PubMed

Cell Rep. 2023 May 18;42(5):112530. doi: 10.1016/j.celrep.2023.112530. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder caused by overnutrition and can lead to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The transcription factor Forkhead box K1 (FOXK1) is implicated in regulation of lipid metabolism downstream of mechanistic target of rapamycin complex 1 (mTORC1), but its role in NAFLD-NASH pathogenesis is understudied. Here, we show that FOXK1 mediates nutrient-dependent suppression of lipid catabolism in the liver. Hepatocyte-specific deletion of Foxk1 in mice fed a NASH-inducing diet ameliorates not only hepatic steatosis but also associated inflammation, fibrosis, and tumorigenesis, resulting in improved survival. Genome-wide transcriptomic and chromatin immunoprecipitation analyses identify several lipid metabolism-related genes, including Ppara, as direct targets of FOXK1 in the liver. Our results suggest that FOXK1 plays a key role in the regulation of hepatic lipid metabolism and that its inhibition is a promising therapeutic strategy for NAFLD-NASH, as well as for HCC.PMID:37209098 | DOI:10.1016/j.celrep.2023.112530

Insect Mol Biol. 2023 May 20. doi: 10.1111/imb.12850. Online ahead of print.ABSTRACTThe white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine-fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.PMID:37209025 | DOI:10.1111/imb.12850

J Cachexia Sarcopenia Muscle. 2023 May 20. doi: 10.1002/jcsm.13251. Online ahead of print.ABSTRACTBACKGROUND: Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood.METHODS: Male ARskm-/y (n = 7-12) and female ARskm-/- mice (n = 9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm-/y , in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n = 6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n = 6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm-/y mice was analysed at the age of 9 weeks (P < 0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR] < 0.1) and H3K4me2 (47 225 peaks with FDR < 0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice.RESULTS: We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of ARskm-/y mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H2 O2 levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes involved in glycolysis, oxidative metabolism and muscle contraction.CONCLUSIONS: Our study provides important insights into diseases caused by impaired AR function in musculoskeletal system and delivers a deeper understanding of skeletal muscle pathophysiological dynamics that is instrumental to develop effective treatment for muscle disorders.PMID:37208984 | DOI:10.1002/jcsm.13251

Biotechnol Biofuels Bioprod. 2023 May 19;16(1):84. doi: 10.1186/s13068-023-02338-8.ABSTRACTBACKGROUND: Diatoms have been viewed as ideal cell factories for production of some high-value bioactive metabolites, such as fucoxanthin, but their applications are restrained by limited biomass yield. Mixotrophy, by using both CO2 and organic carbon source, is believed effective to crack the bottleneck of biomass accumulation and achieve a sustainable bioproduct supply.RESULTS: Glycerol, among tested carbon sources, was proved as the sole that could significantly promote growth of Cylindrotheca sp. with illumination, a so-called growth pattern, mixotrophy. Biomass and fucoxanthin yields of Cylindrotheca sp., grown in medium with glycerol (2 g L-1), was increased by 52% and 29%, respectively, as compared to the autotrophic culture (control) without compromise in photosynthetic performance. As Cylindrotheca sp. was unable to use glycerol without light, a time-series transcriptomic analysis was carried out to elucidate the light regulation on glycerol utilization. Among the genes participating in glycerol utilization, GPDH1, TIM1 and GAPDH1, showed the highest dependence on light. Their expressions decreased dramatically when the alga was transferred from light into darkness. Despite the reduced glycerol uptake in the dark, expressions of genes associating with pyrimidine metabolism and DNA replication were upregulated when Cylindrotheca sp. was cultured mixotrophically. Comparative transcriptomic and metabolomic analyses revealed amino acids and aminoacyl-tRNA metabolisms were enhanced at different timepoints of diurnal cycles in mixotrophic Cylindrotheca sp., as compared to the control.CONCLUSIONS: Conclusively, this study not only provides an alternative for large-scale cultivation of Cylindrotheca, but also pinpoints the limiting enzymes subject to further metabolic manipulation. Most importantly, the novel insights in this study should aid to understand the mechanism of biomass promotion in mixotrophic Cylindrotheca sp.PMID:37208696 | DOI:10.1186/s13068-023-02338-8

