Fatty Acid Pathways Research Articles

Identification of biomarkers for the diagnosis in colorectal polyps and metabolic dysfunction-associated steatohepatitis (MASH) by bioinformatics analysis and machine learning

Colorectal polyps are precursors of colorectal cancer. Metabolic dysfunction associated steatohepatitis (MASH) is one of metabolic dysfunction associated fatty liver disease (MAFLD) phenotypic manifestations. Much evidence has suggested an association between MASH and polyps. This study investigated the biomarkers of MASH and colorectal polyps, and the prediction of targeted drugs using an integrated bioinformatics analysis method. Differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on GSE89632 and GSE41258 datasets, 49 shared genes revealed after intersection. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses depicted they were mainly enriched in apoptosis, proliferation and infection pathways. Machine learning algorithms identified S100P, FOXO1, and LPAR1 were biomarkers for colorectal polyps and MASH, ROC curve and violin plot showed ideal AUC and stable expression patterns in both the discovery and validation sets. GSEA analysis showed significant enrichment of bile acid and fatty acid pathways when grouped by the expression levels of the three candidate biomarkers. Immune infiltration analysis showed a significant infiltration of M0 macrophages and Treg cells in the colorectal polyps group. A total of 9 small molecule compounds were considered as potential chemoprevention agents in MASH and colorectal polyps by using the CMap website. Using integrated bioinformatics analysis, the molecular mechanism between MASH and colorectal polyps has been further explored.

Differential AMF-mediated biochemical responses in sorghum and oat plants under environmental impacts of neodymium nanoparticles

This study investigates the impact of neodymium (Nd) nanoparticle (NdNP) toxicity on the physiological and biochemical responses of sorghum (Sorghum bicolor) and oat (Avena sativa) plants and evaluates the potential mitigating effects of arbuscular mycorrhizal fungi (AMF). Sorghum and oat plants were grown under controlled conditions with and without AMF inoculation, and subjected to NdNPs (500 mg Nd kg−1 soil). Results revealed that Nd nanoparticles significantly reduced biomass in both species, with a 50% decrease in sorghum and a 59% decrease in oats. However, AMF treatment ameliorated these effects, increasing biomass by 69% in oats under Nd nanoparticles toxicity compared to untreated contaminated plants. Soluble sugar metabolism was notably affected; AMF treatment led to significant increases in fructose and sucrose contents in both sorghum (+31% and +23%, respectively) and oat (+25% and +37%, respectively) plants under NdNPs toxicity. Improved sugar metabolism via enhanced activities of sucrose phosphate synthase (+29–54%) and invertase (+39–54%) enzymes resulted in higher proline (+21–81%) and polyamines (+49–52%) levels in AMF-treated plants under NdNPs toxicity, along with alterations in the biosynthesis pathways of amino acids and fatty acids, resulting in better osmoprotection and stress tolerance. Moreover, citrate (+29–55%) and oxalate (+177–312%) levels increased in both plants in response to NdNPs toxicity, which was accompanied by a positive response of isobutyric acid to AMF treatment in stressed plants, which potentially might serve as mechanisms for plants to mitigate NdNPs toxicity. These findings suggest that AMF can significantly mitigate Nd-induced damage and improve plant resilience through enhanced metabolic adjustments, highlighting a potential strategy for managing rare earth element (REE) nanoparticle toxicity in agricultural soils.

Allelopathy and underlying mechanism of mango (Mangifera indica) peel extracts on Alexandrium catenella

Harmful algal blooms (HABs) have always been a worldwide environmental issue. The methods based on the principle of allelopathy provide a novel direction for controlling HABs; however, there are a few studies on the application of allelopathic algaecides to control harmful algae in marine environments. Here we examined the algicidal capacity of 15 fruit peel extracts with biological activity on Alexandrium catenella. The results displayed that the mango peel extracts (MPE) showed efficient inhibition on species growth. The algicidal rate reached 93.32 ± 0.56% at 96 h after adding 5 g/L MPE to the culture medium of A. catenella. Furthermore, we found that the expression of key genes involved in PSII and PSI was downregulated as well as obstructed the electron transportation in the light reaction process and the synthesis of organic matter. The blocked photosynthetic chain induced the accumulation of substantial reactive oxygen species, resulting in severe peroxidation of the membrane lipids. Simultaneously, the expression pattern of key genes involved in the fatty acid, amino acid, and peroxisome breakdown pathways was upregulated, which suggested that the synthesis and decomposition of intracellular organic matter may be in an imbalanced state. The results above indicated that oxidative damage and energy metabolism disequilibrium are two key pathways by which MPE induced algal cell death. Furthermore, several kinds of active substances and their proportion in MPE had been identified by liquid chromatography quadrupole time-of-flight mass spectrometry. It is speculated that esters may be the important component playing an algicidal effect. However, the specific substance that plays a key role in inhibiting the growth of A. catenella and the algicidal mechanism remain to be further studied. This study might provide a new direction in the management of HABs in the future.

