PubMed

Front Vet Sci. 2023 Aug 24;10:1168703. doi: 10.3389/fvets.2023.1168703. eCollection 2023.ABSTRACTINTRODUCTION: The effect of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides from fish oil (FO), and their combination (FO+MCT) on the serum metabolome of dogs (Canis familiaris) was evaluated.METHODS: Dogs (N = 64) were randomized to either a control food, one with 7% MCT, one with FO (0.18% eicosapentaenoate and 1.3% docosahexaenoate), or one with FO+MCT for 28 days following a 14-day washout period on the control food. Serum metabolites were analyzed via chromatography followed by mass spectrometry.RESULTS: Additive effects of serum metabolites were observed for a number of metabolite classes, including fatty acids, phospholipids, acylated amines including endocannabinoids, alpha-oxidized fatty acids, and methyl donors. Some effects of the addition of FO+MCT were different when the oils were combined compared with when each oil was fed separately, namely for acylcarnitines, omega-oxidized dicarboxylic acids, and amino acids. Several potentially beneficial effects on health were observed, including decreased circulating triglycerides and total cholesterol with the addition of FO (with or without MCT) and decreases in N-acyl taurines with the addition of MCT, FO, or FO+MCT.DISCUSSION: Overall, the results of this study provide a phenotypic characterization of the serum lipidomic response to dietary supplementation of long-chain n3-polyunsaturated and medium-chain saturated fats in canines.PMID:37691632 | PMC:PMC10484482 | DOI:10.3389/fvets.2023.1168703

Dis Model Mech. 2023 Sep 11:dmm.050114. doi: 10.1242/dmm.050114. Online ahead of print.ABSTRACTCardiomyopathy is often fatal in Friedreich Ataxia (FA). However, FA hearts maintain adequate function until advanced disease stages, suggesting initial adaptation to the loss of frataxin (FXN). Conditional cardiac knockout mouse models of FXN show transcriptional and metabolic profiles of the mitochondrial integrated stress response (ISRmt), which could play an adaptive role. However, ISRmt has not been investigated in models with disease-relevant, partial decrease of FXN. We characterized the heart transcriptomes and metabolomes of three mouse models with varying degrees of FXN depletion, YG8-800, KIKO-700, and FxnG127V. Few metabolites were changed in YG8-800 mice and did not provide a signature of cardiomyopathy or ISRmt. Instead, several metabolites were altered in FxnG127V and KIKO-700 hearts. Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.PMID:37691621 | DOI:10.1242/dmm.050114

Mol Omics. 2023 Sep 11. doi: 10.1039/d3mo00141e. Online ahead of print.ABSTRACTLactic acid is a versatile, multi-functional organic monomer in various industries, creating worldwide demand. High titer lactic acid production was achieved by novel Bacillus amyloliquefaciens J2V2AA through sugarcane molasses fermentation up to 178 mg mL-1. A metabolomics approach such as combined GC-MS and LC-MS was applied to elucidate the involvement of key metabolites in lactic acid production. The results revealed the participation of 58 known intra-cellular metabolites at various pathways in lactic acid production. Twenty-eight highly up-regulated and down-regulated metabolites were analyzed, and a schematic diagram of a possible lactic acid production pathway was proposed. The produced lactic acid was analyzed through FTIR, UV-Spectrum, and HPLC analysis.PMID:37691617 | DOI:10.1039/d3mo00141e

EMBO Rep. 2023 Sep 11:e57084. doi: 10.15252/embr.202357084. Online ahead of print.ABSTRACTIntestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5-deficient mice. The defects result in severe mucosal damage after exposure to the colitis-inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5-deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single-cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease.PMID:37691494 | DOI:10.15252/embr.202357084

Expert Rev Mol Diagn. 2023 Sep 10. doi: 10.1080/14737159.2023.2258063. Online ahead of print.ABSTRACTINTRODUCTION: This review summarizes current progress in the development of biomarkers to guide immunotherapy in oncology, rheumatology and critical illness.AREAS COVERED: An extensive literature search was performed about biomarkers classifying patients' immune responses to guide immunotherapy in oncology, rheumatology and critical illness. Surface markers, such as programmed death-ligand 1 (PD-L1), genetic biomarkers, such as tumor mutation load, and circulating tumor DNA are biomarkers associated with the effectiveness of immunotherapy in oncology. Genomics, metabolomics and proteomics play a crucial role in selecting the most suitable therapeutic options for rheumatologic patients. Phenotypes and endotypes are a promising approach to detect critically ill patients with hyper- or hypo-inflammation. Sepsis trials using biomarkers such as ferritin, lymphopenia, HLA-DR expression on monocytes and PD-L1 to guide immunotherapy, have been already conducted or are currently ongoing. Immunotherapy in COVID-19 pneumonia, guided by C-reactive protein and soluble urokinase plasminogen activator receptor (suPAR) has improved patient outcomes globally. More research is needed into immunotherapy in other critical conditions.EXPERT OPINION: Targeted immunotherapy has improved outcomes in oncology and rheumatology, paving the way for precision medicine in the critically ill. Transcriptomics will play a crucial role in detecting the most suitable candidates for immunomodulation.PMID:37691280 | DOI:10.1080/14737159.2023.2258063

