PubMed

Biotechnol J. 2023 Dec 2:e2300483. doi: 10.1002/biot.202300483. Online ahead of print.ABSTRACTRhodotorula toruloides can utilize crude glycerol as the low-cost carbon source for lipid production, but its growth is subjected to inhibition by methanol in crude glycerol. Here, transcriptome profiling demonstrated that 1004 genes were significantly regulated in the strain R. toruloides TO2 under methanol stress. Methanol impaired the function of membrane transport and subsequently weakened the utilization of glycerol, activities of the primary metabolism and functions of nucleus and ribosome. Afterwards the tolerance of TO2 to methanol was improved by using two-round adaptive laboratory evolution (ALE). The final strain M2-ale had tolerance up to 3.5% of methanol. 1 H NMR-based metabolome analysis indicated that ALE not only improved the tolerance of M2-ale to methanol but also tuned the carbon flux towards the biosynthesis of glycerolipid-related metabolites. The biomass and lipid titer of M2-ale reached 14.63 ± 0.45 g/L and 7.06 ± 0.44 g/L at 96 h in the crude glycerol medium, which increased up to 17.69% and 31.39%, respectively, comparing with TO2. Afterwards, an effective method for cell lysis was developed by combining sonication and enzymatic hydrolysis (So-EnH). The lytic effect of So-EnH was validated by using confocal imaging and flow cytometry. At last, lipid recovery rate reached 95.4 ± 2.7% at the optimized condition. This article is protected by copyright. All rights reserved.PMID:38041508 | DOI:10.1002/biot.202300483

Andrology. 2023 Dec 1. doi: 10.1111/andr.13565. Online ahead of print.ABSTRACTBACKGROUND: Most commerce of equine seminal doses is carried out using commercial extenders under refrigeration at 5°C.OBJECTIVES: To determine if 10 mm pyruvate in a 67 mm glucose extender and storage at 22°C could be the basis of an alternative storage method to cooling to 5°C.MATERIAL AND METHODS: Stallion ejaculates were extendedin: INRA96 (67 mm glucose, non-pyruvate control), modified Tyrode's (67 mm glucose-10 mm pyruvate), supplemented with 0, 10, 50, and 100 μM itaconate. As itaconate was vehiculated in DMSO, a control vehicle was also included. Sperm motility, viability, mitochondrial membrane potential, and production of reactive oxygen species were measured after collection and again after 48 and 96 h of storage at 22°C. To disclose molecular metabolic changes, spermatozoa were incubated up to 3 h in modified Tyrode's 67 mm glucose-10 mm pyruvate and modified Tyrode's 67 mm glucose, and metabolic analysis conducted.RESULTS: After 96 h of storage aliquots stored in the control, INRA96 had a very poor total motility of 5.6% ± 2.3%, while in the 67 mm glucose-10 mm pyruvate/10 μm itaconate extender, total motility was 34.7% ± 3.8% (p = 0.0066). After 96 h, viability was better in most pyruvate-based media, and the mitochondrial membrane potential in spermatozoa extended in INRA96 was relatively lower (p < 0.0001). Metabolomics revealed that in the spermatozoa incubated in the high pyruvate media, there was an increase in the relative amounts of NAD+ , pyruvate, lactate, and ATP.DISCUSSION AND CONCLUSIONS: Aliquots stored in a 67 mm glucose-10 mm pyruvate-based medium supplemented with 10 μM itaconate, maintained a 35% total motility after 96 h of storage at 22°C, which is considered the minimum acceptable motility for commercialization. Improvements may be related to the conversion of pyruvate to lactate and regeneration of NAD+ .PMID:38041502 | DOI:10.1111/andr.13565

