PubMed

Pharmaceuticals (Basel). 2024 Dec 21;17(12):1733. doi: 10.3390/ph17121733.ABSTRACTBackground and Objective: In Saudi Arabia, numerous plant species with promising medicinal properties are cultivated, widely traded, and commonly utilized in traditional medicine, including fenugreek (Trigonella foenum-graecum). This study aimed to comprehensively assess the phytochemical composition and antimicrobial potential of the Saudi cultivar of fenugreek using an integrative approach combining in vitro and in silico methodologies. Methods: A comprehensive investigation was conducted on the ethanol extract of fenugreek seeds, assessing its antibacterial, antifungal, properties. Computational modeling was employed to predict pharmacokinetic behavior and potential toxicity of the identified bioactive compounds. Results: Qalitative phytochemical analysis showed presence of alkaloids, tannins, saponins, glycosides, flavonoids, and steroids, while terpenoids were notably absent. GC-MS analysis of Trigonella foenum-graecum (fenugreek) seeds identified 25 bioactive compounds, with Ethyl methane sulfonate (12.41%) being the predominant component. Other key compounds included n-Hexadecanoic acid, 4-Butyl-2(4-nitrophenyl)-1,3-thiazole, and α-Tocopherol. In silico modeling of fenugreek phytochemicals supported their antibacterial, antioxidant, and neuroprotective potential, with compounds 21 and 24 showing strong binding to key targets like Tyrosyl-tRNA Synthetase (TyrRS) of Staphylococcus aureus (S. aureus), Aspartic proteinase from Candida albicans (C. albicans) and human peroxiredoxin 5. Pharmacokinetic analysis indicated good oral bioavailability, minimal CYP inhibition, and blood-brain barrier penetration, suggesting potential for treating neurodegenerative diseases. These bioactive compounds, including diosgenin and trigonelline, support fenugreek's therapeutic promise and warrant further in vitro, in vivo, and clinical studies. Conclusion: The Saudi fenugreek cultivar is rich in bioactive compounds with good antibacterial potential. These findings establish a robust foundation for continued pharmacological research on the Saudi cultivar of T. foenum-graecum, highlighting its potential as a rich source of bioactive compounds with significant medicinal value.PMID:39770575 | DOI:10.3390/ph17121733

Pharmaceuticals (Basel). 2024 Dec 10;17(12):1665. doi: 10.3390/ph17121665.ABSTRACTRhein is a natural active ingredient in traditional Chinese medicine that has attracted much attention due to its wide range of pharmacological activities. However, its clinical application is limited by low water solubility, poor oral absorption, and potential toxicity to the liver and kidneys. Recently, advanced extraction and synthesis techniques have made it possible to develop derivatives of rhein, which have better pharmacological properties and lower toxicity. This article comprehensively summarizes the biological activity and action mechanism of rhein. Notably, we found that TGF-β1 is the target of rhein improving tissue fibrosis, while NF-κB is the main target of its anti-inflammatory effect. Additionally, we reviewed the current research status of the pharmacokinetics, toxicology, structural optimization, and potential drug applications of rhein and found that the coupling and combination therapy of rhein and other active ingredients exhibit a synergistic effect, significantly enhancing therapeutic efficacy. Finally, we emphasize the necessity of further studying rhein's pharmacological mechanisms, toxicology, and development of analogs, aiming to lay the foundation for its widespread clinical application as a natural product and elucidate its prospects in modern medicine.PMID:39770507 | DOI:10.3390/ph17121665