BMC Genomics. 2023 May 19;24(1):272. doi: 10.1186/s12864-023-09361-x.ABSTRACTMacrophages are important effector cells in tumor progression and immune regulation. Previously, we demonstrated that the transcription suppressor homeobox containing 1(HMBOX1) exhibits immunosuppressive activity in LPS-induced acute liver injury by impeding macrophage infiltration and activation. We also observed a lower proliferation in HMBOX1-overexpressed RAW264.7 cells. However, the specific mechanism was unclear. Here, a work was performed to characterize HMBOX1 function related to cell proliferation from a metabolomics standpoint by comparing the metabolic profiles of HMBOX1-overexpressed RAW264.7 cells to those of the controls. Firstly, we assessed HMBOX1 anti-proliferation activity in RAW264.7 cells with CCK8 assay and clone formation. Then, we performed metabolomic analyses by ultra-liquid chromatography coupled with mass spectrometry to explore the potential mechanisms. Our results indicated that HMBOX1 inhibited the macrophage growth curve and clone formation ability. Metabolomic analyses showed significant changes in HMBOX1-overexpressed RAW264.7 metabolites. A total of 1312 metabolites were detected, and 185 differential metabolites were identified based on the criterion of OPLS-DA VIP > 1 and p value < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the elevated HMBOX1 in RAW264.7 inhibited the pathways of amino acid and nucleotide metabolism. Glutamine concentrations decreased significantly in HMBOX1-overexpressed macrophages, and glutamine-related transporter SLC1A5 was also downregulated. Furthermore, SLC1A5 overexpression reversed HMBOX1 inhibition of macrophage proliferation. This study demonstrated the potential mechanism of the HMBOX1/SLC1A5 pathway in cell proliferation by regulating glutamine transportation. The results may help provide a new direction for therapeutic interventions in macrophage-related inflammatory diseases.PMID:37208615 | DOI:10.1186/s12864-023-09361-x

BMC Gastroenterol. 2023 May 19;23(1):161. doi: 10.1186/s12876-023-02803-6.ABSTRACTINTRODUCTION: Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic.OBJECTIVES: The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics.METHODS: Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student's t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients.RESULTS: By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9.CONCLUSIONS: In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.PMID:37208605 | DOI:10.1186/s12876-023-02803-6

BMC Genomics. 2023 May 19;24(1):267. doi: 10.1186/s12864-023-09317-1.ABSTRACTBACKGROUND: Oriental river prawn Macrobrachium nipponense is an economically important aquaculture species in China, Japan, and Vietnam. In commercial prawn farming, feed cost constitutes about 50 to 65% of the actual variable cost. Improving feed conversion efficiency in prawn culture will not only increase economic benefit, but also save food and protect the environment. The common indicators used for feed conversion efficiency include feed conversion ratio (FCR), feed efficiency ratio (FER), and residual feed intake (RFI). Among these, RFI is much more suitable than FCR and FER during the genetic improvement of feed conversion efficiency for aquaculture species.RESULTS: In this study, the transcriptome and metabolome of hepatopancreas and muscle of M. nipponense from high RFI low RFI groups, which identified after culture for 75 days, were characterized using combined transcriptomic and metabolomic analysis. A total of 4540 differentially expressed genes (DEGs) in hepatopancreas, and 3894 DEGs in muscle were identified, respectively. The DEGs in hepatopancreas were mainly enriched in KEGG pathways including the metabolism of xenobiotics by cytochrome P450 (down-regulated), fat digestion and absorption (down-regulated) and aminoacyl-tRNA biosynthesis (up-regulated), etc. The DEGs in muscle were mainly enriched in KEGG pathways including the protein digestion and absorption (down-regulated), glycolysis/gluconeogenesis (down-regulated), and glutathione metabolism (up-regulated), etc. At the transcriptome level, the RFI of M. nipponense was mainly controlled in biological pathways such as the high immune expression and the reduction of nutrients absorption capacity. A total of 445 and 247 differently expressed metabolites (DEMs) were identified in the hepatopancreas and muscle, respectively. At the metabolome level, the RFI of M. nipponense was affected considerably by amino acid and lipid metabolism.CONCLUSIONS: M. nipponense from higher and lower RFI groups have various physiological and metabolic capability processes. The down-regulated genes, such as carboxypeptidase A1, 6-phosphofructokinase, long-chain-acyl-CoA dehydrogenase, et. al., in digestion and absorption of nutrients, and the up-regulated metabolites, such as aspirin, lysine, et. al., in response to immunity could be potential candidate factors contributed to RFI variation for M. nipponense. Overall, these results would provide new insights into the molecular mechanism of feed conversion efficiency and assist in selective breeding to improve feed conversion efficiency in M. nipponense.PMID:37208591 | DOI:10.1186/s12864-023-09317-1