Curr Mol Pharmacol. 2023 Sep 6. doi: 10.2174/1874467217666230906092236. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are therapy resistant and the cause of relapse. A state of deep quiescence appears to enable cancer stem cells (CSC) to acquire new somatic mutations essential for disease progression and therapy resistance. Both normal hematopoietic stem cells (HSC) and LSC share many common features, thereby complicating the safe elimination of LSC. A recent study demonstrated that long lived normal oocytes exist without mitochondrial complex I (MC-1), expressing it in a developmentally regulated fashion, thereby mitigating their vulnerability to ROS. Quiescent CSC rely on mitochondrial FAO, without complex I expression, thereby avoiding the generation of damaging ROS, similar to long lived normal human stem cells. A deeper understanding of the biology of therapy resistance is important for the development of optimal strategies to attain complete leukemia cures.METHODS: Here, using scRNA-sequencing and ATAC-seq on primary chronic myelogenous leukemia (CML) patient samples, combined with bioinformatics analyses, we further examine the heterogeneity of a previously characterized in vitro imatinib-selected CD34-CD38- CML LSC population. We utilized a series of functional analyses, including single-cell metabolomic and Seahorse analyses, to validate the existence of the deepest quiescent leukemia initiators (LI) subset.RESULTS: Current study revealed heterogeneity of therapy resistant LSC in CML patients and their existence of two functionally distinct states. The most deeply quiescent LI suppress the expression of MC-1, yet are highly dependent on fatty acid oxidation (FAO) for their metabolic requirements and ATAC-seq demonstrated increased chromatin accessibility in this population, all consistent with an extremely primitive, quiescent stemness transcriptional signature. Importantly, the specific CREB binding protein (CBP)/β-catenin antagonist ICG-001 initiates the differentiation of LSC, including LI, decreases chromatin accessibility with differentiation and increasing expression of MC-1, CD34, CD38 and BCR-ABL1, thereby re-sensitizing them to imatinib.CONCLUSION: We investigated the biological aspects related to LSC heterogeneity in CML patients and demonstrated the ability of specific small molecule CBP/β-catenin antagonists to safely eliminate deeply quiescent therapy resistant CSC. These observations may represent an attractive generalizable therapeutic strategy that could help develop better protocols to eradicate the quiescent LSC population.PMID:37691195 | DOI:10.2174/1874467217666230906092236

Food Res Int. 2023 Oct;172:113147. doi: 10.1016/j.foodres.2023.113147. Epub 2023 Jun 17.ABSTRACTNowadays, plant-based milk consumption, as part of a healthy diet, is continuously increasing. In this paper, for the first time a lipidomic analysis on molecular species of triacylglycerol (TG) fraction of plant-based beverages (almond, soy, coconut) was performed by liquid chromatography quadrupole time-of-flight mass spectrometry. A total of 557 TG molecular species was measured, showing significantly different profiles between milk alternatives, compared with bovine milk. The most abundant TG molecular species were TG 18:1_18:1_18:1 and 18:1_18:1_18:2 for almond, TG 18:2_18:2_18:2 and 16:0_18:2_18:2 for soy, TG 12:0_10:0_12:0 and 12:0_12:0_14:0 for coconut. Unconventional fatty acids were detected in almond and soy. The main TG with ethereal linkage were TG-O 56:2, TG-O 56:4, and TG-O 56:5, while the main oxygenated TG was TG 54:5;1O. A total of 30 molecular species were identified as biomarkers for milk differentiation by principal component analysis, providing an interesting support for milk authentication and detection of adulteration on a larger sampling.PMID:37689910 | DOI:10.1016/j.foodres.2023.113147