Environ Toxicol. 2023 Dec 2. doi: 10.1002/tox.24063. Online ahead of print.ABSTRACTThis study aims to explore the roles of phenylacetyl glutamine (PAGln) on myocardial infarction (MI) pathogenesis. Here, using targeted metabolomics analysis, it was found that the plasma metabolite PAGln was upregulated in coronary artery disease (CAD) patients and MI mice and could be an independent risk factor for CAD. In vivo and in vitro functional experiments revealed that PAGln pretreatment enhanced MI-induced myocardial injury and cardiac fibrosis, as evident by the increased infarct size, cardiomyocyte death, and the upregulated expression of cardiac fibrosis markers (Col1a1 and α-SMA). Combined with RNA-sequencing analysis and G protein-coupled receptor (GPCR) inhibitor, we found that the GPCR signaling activation is essential for PAGln-mediated effects on cardiomyocyte death. Furthermore, drug affinity responsive target stability and cellular thermal shift assay demonstrated that PAGln could interact with β1-adrenergic receptor (AR). Moreover, β1-AR blocker treatment indeed extended the cardiac remodeling after PAGln-enhanced MI. These results suggest that PAGln might be a potential therapeutic target for extending the cardiac remodeling window in MI patients that signals via β1-AR.PMID:38041472 | DOI:10.1002/tox.24063

Eur J Clin Invest. 2023 Dec 1:e14138. doi: 10.1111/eci.14138. Online ahead of print.ABSTRACTMitochondrial dysfunction is a major hallmark of ageing and related chronic disorders. Controlled removal of damaged mitochondria by the autophagic machinery, a process known as mitophagy, is vital for mitochondrial homeostasis and cell survival. The central role of mitochondria in cellular metabolism places mitochondrial removal at the interface of key metabolic pathways affecting the biosynthesis or catabolism of acetyl-coenzyme A, nicotinamide adenine dinucleotide, polyamines, as well as fatty acids and amino acids. Molecular switches that integrate the metabolic status of the cell, like AMP-dependent protein kinase, protein kinase A, mechanistic target of rapamycin and sirtuins, have also emerged as important regulators of mitophagy. In this review, we discuss how metabolic regulation intersects with mitophagy. We place special emphasis on the metabolic regulatory circuits that may be therapeutically targeted to delay ageing and mitochondria-associated chronic diseases. Moreover, we identify outstanding knowledge gaps, such as the ill-defined distinction between basal and damage-induced mitophagy, which must be resolved to boost progress in this area.PMID:38041247 | DOI:10.1111/eci.14138

Chin Med. 2023 Dec 1;18(1):158. doi: 10.1186/s13020-023-00862-1.ABSTRACTBACKGROUND: Rhein can significantly delay the progression of chronic nephropathy. However, its mechanism of action has not been adequately elaborated, which hinders its extensive clinical application. In this work, the effects of rhein on models of TGF-β-induced NRK-49F cellular fibrosis and rat renal ischemia-reperfusion fibrosis were evaluated using metabolomics and western blotting.METHODS: The metabolic profiles of NRK-49F cells and rat urine, serum, and kidney tissues in the control, model, and rhein groups were investigated using UPLC-QTOF-MS. The levels of p-P65, p-IKK, p-AKT, p-P38, p-JNK and AP-1 in NRK-49F cells were measured using western blotting and immunofluorescence methods. Molecular docking and network pharmacology methods were employed to explore the relationship between the potential targets of rhein and key proteins in the NF-κB and MAPK signaling pathways.RESULTS: Various potential metabolites, including sphingolipids, ceramides, phosphatidylcholine, and lysophosphatidylcholine,14-hydroxy-E4-neuroprostane E, and 5-HPETE, were present in the cell, tissue, urine, and serum samples; however, few metabolites matches exactly among the four type of biological samples. These differential metabolites can effectively differentiated between the control, model, and rhein groups. Pathway enrichment analysis of differential metabolites unveiled that sphingolipid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were closely related to nephropathy. Phosphorylation levels of AKT, IKK, P65 and AP-1 in NRK-49F cells was reduced by rhein treatment. Network pharmacology and molecular docking showed that the potential targets of rhein might regulated the expression of MAPK and AKT in the NF-κB and MAPK signaling pathways.CONCLUSION: In brief, rhein might delays the progression of chronic nephropathy via the metabolic pathways, NF-κB and MAPKs signaling pathways, which provides the foundation for its development and clinical application.PMID:38041193 | DOI:10.1186/s13020-023-00862-1

