Differences In Metabolite Profiles Research Articles

Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans—A Pilot Study

Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans—A Pilot Study

Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder.

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex-a key region of the DMN-between patients with ADHD and controls. Five brain metabolites-glutamate, inositol, N-acetyl aspartate, choline, and creatine-were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

Integrated metabolomic and transcriptomic analysis of metabolic diversity and biosynthesis of glucosinolates and flavonoids in various cultivars of radish microgreens

Microgreens, with their distinctive flavor and rapid growth, have garnered significant attention as a functional and nutritious food. In this study, we performed a thorough targeted metabolomic study using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS) on four distinct cultivars of radish microgreens, namely Champion Radish (CR), White Radish (WR), Hailstone Radish (HR), and China Rose Radish (CRR), in order to better understand the metabolic foundation of the nutritional value of these microgreens. A total of 1411 metabolites were found and more than a third of the total number of metabolites were accounted for by flavonoids (FL), phenolic acids, lignans, coumarins and glucosinolates (GL). Significant variations were found in the differentially accumulated metabolites (DAM) and differentially expressed genes (DEG) in each pairwise comparison of cultivars, according to further comparative analysis. The comparison of CR with the other groups identified more than 400 DAM and about 10,000 DEG, the most abundant DAM being FL, and the results showed that CR was very different from WR, HR and CRR. A total of 33 GL were newly found in radish microgreens and classified into 8 categories according to their side chains. Weighted gene co-expression network analysis and biosynthetic pathway analysis revealed the distinctive relationship between gene expression levels and characteristic GL and FL. This work aimed to provide fresh insights into the differences in metabolite profiles among radish microgreens of various cultivars in addition to establishing a theoretical framework for improving the genetic quality of radish microgreens.

Crataegus pentagyna willd. Fruits, leaves and roots: phytochemicals, antioxidant and antimicrobial potentials

BackgroundThe hawthorn has recently been used as a popular herbal medicine in food applications and phytotherapy, especially for the cardiovascular system.MethodsIn this study, phytochemicals were evaluated by LC-ESI-MS, GC-MS, and biological activity, including antioxidant (DPPH test) and antibacterial (broth dilution assay), in different extracts of Crataegus pentagyna fruit, leaf, and root.ResultsGlobally, 49 phenolics were tentatively identified using HPLC-ESI-MS/MS in the hydro-methanolic extract of the fruit (major apigenin, caffeoylquinic acid derivative, and 4-O-(3′-O-glucopyranosyl)-caffeoyl quinic acid), 42 in the leaf (major salicylic acid, naringenin-6-C-glucoside, and naringin), and 33 in the root (major naringenin-7-O-neohesperidoside, isovitexin-2″-O-rhamnoside, and 4-O-(3′-O-glucopyranosyl)-caffeoyl quinic acid). The major group compounds analyzed by GC-MS in petroleum ether extracts were hydrocarbons (63.80%) and fatty acids and their derivatives (11.77%) in fruit, hydrocarbons (49.20%) and fatty acids and their derivatives (13.85%) in leaf, and hydrocarbons (53.96%) and terpenes (13.06%) in root. All samples exhibited promising phytochemical profile (total phenol, flavonoid, phenolic acid, and anthocyanin), antioxidant and antibacterial capacities, especially in hydro-methanolic extract of fruit (210.22 ± 0.44 mg GAE/g DE; 79.93 ± 0.54 mg QE/g DE; 194.64 ± 0.32 mg CAE/g DE; 85.37 ± 0.13 mg cyanidin 3-glucoside/100 g FW; DPPH: 15.43 ± 0.65 µg/mL; MIC: 0.15–0.62 µg/mL; and MBC: 0.62–1.25 mg/mL), followed by the leaf and root extracts, respectively. The PCA and heatmap analysis results distinguished metabolite profile differences for samples.ConclusionThe results of the present work provide scientific support for C. pentagyna as antimicrobial agents and natural antioxidants in human health and food preservation.