Curr Obes Rep. 2023 May 19. doi: 10.1007/s13679-023-00503-6. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: The review aims to describe short-chain fatty acids (SCFAs) as metabolites of bacteria, their complex influence on whole-body metabolism, and alterations in the SCFA profile in obesity and after bariatric surgery (BS).RECENT FINDINGS: The fecal profile of SCFAs in obese patients differs from that of lean patients, as well as their gut microbiota composition. In obese patients, a lower diversity of bacteria is observed, as well as higher concentrations of SCFAs in stool samples. Obesity is now considered a global epidemic and bariatric surgery (BS) is an effective treatment for severe obesity. BS affects the structure and functioning of the digestive system, and also alters gut microbiota and the concentration of fecal SCFAs. Generally, after BS, SCFA levels are lower but levels of branched short-chain fatty acids (BSCFAs) are elevated, the effect of which is not fully understood. Moreover, changes in the profile of circulating SCFAs are little known and this is an area for further research. Obesity seems to be inherently associated with changes in the SCFA profile. It is necessary to better understand the impact of BS on microbiota and the metabolome in both feces and blood as only a small percentage of SCFAs are excreted. Further research may allow the development of a personalized therapeutic approach to the BS patient in terms of diet and prebiotic intervention.PMID:37208544 | DOI:10.1007/s13679-023-00503-6

Nat Commun. 2023 May 19;14(1):2876. doi: 10.1038/s41467-023-38403-x.ABSTRACTTumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma.PMID:37208361 | DOI:10.1038/s41467-023-38403-x

Fish Shellfish Immunol. 2023 May 17:108840. doi: 10.1016/j.fsi.2023.108840. Online ahead of print.ABSTRACTGrass carp reovirus genotype Ⅱ (GCRV Ⅱ) causes hemorrhagic disease in a variety fish, seriously affecting the aquaculture industry in China. However, the pathogenesis of GCRV Ⅱ is unclear. Rare minnow is an ideal model organism to study the pathogenesis of GCRV Ⅱ. Herein, we applied liquid chromatography-tandem mass spectrometry metabolomics to investigate metabolic responses in the spleen and hepatopancreas of rare minnow injected with virulent GCRV Ⅱ isolate DY197 and attenuated isolate QJ205. Results indicated that marked metabolic changes were identified in both the spleen and hepatopancreas after GCRV Ⅱ infection, and the virulent DY197 strain induced more significantly different metabolites (SDMs) than the attenuated QJ205 strain. Moreover, most SDMs were downregulated in the spleen and tend to be upregulated in hepatopancreas. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that tissue-specific metabolic responses were identified after viruses infection, and the virulent DY197 strain induced more SDMs involved in amino acid metabolism in the spleen, especially the tryptophan metabolism, cysteine and methionine metabolism, which were essential for immune regulation in host; Meanwhile, nucleotide metabolism, protein synthesis and metabolism related pathways were enriched in the hepatopancreas by both virulent and attenuated strains. Our findings revealed the large scale metabolic alterations in rare minnow in response to attenuated and virulent GCRV Ⅱ infection, which will lead to a better understanding of the pathogenesis of viruses and host-pathogens interactions.PMID:37207884 | DOI:10.1016/j.fsi.2023.108840