Pathogens. 2024 Nov 23;13(12):1035. doi: 10.3390/pathogens13121035.ABSTRACTGram-negative bacteria possess an asymmetric outer membrane, where the outer leaflet consists of LPSs and the inner leaflet comprises phospholipids. Cronobacter sakazakii, an opportunistic milk-borne pathogen that causes severe neonatal meningitis and bacteremia, displays diverse lipopolysaccharide (LPS) structures. As a barrier of the bacterial cell, LPSs likely influenced C. sakazakii resistance to environment stresses; however, there are no research reports on this aspect, hindering the development of novel bactericidal strategies overcoming the pathogen's resilience. In the present study, therefore, C. sakazakii BAA894 and two LPS mutants (ΔlpxM and ΔwaaC) were employed to investigate its influences. The ΔwaaC mutant showed lower resistance to acidic, alkali, oxidative, and osmotic stresses compared to the wild-type strain BAA894, and the ΔlpxM mutant exhibited lower desiccation resistance but higher osmotic resistance. To uncover potential reasons for these differences, comparative lipidomics was conducted. The results showed that compared to BAA894, both mutants showed drastic changes in lipid quantity, and many changed lipids were unsaturated. Additionally, eleven lipid classes exhibited significant variation in the relative content. In particular, the polyunsaturated TGs with double bonds at 5, 7, 12, and 14 displayed significant variation between the wild type and two mutants. Our study is the first to reveal that the changes in the LPS structure of C. sakazakii resulted in altered lipid profiles and intensities, which may be a critical biochemical basis for bacterial resistance to harsh stresses.PMID:39770295 | DOI:10.3390/pathogens13121035

Molecules. 2024 Dec 16;29(24):5934. doi: 10.3390/molecules29245934.ABSTRACTTargeted metabolomics and lipidomics are increasingly utilized in clinical research, providing quantitative and comprehensive assessments of metabolic profiles that underlie physiological and pathological mechanisms. These approaches enable the identification of critical metabolites and metabolic alterations essential for accurate diagnosis and precision treatment. Mass spectrometry, in combination with various separation techniques, offers a highly sensitive and specific platform for implementing targeted metabolomics and lipidomics in clinical settings. Nevertheless, challenges persist in areas such as sample collection, quantification, quality control, and data interpretation. This review summarizes recent advances in targeted metabolomics and lipidomics, emphasizing their applications in clinical research. Advancements, including microsampling, dynamic multiple reaction monitoring, and integration of ion mobility mass spectrometry, are highlighted. Additionally, the review discusses the critical importance of data standardization and harmonization for successful clinical implementation.PMID:39770023 | DOI:10.3390/molecules29245934

Molecules. 2024 Dec 13;29(24):5895. doi: 10.3390/molecules29245895.ABSTRACTMachine learning and artificial intelligence tools were used to investigate the discriminatory potential of blood serum metabolites for thromboembolism and antiphospholipid syndrome (APS). 1H-NMR-based metabonomics data of the serum samples of patients with arterial or venous thromboembolism (VTE) without APS (n = 32), thrombotic primary APS patients (APS, n = 32), and healthy controls (HCs) (n = 32) were investigated. Unique metabolic profiles between VTE and HCs, APS and HCs, and between VTE and triple-positive APS groups were indicative of the significant alterations in the metabolic pathways of glycolysis, the TCA cycle, lipid metabolism, and branched-chain amino acid (BCAA) metabolism, and pointed to the complex pathogenesis mechanisms of APS and VTE. Histidine, 3-hydroxybutyrate, and threonine were shown to be the top three metabolites with the most substantial impact on model predictions, suggesting that these metabolites play a pivotal role in distinguishing among APS, VTE, and HCs. These metabolites might be potential biomarkers to differentiate APS and VTE patients.PMID:39769984 | DOI:10.3390/molecules29245895