A time-course transcriptome reveals the response of watermelon to low-temperature stress

Watermelon (Citrullus lanatus) is an economically important horticultural crop. However, it is susceptible to low-temperature stress, which poses a significant challenge to its production and supply. Despite the great economic importance of watermelon, little is known about its response to low-temperature stress at the transcriptional level. In this study, we performed a time-course transcriptome analysis to systematically investigate the regulatory network of watermelon under low-temperature stress. Six low-temperature-responsive gene clusters representing six expression patterns were identified, revealing diverse regulation of metabolic pathways in watermelon under low-temperature stress. Analysis of temporally specific differentially expressed genes revealed the time-dependent nature of the watermelon response to low temperature. Moreover, ClMYB14 was found to be a negative regulator of low-temperature tolerance as ClMYB14-OE lines were more susceptible to low-temperature stress. Co-expression network analysis demonstrated that ClMYB14 participates in the low-temperature response by regulating the unsaturated fatty acid pathway and heat shock transcription factor. This study provides substantial information for understanding the regulatory network of watermelon in response to low-temperature stress, as well as identifies candidate genes for the genetic improvement of watermelon with higher low-temperature tolerance.

Bempedoic Acid, the First-in-Class Oral ATP Citrate Lyase Inhibitor with Hypocholesterolemic Activity: Clinical Pharmacology and Drug-Drug Interactions.

Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug-drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg. The dicarboxylic acid is enzymatically activated by conjugation with coenzyme A (CoA) to form the pharmacologically active thioester (bempedoic acid-CoA). This process is catalyzed by very-long-chain acyl-CoA synthetase 1 (ACSVL1), expressed almost exclusively at the hepatic level. Bempedoic acid-CoA is a potent and selective inhibitor of ATP citrate lyase (ACL), a key enzyme in the biosynthetic pathway of cholesterol and fatty acids. The drug reduces low-density lipoprotein-cholesterol (LDL-C) (20-25%), non-high-density lipoprotein-cholesterol (HDL-C) (19%), apolipoprotein B (apoB) (15%), and total cholesterol (16%) in patients with hypercholesterolemia or mixed dyslipidemia. The drug has a favorable pharmacokinetics profile. Bempedoic acid and its metabolites are not substrates or inhibitors/inducers of cytochrome P450 (CYP450) involved in drug metabolism. On the other hand, bempedoic acid-glucuronide is a substrate for organic anion transporter 3 (OAT3). Bempedoic acid and its glucuronide are weak inhibitors of the OAT2, OAT3, and organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3). Thus, bempedoic acid could inhibit (perpetrator) the hepatic uptake of OATP1B1/3 substrate drugs and the renal elimination of OAT2 and OAT3 substrates and could suffer (victim) the effect of OAT3 transporter inhibitors, reducing its renal elimination. Based on these pharmacological characteristics, here, we describe the potential DDIs of bempedoic acid with concomitant medications and the possible clinical implications.

Allelopathic Molecular Mechanisms of the Two Main Allelochemicals in Sweet Potato.