Comparative Metabolomic Profiling of Eggs from 3 Diverse Chicken Breeds Using GC-MS Analysis

Eggs, as a crucial source of essential nutrients for consumers, possess a high nutritional value owing to their rich composition of vital components essential for human health. While previous research has extensively investigated genetic factors influencing egg quality, there has been a limited focus on exploring the impact of specific strains, particularly within the African context, on the polar metabolite profile of eggs. In this extensive study, we conducted an untargeted analysis of the chemical composition of both albumen and yolk from 3 distinct strains of hens-Blue Holland, Sasso, and Wassache-raised under identical feeding conditions. Utilizing gas chromatography coupled with mass spectrometry (GC-MS), we meticulously examined amino acids, carbohydrates, fatty acids, and other small polar metabolites. In total, 38 and 44 metabolites were identified in the whites and yolk, respectively, of the 3 studied strains. The application of chemometric analysis revealed notable differences in metabolite profiles with 8 relevant metabolites in each egg part. These metabolites include amino acids (N-α-Acetyl-L-lysine, lysine, L-valine, L-Tryptophan), fatty acids (oleic acid, linoleic acid, palmitic acid and stearic acid), and carbohydrates (d-glucose, maltose, lactose). These findings shed light on strain-specific metabolic nuances within eggs, emphasizing potential nutritional implications. The ensuing discussion delves into the diverse metabolic pathways influenced by the identified metabolites, offering insights that contribute to a broader understanding of egg composition and its significance in tailoring nutritional strategies for diverse populations.

Analysis of metabolic differences between Jiaosu fermented from dendrobium flowers and stems based on untargeted metabolomics

Dendrobium officinale is an important traditional Chinese medicinal herb containing bioactive polysaccharides and alkaloids. This study characterized metabolite differences between jiaosu (fermented plant product) from Dendrobium flowers versus stems using untargeted metabolomics. The jiaosu was fermented by mixed fermentation of Saccharomyces cerevisiae, Lactobacillus bulgaricus and Streptococcus thermophilus. Liquid chromatography-mass spectrometry analysis identified 476 differentially expressed metabolites between the two Jiaosu products. Key results showed downregulation of flavonoid metabolism in Dendrobium Stems Edible Plant Jiaosu (SEP) but increased flavonoid synthesis in Dendrobium Flowers Edible Plant Jiaosu (FEP), likely an antioxidant response. SEP displayed upregulation of lignin metabolites with potential antioxidant properties. The findings demonstrate significant metabolite profile differences between SEP and FEP, providing the basis for developing functional jiaosu products targeting specific health benefits.

Identification of the characteristic chemical constituents in fermented Toona sinensis buds and exploration of their hypoglycemic efficacy by widely targeted metabolomics

Toona sinensis is a unique perennial deciduous tree in China, and its buds are popular vegetables with unique flavors and high nutritional value. In this study, we produced fermented T. sinensis buds using a commercial strain of Lactiplantibacillus plantarum and utilized widely targeted metabolomics to investigate the effect of each Lactobacillus fermentation method on the metabolite composition of fermented T. sinensis buds. Multivariate analysis revealed a significant difference in the metabolic profile between each fermented T. sinensis bud group and the control group. The metabolite profiles of T. sinensis buds fermented for 48 h and 68 h were similar, but both differed significantly from the metabolite profiles of T. sinensis buds fermented for 0 h. Compared with the control group, the T. sinensis buds fermented for 48 h and 68 h had high levels of flavonoids, alkaloids and lipids. In addition, the hypoglycemia test data showed that fermentation significantly increased the ability of T. sinensis buds to inhibit α-amylase and α-glucosidase activities, and the extract of fermented T. sinensis buds significantly improved glucose uptake by IR-HepG2 cells. This study suggests that metabolomics is an effective approach for revealing the differences in metabolite profiles in T. sinensis buds fermented for different durations and is useful for clarifying the mechanism by which fermented T. sinensis buds enhance hypoglycemic activity.