Malar J. 2023 Dec 1;22(1):368. doi: 10.1186/s12936-023-04795-w.ABSTRACTBACKGROUND: Anopheles pharoensis has a major role in transmitting several human diseases, especially malaria, in Egypt?. Controlling Anopheles is considered as an effective strategy to eliminate the spread of malaria worldwide. Galaxaura rugosa is a species of red algae found in tropical to subtropical marine environments. The presence of G. rugosa is indicative of the ecosystem's overall health. The current work aims to investigate UPLC/ESI/MS profile of G. rugosa methanol and petroleum ether extracts and its activity against An. pharoensis and non-target organisms, Danio rerio and Daphnia magna.METHODS: Galaxaura rugosa specimens have been identified using DNA barcoding for the COI gene and verified as G. rugosa. The UPLC/ESI/MS profiling of G. rugosa collected from Egypt was described. The larvicidal and repellent activities of G. rugosa methanol and petroleum ether extracts against An. pharoensis were evaluated, as well as the toxicity of tested extracts on non-target organisms, Dan. rerio and Dap. magna.RESULTS: The UPLC/ESI/MS analysis of methanol and petroleum ether extracts led to the tentative identification of 57 compounds belonging to different phytochemical classes, including flavonoids, tannins, phenolic acids, phenyl propanoids. Larval mortality was recorded at 93.33% and 90.67% at 80 and 35 ppm of methanol and petroleum ether extracts, respectively, while pupal mortality recorded 44.44 and 22.48% at 35 and 30 ppm, respectively. Larval duration was recorded at 5.31 and 5.64 days by methanol and petroleum ether extracts at 80 and 35 ppm, respectively. A decrease in acetylcholinesterase (AChE) level and a promotion in Glutathione-S-transferase (GST) level of An. pharoensis 3rd instar larvae were recorded by tested extracts. The petroleum ether extract was more effective against An. pharoensis starved females than methanol extract. Also, tested extracts recorded LC50 of 1988.8, 1365.1, and 11.65, 14.36 µg/mL against Dan. rerio, and Dap. magna, respectively.CONCLUSIONS: Using red algae derivatives in An. pharoensis control could reduce costs and environmental impact and be harmless to humans and other non-target organisms.PMID:38041142 | DOI:10.1186/s12936-023-04795-w

Lipids Health Dis. 2023 Dec 1;22(1):211. doi: 10.1186/s12944-023-01967-0.ABSTRACTCardiac cachexia is a deadly consequence of advanced heart failure that is characterised by the dysregulation of adipose tissue homeostasis. Once cachexia occurs with heart failure, it prevents the normal treatment of heart failure and increases the risk of death. Targeting adipose tissue is an important approach to treating cardiac cachexia, but the pathogenic mechanisms are still unknown, and there are no effective therapies available. Transcriptomics, metabolomics, and lipidomics were used to examine the underlying mechanisms of cardiac cachexia. Transcriptomics investigation of cardiac cachexia adipose tissue revealed that genes involved in fibrosis and monocyte/macrophage migration were increased and strongly interacted. The ECM-receptor interaction pathway was primarily enriched, as shown by KEGG enrichment analysis. In addition, gene set enrichment analysis revealed that monocyte chemotaxis/macrophage migration and fibrosis gene sets were upregulated in cardiac cachexia. Metabolomics enrichment analysis demonstrated that the sphingolipid signalling pathway is important for adipose tissue remodelling in cardiac cachexia. Lipidomics analysis showed that the adipose tissue of rats with cardiac cachexia had higher levels of sphingolipids, including Cer and S1P. Moreover, combined multiomics analysis suggested that the sphingolipid metabolic pathway was associated with inflammatory-fibrotic changes in adipose tissue. Finally, the key indicators were validated by experiments. In conclusion, this study described a mechanism by which the sphingolipid signalling pathway was involved in adipose tissue remodelling by inducing inflammation and fat fibrosis in cardiac cachexia.PMID:38041133 | DOI:10.1186/s12944-023-01967-0