Sweet potato (Ipomoea batatas L.) is one of the most important global food crops. This crop exhibits excellent allelopathic potential against various weeds, but its allelopathic mechanism at the molecular level is unclear. Therefore, metabolomic and transcriptomic analyses were performed to explore the allelopathic effects, metabolic pathway, and associated genes for two major compounds with allelopathic activity, palmitic acid and linoleic acid. The sweet potato variety Ningshu 25 was employed in the current study. The results showed that palmitic acid and linoleic acid had strong allelopathic effects on seed germination, plant growth, antioxidant enzyme activity, and chlorophyll content of two weeds Digitaria sanguinalis and Bidens pilosa. The content of the two targeted metabolites was affected by different environmental conditions and was significantly increased under low temperature (15 °C). Five metabolic pathways involved in the two targeted metabolites of fatty acids were found: fatty acid biosynthesis, fatty acid elongation, fatty acid degradation, biosynthesis of cutin, suberine, and wax, and the linoleic acid metabolism pathway. The synthesis of palmitic acid is significantly enriched in the biosynthesis pathways of fatty acids, cutin, suberine, and wax, and the synthesis of linoleic acid is significantly enriched in the linoleic acid metabolism pathway. Under different environmental conditions, there were three key genes expressed-g4988, g11881, and g19673-located in the biosynthesis pathways of cutin, suberine, and wax; four key genes expressed-g31191, g60956, g49811, and g59542-located in the biosynthesis pathway of fatty acids; and six key expressed genes-g26575, g24787, g23517, g57649, g58562, and g4314-located in biosynthesis pathway of linoleic acid, respectively. Our study advances understanding of the molecular mechanisms behind allelopathic traits in sweet potato and provides a set of candidate genes for use in improving allelopathic potential in sweet potato germplasm resources.

Artemisia Argyi essential oil ameliorates acetaminophen-induced hepatotoxicity via CYP2E1 and γ-glutamyl cycle reprogramming

BackgroundThe hepatotoxicity induced by acetaminophen (APAP), a commonly used antipyretic, analgesic and anti-inflammatory drug in clinical practice, has received accumulated attention. Artemisia argyi essential oil (AAEO), a volatile oil component extracted from traditional Chinese medicine Artemisia argyi H.Lév. & Vaniot, has great hepatoprotective effects. However, the potential role of AAEO in APAP-induced hepatotoxicity has not been characterized. The present study aimed to investigate the effects of AAEO on hepatic metabolic changes in mice exposed to APAP. MethodsIn this study, 300.00 mg/kg acetaminophen was used to establish liver injury model in C57BL/6 J mice. Hepatoprotective effect of AAEO on APAP-induced hepatotoxicity in mice was investigated by detecting liver function enzymes and histopathological examination. Secondly, UPLC-MS/MS was used to analyze the to analyze the small molecule metabolites and metabolic pathways induced by AAEO treatment; In addition, the effect of AAEO on APAP-induced oxidative stress and inflammation were evaluated by detecting the levels of glutathione peroxidase 4, malondialdehyde, reactive oxygen species and inflammatory factors. Finally, the active components of AAEO were preliminarily screened by cellular assays. The hepatoprotective effect of AAEO against APAP-induced hepatotoxicity was examined through the Western blotting, after the CYP2E1 gene was knocked down in AML12 cells by siRNA transfection. ResultsCompared with the APAP group, AAEO could reduce the abnormal increase in the levels of liver function enzymes caused by APAP. AAEO could enhance the antioxidant capacity by down-regulating the biosynthesis pathway of unsaturated fatty acids and promoting the activity of antioxidant enzymes SOD and CAT in liver tissue induced by APAP. Our study revealed that AAEO promoted GSH synthesis and covalently combined to form APAP-GSH conjugates to reduce the accumulation of APAP in liver tissue. In addition, the chemical constituents in AAEO were analyzed by GC–MS/MS, and it was determined to identify that dihydro-beta-ionone and (-)-verbenone in AAEO might have a significant protective effect on hepatocyte survival after APAP exposure. Further studies on the hepatoprotective mechanism of AAEO indicated that it might reduce the production of toxic metabolites by regulating CYP2E1 levels. ConclusionAAEO exerted hepatoprotective effects on acetaminophen-induced hepatotoxicity in mice via regulating the activity of CYP2E1 and regulating the γ-glutamyl cycle pathway.

Immunometabolic Chaos in Septic Shock.

