLUSION: In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.PMID:37124739 | PMC:PMC10130405 | DOI:10.3389/fendo.2023.1095550

Front Oncol. 2023 Apr 14;13:1164266. doi: 10.3389/fonc.2023.1164266. eCollection 2023.ABSTRACTMetabolomic analysis is a vital part of studying cancer progression. Metabonomic crosstalk, such as nutrient availability, physicochemical transformation, and intercellular interactions can affect tumor metabolism. Many original studies have demonstrated that metabolomics is important in some aspects of tumor metabolism. In this mini-review, we summarize the definition of metabolomics and how it can help change a tumor microenvironment, especially in pathways of three metabonomic tumors. Just as non-invasive biofluids have been identified as early biomarkers of tumor development, metabolomics can also predict differences in tumor drug response, drug resistance, and efficacy. Therefore, metabolomics is important for tumor metabolism and how it can affect oncology drugs in cancer therapy.PMID:37124524 | PMC:PMC10140396 | DOI:10.3389/fonc.2023.1164266

Front Pharmacol. 2023 Apr 12;14:1102465. doi: 10.3389/fphar.2023.1102465. eCollection 2023.ABSTRACTRecent interest in mushrooms and their components as potential therapies for mental health, along with recent government and health authority approvals, has necessitated a more comprehensive understanding of their effects on the cellular microenvironment of the brain. Amanita muscaria has been ingested as a treatment for a variety of ailments for centuries, most notably those affecting the central nervous system and conditions associated with neuroinflammation. However, the effects of these extracts on neuroinflammatory cells, such as microglia, are unknown. The effect of commercially-sourced A. muscaria extract (AME-1) on human microglial cell line (HMC3) expression of surface receptors such as CD86, CXCR4, CD45, CD125 and TLR4 was determined by flow cytometry. AME-1 upregulated expression of all of these receptors. The effect of AME-1 on HMC3 production of IL-8 and IL-6 was determined and compared to tumor necrosis factor (TNF), polyinosinic-polycytidylic acid [poly(I:C)], substance P and lipopolysaccharide (LPS), all known activators of HMC-3 and primary microglia. HMC3 produced both IL-8 and IL-6 when activated with LPS, TNF and poly(I:C) but not when they were activated with substance P. Although AME-1 at higher concentrations increased IL-8 production of HMC3 on its own, AME-1 notably potentiated HMC3 production of IL-8 in response to poly(I:C). AME-1 altered expression of toll-like receptor 3 (TLR3) mRNA but not surface protein by HMC3. AME-1 also did not significantly alter expression of retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), both cytosolic sensors of dsRNA. Metabolomics analysis showed that AME-1 contained several metabolites, including the autophagy inducer, trehalose. Like AME-1, trehalose also potentiated HMC3 poly(I:C) mediated production of IL-8. This study suggests that A. muscaria extracts can modify HMC3 inflammatory responses, possibly due to their trehalose content.PMID:37124206 | PMC:PMC10130647 | DOI:10.3389/fphar.2023.1102465

AoB Plants. 2023 Apr 10;15(2):plad014. doi: 10.1093/aobpla/plad014. eCollection 2023 Feb.ABSTRACTThe dynamic trajectory of metabolites and gene expression related to phosphorus absorption and utilization in soybean seedling roots were determined under short- and long-term phosphorus deficiency stress. The metabolome results showed that TCA and GS/GOGAT cycles were enhanced after 2 days of phosphorus deficiency stress; however, they were inhibited after 15 days. GC-TOF-MS showed that phosphorus deficiency increased the accumulation of amino acids significantly after 2 days, whereas organic acids and lipid substances increased significantly after 15 days. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed that transcriptional levels of five key genes related to phosphorus activation and phosphorus starvation signal transduction increased continuously with phosphorus deficiency. The expression of GmPHT1 and GmSPX triggered the phosphorus starvation signal pathway and induced the expression of the GmPS and GmPAP genes to enhance the synthesis and secretion of organophosphorus hydrolase and organic acid in soybean roots under phosphorus deficiency. The phospholipid metabolism was enhanced significantly after 15 days of stress and when GmSQD, a crucial enzyme in lipid biosynthesis, was up-regulated. Thus, we propose that future investigations on stress caused by phosphorus deficiency should include more organs obtained at different developmental stages.PMID:37124081 | PMC:PMC10132309 | DOI:10.1093/aobpla/plad014

