Differences In Metabolic Pathways Research Articles

Impacts of a highly pathogenic ovine Eimeria ovinoidalis on the growth of Hu lambs

The apicomplexan Eimeria ovinoidalis is distributed worldwide. It can cause clinical coccidiosis, which is one of the most pathogenic species in sheep, reducing growth rates and resulting in significant economic losses in the industry. Its principal clinical sign is profuse diarrhoea in young animals. In this study, we established a model of E. ovinoidalis infection in lambs to understand its pathogenicity and evaluate the gut microbiota and fecal metabolite profiles. Specifically, we observed a significant shift in the abundance of bacteria and disrupted metabolism in lambs. Especially during the peak period of excrete oocysts, it promoted the reproduction of some harmful bacteria in Proteobacteria and Actinobacteriota, and reduced the abundance of beneficial bacteria such as Lachnospiraceae and Rikenellaceae. In the later stage of the patent period, the abundance of harmful bacteria in the intestine decreased, the abundance of beneficial bacteria which could produce anti-inflammatory substances began to increase, and the abundance and diversity of intestinal flora also tended to parallel with the control group. Coccidia infection could lead to the increase of differential metabolites and metabolic pathways between infected and control group, but the difference decreased with time. During the peak period of excrete oocysts, although the antimicrobial metabolites such as Lividamine were up-regulated, the excess of these metabolites could still induce the production of endotoxin, while Butanoic acid and other anti-inflammatory metabolites decreased significantly. A metabolomics analysis showed that E. ovinoidalis infection altered metabolites and metabolic pathways, with biosynthesis of unsaturated fatty acids, Teichoic acid biosynthesis and Butanoate metabolism as the major disrupted metabolic pathways. Details of the gut microbiota and the metabolome after infection with E. ovinoidalis may aid in the discovery of specific diagnostic markers and help us understand the changes in parasite metabolic pathways.

Widely targeted metabolomics reveals the phytoconstituent changes in Platostoma palustre leaves and stems at different growth stages.

Platostoma palustre (Blume) A. J. Paton is an important edible and medicinal plant. To gain a comprehensive and clear understanding of the variation patterns of metabolites in P. palustre, we employed the UPLC-MS platform along with widely targeted metabolomics techniques to analyze the metabolites in the stems and leaves of P. palustre at different stages. Our results revealed a total of 1228 detected metabolites, including 241 phenolic acids, 203 flavonoids, 152 lipids, 128 terpenes, 106 amino acids, 79 organic acids, 74 saccharides, 66 alkaloids, 44 lignans, etc. As the growth time increased, the differential metabolites (DAMs) mainly enriched in P. palustre leaves were terpenoids, phenolic acids, and lipids, while the DAMs primarily enriched in stems were terpenoids. Compared to stems, there were more differential flavonoids in leaves, and saccharides and flavonoids were significantly enriched in leaves during the S1 and S2 stages. Additionally, we identified 13, 10, and 23 potential markers in leaf, stem, and leaf vs. stem comparison groups. KEGG enrichment analysis revealed that arginine biosynthesis was the common differential metabolic pathway in different growth stages and tissues. Overall, this study comprehensively analyzed the metabolic profile information of P. palustre, serving as a solid foundation for its further development and utilization.

Plasma metabolomics signatures of developmental dysplasia of the hip in Tibet plateau

BackgroundDevelopmental dysplasia of the hip (DDH) is a common childhood health complaint, whose etiology is multifactorial. The incidence of DDH is variable and higher in Tibet plateau. Here, we collected plasma samples and studied the metabolomics signatures of DDH.MethodsFifty babies were enrolled: 25 with DDH and 25 age-matched non-DDH healthy controls (HC group). We collected plasma samples, laboratory parameters and conducted untargeted metabolomics profiling.ResultsThere are many differential metabolites among patients with DDH, including 4-β-hydroxymethyl-4-α-methyl-5-α-cholest-7-en-3-beta-ol, β-cryptoxanthin, α-tocopherol, taurocholic acid, glycocholic acid, 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, arabinosylhypoxanthine, leucyl-hydroxyproline, hypoxanthine. The main differential metabolic pathways focused on primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism, histidine metabolism, purine metabolism.ConclusionsTo our knowledge, this is the first report of metabolomics profile in babies with DHH. By combining the α-tocopherol and taurocholic acid, we could achieve the differential diagnosis of DDH.