Septic shock is associated with over 40% mortality. The immune response in septic shock is tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible to secondary infections during hypo-inflammation. The magnitude of the metabolic dysregulation and the effect of plasma metabolites on the circulating immune cells in septic shock are not reported. We hypothesized that the accumulated plasma metabolites affect the immune response in septic shock during hypo-inflammation. Our study took a unique approach. Using peripheral blood from adult septic shock patients and healthy controls, we studied: 1. Whole blood stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) to analyze plasma TNF protein, and 2. Plasma metabolomic profile by Metabolon. Inc. 3. We exposed peripheral blood mononuclear cells (PBMCs) from healthy controls to commercially available carbohydrate, amino acid, and fatty acid metabolites and studied the response to LPS. We report that: 1. The whole blood stimulation of the healthy control group showed a significantly upregulated TNF protein, while the septic shock group remained endotoxin tolerant, a biomarker for hypo-inflammation. 2. A significant accumulation of carbohydrate, amino acid, fatty acid, ceramide, sphingomyelin, and TCA cycle pathway metabolites in septic shock plasma. 3. In vitro exposure to five metabolites repressed while two metabolites upregulated the inflammatory response of PBMCs to LPS. We conclude that the endotoxin-tolerant phenotype of septic shock is associated with a simultaneous accumulation of plasma metabolites from multiple metabolic pathways, and these metabolites fundamentally influence the immune response profile of circulating cells.

A tomato a day keeps the beetle away - the impact of Solanaceae glycoalkaloids on energy management in the mealworm Tenebrio molitor.

Solanine (SOL), chaconine (CHA), and tomatine (TOM) are plant secondary metabolites produced mainly by the species of Solanaceae family, such as tomato Solanum lycopersicum L. These glycoalkaloids (GAs) have a wide range of biological activity, also in insects. However, their mechanisms of action are not precisely understood. The purpose of the study was to investigate how pure GAs and tomato leaf extract (EXT) affect glycolysis, Krebs cycle and β-oxidation of fatty acid pathways in Tenebrio molitor L. beetle. For this purpose, the larvae were injected with SOL, CHA, TOM, and EXT at two concentrations (10-8 and 10-5M). For experiments, fat body, gut, and heamolymph samples were collected 2 and 24h after injection. Then, the changes in the expression level of phosphofructokinase, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase were measured using the RT-qPCR technique. The catalytic activity of these enzymes and the carbohydrate level in insects after GA treatment were determined by spectrophotometric method. Furthermore, the analysis of the amount of amino acids in tissues was performed with a GC-MS technique. The results obtained show that the GAs changed the activity and expression of the genes encoding key enzymes of crucial metabolic pathways. The effect depends on the type of GA compound, the tissue tested, and the incubation time after treatment. Furthermore, TOM and EXT affected trehalose concentration in the insect hemolymph and led to accumulation of amino acids in the fat body. The observed changes may indicate a protein degradation and/or enhanced catabolism reactions for the production of ATP used in detoxification processes. These results suggest that GAs alter energy metabolism in the mealworm T. molitor. The study contributes to our understanding of the mechanisms of action of secondary metabolites of plants in insects. This knowledge may allow the design of new natural biopesticides against insect pests because proper energy metabolism is necessary for the survival of the organism.

Structure based exploration of mitochondrial alpha carbonic anhydrase inhibitors as potential leads for anti-obesity drug development.

Obesity has emerged as a major health challenge globally in the last two decades. Dysregulated fatty acid metabolism and de novo lipogenesis are prime causes for obesity development which ultimately trigger other co-morbid pathological conditions thereby risking life longevity. Fatty acid metabolism and de novo lipogenesis involve several biochemical steps both in cytosol and mitochondria. Reportedly, the high catalytically active mitochondrial carbonic anhydrases (CAVA/CAVB) regulate the intercellular depot of bicarbonate ions and catalyze the rapid carboxylation of pyruvate and acetyl-co-A to acetyl-co-A and malonate respectively, which are the precursors of fatty acid synthesis and lipogenesis. Several in vitro and in vivo investigations indicate inhibition of mitochondrial carbonic anhydrase isoforms interfere in the functioning of pyruvate, fatty acid and succinate pathways. Targeting of mitochondrial carbonic anhydrase isoforms (CAVA/CAVB) could thereby modulate gluconeogenetic as well as lipogenetic pathways and pave way for designing of novel leads in the development pipeline of anti-obesity medications. The present review unveils a diverse chemical space including synthetic sulphonamides, sulphamates, sulfamides and many natural bioactive molecules which selectively inhibit the mitochondrial isoform CAVA/CAVB with an emphasis on major state-of-art drug design strategies. More than 60% similarity in the structural framework of the carbonic anhydrase isoforms has converged the drug design methods towards the development of isoform selective chemotypes. While the benzene sulphonamide derivatives selectively inhibit CAVA/CAVB in low nanomolar ranges depending on the substitutions on the phenyl ring, the sulpamates and sulpamides potently inhibit CAVB. The virtual screening and drug repurposing methods have also explored many non-sulphonamide chemical scaffolds which can potently inhibit CAVA. The review could pave way for the development of novel and effective anti-obesity drugs which can modulate the energy metabolism.