Sci Total Environ. 2023 Sep 8:166841. doi: 10.1016/j.scitotenv.2023.166841. Online ahead of print.ABSTRACTThe plasticizer Diethylhexyl phthalate (DEHP), one of the most common contaminants, is widely detected in environmental and biological samples. However, the accumulation of DEHP in tissue and the molecular mechanisms underlying its physiological damage in the spleen of aquatic organisms have not yet been reported. In this study, gas chromatography-mass spectrometry (GC-MS), histology and multi-omics analysis were used to investigate DEHP exposure-induced alterations in transcriptomic profiles and metabolic network of zebrafish model. After exposure to DEHP, higher concentrations of DEHP were found in the intestine, liver and spleen. Anatomical and histological analyses showed that the zebrafish spleen index was significantly increased and inflammatory damage was observed. Increased splenic neutrophil counts indicate inflammation and tissue damage. Transcriptomic filtering showed that 3579 genes were significantly altered. Metabolomic analysis detected 543 differential metabolites. Multi-omics annotation results indicated that arachidonic acid and 12-Hydroperoxyicosatetraenoic acid (HPETE) are involved in the key inflammatory pathway "Inflammatory mediator regulation of TRP channels". This study demonstrated the accumulation characteristics of DEHP in aquatic zebrafish and the mechanisms of inflammation and tissue damage in the spleen which involve endogenous arachidonic acid. This will provide theoretical basis and data support for health risk assessments and tissue damage of DEHP.PMID:37690753 | DOI:10.1016/j.scitotenv.2023.166841

J Dairy Sci. 2023 Sep 8:S0022-0302(23)00619-7. doi: 10.3168/jds.2022-23066. Online ahead of print.ABSTRACTThe transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB) and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome and metabolome of 30 dairy cows during transition (-21d, -7d, +7d, +21d relative to calving). Then the Bayesian network and 9 machine learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21d, -7d, +7d was higher than +21d (P < 0.001). The plasma concentration of nonesterified fatty acids (NEFA) peaked on +7d (P < 0.001). For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum (P < 0.001) and in bacterial interactions at +7d (P = 0.014). Conversely, microbial metabolites involved in carbohydrate, lipid and energy metabolism increased on +7d (P < 0.05). A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (Arc. strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.PMID:37690725 | DOI:10.3168/jds.2022-23066

Clin Chim Acta. 2023 Sep 8:117553. doi: 10.1016/j.cca.2023.117553. Online ahead of print.ABSTRACTA significant number of patients diagnosed with localized urological cancers experience relapse and disease progression after surgery. Hence, molecular markers for patient risk stratification are needed to improve the current management guidelines. This article critically reviews for the first time, to our knowledge, the promise of metabolomics-based approaches to identify metabolic signatures as candidate prognostic biomarkers to predict recurrences at the time of surgery in prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). Dysregulations in the levels of several tumoral, circulating, and excreted metabolites have been reported in PCa patients experiencing recurrence within 1.5 to 8 years of follow-up. The combination of these metabolic biomarkers with clinical parameters (e.g., pathological T stage, Gleason score) has shown great potential to improve the predictive ability of PCa recurrence. In contrast, predictive biomarkers of recurrence in BCa and RCC have been poorly explored. Overall, this review highlights the great potential of metabolomics in discovering prognostic biomarkers for a more accurate patient risk stratification in urological cancers.PMID:37690663 | DOI:10.1016/j.cca.2023.117553

Pharmacol Res. 2023 Sep 8:106916. doi: 10.1016/j.phrs.2023.106916. Online ahead of print.ABSTRACTIn the wake of the development of metagenomic, metabolomic, and metatranscriptomic approaches, the intricate interactions between the host and various microbes are now being progressively understood. Numerous studies have demonstrated evident changes in gut microbiota during the process of a variety of diseases, such as diabetes, obesity, aging, and cancers. Notably, gut microbiota is viewed as a potential source of novel therapeutics. Currently, Next-generation probiotics (NGPs) are gaining popularity as therapeutic agents that alter the gut microbiota and affect cancer development. Akkermansia muciniphila (A. muciniphila), a representative commensal bacterium, has received substantial attention over the past decade as a promising NGP. The components and metabolites of A. muciniphila can directly or indirectly affect tumorigenesis, in particular through its effects on antitumor immunosurveillance, including the stimulation of pattern recognition receptors (PRRs), which also leads to better outcomes in a variety of situations, including the prevention and curation of cancers. In this article, we systematically summarize the role of A. muciniphila in tumorigenesis (involving gastrointestinal and non-gastrointestinal cancers) and in tumor therapy. In particular, we carefully discuss some critical scientific issues that need to be solved for the future using A. muciniphila as a representative beneficial bacterium in tumor treatment, which might provide bright clues and assistance for the application of drugs targeting A. muciniphila in clinical oncotherapy.PMID:37690533 | DOI:10.1016/j.phrs.2023.106916