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang ()-Taoren () herb pair.

To explore the material basis of the difference of efficacy of Dahuang (Radix Et Rhizoma Rhei Palmati)-Taoren (Semen Persicae) (DT) drugs with different proportions. Samples of different ratios of Dahuang (Radix et Rhizoma Rhei Palnati, DH) to Taoren (Semen Persicae, TR) (Group A 1:1, B 2:3, C 3:2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid (phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1:1.

Neuroinflammation Plays a Potential Role in the Medulla Oblongata After Moderate Traumatic Brain Injury in Mice as Revealed by Nontargeted Metabonomics Analysis.

Moderate traumatic brain injury (mTBI) involves a series of complex pathophysiological processes in not only the area in direct contact with mechanical violence but also in other brain regions far from the injury site, which may be important factors influencing subsequent neurological dysfunction or death. The medulla oblongata (MO) is a key area for the maintenance of basic respiratory and circulatory functions, whereas the pathophysiological processes after mTBI have rarely drawn the attention of researchers. In this study, we established a closed-head cortical contusion injury model, identified 6 different time points that covered the acute, subacute, and chronic phases, and then used nontargeted metabolomics to identify and analyze the changes in differential metabolites (DMs) and metabolic pathways in the MO region. Our results showed that the metabolic profile of the MO region underwent specific changes over time: harmaline, riboflavin, and dephospho-coenzyme A were identified as the key DMs and play important roles in reducing inflammation, enhancing antioxidation, and maintaining homeostasis. Choline and glycerophospholipid metabolism was identified as the key pathway related to the changes in MO metabolism at different phases. In addition, we confirmed increases in the levels of inflammatory factors and the activation of astrocytes and microglia by Western blot and immunofluorescence staining, and these findings were consistent with the nontargeted metabolomic results. These findings suggest that neuroinflammation plays a central role in MO neuropathology after mTBI and provide new insights into the complex pathophysiologic mechanisms involved after mTBI.

Metabolic Profiling for Unveiling Mechanisms of Kushenol F against Imiquimod-Induced Psoriasis with UHPLC/MS Analysis.

Psoriasis is a common chronic immune-mediated inflammatory skin disorder. Sophora flavescens Alt. (S. flavescens) has been widely acknowledged in the prevention and treatment of psoriasis. Kushenol F (KSCF) is a natural isopentenyl flavonoid extracted from the root of S. flavescens. We aimed to investigate the effect and mechanism of KSCF on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. A mouse model of psoriasis was induced with 5% IMQ for 5 days, and the mice were given KSCF dermally for 5 days. Changes in skin morphology, the psoriasis area, the severity index (PASI), and inflammatory factors of psoriasis-like skin lesions were evaluated. Metabolites in the psoriasis-like skin lesions were analyzed with ultra-high-performance liquid chromatography/mass spectrometry followed by a multivariate statistical analysis to identify the differential metabolites and metabolic pathway. The results of the present study confirmed that KSCF significantly reduced PASI scores, epidermal thickening, and epidermal cell proliferation and differentiation. KSCF also reduced the levels of interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, IL-23, and tumor necrosis factor (TNF)-α in the injured skin tissues while increasing IL-10 content. KSCF significantly regulated metabolites in the skin samples, and a total of 161 significant metabolites were identified. These differential metabolites involved sphingolipid and linoleic acid metabolism and steroid hormone biosynthesis. Collectively, KSCF inhibited the inflammatory response to prevent IMQ-induced psoriasis-like skin lesions in mice by call-backing the levels of 161 endogenous metabolites and affecting their related metabolic pathways. KSCF has the potential to be developed as a topical drug for treating psoriasis symptoms.

Dysregulation of Gut Microbiota-Derived Neuromodulatory Amino Acid Metabolism in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: An Integrative Metagenomic and Metabolomic Analysis.

Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024.

Modulation of glycolipid metabolism in T2DM rats by Rubus irritans Focke extract: Insights from metabolic profiling and ERK/IRS-1 signaling pathway

Ethnopharmacological relevanceThe extracellular regulated protein kinase (ERK) plays a crucial role in the mitogen-activated protein kinase (MAPK) family, influencing apoptosis, proliferation, and differentiation. It connection to the insulin (INS) signaling cascade and the development of type 2 diabetes mellitus (T2DM) has been established. Rubus irritans Focke, an indispensable herb in Chinese Tibetan medicine for diabetes mellitus treatment, lacks a comprehensive understanding of its effects and pharmacological mechanisms in T2DM. Aim of the studyThis study aimed to elucidate the effects of Rubus irritans Focke extract (Rife) on a T2DM rat model, exploring its impact on glycemic and lipid metabolism, histopathological changes, and its potential targeting of the extracellular regulated protein kinase/insulin receptor substrate-1 (ERK/IRS-1) signaling pathway. Materials and methodsA T2DM rat model was induced by streptozotocin (STZ) injection (40 mg/kg) in high-fat diet-fed (HFD) male Wistar rats. Rife and metformin (Met) were administered for 4 weeks, and glycemic, lipid metabolism indices, and histopathological changes were assessed. Protein expression of ERK, IRS-1 in rat liver tissues was examined to evaluate the impact on the ERK/IRS-1 pathway. ResultsRife reducing hepatic ERK and IRS-1 protein expression in T2DM rats. Untargeted metabolomics identified 13 potential biomarkers and 4 differential metabolic pathways related to glycolipid metabolism disorders. ConclusionsRife demonstrated improved glycolipid metabolism in T2DM rats by inhibiting the ERK/IRS-1 related signaling pathway and influencing multiple metabolic pathways. This study provides valuable insights into the potential therapeutic mechanisms of Rife in the context of T2DM.

Abstract PO1-03-10: Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer

Abstract Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer Background: It has previously been shown that microbial metabolic pathways are differentially activated in immunotherapy resistance, hence can serve as potential targets for therapeutic intervention. With the advent of Immune Checkpoint Blockers in the neoadjuvant setting of locally advanced (LA) TNBC, we hypothesized that similar microbial metabolite mediated resistance may be at play. We are presenting the real world data for neoadjuvant treatment in early TNBC along with a subset of tumor metabolite analysis. Method: 35 patients who received neoadjuvant pembrolizumab and chemotherapy for LA TNBC were identified at Moffitt Cancer Center between July 2019 to January 2023. These included 22 Caucasian, 5 African American, 2 Hispanic and 6 patients with undisclosed race. The age range was 33-78 years. The weight and Body Mass Index range was 55.3 kg-127.3 kg and 20.96-45.43 kg/m2 respectively. Nine patients had stage III disease while 24 had stage II breast cancer. The response was assessed in 33 patients; 20 patients (60.6%) achieved pathological complete response (pCR) and 13 (39.4%) had residual disease (RD). 1 patient developed severe immune mediated toxicity with colitis, hepatitis, myasthenia gravis leading to death while 1 patient had disease progression leading to drug discontinuation. Six patients developed immune mediated adverse events. We conducted untargeted metabolomic profiling on 24 patients to identify differentially abundant metabolites associated with pCR (ypT0/is ypN0) vs RD; 16 vs 8 patients respectively. Formalin fixed paraffin embedded (FFPE) slides from tumor tissue vs tumor bed were retrieved and histopathological evaluation of tumor cells was performed. 20 μm sections of FFPE block were used for untargeted metabolomics via liquid chromatography/mass spectrometry. Among the 200 metabolites detected, 63 were differentially abundant between pCR and tumor samples with RD. After correcting for false discovery rate, we observed striking differential activation of two microbial metabolic pathways. Samples with RD had significantly elevated kynurenine (OR-3.64 X1034, P-1.94 X 10-74 and kynurenine/Tryptophan ratio). The tryptophan, kynurenine pathway has been known to be overexpressed in patients resistant to immunotherapy and modulated by the microbiome. Similarly, the purine metabolic pathway, specifically microbiota-derived immunostimulatory metabolites- inosine, hypoxanthine, uric acid were significantly depleted in patients with RD (Inosine OR-0.54, p-0.007, Hypoxanthine OR-0.5, p-0.00039, uric acid OR: 0.41, P-0.003). Previously Inosine has been shown to increase the anti-tumor effects of immune checkpoint blockade by enhancing CD8+ effector T-cell function. Hence depletion of inosine, hypoxanthine and uric acid signals lack of an effector CD8 T cell response. Conclusion: Despite being a small study, it corroborates pCR rates noted in KEYNOTE 522 in the real world setting but shows significant concern for serious immune mediated adverse effects. This highlights the importance of stratifying patients who might be resistant to ICB or develop significant toxicities, thus deriving little to no benefit from standard neoadjuvant treatment. This underscores the need to develop precision-based treatment algorithms. The study represents one of the first investigations of differential abundance of microbial metabolites with immunotherapy resistance in LA TNBC. Our results highlight two microbially mediated mechanisms that could be targeted to improve pCR rates in LA TNBC. We are working to identify microbial metabolic pathways associated with immune mediated toxicity. Citation Format: Humaira Sarfraz, Brian Czerniecki, Zena Jameel, Michael Jaglal, Mostafa Eysha, Turkan Ozkul, Jameel Muzaffar, Aditi Saha, Sara Sarfraz, Fatima Zahra, Min Liu, Khushali Jhaveri, Melissa Sur, Adrianna Bagos-Estevez, Shahla Bari. Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-10.