The iodinated contrast agent diatrizoic acid has an impact on the metabolome of the mollusc Dreissena polymorpha

The occurrence of iodinated contrast agents (ICAs) in the aquatic environment is relatively well documented, showing that these compounds can be found at several µg/L in natural waters, and up to hundreds of µg/L in waste water treatment plants inlets. Nevertheless, only few studies address their potential impacts and fate in aquatic organisms mainly because these compounds are considered non-toxic due to their intrinsic properties. However, as aquatic organisms are continuously exposed to these compounds, they could nonetheless induce some adverse effects on aquatic populations like filter feeder organisms. To verify this, we exposed model organisms, Dreissena polymorpha mollusks, to 100 µg/L of an ICA, diatrizoic acid (DTZ), to determine the potential biological effects caused by this compound using a non-targeted metabolomic approach based on liquid chromatography coupled to high resolution mass spectrometry. Metabolic profiles showed a slight effect of DTZ, with some metabolome variations linked to exposure. Indeed, to avoid any misinterpretation of DTZ effects, we also studied the natural evolution of the metabolome over time in unexposed mussels, showing that control mussels exhibited metabolomic changes over the exposure period. During DTZ exposure, we showed that the carnitine shuttle pathway of fatty acids and pyrimidine metabolisms were impacted, leading to dysregulation of mussels’ energy metabolism. Thus, this study demonstrates for the first time that compounds considered non-toxic like ICAs can have an impact on aquatic organisms such as bivalves by slightly modulating their metabolome.

Low temperature conditioning and nitric oxide treatment reduced chilling injury and altered fatty acid metabolism of flat peaches

Low-temperature conditioning is a recognized method for alleviating chilling injuries in flat peaches. However, long-term low-temperature storage can mitigate volatile organic compounds, thereby limiting fruit availability. To improve the supply of flat peaches, we investigated the combined effects of low-temperature conditioning and nitric oxide treatment on various parameters including physiological quality, volatile organic compounds, fatty acids, associated enzymes, and genes involved in the fatty acid pathway with the transcriptome sequencing analysis. The results indicated that low-temperature conditioning coordinated with 10 µL L−1 nitric oxide treatment possessed higher firmness and vitamin C content and restricted the content of malonaldehyde and relative electrical conductivity, thus maintaining the overall quality of flat peaches. In the study, 10 µL L−1 nitric oxide was employed for subsequent experiments. Moreover, higher contents of volatile organic compounds were supported by increased contents of palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, alcohol dehydrogenase, hydroperoxide lyase, and up-regulated genes of LOX2, LOX3, LOX6, ADH2, and ADH3. In summary, nitric oxide treatment effectively facilitated the recovery of volatile organic compounds in flat peaches during cold storage. Therefore, low-temperature conditioning and nitric oxide treatment can be a promising strategy to prevent the loss of volatile organic compounds by modulating the fatty acid pathway and associated genes.

Identification of OncoMir Biomarkers: Comprehensive Analysis of Fatty Acid Pathway Genes in Colorectal Cancer Progression and Their Prognostic Implications

Identification of OncoMir Biomarkers: Comprehensive Analysis of Fatty Acid Pathway Genes in Colorectal Cancer Progression and Their Prognostic Implications

Landscape of the Lumbar Cartilaginous End Plate Microbiota and Metabolites in Patients with Modic Changes.