J Ethnopharmacol. 2023 May 17:116590. doi: 10.1016/j.jep.2023.116590. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The skeletal complications associated with chronic kidney diseases from stages 3-5 in individuals are called Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), which increases the incidence of cardiovascular diseases drastically and affects the quality of life of patients seriously. Eucommia cortex has the effect of tonifying kidneys and strengthening bones, and salt Eucommia cortex is one of the most commonly used traditional Chinese medicines in the clinical treatment of CKD-MBD instead of Eucommia cortex. However, its mechanism still remains unexplored.AIM OF THE STUDY: The aim of this study was to investigate the effects and mechanisms of salt Eucommia cortex on CKD-MBD by integrating network pharmacology, transcriptomics, and metabolomics.MATERIALS AND METHODS: The CKD-MBD mice induced by 5/6 nephrectomy and low calcium/high phosphorus diet were treated with salt Eucommia cortex. The renal functions and bone injuries were evaluated by serum biochemical detection, histopathological analyses, and femur Micro-CT examinations. Differentially expressed genes (DEGs) between the control group and model group, model group and high-dose Eucommia cortex group, model group and high-dose salt Eucommia cortex group were analyzed by transcriptomic analysis. The differentially expressed metabolites (DEMs) between the control group and model group, model group and high-dose Eucommia cortex group, model group and high-dose salt Eucommia cortex group were analyzed by metabolomics analysis.The common targets and pathways were obtained by integrating transcriptomics, metabolomics and network pharmacology, which were identified and verified by in vivo experiments.RESULTS: The negative impacts on the renal functions and bone injuries were alleviated with salt Eucommia cortex treatment effectively. Compared with CKD-MBD model mice, the levels of serum BUN, Ca and urine Upr were significantly decreased in the salt Eucommia cortex group. And the Integrated network pharmacology, transcriptomics and metabolomics analysis revealed that Peroxisome Proliferative Activated Receptor, Gamma (PPARG) was the only common target, mainly involved by AMPK signaling pathways. The activation of PPARG in the kidney tissue was significantly decreased in CKD-MBD mice but increased in the salt Eucommia cortex treatment. The AMPK signaling pathway were verified that AMPK expression levels were decreased in CKD-MBD mice but increased in the salt Eucommia cortex treatment.CONCLUSIONS: Our study presented that salt Eucommia cortex alleviated the negative impact of CKD-MBD on the renal injury and bone injury of mice induced by 5/6 nephrectomy with the low calcium/high phosphorus diet effectively, which is highly likely achieved through the PPARG/AMPK signaling pathway.PMID:37207881 | DOI:10.1016/j.jep.2023.116590

J Proteomics. 2023 May 17:104928. doi: 10.1016/j.jprot.2023.104928. Online ahead of print.ABSTRACTTuberous sclerosis complex (TSC) is a rare, multisystem genetic disorder that leads to the development of benign tumors in multiple organs and neurological symptoms. TSC clinical manifestations show a great heterogenicity, with most patients presenting severe neuropsychiatric and neurological disorders. TSC is caused by loss-of-function mutations in either Tsc1 or Tsc2 genes, leading to overexpression of the mechanistic target of rapamycin (mTOR) and, consequently, abnormal cellular growth, proliferation and differentiation as well as to cell migration defects. Beside the growing interest, TSC remains a disorder poorly understood, with limited perspectives in the field of therapeutic strategies. Here we used murine postnatal subventricular zone (SVZ) neural stem progenitor cells (NSPCs) deficient of Tsc1 gene as a TSC model to unravel novel molecular aspects of the pathophysiology of this disease. 2D-DIGE-based proteomic analysis detected 55 differently represented spots in Tsc1-deficient cells, compared to wild-type counterparts, which were associated with 36 protein entries after corresponding trypsinolysis and nanoLC-ESI-Q-Orbitrap-MS/MS analysis. Proteomic results were validated using various experimental approaches. Bioinformatics associated differently represented proteins with oxidative stress and redox pathways, methylglyoxal biosynthesis, myelin sheath, protein S-nitrosylation and carbohydrate metabolism. Because most of these cellular pathways have already been linked to TSC features, these results were useful to clarify some molecular aspects of TSC etiopathogenesis and suggested novel promising therapeutic protein targets. SIGNIFICANCE: Tuberous Sclerosis Complex (TSC) is a multisystemic disorder caused by inactivating mutations of TSC1 or TSC2 genes, which induce overactivation of the mTOR component. The molecular mechanisms underlying the pathogenesis of TSC remain unclear, probably due to complexity of mTOR signaling network. To have a picture of protein abundance changes occurring in TSC disorder, murine postnatal subventricular zone (SVZ) neural stem progenitor cells (NSPCs) deficient of Tsc1 gene were used as a model of disease. Thus, Tsc1-deficient SVZ NSPCs and wild-type cells were comparatively evaluated by proteomics. This analysis evidenced changes in the abundance of proteins involved in oxidative/nitrosative stress, cytoskeleton remodelling, neurotransmission, neurogenesis and carbohydrate metabolism. These proteins might clarify novel molecular aspects of TSC etiopathogenesis and constitute putative molecular targets for novel therapeutic management of TSC-related disorders.PMID:37207814 | DOI:10.1016/j.jprot.2023.104928