Insects. 2024 Nov 28;15(12):940. doi: 10.3390/insects15120940.ABSTRACTIn this study, we selected Sitona callosus, one of the primary insect pests of alfalfa, as the experimental insect and infected it with Beauveria bassiana. Transcriptomic and metabolomic analyses were conducted to explore alterations in gene expression and metabolic processes in S. callosus at 48, 96, and 144 h post infection with B. bassiana. The transcriptomic analysis unveiled that B. bassiana infection boosted immune responses in tubercula, affecting carbohydrate metabolism, cytochrome P450 activity, lysosome function, apoptosis regulation, phagosome formation, glutathione metabolism, amino acid metabolism, and pathogen response pathways. Subsequent metabolomics analysis confirmed that glycerophospholipids, carboxylic acids and derivatives, organooxygen compounds, keto acids and derivatives, and azane immune metabolites were significantly upregulated in response to B. bassiana infection. Additionally, we utilized the Pearson correlation coefficient method to examine the relationships between differentially expressed immune-related genes and metabolites, revealing notably strong correlations between these two sets of variables. By leveraging the WGCNA method to analyze immune metabolite data for immune-related genes, we identified hub genes crucial at various stages of immune activation. These central genes predominantly included C-type lectin receptors for pattern recognition, cytochrome P450 enzymes linked to detoxification processes, and cathepsin proteases. By combining transcriptome and metabolome analyses, it was determined that autophagy and arachidonic acid metabolism play significant roles in the response of S. callosus to infection by B. bassiana. This research will facilitate the understanding of the immune response to B. bassiana infection in adult S. callosus, laying a theoretical groundwork for future biological control strategies targeting S. callosus.PMID:39769543 | DOI:10.3390/insects15120940

Int J Mol Sci. 2024 Dec 23;25(24):13739. doi: 10.3390/ijms252413739.ABSTRACTRecent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The aim of the presented study was to identify translational biomarkers for acute liver injury in human patients that can serve as biomarkers for hepatocellular injury in vivo and in vitro in simple cell models. Therefore, 188 different metabolites from patients with acute-on-chronic liver failure before and after liver transplantation were analyzed with mass spectrometry. The identified potential metabolic biomarker set, including acylcarnitines, phosphatidylcholines and sphingomyelins, was used to screen primary and permanent hepatocyte culture models for their ability to model hepatotoxic responses caused by different drugs with known and unknown hepatotoxic potential. The results obtained suggest that simple in vitro cell models have the capability to display metabolic responses in biomarkers for liver cell damage in course of the treatment with different drugs and therefore can serve as a basis for in vitro models for metabolic analysis in drug toxicity testing. The identified metabolites should further be evaluated for their potential to serve as a metabolic biomarker set indicating hepatocellular injury in vitro as well as in vivo.PMID:39769500 | DOI:10.3390/ijms252413739

Int J Mol Sci. 2024 Dec 22;25(24):13707. doi: 10.3390/ijms252413707.ABSTRACTCistus monspeliensis L. (C. monspeliensis) is used in Italian folk medicine. This study was performed to determine genotoxic and antigenotoxic effects of C. monspeliensis leaf extract against mitomycin C (MMC) using an in vitro cytokinesis-block micronucleus assay (CBMN) in the Chinese Hamster Ovarian K1 (CHO-K1) cell line. The phytochemical composition of C. monspeliensis extract was evaluated using an untargeted metabolomic approach by employing UPLC-PDA-ESI/MS. The automated in vitro CBMN assay was carried out using image analysis systems with a widefield fluorescence microscope and the ImageStreamX imaging flow cytometer. The phytochemical profile of C. monspeliensis extract showed, as the most abundant metabolites, punicalagin, myricetin, gallocathechin, and a labdane-type diterpene. C. monspeliensis, at the tested concentrations of 50, 100, and 200 μg/mL, did not induce significant micronuclei frequency, thus indicating the absence of a genotoxic potential. When testing the C. monspeliensis extract for antigenotoxicity in the presence of MMC, we observed a hormetic concentration-dependent effect, where low concentrations resulted in a significant protective effect against MMC-induced micronuclei frequency, and higher concentrations resulted in no effect. In conclusion, our findings demonstrate that C. monspeliensis extract is not genotoxic and, at low concentration, exhibits an antigenotoxic effect. In relation to this final point, C. monspeliensis may act as a potential chemo-preventive against genotoxic agents.PMID:39769467 | DOI:10.3390/ijms252413707