Metabolomics reveals differences in metabolite profiles between wild and cultivated Tetrastigmae Radix

Tetrastigmae Radix (TR) is the tuber of Tetrastigma hemsleyanum Diels et Gilg, which is frequently used in Chinese folklore medicine as a therapeutic food. TR is becoming more popular because of its superior pharmacological properties, including anticancer and antioxidant properties. However, wild-TR (WTR) resources are few in the market, and cultivated-TR (CTR) is progressively replacing WTR as the primary source of commercial herbs. Furthermore, because of its diverse growing environment, CTR may differ from WTR in terms of characteristics, metabolites, and pharmacological actions. There are currently fewer investigations on the two ecotypes, and their distinctions are unclear. As a result, this study used UFLC-Triple TOF-MS/MS to undertake untargeted metabolomics analysis of CTR and WTR, and then used statistical analysis to screen for differential accumulate metabolites (DAMs). KEGG enrichment analysis was performed on the DAMs, and the active pharmaceutical DAMs in the enrichment pathway were measured using UFLC-QTRAP-MS/MS. The results reveal that 152 metabolites of 14 different categories were discovered, with flavonoids and lipids accounting for the majority of the 35 DAMs tested by OPLS-DA. Some lipids were up-regulated in the CTR, whereas flavonoids were up-regulated in the WTR; and 777 pairs of DAM metabolites exhibited significant connection based on Pearson correlation analysis. The mainly enriched pathways were flavone and flavonol biosynthesis, TCA cycle, galactose metabolism, and others. KEGG enrichment analysis revealed four active pharmaceutical metabolites in the enriched pathways, and demonstrated that their concentrations were greater in WTR than in CTR. Overall, this work used a comprehensive metabolomic analysis to provide a theoretical foundation for resource identification, diet formulation, and pharmacological studies of CTR and WTR.

SAT266 Transcriptional Changes Associated With Loss Of Function Of Fumarate Hydratase In A Cellular Model Of Pheochromocytoma

Abstract Disclosure: C.L. Hall: None. J.E. Read: None. G. Salsbury: None. E. Lim: None. S. Akker: None. P. Chapple: None. Mutations in fumarate hydratase (FH) predispose to development of pheochromocytomas and paragangliomas (PPGLs), as well as leiomyomas and renal cell carcinoma. Loss of FH function leads to accumulation of fumarate which acts as an oncometabolite to drive tumorigenesis, although the molecular mechanisms leading to the development of these rare tumours are not fully understood. We have used CRISPR/Cas9 genome editing to generate a series of FH knockouts in the PC-12 cell line, derived from MAX-mutated pheochromocytoma in rat. Our knockout cell lines were used as a model to investigate the molecular consequences of loss of FH function. Comparison of the transcriptome of FH knockout cells with isogenic controls identified 1016 differentially expressed genes (adjusted p<0.05 Log2fold±1). This list of differentially expressed genes was then analysed to identify cellular pathways that were dysregulated in the absence of FH. Canonical pathways that were significantly altered, based on transcript expression relative to controls, included axonal signalling pathway (p=7.29x10-11), wound healing signalling pathway (p=1.74x10-07), pulmonary fibrosis idiopathic signalling pathway (p=4.10x10-07) and IL-15 production (p=1.03x10-05). Our results suggest cell adhesion and immune regulation pathways may be relevant to the development of PPGLs with germline mutations in FH, but will require validation in the context of human tissue. We have also performed metabolic flux analysis to identify differences in metabolite profile associated with loss of FH. Interestingly, changes in gene expression, revealed by our transcriptomic analysis, may explain some alterations in cellular metabolism of FH knockout cells. Presentation: Saturday, June 17, 2023

Metabolomic profiling implicates mitochondrial and immune dysfunction in disease syndromes of the critically endangered black rhinoceros (Diceros bicornis)