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Sep 8;1229:123880. doi: 10.1016/j.jchromb.2023.123880. Online ahead of print.ABSTRACTThe aim of this study was to use the commercial kit AbsoluteIDQ p180 (Biocrates) for the quantification of metabolites in aqueous humor (AH), as well as to determine the optimal volume of AH that is necessary to obtain reliable and reproducible results. Different volumes of AH (10 µl, 20 µl, and 30 µl) were tested. Of the 188 metabolites measurable with the Biocrates kit, 69 were detected in AH. Depending on the volume used, 41, 51, and 63 metabolites were measured using 10 µl, 20 µl, and 30 µl of AH, respectively. The repeatability of the measurements improved with increasing AH volume. Considering only those metabolites that were obtained with a CV < 15%, 34 metabolites at 10 µl, 41 at 20 µl, and 44 at 30 µl AH were received. On this basis, it can be concluded that the tested method can be successfully applied to analyze metabolites in the human AH. To achieve the most comprehensive detection range and highest repeatability of measurements, it is recommended to use 30 µl AH.PMID:37690387 | DOI:10.1016/j.jchromb.2023.123880

Phytomedicine. 2023 Sep 8;120:155066. doi: 10.1016/j.phymed.2023.155066. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by the replacement of lung parenchyma with fibrous scar tissue, usually as the final stage of lung injury like COPD. Astragaloside IV (AST), a bioactive compound found in the Astragalus membranaceus (Fisch.) used in traditional Chinese medicine, has been shown to improve pulmonary function and exhibit anti-pulmonary fibrosis effects. However, the exact molecular mechanisms through which it combats pulmonary fibrosis, especially in COPD, remain unclear.PURPOSE: This study aimed to identify the potential therapeutic target and molecular mechanisms for AST in improving lung injury especially treating COPD type pulmonary fibrosis both in vivo and in vitro.METHODS: Multi lung injury models were established in mice using lipopolysaccharide (LPS), cigarette smoke (CS), or LPS plus CS to simulate the processes of pulmonary fibrosis in COPD. The effect of AST on lung function protection was evaluated, and proteomic and metabolomic analysis were applied to identify the signaling pathway affected by AST and to find potential targets of AST. The interaction between AST and wild-type and mutant RAS proteins was studied. The RAS/RAF/FoxO signaling pathway was stimulated in BEAS-2B cells and in mice lung tissues by LPS plus CS to investigate the anti-pulmonary fibrosis mechanism of AST analyzed by western blotting. The regulatory effects of AST on the RAS/RAF/FoxO pathway dependent on RAS were further confirmed using RAS siRNA.RESULTS: RAS was predicted and identified as the target protein of AST in anti-pulmonary fibrosis in COPD and improving lung function. The administration of AST was observed to impede the conversion of fibroblasts into myofibroblasts, reduce the manifestation of inflammatory factors and extracellular matrix, and hinder the activation of epithelial mesenchymal transition (EMT). Furthermore, AST significantly suppressed the RAS/RAF/FoxO signaling pathway in both in vitro and in vivo settings.CONCLUSION: AST exhibited lung function protection and anti-pulmonary fibrosis effect by inhibiting the GTP-GDP domain of RAS, which downregulated the RAS/RAF/FoxO signaling pathway. This study revealed AST as a natural candidate molecule for the protection of pulmonary fibrosis in COPD.PMID:37690229 | DOI:10.1016/j.phymed.2023.155066

Phytomedicine. 2023 Sep 4;120:155068. doi: 10.1016/j.phymed.2023.155068. Online ahead of print.ABSTRACTBACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied.PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis.STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices).RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and β-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis.CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.PMID:37690228 | DOI:10.1016/j.phymed.2023.155068

Environ Int. 2023 Sep 3;179:108183. doi: 10.1016/j.envint.2023.108183. Online ahead of print.ABSTRACTBACKGROUND: Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods.METHODS: In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.RESULTS: Metal's levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.CONCLUSION: This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.PMID:37690219 | DOI:10.1016/j.envint.2023.108183