Urinary metabolomic profiling of a cohort of Colombian patients with systemic lupus erythematosus

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

Mechano-induced cell metabolism disrupts the oxidative stress homeostasis of SAOS-2 osteosarcoma cells.

There has been an increasing focus on cancer mechanobiology, determining the underlying-induced changes to unlock new avenues in the modulation of cell malignancy. Our study used LC-MS untargeted metabolomic approaches and real-time polymerase chain reaction (PCR) to characterize the molecular changes induced by a specific moderate uniaxial stretch regimen (i.e., 24h-1Hz, cyclic stretch 0,5% elongation) on SAOS-2 osteosarcoma cells. Differential metabolic pathway analysis revealed that the mechanical stimulation induces a downregulation of both glycolysis and the tricarboxylic acid (TCA) cycle. At the same time, the amino acid metabolism was found to be dysregulated, with the mechanical stimulation enhancing glutaminolysis and reducing the methionine cycle. Our findings showed that cell metabolism and oxidative defense are tightly intertwined in mechanically stimulated cells. On the one hand, the mechano-induced disruption of the energy cell metabolism was found correlated with an antioxidant glutathione (GSH) depletion and an accumulation of reactive oxygen species (ROS). On the other hand, we showed that a moderate stretch regimen could disrupt the cytoprotective gene transcription by altering the expression levels of manganese superoxide dismutase (SOD1), Sirtuin 1 (SIRT1), and NF-E2-related factor 2 (Nrf2) genes. Interestingly, the cyclic applied strain could induce a cytotoxic sensitization (to the doxorubicin-induced cell death), suggesting that mechanical signals are integral regulators of cell cytoprotection. Hence, focusing on the mechanosensitive system as a therapeutic approach could potentially result in more effective treatments for osteosarcoma in the future.

Metagenomic analysis of soil microbial communities associated with Poa alpigena Lindm in Haixin Mountain, Qinghai Lake.