The critically endangered black rhinoceros (Diceros bicornis; black rhino) experiences extinction threats from poaching in-situ. The ex-situ population, which serves as a genetic reservoir against impending extinction threats, experiences its own threats to survival related to several disease syndromes not typically observed among their wild counterparts. We performed an untargeted metabolomic analysis of serum from 30 ex-situ housed black rhinos (Eastern black rhino, EBR, n = 14 animals; Southern black rhino, SBR, n = 16 animals) and analyzed differences in metabolite profiles between subspecies, sex, and health status (healthy n = 13 vs. diseased n = 14). Of the 636 metabolites detected, several were differentially (fold change > 1.5; p < 0.05) expressed between EBR vs. SBR (40 metabolites), female vs. male (36 metabolites), and healthy vs. diseased (22 metabolites). Results suggest dysregulation of propanoate, amino acid metabolism, and bile acid biosynthesis in the subspecies and sex comparisons. Assessment of healthy versus diseased rhinos indicates involvement of arachidonic acid metabolism, bile acid biosynthesis, and the pentose phosphate pathway in animals exhibiting inflammatory disease syndromes. This study represents the first systematic characterization of the circulating serum metabolome in the black rhinoceros. Findings further implicate mitochondrial and immune dysfunction as key contributors for the diverse disease syndromes reported in ex-situ managed black rhinos.

Metabolomics Analysis Provides Novel Insights into the Difference in Meat Quality between Different Pig Breeds.

The Chuanzang black (CB) pig is a new crossbred between Chinese local breeds and modern breeds. Here, we investigated the growth performance, plasma indexes, carcass traits, and meat quality characteristics of conventional DLY (Duroc × Landrace × Yorkshire) crossbreed and CB pigs. The LC-MS/MS-based metabolomics of pork from DLY and CB pigs, as well as the relationship between the changes in the metabolic spectrum and meat quality, were analyzed. In this study, CB pigs presented lower final body weight, average daily gain, carcass weight, and eye muscle area than DLY pigs (p ˂ 0.05). Conversely, the ratio of feed to gain, marbling score, and meat color score of longissimus dorsi (LD) were higher in CB than DLY pigs (p ˂ 0.05). Moreover, psoas major (PM) showed a higher meat color score and a lower cooking loss in CB than DLY pigs (p ˂ 0.05). Interestingly, CB pigs showed lower myofiber diameter and area but higher myofiber density than DLY pigs (p ˂ 0.05). Furthermore, the mRNA expression levels of MyHC I, PPARδ, MEF2C, NFATC1, and AMPKα1 were higher in CB than DLY pigs (p ˂ 0.05). Importantly, a total of 753 metabolites were detected in the two tissues (e.g., psoas major and longissimus dorsi) of CB and DLY pigs, of which the difference in metabolite profiles in psoas major between crossbreeds was greater than that in longissimus dorsi. Specifically, palmitic acid, stearic acid, L-aspartic acid, corticosterone, and tetrahydrocorticosterone were the most relevant metabolites of psoas major meat quality, and tetrahydrocorticosterone, L-Palmitoylcarnitine, arachidic acid, erucic acid, and 13Z,16Z-docosadienoic acid in longissimus dorsi meat were positively correlated with meat quality. The most significantly enriched KEGG pathways in psoas major and longissimus dorsi pork were galactose metabolism and purine metabolism, respectively. These results not only indicated improved meat quality in CB pigs as compared to DLY pigs but may also assist in rational target selection for nutritional intervention or genetic breeding in the swine industry.

Validation of a batch cultivation protocol for fecal microbiota of Kenyan infants

BackgroundThe combination of cultivation studies with molecular analysis approaches allows characterization of the complex human gut microbiota in depth. In vitro cultivation studies of infants living in rural sub-Saharan Africa are scarce. In this study, a batch cultivation protocol for Kenyan infant fecal microbiota was validated.MethodsFresh fecal samples were collected from 10 infants living in a rural area of Kenya. Samples were transported under protective conditions and subsequently prepared for inoculation within less than 30 h for batch cultivation. A diet-adapted cultivation medium was used that mimicked the daily intake of human milk and maize porridge in Kenyan infants during weaning. 16 S rRNA gene amplicon sequencing and HPLC analyses were performed to assess the composition and metabolic activity, respectively, of the fecal microbiota after 24 h of batch cultivation.ResultsHigh abundance of Bifidobacterium (53.4 ± 11.1%) and high proportions of acetate (56 ± 11% of total metabolites) and lactate (24 ± 22% of total metabolites) were detected in the Kenyan infant fecal microbiota. After cultivation started at an initial pH 7.6, the fraction of top bacterial genera (≥ 1% abundant) shared between fermentation and fecal samples was high at 97 ± 5%. However, Escherichia-Shigella, Clostridium sensu stricto 1, Bacteroides and Enterococcus were enriched concomitant with decreased Bifidobacterium abundance. Decreasing the initial pH to 6.9 lead to higher abundance of Bifidobacterium after incubation and increased the compositional similarity of fermentation and fecal samples. Despite similar total metabolite production of all fecal microbiota after cultivation, inter-individual differences in metabolite profiles were apparent.ConclusionsProtected transport and batch cultivation in host and diet adapted conditions allowed regrowth of the top abundant genera and reproduction of the metabolic activity of fresh Kenyan infant fecal microbiota. The validated batch cultivation protocol can be used to study the composition and functional potential of Kenyan infant fecal microbiota in vitro.