Int J Mol Sci. 2024 Dec 21;25(24):13678. doi: 10.3390/ijms252413678.ABSTRACTMatrix Assisted Laser Desorption/Ionisation-Mass Spectrometry Imaging (MALDI-MSI) is a well-established spatial omic technique which enables the untargeted mapping of various classes of biomolecules, including tryptic peptides, directly on tissue. This method relies on the use of matrices for the ionisation and volatilisation of analytes, and α-Cyano-4-hydroxycinnamic acid (CHCA) represents the most widespread matrix for tryptic peptides analysis. However, CHCA also presents certain limitations that foster the quest for novel matrix compounds. 6-aza-2-thiothymine (ATT), traditionally used in MALDI mass spectrometry (MS) for oligonucleotides, small molecules and oxidised phospholipids, has not been thoroughly investigated as a potential matrix for tryptic peptide analysis in MALDI-MS or MALDI-MSI. Therefore, this study addresses this gap by evaluating the capability of ATT to ionise tryptic peptides from Bovine Serum Albumin (BSA) and map in situ-digested peptides from formalin-fixed paraffin-embedded (FFPE) tissue sections in these respective applications. Comparative analysis with CHCA demonstrated the complementary strengths of these matrices for detecting tryptic peptides, establishing ATT as a feasible alternative to CHCA in the MALDI-MSI field and paving the way for future advancements in spatial proteomics.PMID:39769439 | DOI:10.3390/ijms252413678

Int J Mol Sci. 2024 Dec 20;25(24):13651. doi: 10.3390/ijms252413651.ABSTRACTIn the present work, we examined the effects of exogenous abscisic acid (ABA) under ultraviolet B (UV-B) exposure on gibberellin (GA) production, signaling, and antioxidant-related genes in Rhododendron chrysanthum Pall (R. chrysanthum). Using transcriptomics, acetylated proteomics, and widely targeted metabolomics, the effects of UV-B stress on R. chrysanthum and the regulatory effects of exogenous ABA on it were revealed from multiple perspectives. The findings revealed that R. chrysanthum's antioxidant enzyme genes were differentially expressed by UV-B radiation and were substantially enriched in the glutathione metabolic pathway. Exogenous ABA supplementation boosted plant resistance to UV-B damage and further enhanced the expression of antioxidant enzyme genes. Furthermore, under UV-B stress, glutathione reductase, glutathione peroxidase, and L-ascorbate peroxidase were found to be the primary antioxidant enzymes controlled by exogenous ABA. In addition, gibberellin content was altered due to UV-B and exogenous ABA treatments, with greater effects on GA3 and GA53. The acetylation proteomics study's outcomes disclosed that the three main oxidative enzymes' acetylation modifications were dramatically changed during UV-B exposure, which may have an impact on the antioxidant enzymes' functions and activities. The protective impact of exogenous ABA and gibberellin on R. chrysanthum's photosynthetic system was further established by measuring the parameters of chlorophyll fluorescence. This research offers a theoretical foundation for the development of breeding highly resistant plant varieties as well as fresh insights into how hormone levels and antioxidant systems are regulated by plants in response to UV-B damage.PMID:39769416 | DOI:10.3390/ijms252413651

Int J Mol Sci. 2024 Dec 20;25(24):13638. doi: 10.3390/ijms252413638.ABSTRACTBioactive lipids have a multifaceted role in health and disease and are recognized to play an important part in gut immunity and disease conditions such as inflammatory bowel disease and colon cancer. Advancements in lipidomics, enabled by mass spectrometry and chromatographic techniques, have enhanced our understanding of lipid diversity and functionality. Bioactive lipids, including short-chain fatty acids, saturated fatty acids, omega-3 fatty acids, and sphingolipids, exhibit diverse effects on inflammation and immune regulation. Short-chain fatty acids like butyrate demonstrate anti-inflammatory properties, enhancing regulatory T cell function, gut barrier integrity, and epigenetic regulation, making them promising therapeutic targets for inflammatory bowel disease and colon cancer. Conversely, saturated fatty acids promote inflammation by disrupting gut homeostasis, triggering oxidative stress, and impairing immune regulation. Omega-3 lipids counteract these effects, reducing inflammation and supporting immune balance. Sphingolipids exhibit complex roles, modulating immune cell trafficking and inflammation. They can exert protective effects or exacerbate colitis depending on their source and context. Additionally, eicosanoids can also prevent pathology through prostaglandin defense against damage to epithelial barriers. This review underscores the importance of dietary lipids in shaping gut health and immunity and also highlights the potential use of lipids as therapeutic strategies for managing inflammatory conditions and cancer.PMID:39769399 | DOI:10.3390/ijms252413638