Modic changes (MCs), vertebral end plate and bone marrow damage observed by magnetic resonance imaging, are an independent risk factor for low back pain. The compositions of and interaction between microbiota and metabolites in the lumbar cartilaginous end plates (LCEPs) of patients with MCs have not been identified. Patients with lumbar disc degeneration who were undergoing lumbar spinal fusion surgery were recruited between April 2020 and April 2021. LCEPs were collected for 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS)-based targeted metabolomic profiling. Of the 54 patients recruited, 24 had no MCs and 30 had changes classified as Modic type 2 or 3. The primary goal was to identify specific genera of microbiota associated with MCs, and secondary goals included investigating differences in metabolites between patients with and without MCs and exploring the correlation between these metabolites and microorganisms. Investigation of the microbiota community structure revealed that both alpha diversity and beta diversity were significantly different between patients with and without MCs, and the abundances of 26 genera were significantly different between these 2 groups. Metabolomic analysis revealed that 26 metabolites were significantly different between the 2 groups. The unsaturated fatty acid pathway was found to be the main pathway related to MCs. Multiomic correlation analysis suggested that Caulobacteraceae (unclassified) and Mycobacterium, Clostridium, Blautia, and Bifidobacterium at the genus level were linked to dysregulation of fatty acid metabolism, contributing to the pathogenesis of MCs. Our study represents a foundational effort to examine the landscape of the microbiota and metabolites in patients with MCs, informing future studies on the pathogenesis of and targeted therapy for MCs. Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Circulating miRNA Signaling for Fatty Acid Metabolism in Response to a Maximum Endurance Test in Elite Long-Distance Runners.

Maximal oxygen uptake (VO2max) is a determining indicator for cardiorespiratory capacity in endurance athletes, and epigenetics is crucial in its levels and variability. This initial study examined a broad plasma miRNA profile of twenty-three trained elite endurance athletes with similar training volumes but different VO2max in response to an acute maximal graded endurance test. Six were clustered as higher/lower levels based on their VO2max (75.4 ± 0.9 and 60.1 ± 5.0 mL.kg-1.min-1). Plasma was obtained from athletes before and after the test and 15 ng of total RNA was extracted and detected using an SYBR-based 1113 miRNA RT-qPCR panel. A total of 51 miRNAs were differentially expressed among group comparisons. Relative amounts of miRNA showed a clustering behavior among groups regarding distinct performance/time points. Significantly expressed miRNAs were used to perform functional bioinformatic analysis (DIANA tools). Fatty acid metabolism pathways were strongly targeted for the significantly different miRNAs in all performance groups and time points (p < 0.001). Although this pathway does not solely determine endurance performance, their significant contribution is certainly achieved through the involvement of miRNAs. A highly genetically dependent gold standard variable for performance evaluation in a homogeneous group of elite athletes allowed genetic/epigenetic aspects related to fatty acid pathways to emerge.

Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation.

Decidualization denotes the morphological and biological differentiating process of human endometrial stromal cells (HESCs). Fatty acid pathways are critical for endometrial decidualization. However, the participation of fatty acids as an energy source and their role in endometrial decidualization have received little attention. To identify fatty acids and clarify their role in decidualization, we comprehensively evaluated free fatty acid profiles using liquid chromatography/Fourier transform mass spectrometry (LC/FT-MS). LC/FT-MS analysis detected 26 kinds of fatty acids in the culture medium of decidualized or un-decidualized HESCs. Only the production of octanoic acid, which is an essential energy source for embryonic development, was increased upon decidualization. The expressions of genes related to octanoic acid metabolism including ACADL, ACADM, and ACADS; genes encoding proteins catalyzing the first step of mitochondrial fatty acid beta-oxidation; and ACSL5 and ACSM5; genes encoding fatty acid synthesis proteins were significantly altered upon decidualization. These results suggest that decidualization promotes lipid metabolism, implying that decidualized HESCs require energy metabolism of the mitochondria in embryo implantation.

The mitigating effects and mechanisms of Bacillus cereus on chronic cadmium poisoning in Litopenaeus vannamei based on histopathological, transcriptomic, and metabolomic analyses

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Escherichia coli Nissle 1917 Protects against Sepsis-Induced Intestinal Damage by Regulating the SCFA/GPRs Signaling Pathway.