J Proteomics. 2023 May 17:104926. doi: 10.1016/j.jprot.2023.104926. Online ahead of print.ABSTRACTMetabolites are the final products of metabolism and provide insights into the biochemical balance of tissue systems. A cascade of reactions involving proteins, carbohydrates, and lipids affects meat color, tenderness, and flavor, specifically, metabolites that are key biomolecules in biochemical reactions associated with attainment of acceptable meat quality. Bioinformatics platforms, such as Kyoto Encyclopedia of Genes and Genomes (KEGG) databases and MetaboAnalyst, are utilized to help understanding the role of differentially abundant metabolites and characterizing their roles in cellular function/metabolism. However, the inability to identify all metabolites using a single platform and limited metabolite libraries specifically for meat/food remains a challenge. Therefore, the advances in metabolite separation, easy-to-use data processing, increased resolution of mass-spectrometry, and data analysis will help to make inferences or develop biomarkers related to meat quality. This review discusses how metabolomics can be exploited to characterize meat quality, the challenges, and current trends. SIGNIFICANCE: Metabolites are the final products of metabolism and provide insights into the biochemical balance of tissue systems. They play an important role in quality traits (i.e., color, texture, and flavor) and nutritive value of foods. Visual appearance of fresh foods, such as muscle foods, are utilized by consumers to assess the quality at the retail market before making purchases. Similarly, tenderness and flavor of meats influence eating satisfaction and re-purchase decisions. Inconsistencies in meat quality lead to huge economic losses to food industry. For instance, consumers often associate a bright-cherry red color with freshness, and the US beef industry loses $3.74 billion annually due to discoloration during storage. Both pre-and post-harvest factors influence the extent of meat quality changes. Metabolomics offer robust tools to get a snapshot of small molecules such as acids, amino acids, glycolytic- and tricarboxylic acids, fatty acids, and sugars present in post-mortem muscle tissue and their role in meat quality. Further, using bioinformatics platforms enables characterizing the role of differentially present metabolites in meat quality as well as identifying biomarkers for desirable quality traits such as tender meat or color-stable carcasses. Innovative applications of metabolomics can be exploited to elucidate the underpinnings of meat quality and to develop novel strategies to enhance marketability of retail fresh meats.PMID:37207813 | DOI:10.1016/j.jprot.2023.104926

Fitoterapia. 2023 May 17:105540. doi: 10.1016/j.fitote.2023.105540. Online ahead of print.ABSTRACTA comprehensive study of leaves, flowers, fruits, bark, and seeds' extracts of Gmelina arborea Roxb was performed for first time to investigate their anti-inflammatory, anti-Alzheimer, and antidiabetic activities. A thorough comparative phytochemical investigation of the five organs was performed using Tandem ESI-LC-MS. The biological investigation, further aided by multivariate data analysis and molecular docking proved the highly significant potential of using G.arborea organs' extracts as medicinal agents. Chemometric analysis of the obtained data revealed 4 distinct clusters among different samples of the 5 G.arborea (GA)organs and also confirmed that each organ was chemically distinct from the others, except for fruits and seeds which were closely correlated. Compounds anticipated to be responsible for activity were identified by LC-MS/MS. To clarify the differential chemical biomarkers of G. arborea organs, an orthogonal partial least squares discriminant analysis (OPLS-DA) was constructed. Bark exhibited it's in vitro anti-inflammatory activity through down regulation of COX-1 pro-inflammatory markers while fruits and leaves affected mainly DPP4 the marker for diabetes, and flowers were the most potent against Alzheimer maker acetylcholine (ACE) esterase. The metabolomic profiling of the 5 extracts lead to the identification of 27 compounds in negative ion mode and the differences in chemical composition were correlated to difference in activity. Iridoid glycosides were the major class of identified compounds. Molecular docking proved the different affinities of our metabolite towards different targets. Gmelina arborea Roxb. is a very important plant both economically and medicinally.PMID:37207792 | DOI:10.1016/j.fitote.2023.105540