J Pharm Biomed Anal. 2023 Sep 6;236:115709. doi: 10.1016/j.jpba.2023.115709. Online ahead of print.ABSTRACTThe co-administration of isoniazid (INH) and rifampicin (RIF) is associated with hepatotoxicity and neurotoxicity. To systematically investigate the mechanisms of hepatotoxicity and neurotoxicity induced by INH/RIF, we used high performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics to analyze urine from a mouse model and screened a range of urinary biomarkers. Mice were orally co-administered with INH (120 mg/kg) and RIF (240 mg/kg) and urine samples were collected on days 0, 7, 14 and 21. Hepatotoxicity and neurotoxicity were assessed by samples of liver, brain and kidney tissue which were harvested for histological analysis. Toxicity analysis revealed that INH/RIF caused hepatotoxicity and neurotoxicity in a time-dependent manner; compared with day 0, the levels of 35, 82 and 86 urinary metabolites were significantly different on days 7, 14 and 21, respectively. Analysis showed that by day 21, exposure to INH+RIF had caused disruption in vitamin B6 metabolism; the biosynthesis of unsaturated fatty acids; tyrosine, taurine, hypotaurine metabolism; the synthesis of ubiquinone and other terpenoid-quinones; and the metabolism of tryptophan, nicotinate and nicotinamide. Nicotinic acid, nicotinuric acid and kynurenic acid were identified as sensitive urinary biomarkers that may be useful for the diagnosis and evaluation of toxicity.PMID:37690188 | DOI:10.1016/j.jpba.2023.115709

Ecotoxicol Environ Saf. 2023 Sep 8;264:115434. doi: 10.1016/j.ecoenv.2023.115434. Online ahead of print.ABSTRACTBactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.PMID:37690174 | DOI:10.1016/j.ecoenv.2023.115434

Proteomics. 2023 Sep 10:e2200289. doi: 10.1002/pmic.202200289. Online ahead of print.ABSTRACTHeart disease remains a leading cause of death in North America and worldwide. Despite advances in therapies, the chronic nature of cardiovascular diseases ultimately results in frequent hospitalizations and steady rates of mortality. Systems biology approaches have provided a new frontier toward unraveling the underlying mechanisms of cell, tissue, and organ dysfunction in disease. Mapping the complex networks of molecular functions across the genome, transcriptome, proteome, and metabolome has enormous potential to advance our understanding of cardiovascular disease, discover new disease biomarkers, and develop novel therapies. Computational workflows to interpret these data-intensive analyses as well as integration between different levels of interrogation remain important challenges in the advancement and application of systems biology-based analyses in cardiovascular research. This review will focus on summarizing the recent developments in network biology-level profiling in the heart, with particular emphasis on modeling of human heart failure. We will provide new perspectives on integration between different levels of large "omics" datasets, including integration of gene regulatory networks, protein-protein interactions, signaling networks, and metabolic networks in the heart.PMID:37691071 | DOI:10.1002/pmic.202200289

Mol Nutr Food Res. 2023 Sep 10:e2300218. doi: 10.1002/mnfr.202300218. Online ahead of print.ABSTRACTAcute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.PMID:37691068 | DOI:10.1002/mnfr.202300218

Plant Physiol Biochem. 2023 Sep 6;203:108008. doi: 10.1016/j.plaphy.2023.108008. Online ahead of print.ABSTRACTPlants encounter combinations of different abiotic stresses such as salinity (S) and high light (HL). These environmental conditions have a detrimental effect on plant growth and development, posing a threat to agricultural production. Metabolic changes play a crucial role in enabling plants to adapt to fluctuations in their environment. Furthermore, hormones such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) have been previously identified as regulators of plant responses to different abiotic stresses. Here we studied the response of Arabidopsis wild type (Col and Ler) plants and mutants impaired in hormone biosynthesis (aba2-11 and aba1-1 in ABA, aos in JA and sid2 in SA) to the combination of S and HL (S + HL). Our findings showed that aba2-11 plants displayed reduced growth, impaired photosystem II (PSII) function, increased leaf damage, and decreased survival compared to Col when subjected to stress combination. However, aos and sid2 mutants did not display significant changes in response to S + HL compared to Col, indicating a key role for ABA in promoting plant tolerance to S + HL and suggesting a marginal role for JA and SA in this process. In addition, we revealed differences in the metabolic response of plants to S + HL compared to S or HL. The analysis of altered metabolic pathways under S + HL suggested that the accumulation of flavonoids is ABA-dependent, whereas the accumulation of branched-chain amino acids (BCAAs) and proline is ABA-independent. Therefore, our study uncovered a key function for ABA in regulating the accumulation of different flavonoids in plants during S + HL.PMID:37690143 | DOI:10.1016/j.plaphy.2023.108008