Front Plant Sci. 2023 Apr 14;14:1125065. doi: 10.3389/fpls.2023.1125065. eCollection 2023.ABSTRACTAbove-ground material of members of the mint family is commercially distilled to extract essential oils, which are then formulated into a myriad of consumer products. Most of the research aimed at characterizing the processes involved in the formation of terpenoid oil constituents has focused on leaves. We now demonstrate, by investigating three mint species, peppermint (Mentha ˣ piperita L.), spearmint (Mentha spicata L.) and horsemint (Mentha longifolia (L.) Huds.; accessions CMEN 585 and CMEN 584), that other organs - namely stems, rhizomes and roots - also emit volatiles and that the terpenoid volatile composition of these organs can vary substantially from that of leaves, supporting the notion that substantial, currently underappreciated, chemical diversity exists. Differences in volatile quantities released by plants whose roots had been dipped in a Verticillium dahliae-spore suspension (experimental) or dipped in water (controls) were evident: increases of some volatiles in the root headspace of mint species that are susceptible to Verticillium wilt disease (peppermint and M. longifolia CMEN 584) were detected, while the quantities of certain volatiles decreased in rhizomes of species that show resistance to the disease (spearmint and M. longifolia CMEN 585). To address the genetic and biochemical basis underlying chemical diversity, we took advantage of the newly sequenced M. longifolia CMEN 585 genome to identify candidate genes putatively coding for monoterpene synthases (MTSs), the enzymes that catalyze the first committed step in the biosynthesis of monoterpenoid volatiles. The functions of these genes were established by heterologous expression in Escherichia coli, purification of the corresponding recombinant proteins, and enzyme assays, thereby establishing the existence of MTSs with activities to convert a common substrate, geranyl diphosphate, to (+)-α-terpineol, 1,8-cineole, γ-terpinene, and (-)-bornyl diphosphate, but were not active with other potential substrates. In conjunction with previously described MTSs that catalyze the formation of (-)-β-pinene and (-)-limonene, the product profiles of the MTSs identified here can explain the generation of all major monoterpene skeletons represented in the volatiles released by different mint organs.PMID:37123862 | PMC:PMC10140540 | DOI:10.3389/fpls.2023.1125065

Front Plant Sci. 2023 Apr 14;14:1173489. doi: 10.3389/fpls.2023.1173489. eCollection 2023.ABSTRACTPyrrosia petiolosa (Christ) Ching has both medicinal and health benefits in China. The potential antioxidant activities of P. petiolosa, which are mainly attributed to its flavonoids, have attracted much attention in recent years. The present study aimed to determine the concentration of flavonoid components and evaluate the relative antioxidant activities of P. petiolosa from different geographic origins using a UPLC-MRM-MS-based metabolomics approach. In total, 97 flavonoid components were identified, and their concentrations in the samples from different geographic locations showed significant variation. Thirteen flavonoid components were identified as potential biomarkers for distinguishing between the two major regions, Guizhou (GZ) and Guangxi (GX). The GZ group showed higher total flavonoid content, free radical scavenging activities, and ferric reducing antioxidant power. The well positive correlations were found between the antioxidant capacities and some flavonoid markers. The ecogeographic factors, namely altitude and longitude, play a crucial role in the difference of antioxidant activities and flavonoids concentration. These results indicate that P. petiolosa is rich in flavonoid compounds and is a promising source of natural antioxidants, providing a basis for the quality control of P. petiolosa.PMID:37123848 | PMC:PMC10140315 | DOI:10.3389/fpls.2023.1173489