Comprehensive Metabolite Profiling of Two Edible Garcinia Species Based on UPLC-ESI-QTOF-MSE Coupled with Bioactivity Assays.

In China, the endemic species Garcinia yunnanensis and native Garcinia xanthochymus are known as edible and medicinal plants. However, a systematic metabolomic and bioactivity evaluation of different plant parts from both species is lacking. In this study, comprehensive investigations of 11 plant parts of G. yunnanensis and 10 of G. xanthochymus employing UPLC-ESI-QTOF-MSE-based metabolomic analysis in conjunction with three bioactivity assays were undertaken. A customized chemotaxonomic-based in-house library containing 6456 compounds was constructed and coupled to the Progenesis QI informatic platform for metabolite annotations. From these two species, a total of 235 constituents were characterized using multiple criteria. Differences in metabolite profiles between the plant parts within each species were uncovered using multivariate analysis. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA), 23 markers were identified as highly differential metabolites from G. xanthochymus and 20 from G. yunnanensis. Comparative assessment of the biological assays revealed the activity variations among different plant parts. The seeds of both species and G. yunnanensis latex exhibited excellent cytotoxic and antibacterial activities, while G. xanthochymus roots and G. yunnanensis arils showed strong anti-inflammatory effects. S-plot analysis identified 26 potential biomarkers for the observed activities, including the known cytotoxic agent cycloxanthochymol and the anti-inflammatory compound garcimultiflorone B, which likely explains some of the potent observed bioactivity.

Characterization of metabolite landscape distinguishes wild from cultivated Polygonati Rhizomes by UHPLC-Q-TOF-MS untargeted metabolomics

Rhizome, a modified subterranean plant stem, has been used in China for centuries as a Traditional Chinese Medicine (TCM). Polygonati Rhizome (PR) is a well-known species in the Rhizome family. Previous studies show that PR might be beneficial in the treatment of osteoporosis, cancer, diabetes, and many other diseases because of its properties such as antioxidant property. Thus cultivated PR strains were developed to fulfil the increasing demands. However, the metabolite profile differences between wild-type and cultivated PR remain largely unknown. Here, we performed unbiased and untargeted quantitative mass spectrometry-based metabolomics on 1 wild strain and 3 cultivated strains. A total of 1126 metabolites were identified on all 4 strains. Analyses of these data with unsupervised and supervised approaches identified common metabolites in all 4 strains as well as strain-specific metabolites. Next, we conducted a metabolomic-wide pairwise correlation analysis on metabolite abundance and discovered 577 significantly correlated metabolite-metabolite pairs by Pearson's correlation test. Importantly, KEGG enrichment analysis indicated that phenylpropanoids biosynthesis was the most differentially expressed pathway between cultivated and wild-type PR. By contrast, common metabolites on all 4 strains might suggest shared therapeutic targets. In summary, the systematic, untargeted metabolomics profiling of 4 PR strains and comprehensive data analyses provide invaluable resources to the understanding of the metabolite landscape and shed light on potential therapeutic applications for the treatment of diseases.

Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer.