Physiol Rep. 2023 Dec;11(23):e15870. doi: 10.14814/phy2.15870.ABSTRACTCytokinins (CTKs) are a diverse collection of evolutionarily conserved adenine-derived signaling molecules classically studied as phytohormones; however, their roles and production have been less studied in mammalian systems. Skeletal muscles are sensitive to cellular cues such as inflammation and in response, alter their secretome to regulate the muscle stem cell and myofiber niche. Using cultured C2C12 muscle cells, we profiled CTK levels to understand (1) whether CTKs are part of the muscle secretome and (2) whether CTKs are responsive to cellular stress. To induce cellular stress, C2C12 myotubes were treated with lipopolysaccharides (LPS) for 24 h and then media and cell fractions were collected for ultra high-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-(ESI+)-HRMS/MS) for metabolomics and CTK profiling. Across LPS-treated and control cells, 11 CTKs were detected in the extracellular space while 6 were detected intracellularly. We found that muscle cells are enriched in isopentenyladenine (iP) species (from free base, riboside to nucleotide forms), and that extracellular levels are increased after LPS treatment. Our study establishes that muscle cells express various forms of CTKs, and that CTK levels are responsive to LPS-induced cell stress, suggesting a role for CTKs in intra- and extracellular signaling of mammalian cells.PMID:38040455 | DOI:10.14814/phy2.15870

Sci Total Environ. 2023 Nov 29:168980. doi: 10.1016/j.scitotenv.2023.168980. Online ahead of print.ABSTRACTPyrite and humic acid are common substances in nature, and the combined effects of pyrite and humic acid on arsenic phytotoxicity are more widespread in the actual environments than that of a single substance, but have received less attention. In this study, the interaction between pyrite and humic acid in arsenate solution was studied, and the effects of pyrite and humic acid on plant toxicity of arsenate were evaluated. The results showed that arsenate + pyrite + fulvic acid (V-PF) treatment immobilized more arsenic by forming chemical bonds such as AsS and Fe-As-O and reduced the migration of arsenic to plants. Compared to the arsenate + fulvic acid (VF), arsenate + pyrite (VP) and arsenate (V) group, the inorganic arsenic content of lettuce leaves in the V- PF group was reduced by 19.8 %, 13.4 % and 13.4 %, respectively. In addition, the V-PF group increased the absorption of Ca, Fe and Cu in plant roots, and improved the activity of superoxide dismutase (SOD) in plant leaves. Compared to the VF group, SOD and MDA in the V-PF group increased by 34.1 % in 30 days and decreased by 47.3 % in 40 days, respectively. The biomass of lettuce in V-PF group was increased by 29.3 % compared with that in VF group on day 50. The protein content of the V-PF group was 58.3 % higher than that of the VF group and 23.1 % higher than that of the VP group. Furthermore, metabolomics analysis showed that the V-PF group promoted glycolysis by up-regulating glyoxylic acid and dicarboxylic acid metabolism, thus reducing carbohydrate accumulation. Phosphocreatine metabolism was also up-regulated, which decreased the oxidative damage in lettuce induced by arsenic. This study will provide new ideas for scientifically and rationally assessing the ecological environmental risks of arsenic and regulating its toxicity.PMID:38040366 | DOI:10.1016/j.scitotenv.2023.168980

Chemosphere. 2023 Nov 29:140824. doi: 10.1016/j.chemosphere.2023.140824. Online ahead of print.ABSTRACTAnaerobic digestion (AD) is a promising waste management strategy that reduces landfilling while generating biogas. Anaerobic co-digestion involves mixing two or more substrates to enhance the nutrient balance required for microorganism growth and thus improve the degradation. Monitoring AD is crucial for comprehending the biological process, optimizing process stability, and achieving efficient biogas production. In this work, we have used three dimensional excitation emission fluorescence spectroscopy and mass spectrometry metabolomics, two complementary techniques, to monitor the anaerobic co-digestion (AcoD) of cellulose, ash wood or oak wood with food waste. The two approaches were compared together and to the biogas production records. Results of this experiment demonstrated the complementarity of both analytical techniques with the measurement of the biogas production since 3D fluorescence spectroscopy and MS metabolomics revealed the earlier molecular changes occurring in the bioreactors, mainly associated with the hydrolysis step, whereas the biogas production data reflected the biological activity in the last step of the digestion. Moreover, in all cases, the three data sets effectively delineated the differences among the substrates. While the two wood substrates were poorly degradable as they were richer in aromatic compounds, cellulose was highly degradable and was characterized by the production of several glycolipids. Then, the three tested AcoDs resulted in a similar 3D EEM fluorescence and metabolomics profiles, close to the one observed for the AD of food waste alone, indicating that the incorporation of the food waste drove the molecular degradation events in the AcoDs. Substrate-specific differences were appreciated from the biogas production data. The overall results of this research are expected to provide insight into the design of guidelines for monitoring AcoD.PMID:38040263 | DOI:10.1016/j.chemosphere.2023.140824