This study explores whether Escherichia coli Nissle 1917 (EcN) can preserve the integrity of the intestinal barrier by modulating the metabolism pathway of short-chain fatty acids (SCFAs) in a C57BL/6J mouse model of lipopolysaccharide (LPS)-induced acute enteritis and a model of a Caco-2 monolayer. The study involved establishing a septic shock model in mice through lipopolysaccharide (LPS) injection. Clinical scores and intestinal permeability were meticulously documented. Immunofluorescence was utilized to localize the tight junction proteins. A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the expression of G protein-coupled receptors (GPRs) signaling. Additionally, the supplement of acetate and butyrate with Caco-2 monolayers to elucidate the potential of EcN in augmenting the intestinal barrier primarily via the modulation of SCFAs and qRT-PCR was performed to detect the expression of tight junction proteins and the activation of the GPRs protein signaling pathway. EcN mitigated the clinical symptoms and reduced intestinal permeability in the colon of LPS-induced mice. It also enhanced the production of SCFAs in the gut and upregulated the expression of SCFA receptor proteins GPR41 and GPR43 in the colon tissue. Our findings reveal that EcN activates the SCFA/GPRs pathway, thereby preserving intestinal barrier function and alleviating inflammation in a mouse sepsis model.

High-fat intake induces gut microbiota disorders, inflammatory responses and oxidative stress in Nyctereutes procyonoides

The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur, which renders artificial feeding a crucial aspect. However, high-fat diets have always been associated with a variety of digestive disorders. This study aimed to investigate the impact of high-fat diets on the gut microbiota and the mechanisms of gut damage in Nyctereutes procyonoides. 16S rRNA sequencing demonstrated that high-fat diets caused diarrhea and intestinal damage through alterations in the gut microbiota: a decrease in the abundance of Firmicutes, an increase in the abundance of Proteobacteria and Actinobacteria, and an increase in the abundance of Enterococcaceae, Escherichia coli-Shigella, Clostridium and Lactobacillus. Subsequently, changes in metabolic pathways, such as amino and fatty acid pathways, were identified by KEGG and COG enrichment analysis, and the TLR4/NF-κB/NLRP3 inflammatory signaling pathway was shown to be activated by high-fat diets. In addition, high-fat diets lead to the accumulation of ROS and MDA and reduce the activity of the antioxidant enzymes GSH-PX and SOD. Correspondingly, the levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α) were significantly increased, and the apoptosis and necrosis signaling pathways of colonic cells were detected, causing a dramatic decrease in the expression of intestinal tight junction proteins (Occludin, E-cadherin, ZO-1 and ZO-2). In conclusion, high-fat diets altered the structure of the Nyctereutes procyonoides gut microbiota community and led to colon damage. This study provides new insights into the intestinal health of Nyctereutes procyonoides.Graphical

Metabolite comparative variation related lipid metabolisms among fruit, leaf, and stem of Jatropha curcas

The issue of non-renewable energy scarcity has persisted over an extended period, primarily due to the depletion of fossil fuel reserves and the adverse effects of their utilization. This scarcity stems from the finite nature of fossil energy resources. The development of oil energy or biofuels aims to utilize oil-producing plants such as Jatropha curcas to develop alternative energy resources. However, metabolomic studies in Jatropha curcas are limited and need more investigations. Therefore, this research was essential to find biomarkers of metabolites among the fruit, leaf, and stem of Jatropha curcas using the GC-MS technique. We tested the metabolite profile with the R program, especially the metaboanalystR package, to determine fold change metabolite and pathway analysis. We found that 54 metabolites were detected in both fruit, leaf, and stem tissues of Jatropha curcas L, of which 19 metabolites were upregulated in the fruit, 20 metabolites in the leaf, and 15 up-regulated metabolites in the stem. The metabolites found formed three clusters based on correlation and networking metabolites analysis. The three clusters showed a relationship with the lipid biosynthesis pathway. In this study, provisional information was obtained that there was a different pattern of expression of metabolites between fruit, leaf, and stem tissues in Jatropha curcas, which was thought to be related to the critical metabolites of oleic acid and methylcyclohexane carboxylate in the biosynthetic pathway of fatty acids and unsaturated fatty acids. This information is essential as an initial reference for genetic engineering Jatropha curcas so that it can be used to transform plants, especially lipid-producing plants, as a source of oil.