Multiple primary lung cancer (MPLC) is becoming increasingly common in clinical practice. Imaging examination is sometimes difficult to differentiate from intrapulmonary metastasis (IM) or single primary lung cancer (SPLC) before surgery. There is a lack of effective blood biomarkers as an auxiliary diagnostic method. A total of 179 patients who were hospitalized and operated in our department from January to June 2019 were collected, and they were divided into SPLC with 136 patients, MPLC with 24 patients, and IM with 19 patients. In total, 96 healthy people without lung cancer were enrolled. Medical history, imaging, and pathology data were assembled from all participants. Plasma metabolomics analysis was performed by quadrupole time-of-flight tandem mass spectrometry, and data were analyzed using SPSS19.0/Simca 14.1/MetaboAnalyst5.0 software. Significant metabolites were selected by variable importance in projection, P value, and fold change. The area under the receiver operating characteristic curve was used to evaluate their diagnostic ability. There were significant differences in plasma metabolite profiles between IM and MPLC. Seven metabolites were screened out. Two metabolites had higher levels in IM, and five metabolites had higher levels in MPLC. All had favorable discriminating capacity. Phosphatidyl ethanolamine (38:5) showed the highest sensitivity (0.95) and specificity (0.92). It was followed by l -histidine with sensitivity 0.92 and specificity 0.84. l -tyrosine can be used to identify SPLC and MPLC. The panel composed of related metabolites exhibited higher diagnostic ability. Eight principal metabolites caused remarkable differences between healthy people and MPLC, and five of them had area under the curves greater than 0.85, showing good discriminating power. Through the study of plasma metabolomics, it was found that there were obvious differences in the metabolite profiles of MPLC, IM, SPLC, and the healthy population. Some discovered metabolites possessed excellent diagnostic competence with high sensitivity and specificity. They had the potential to act as biomarkers for the screening and differential diagnosis of MPLCs.

Progress of metabolomics in atopic dermatitis: a systematic review.

Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and intense pruritus, is a major skin-related burden worldwide. The diagnosis and treatment of AD is often challenging due to the high heterogeneity of AD, and its exact etiology is unknown. Metabolomics offers the opportunity to follow continuous physiological and pathological changes in individuals, which allows accurate diagnosis and management as well as providing deep insights into the etiopathogenesis of AD. Several metabolomic studies of AD have been published over the past few years. The aim of this review is to summarize these findings and help researchers to understand the rapid development of metabolomics for AD. A comprehensive and systematic search was performed using the PubMed, Embase, Cochrane Library and Web of Science databases. Twenty-six papers were finally included in the review after quality assessment. Significant differences in metabolite profiles were found between patients with AD and healthy individuals. This study provides a comprehensive overview of metabolomic research in AD. A better understanding of the metabolomics of AD may offer novel diagnostic, prognostic, and therapeutic approaches.

Metabolomic study combined with the low-level light therapy of Chinese acupuncture points and combined oral contraceptives in treatment of primary dysmenorrhea: A prospective, multicenter, randomized controlled study

ObjectiveTo compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles. MethodsA multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16–35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named “Guanyuan” (CV4) and “Qihai” (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment. Results76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC. ConclusionLLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.

Targeted Metabolomic Biomarkers for Stroke Subtyping.

Ischemic stroke is a heterogeneous disease with various etiologies. The current subtyping process is complicated, time-consuming, and costly. Metabolite-based biomarkers have the potential to improve classification and deliver optimal treatments. We here aimed to identify novel, targeted metabolomics-based biomarkers to discriminate between large-artery atherosclerosis (LAA) and cardioembolic (CE) stroke. We acquired serum samples and clinical data from a hospital-based acute stroke registry (ischemic stroke within 3 days from symptom onset). We included 346 participants (169 LAA, 147 CE, and 30 healthy older adults) and divided them into training and test sets. Targeted metabolomic analysis was performed using quantitative and quality-controlled liquid chromatography with tandem mass spectrometry. A multivariate regression model using metabolomic signatures was created that could independently distinguish between LAA and CE strokes. The training set (n = 193) identified metabolomic signatures that were different in patients with LAA and CE strokes. Six metabolomic biomarkers, i.e., lysine, serine, threonine, kynurenine, putrescine, and lysophosphatidylcholine acyl C16:0, could discriminate between LAA and CE stroke after adjusting for sex, age, body mass index, stroke severity, and comorbidities. The enhanced diagnostic power of key metabolite combinations for discriminating between LAA and CE stroke was validated using the test set (n = 123). We observed significant differences in metabolite profiles in LAA and CE strokes. Targeted metabolomics may provide enhanced diagnostic yield for stroke subtypes. The pathophysiological pathways of the identified metabolites should be explored in future studies.