Phytomedicine. 2023 Nov 15;123:155221. doi: 10.1016/j.phymed.2023.155221. Online ahead of print.ABSTRACTBACKGROUND: Drug-induced liver injury, particularly from acetaminophen (APAP), has emerged as a significant public health concern. Unfortunately, there is currently no effective treatment strategy available. Qiwei Tiexie pills (QWTX), a traditional Tibetan medicine, have demonstrated considerable clinical efficacy in treating various liver diseases. Nevertheless, the protective effect of QWTX against drug-induced liver injury and its underlying mechanism remains poorly understood.PURPOSE: This study aimed to assess the therapeutic potential of QWTX, a Tibetan medicine, in an animal model of APAP-induced liver injury. Additionally, we sought to investigate the molecular mechanism through which QWTX exerts its effects.METHODS: We employed LC-MS and network pharmacology to predict the potential targets of QWTX in drug-induced liver injury. Subsequently, we employed HE staining, transcriptomics, metabolomics, and qRT-PCR to analyze the mechanism underlying QWTX treatment in drug-induced liver injury.RESULTS: Network pharmacology analysis revealed that the active components of QWTX are involved in inflammatory and drug metabolism-related pathways. In mouse models, pretreatment with QWTX effectively mitigated the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory factors (IL-1β, IL-6, and TNF-α) induced by APAP overdose. Moreover, APAP inhibited 1459 differentially expressed genes (DEGs) and 874 differential accumulation metabolites (DAMs), while QWTX promoted their expression. Conversely, APAP promoted 874 genes and 119 metabolites, which were inhibited by QWTX. Further analysis demonstrated that QWTX ameliorated the metabolic disorders induced by APAP overdose and potentially exerted a protective effect by inhibiting the expression of critical genes in crucial inflammatory pathways. QWTX also up-regulated antioxidant enzymes, thereby mitigating the oxidative stress resulting from APAP overdose.CONCLUSION: QWTX treatment effectively protects against APAP-induced liver damage in mice. Transcriptomic and metabolomic analyses further revealed that QWTX ameliorated hepatic metabolic disorders induced by APAP overdose while significantly suppressing the inflammatory response and oxidative stress associated with drug-induced liver injury. This study provides a new insight into the treatment of drug-induced liver injury by the TCM system and provides a basis for the development of new therapies for drug-induced liver injury by QWTX and its active ingredients.PMID:38039903 | DOI:10.1016/j.phymed.2023.155221

Ecotoxicol Environ Saf. 2023 Nov 30;269:115752. doi: 10.1016/j.ecoenv.2023.115752. Online ahead of print.ABSTRACTFluoride could cause developmental neurotoxicity and significantly affect the intelligence quotient (IQ) of children. However, the systematic mechanism of neuronal damage caused by excessive fluoride administration in offspring is largely unknown. Here, we present a comprehensive integrative transcriptome and metabolome analysis to study the mechanism of developmental neurotoxicity caused by chronic fluoride exposure. Comparing the different doses of fluoride treatments in two generations revealed the exclusive signature of metabolism pathways and gene expression profiles. In particular, neuronal development and synaptic ion transport are significantly altered at the gene expression and metabolite accumulation levels for both generations, which could act as messengers and enhancers of fluoride-induced systemic neuronal injury. Choline and arachidonic acid metabolism, which highlighted in the integrative analysis, exhibited different regulatory patterns between the two generations, particularly for synaptic vesicle formation and inflammatory factor transport. It may suggest that choline and arachidonic acid metabolism play important roles in developmental neurotoxic responses for offspring mice. Our study provides comprehensive insights into the metabolomic and transcriptomic regulation of fluoride stress responses in the mechanistic explanation of fluoride-induced developmental neurotoxicity.PMID:38039848 | DOI:10.1016/j.ecoenv.2023.115752