Cancer Cell. 2023 May 6:S1535-6108(23)00141-1. doi: 10.1016/j.ccell.2023.04.015. Online ahead of print.ABSTRACTCalreticulin (CALR) exposure on the cell surface is known to deliver robust pro-phagocytic signals to myeloid cells. In Nature, Sen Santara et al. demonstrate that surface-exposed CALR also operates as an endogenous activator of natural killer (NK) cells. Collectively, these findings suggest that CALR exposure orchestrates multiple facets of innate immunosurveillance.PMID:37207656 | DOI:10.1016/j.ccell.2023.04.015

J Breath Res. 2023 May 19. doi: 10.1088/1752-7163/acd715. Online ahead of print.ABSTRACTProlonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO2tox). PO2tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO2tox. &#xD;Using a double-blind, randomized "sham" controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 hours. One test gas consisted of 100% O2 (HBO) and the other was a gas mixture containing 30.6% O2 with the balance N2 (Nitrox). The high O2 stress dive (HBO) and low O2 stress dive (nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). &#xD;Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO2tox and one subject terminated the dive early due to severe symptoms of PO2tox. No symptoms of PO2tox were reported following the nitrox dive. A Partial Least-Squares Discriminant Analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (± 2%) and sensitivity and specificity of 0.93 (± 10%) and 0.94 (± 10%), respectively. The resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.&#xD;&#xD.PMID:37207635 | DOI:10.1088/1752-7163/acd715

Biochem Biophys Res Commun. 2023 May 4;667:34-42. doi: 10.1016/j.bbrc.2023.05.018. Online ahead of print.ABSTRACTIslet regeneration is a complex process involving multiple metabolic adaptions, but the specific characterization of the islet metabolome in relation to cell proliferation has not been established. This study aimed to investigate the metabolomic changes of regenerative islets from partial pancreatectomy (Ppx) mice and speculate underlying mechanisms. Islet samples were collected from C57/BL6 mice undergoing 70-80% Ppx or sham surgery, followed by analyses of glucose homeostasis, islet morphology, and untargeted metabolomics profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS). There is no difference in blood glucose and body weight between sham and Ppx mice. After surgery, the Ppx mice showed impaired glucose tolerance, increased Ki67 positive beta cells, and elevated beta-cell mass. LC-MS/MS analysis identified fourteen differentially changed metabolites in islets of Ppx mice, including long-chain fatty acids (e.g., docosahexaenoic acid) and amino acid derivatives (e.g., creatine). Pathway analysis based on the KEGG database revealed five significantly enriched signaling pathways including cAMP signaling pathway. Further immunostaining assay on pancreatic tissue sections showed the levels of p-CREB, a transcription factor downstream of cAMP, elevated in islets from Ppx mice. In conclusion, our results demonstrate that islet regeneration involves metabolic alterations in long-chain fatty acids and amino acid derivatives, as well as the activation of the cAMP signaling pathway.PMID:37207562 | DOI:10.1016/j.bbrc.2023.05.018