To investigate the impact of Poa alpigena Lindm on rhizosphere and bulk soil microorganisms in Haixin Mountain, Qinghai Lake, this study employed metagenomics technology to analyze the microbial communities of the samples. Results showed that 65 phyla, 139 classes, 278 orders, 596 families, 2376 genera, and 5545 species of soil microorganisms were identified from rhizosphere and bulk soil samples. Additionally, a microbial gene library specific to Poa alpigena Lindm was established for Qinghai Lake. Through α-diversity analysis, the richness and diversity of bulk microorganisms both significantly had a higher value than that in rhizosphere soil. The indicator microorganisms of rhizosphere and bulk soil at class level were Actinobacteria and Alphaproteobacteria, respectively. KEGG pathway analysis indicated that Carotenoid biosynthesis, Starch and sucrose metabolism, Bacterial chemotaxis, MAPK signaling pathway, Terpenoid backbone biosynthesis, and vancomycin resistance were the key differential metabolic pathways of rhizosphere soil microorganisms; in contrast, in bulk soil, the key differential metabolic were Benzoate degradation, Glycolysis gluconeogenesis, Aminobenzoate degradation, ABC transporters, Glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, Degradation of aromatic compounds, Methane metabolism, Pyruvate metabolism and Microbial metabolism diverse environments. Our results indicated that Poa alpigena Lindm rhizosphere soil possessed selectivity for microorganisms in Qinghai Lake Haixin Mountain, and the rhizosphere soil also provided a suitable survival environment for microorganisms.

Exploration of TCM syndrome types of the material basis and risk prediction of Wilson disease liver fibrosis based on 1H NMR metabolomics

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

Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia

To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Integrated strategy for mechanism of Shenling Baizhu San in treating ulcerative colitis based on colonic metabolomics and network pharmacology

Shenling Baizhu San(SLBZS) is a commonly used medicine for the treatment of ulcerative colitis(UC). This study aims to explore the mechanism of SLBZS in treating UC by using colonic metabolomics and network pharmacology. BALB/c mice were randomly divided into four groups: a blank group, a model group, an SLBZS group, and a sulfasalazine group. UPLC-Q-TOF-MS/MS technology was utilized to analyze the metabolic profiles of colonic tissue in mice, and differential metabolites and related metabolic pathways were screened. Based on the online database, active ingredients, action targets, and UC disease targets of SLBZS were screened. The protein-protein interaction(PPI) network of core targets of SLBZS in treating UC was constructed using STRING and Cytoscape 3.9.1. Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed using the DAVID database. A &quot;metabolite-reaction-enzyme-gene&quot; network was constructed to conduct a combined analysis of metabolomics and network pharmacology. SLBZS reversed the levels of 25 metabolites involved in various pathways such as D-glutamine and D-glutamate metabolism, caffeine metabolism, sphingolipid metabolism, arginine biosynthesis, lysine degradation, alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, and pyrimidine metabolism in UC colonic tissue. 47 core targets of SLBZS in treating UC were involved in pathways including the MAPK signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, lipid and atherosclerosis, inflammatory bowel disease, and Th17 cell differentiation. Integrated analysis showed that glycerophospholipid metabolism and pyrimidine metabolism were key metabolic pathways in the treatment of UC with SLBZS. The results suggested that SLBZS improved colonic mucosal morphology by regulating colonic metabolites, down-regulated the expression of inflammation-related core target genes to reduce inflammation levels, and alleviated lipid metabolism disorders, thereby exerting a therapeutic effect on UC.

Analysis of alterations in serum vitamins and correlations with gut microbiome, microbial metabolomics in patients with sepsis

BackgroundVitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis. MethodsThe serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis. ResultsIn the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas. ConclusionSepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.

Photoheterotroph improved the growth and nutrient levels of Chlorella vulgaris and the related molecular mechanism