The metabolic differences of anestrus, heat, pregnancy, pseudopregnancy, and lactation in 800 female dogs.

Reproduction causes major hormonal and physiological changes to the female body. However, the metabolic changes occurring during canine reproduction are scarcely studied. In this cross-sectional study, we assessed the metabolic effects of canine reproductive status using a 1H NMR metabolomics platform optimized and validated for canine use. The study population consisted of a total of 837 healthy, intact female dogs in breeding age, of which 663 dogs were in anestrus, 78 in heat, 43 were pseudopregnant, 15 were pregnant, and 38 were lactating. The differences in metabolite profiles between these states were studied by the Kruskal-Wallis test with post-hoc tests performed using the Dunn's test, and visualized by box plots and a heatmap. The ability of the metabolite profile to differentiate pregnant dogs from non-pregnant ones was assessed by creating a multivariate Firth logistic regression model using forward stepwise selection. Lactation, pregnancy and heat all were associated with distinct metabolic changes; pregnancy caused major changes in the concentrations of glycoprotein acetyls, albumin and creatinine, and smaller changes in several lipids, citrate, glutamine, and alanine. Pseudopregnancy, on the other hand, metabolically largely resembled anestrus. Lactation caused major changes in amino acid concentrations and smaller changes in several lipids, albumin, citrate, creatinine, and glycoprotein acetyls. Heat, referring to proestrus and estrus, affected cholesterol and LDL metabolism, and increased HDL particle size. Albumin and glycoprotein acetyls were the metabolites included in the final multivariate model for pregnancy detection, and could differentiate pregnant dogs from non-pregnant ones with excellent sensitivity and specificity. These results increase our understanding of the metabolic consequences of canine reproduction, with the possibility of improving maternal health and ensuring reproductive success. The identified metabolites could be used for confirming canine pregnancy.

Normal Appearing White Matter N-Acetylaspartate Changes Impact on Fatigue in Multiple Sclerosis

Background: Fatigue is one of the most frequent complaints presented by multiple sclerosis patients. Fatigue may be multifactorial. Proton magnetic resonance spectroscopy studies have shown significant reductions in N-acetylaspartate/creatine ratios in multiple brain regions among fatigued multiple sclerosis patients in comparison to non-fatigued multiple sclerosis patients, suggesting axonal loss as a contributing factor. Females are twice as likely to develop the disease. Aim: To evaluate gender variability in fatigue scores in relapsing-remitting multiple sclerosis patients. To explore potential gender differences in metabolite profiles of normal appearing white matter. To correlate metabolite changes distribution with fatigue severity and to evaluate the gender impact. Methods: We enrolled 50 relapsing-remitting multiple sclerosis patients on disease modifying treatment and 28 healthy controls. All participants underwent proton magnetic resonance spectroscopy of normal appearing white matter corresponding regions and fatigue severity evaluation. Results: We found higher fatigue scores in the multiple sclerosis group, due to greater severity in female subjects. We found a significant decrease of N-acetylaspartate/creatine ratio with increase in N-acetylaspartate, choline, and creatine levels in multiple sclerosis subjects. N-acetylaspartate and choline levels were significantly higher in the multiple sclerosis males. Female multiple sclerosis patients presented with lower N-acetylaspartate levels than healthy controls and greater increases in Fatigue Severity Scale score. Regression analysis revealed metabolite specific relationships between fatigue against metabolite variables. Conclusion: Proton magnetic resonance spectroscopy registered differences in metabolite profiles in normal appearing white matter male and female multiple sclerosis subjects. We might presume gender dependent specifiers in metabolite profiles in relapsing- remitting multiple sclerosis. They impact fatigue severity. N- acetyaspartate might be crucial contributor in central fatigue in multiple sclerosis. Bioenergetic role of N-acetylaspartate needs further collaborative research on genetics and electrical properties of neurons to reveal the underlying mechanism of fatigue and conductivity deterioration.