Pathol Res Pract. 2023 Nov 20;253:154953. doi: 10.1016/j.prp.2023.154953. Online ahead of print.ABSTRACTOral cancer tumors occur in the mouth and are mainly derived from oral mucosa linings. It is one of the most common and fatal malignant diseases worldwide. The intratumor heterogeneity (ITH) of oral cancerous tumor is vast, so it is challenging to study and interpret. Due to environmental selection pressures, ITH arises through diverse genetic, epigenetic, and metabolic alterations. The ITH also talks about peri-tumoral vascular/ lymphatic growth, perineural permeation, tumor necrosis, invasion, and clonal expansion/ the coexistence of multiple subclones in a single tumor. The heterogeneity offers tumors the adaptability to survive, induce growth/ metastasis, and, most importantly, escape antitumor therapy. Unfortunately, the ITH is prioritized less in determining disease pathology than the traditional TNM classifications or tumor grade. Understanding ITH is challenging, but with the advancement of technology, this ITH can be decoded. Tumor genomics, proteomics, metabolomics, and other modern analyses can provide vast information. This information in clinics can assist in understanding a tumor's severity and be used for diagnostic, prognostic, and therapeutic decision-making. Lastly, the oral tumor ITH can lead to individualized, targeted therapy strategies fighting against OC.PMID:38039738 | DOI:10.1016/j.prp.2023.154953

Food Chem. 2023 Nov 22;439:138035. doi: 10.1016/j.foodchem.2023.138035. Online ahead of print.ABSTRACTCeratocystis paradoxa is a major cause of postharvest disease in tender coconuts worldwide. We conducted a comprehensive study using widely targeted metabolomics, electronic tongue (E-tongue), and electronic nose (E-nose) analyses to investigate the impacts of C. paradoxa invasion on the quality of tender coconut water (TCW) from fresh control (FC), uninoculated (UN), skin-inoculated (SI), and deep-inoculated (DI) nuts. DI exhibited significantly higher taste indicators associated with bitterness, saltiness, astringency aftertaste, and bitter aftertaste, as well as odor sensor values related to various compounds such as long-chain alkanes, hydrides, methane, organic sulfides, etc. Invasion of C. paradoxa into the endosperm altered the flavor characteristics of TCW mainly through the modulation of carbohydrate and secondary metabolite pathways. Furthermore, significant correlations were observed between the differentially expressed flavorful metabolites and the sensor indicators of the E-nose and E-tongue. These findings offer valuable insights into understanding the impact of C. paradoxa infection on coconuts.PMID:38039614 | DOI:10.1016/j.foodchem.2023.138035

Plant Physiol Biochem. 2023 Nov 27;206:108226. doi: 10.1016/j.plaphy.2023.108226. Online ahead of print.ABSTRACTFlavonoids are momentous bioactive ingredients in orchid plant Dendrobium catenatum (D. catenatum), which are bioactive compounds with great medical and commercial potential. However, the accurate dissection of flavonoids profiling and their accumulation mechanism are largely unknown. In this study, methyl jasmonate (MeJA) treatment was used to investigate the change of flavonoids content and transcripts in two D. catenatum clones (A6 and B1). We identified 40 flavonoids using liquid chromatograph mass spectrometer (LC-MS). By weighted gene co-expressed network analysis (WGCNA) of flavonoids content and transcript expression of MeJA-treated samples, 37 hub genes were identified. Among them, DcCHIL, DcFLS, and DcDFR were highly correlation with two key transcription factors DcWRKY3/4 by correlation analysis of large-scale transcriptome data and above hub genes expression. Furthermore, transient overexpression of DcWRKY3/4 in tobacco leaves significantly increased the content of flavonoids. This study identified flavonoid profiling and built a new approach to mine regulatory mechanism of flavonoids in D. catenatum. These valuable flavonoids and gene resources will be key for understanding and harnessing natural flavonoids products in pharmaceuticals and foods industry of D. catenatum.PMID:38039587 | DOI:10.1016/j.plaphy.2023.108226