Plant Physiol Biochem. 2023 May 12;200:107742. doi: 10.1016/j.plaphy.2023.107742. Online ahead of print.ABSTRACTAnthocyanins and selenium (Se) play critical roles in antioxidant, anticancer, antibacterial, and antiviral treatments. Previous studies indicate that colored-grain wheat accumulates more Se than regular wheat, and Se synergistically promotes anthocyanin synthesis. However, the mechanism through which Se regulates anthocyanin synthesis remains unclear. We studied anthocyanin accumulation during the grain-filling stage of colored-grain wheat development by employing transcriptomics and metabolomics. We show that Se biofortification increased the concentrations of Se, anthocyanin, chlorophyll a and b, and carotenoids in colored-grain wheat. Genes related to biosynthesis of anthocyanins, phenylpropanoids biosynthesis, and flavonoids biosynthesis were significantly upregulated after Se treatment, which led to the accumulation of anthocyanin metabolites in colored-grain wheat. Genetic alterations in the expression profiles of several genes and transcription factors were observed, which slowed down lignin and proanthocyanidin biosynthesis and accelerated anthocyanin synthesis. Our results deepen the understanding of anthocyanin metabolism in Se-treated colored-grain wheat, which will likely promote harvest of these varieties.PMID:37207492 | DOI:10.1016/j.plaphy.2023.107742

Aquat Toxicol. 2023 May 17;260:106569. doi: 10.1016/j.aquatox.2023.106569. Online ahead of print.ABSTRACTCarbonate alkalinity (CA) is one of the environmental factors affecting the survival and growth of aquatic animals. However, the toxic effects of CA stress on Pacific white shrimp Litopenaeus vannamei at the molecular level are completely unclear. In this study, we investigated the changes of the survival and growth, and hepatopancreas histology of L. vannamei under different levels of CA stress, and integrated transcriptomics and metabolomics to explore major functional changes in the hepatopancreas and identify biomarkers. After CA exposure for 14 days, the survival and growth of the shrimp were reduced, and the hepatopancreas showed obvious histological damage. A total of 253 genes were differentially expressed in the three CA stress groups, and immune-related genes such as pattern recognition receptors, phenoloxidase system and detoxification metabolism were affected; substance transport-related regulators and transporters were mostly downregulated. Furthermore, the metabolic pattern of the shrimp was also altered by CA stress, especially amino acids, arachidonic acid and B-vitamin metabolites. The integration analysis of differential metabolites and genes further showed that the functions of ABC transporters, protein digestion and absorption, and amino acid biosynthesis and metabolism were highly altered by CA stress. The results of this study revealed that CA stress caused immune, substance transport, and amino acid metabolic variations in L. vannamei, and identified several potential biomarkers related to stress response.PMID:37207485 | DOI:10.1016/j.aquatox.2023.106569

J Neuroimmunol. 2023 May 11;379:578105. doi: 10.1016/j.jneuroim.2023.578105. Online ahead of print.ABSTRACTTo prioritize circulating metabolites that likely play causal roles in the pathogenesis of multiple sclerosis (MS). Two-sample Mendelian randomization analysis was performed to estimate the causal effects of 571 circulating metabolites on the risk of MS. Genetic instruments for circulating metabolites were obtained from three previous genome-wide association studies (GWAS) of the blood metabolome (N = 7824; 24,925; and 115,078; respectively), while genetic associations with MS were from a large GWAS by the International Multiple Sclerosis Genetics Consortium (14,802 cases and 26,703 control). The primary analysis was performed with the multiplicative random-effect inverse variance-weighted method, while multiple sensitivity analyses were conducted with the weighted median, weighted mode, MR-Egger, and MR-PRESSO. A total of 29 metabolites had suggestive evidence of causal associations with MS. Genetically instrumented levels of serine (OR = 1.56, 95% CI = 1.25-1.95), lysine (OR = 1.18, 95% CI = 1.01-1.38), acetone (OR = 2.45, 95% CI = 1.02-5.90), and acetoacetate (OR = 2.47, 95% CI = 1.14-5.34) were associated with a higher MS risk. Total cholesterol and phospholipids in large very-low-density lipoprotein were associated with a lower MS risk (OR = 0.83, 95% CI = 0.69-1.00; OR = 0.80, 95% CI = 0.68-0.95), but risk-increasing associations (OR = 1.20, 95% CI = 1.04-1.40; OR = 1.13, 95% CI = 1.00-1.28) were observed for the same two lipids in very large high-density lipoprotein. Our metabolome-wide Mendelian randomization study prioritized a list of circulating metabolites, such as serine, lysine, acetone, acetoacetate, and lipids, that likely have causal associations with MS.PMID:37207441 | DOI:10.1016/j.jneuroim.2023.578105