Microalgae are rich in fatty acids, proteins, and other nutrients, which have gained the general attention of researchers all over the world. For the development of Chlorella vulgaris in food and feed industry, this study was conducted to investigate the differences in C. vulgaris’ growth and nutritional components under different culture conditions (autotrophic, heterotrophic, photoheterotrophic) and the internal factors through cell counting in combination with transcriptome and nutrient analyses. The results showed that, under the photoheterotrophic condition, Chlorella’s growth and the contents of lipid and protein were significantly higher than that under the heterotrophic condition, and the moisture content was lower than that under the heterotrophic condition. The saturated fatty acid content under the photoheterotrophic condition was the lowest, while the polyunsaturated fatty acid content was significantly higher than those under the other two conditions. There were 46,583 differentially expressed genes (DEGs), including 33,039 up-regulated DEGs (70.93%) and 13,544 down-regulated DEGs (29.07%), under the photoheterotrophic condition in comparison with the autotrophic condition. The fold change between the two conditions of samples of up-regulated genes was higher than that of the down-regulated genes. The KEGG enrichment showed that the up-regulated DEGs in the photoheterotrophic condition were significantly enriched in 5 pathways, including protein processing in endoplasmic reticulum pathway, photosynthesis pathway, photosynthesis-antenna protein pathway, endocytosis pathway, and phosphonate and phosphinate metabolism pathway. DEGs related to fatty acid metabolic pathways were significantly enriched in the fatty acid biosynthesis pathway and the biosynthesis of unsaturated fatty acid pathway. The qPCR analysis showed that the expression pattern of the selected genes was consistent with that of transcriptome analysis. The results of this study lay a theoretical foundation for the large-scale production of Chlorella and its application in food, feed, and biodiesel.Key points• Nutrient levels under photoheterotrophic condition were higher than other conditions.• Six important pathways were discovered that affect changes in nutritional composition.• Explored genes encode important enzymes in the differential metabolic pathways.

Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics

ObjectiveTo investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. MethodsA rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. ResultsA rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. ConclusionsWYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Identification of Key Factors in Cartilage Tissue During the Progression of Osteoarthritis Using a Non-targeted Metabolomics Strategy

AbstractThis research was to reveal the key factors in the progression of osteoarthritis (OA) using non-targeted metabolomics and to find targeted therapies for patients with OA. Twenty-two patients with knee OA scheduled for total knee arthroplasty were divided into two groups: Kellgren–Lawrence (KL) grade 3 (n = 16) and grade 4 (n = 6), according to plain X-rays of the knee. After the operation, the cartilages of femur samples were analyzed using non-targeted metabolomics. When compared with grade 3 patients, the levels of choline, 2-propylpiperidine, rhamnose, and monomethyl glutaric acid were higher; while 1-methylhistamine, sphingomyelin (SM) (d18:1/14:0), zeranol, 3- (4-hydroxyphenyl)-1-propanol, 5-aminopentanamide, dihydrouracil, 2-hydroxypyridine, and 3-amino-2-piperidone were lower in grade 4 patients. Furthermore, some metabolic pathways were found to be significantly different in two groups such as the pantothenate and coenzyme A (CoA) biosynthesis pathway, the glycerophospholipid metabolism pathway, histidine metabolism pathway, lysine degradation pathway, glycine, serine and threonine metabolism pathway, fructose and mannose metabolism pathway, the pyrimidine metabolism pathway, and beta-alanine metabolism pathway. This work used non-targeted metabolomics and screened out differential metabolites and metabolic pathways, providing a reliable theoretical basis for further study of specific markers and their specific pathways in the progression of OA.

UPLC-ESI-MS/MS-Based Analysis of Various Edible Rosa Fruits Concerning Secondary Metabolites and Evaluation of Their Antioxidant Activities.

The genus Rosa is globally popular with well-established applications since it has a high edible and medicinal value. However, relatively limited research has been conducted on the composition and quality of wild Rosa fruits. The present study aimed to compare the properties and chemical components of five wild edible Rosa fruits, Rosa roxburghii, Rosa sterilis, Rosa laevigata, Rosa davurica, and Rosa sericea. The UPLC-ESI-MS/MS approach identified the key metabolites among the five Rosa fruits as flavonoids, phenolic acids, and organic acids. The main differential metabolites among the five fruits are flavonoids (22.29-45.13%), phenolic acids (17-22.27%), and terpenoids (7.7-24%), respectively. In total, 125 compounds served as potential markers for the five Rosa species. Differential metabolic pathways of five Rosa fruits were analyzed using the KEGG approach. Rosa laevigata fruits showed the highest total polysaccharide (TPS) content of 64.48 g/100 g. All the five Rosa extracts effectively decreased the levels of malondialdehyde while increasing the activities of superoxide dismutase and glutathione peroxidase in the H2O2-induced HaCaT cell model, demonstrating high potential for antioxidant development. Our findings suggest that the five studied Rosa fruits exhibit biological activity and edible value worth further exploration.