Plant Physiol Biochem. 2023 Nov 25;206:108229. doi: 10.1016/j.plaphy.2023.108229. Online ahead of print.ABSTRACTReactive oxygen species (ROS) production is a routine event in plants. ROS function as signalling molecules in regulating plant development and defence. However, their accumulation beyond threshold leads to toxicity. Hence, plants are evolved with specialized ROS scavenging system involving phytohormones (synthesis and signalling), enzymes and metabolites. To understand the role of phytohormone jasmonic acid (JA) signalling in ROS scavenging, tomato coronatine insensitive 1 (SlCOI1), a key gene in JA signalling, was silenced and overexpressed in tomato transgenic hairy roots (HR) under the constitutive promoter. Targeted metabolomics of transgenic HR revealed accumulation of phenolic acids including ferulic acid, coumaric acid, vanillic acid, and flavonoid catechin in SlCOI1 overexpressed line. Moreover, osmolyte amino acids proline, asparagine, and glutamine showed a positive co-relation with transgenic overexpression of SlCOI1. Ascorbic acid-glutathione, a crucial antioxidant system was found to be influenced by COI1-mediated JA signalling. The expression of genes encoding enzymes superoxide dismutase 1, ascorbate peroxidase 1, and dehydroascorbate reductase 2 was found to be down and upregulated in SlCOI1 silenced and overexpressed lines, respectively. Methyl jasmonate and Fusarium oxysporum f.sp. lycopersici crude extract treatment further confirmed the regulatory role of COI1-mediated JA signalling in regulation of enzymatic components involved in ROS scavenging. The COI1-mediated JA signalling could also elevate the expression of RESPIRATORY BURST OXIDASE HOMOLOG-B gene which is involved in ROS wave signal generation. The present study underscores the role of COI1-mediated JA signalling in modulating enzymatic and non-enzymatic components of ROS scavenging system and pathogen associated molecular pattern triggered immunity.PMID:38039582 | DOI:10.1016/j.plaphy.2023.108229

Sci Rep. 2023 Dec 1;13(1):21179. doi: 10.1038/s41598-023-48413-w.ABSTRACTAcrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were exposed to air (0 ppm) or acrolein (3.16 ppm) for 4 h, followed by immediate serum and liver tissue collection. Serum metabolomics in both sexes and liver transcriptomics in males were evaluated to characterize the systemic metabolic response. Of 887 identified metabolites, > 400 differed between sexes at baseline. An acrolein biomarker, 3-hydroxypropyl mercapturic acid, increased 18-fold in males and 33-fold in females, indicating greater metabolic detoxification in females than males. Acrolein exposure changed 174 metabolites in males but only 50 in females. Metabolic process assessment identified higher circulating free-fatty acids, glycerols, and other lipids in male but not female rats exposed to acrolein. In males, acrolein also increased branched-chain amino acids, which was linked with metabolites of nitrogen imbalance within the gut microbiome. The contribution of neuroendocrine stress was evident by increased corticosterone in males but not females. Male liver transcriptomics revealed acrolein-induced over-representation of lipid and protein metabolic processes, and pathway alterations including Sirtuin, insulin-receptor, acute-phase, and glucocorticoid signaling. In sum, acute acrolein inhalation resulted in sex-specific serum metabolomic and liver transcriptomic derangement, which may have connections to chronic metabolic-related diseases.PMID:38040807 | DOI:10.1038/s41598-023-48413-w

Cell Death Dis. 2023 Dec 1;14(12):787. doi: 10.1038/s41419-023-06319-5.ABSTRACTLipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism. This metabolic reprogramming was also associated with impaired apoptosis and ferroptosis responses, and preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis. Redox drivers of ferroptosis derived from oxidative metabolism were also reduced. The relevance of this pathway was demonstrated by overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice, which enhanced oxidative metabolic capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of skeletal muscle oxidative metabolism, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.PMID:38040704 | DOI:10.1038/s41419-023-06319-5

EBioMedicine. 2023 Nov 20:104873. doi: 10.1016/j.ebiom.2023.104873. Online ahead of print.ABSTRACTBACKGROUND: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention.METHODS: This low-risk, non-invasive dietary intervention trial was conducted at MD Anderson Cancer Center (Houston, TX, USA). Following a 4-week equilibration, patients were randomized to continue their usual diet without beans (control) or to add a daily cup of study beans to their usual diet (intervention) with immediate crossover at 8-weeks. Stool and fasting blood were collected every 4 weeks to assess the primary outcome of intra and inter-individual changes in the gut microbiome and in circulating markers and metabolites within 8 weeks. This study was registered on ClinicalTrials.gov as NCT02843425, recruitment is complete and long-term follow-up continues.FINDINGS: Of the 55 patients randomized by intervention sequence, 87% completed the 16-week trial, demonstrating an increase on-intervention in diversity [n = 48; linear mixed effect and 95% CI for inverse Simpson index: 0.16 (0.02, 0.30); p = 0.02] and shifts in multiple bacteria indicative of prebiotic efficacy, including increased Faecalibacterium, Eubacterium and Bifidobacterium (all p < 0.05). The circulating metabolome showed parallel shifts in nutrient and microbiome-derived metabolites, including increased pipecolic acid and decreased indole (all p < 0.002) that regressed upon returning to the usual diet. No significant changes were observed in circulating lipoproteins within 8 weeks; however, proteomic biomarkers of intestinal and systemic inflammatory response, fibroblast-growth factor-19 increased, and interleukin-10 receptor-α decreased (p = 0.01).INTERPRETATION: These findings underscore the prebiotic and potential therapeutic role of beans to enhance the gut microbiome and to regulate host markers associated with metabolic obesity and colorectal cancer, while further emphasizing the need for consistent and sustainable dietary adjustments in high-risk patients.FUNDING: This study was funded by the American Cancer Society.PMID:38040541 | DOI:10.1016/j.ebiom.2023.104873

PLoS One. 2023 Dec 1;18(12):e0291845. doi: 10.1371/journal.pone.0291845. eCollection 2023.ABSTRACTINTRODUCTION: This study examined the effects of acute resistance exercise on circulating endocannabinoid (eCB) and mood responses in trained and untrained healthy adults.METHODS: Thirty-two healthy adults (22.1 ± 2.9 years) were recruited from trained (reporting resistance exercise at least twice per week for ≥ previous three months) and untrained (performing no resistance exercise for ≥ previous three months) groups. Participants (13 male, 19 female) completed three sets of resistance exercise (16 repetitions at 50% 1-repetition max, 12 repetitions at 70% 1-repetition max, 8 repetitions at 80% 1-repetition max). Resistance machines targeted the legs, chest, back, and abdominal muscles. Mood states, affect, and circulating eCB concentrations were evaluated before and after resistance exercise.RESULTS: There were significant decreases in AEA, PEA, and OEA levels following acute resistance exercise (p <0.05; ds = -0.39, -0.48, -0.65, respectively), with no significant group differences or group by time interactions. 2-AG did not change significantly. Positive affect increased significantly following resistance exercise (p = 0.009), while negative affect decreased (p <0.001). Depressive symptoms, anger, confusion, and total mood disturbance decreased significantly (p <0.05), while vigor increased significantly following resistance exercise (p = 0.005). There were no significant group differences or group by time interactions for any psychological outcomes.CONCLUSION: These results indicate that acute resistance exercise may reduce eCB and related lipid concentrations, which is opposite to the increase in lipids typically observed with acute aerobic exercise. Furthermore, psychological improvements occur after resistance exercise regardless of decreases in eCBs, supporting the notion that psychological changes with exercise likely occur through a wide variety of biological and environmental mechanisms.PMID:38039265 | DOI:10.1371/journal.pone.0291845