Int J Mol Sci. 2024 Dec 19;25(24):13611. doi: 10.3390/ijms252413611.ABSTRACTSince their discovery, corticosteroids have been widely used in the treatment of several diseases, including asthma, acute lymphoblastic leukemia, chronic obstructive pulmonary disease, and many other conditions. However, it has been noted that some patients develop undesired side effects or even fail to respond to treatment. The reasons behind this have not yet been fully elucidated. This poses a significant challenge to effective treatment that needs to be addressed urgently. Recent genomic, transcriptomic, and other omics-based approximations have begun to shed light into the genetic factors influencing interindividual variability in corticosteroid efficacy and its side effects. Here, we comprehensively revise the recent literature on corticosteroid response in various critical and chronic diseases, with a focus on omics approaches, and highlight existing knowledge gaps where further investigation is urgently needed.PMID:39769372 | DOI:10.3390/ijms252413611

Int J Mol Sci. 2024 Dec 19;25(24):13609. doi: 10.3390/ijms252413609.ABSTRACTPredicting mortality in intensive care units (ICUs) is essential for timely interventions and efficient resource use, especially during pandemics like COVID-19, where high mortality persisted even after the state of emergency ended. Current mortality prediction methods remain limited, especially for critically ill ICU patients, due to their dynamic metabolic changes and heterogeneous pathophysiological processes. This study evaluated how the serum metabolomic fingerprint, acquired through Fourier-Transform Infrared (FTIR) spectroscopy, could support mortality prediction models in COVID-19 ICU patients. A preliminary univariate analysis of serum FTIR spectra revealed significant spectral differences between 21 discharged and 23 deceased patients; however, the most significant spectral bands did not yield high-performing predictive models. By applying a Fast-Correlation-Based Filter (FCBF) for feature selection of the spectra, a set of spectral bands spanning a broader range of molecular functional groups was identified, which enabled Naïve Bayes models with AUCs of 0.79, 0.97, and 0.98 for the first 48 h of ICU admission, seven days prior, and the day of the outcome, respectively, which are, in turn, defined as either death or discharge from the ICU. These findings suggest FTIR spectroscopy as a rapid, economical, and minimally invasive diagnostic tool, but further validation is needed in larger, more diverse cohorts.PMID:39769370 | DOI:10.3390/ijms252413609

Int J Mol Sci. 2024 Dec 18;25(24):13559. doi: 10.3390/ijms252413559.ABSTRACTSalt stress poses a significant challenge to plant growth and restricts agricultural development. To delve into the intricate mechanisms involved in soybean's response to salt stress and find targets to improve the salt resistance of soybean, this study integrated transcriptomic, proteomic, and metabolomic analyses to explore the regulatory networks involved in soybean salt tolerance. Transcriptomic analysis revealed significant changes in transcription factors, hormone-related groups, and calcium ion signaling. Notably, the biosynthetic pathways of cutin, suberine, and wax biosynthesis play an important role in this process. Proteomic results indicated salt-induced DNA methylation and the enrichment of phosphopyruvate hydrase post-salt stress, as well as its interaction with enzymes from various metabolic pathways. Metabolomic data unveiled the synthesis of various metabolites, including lipids and flavonoids, in soybean following salt stress. Furthermore, the integrated multiomics results highlighted the activation of multiple metabolic pathways in soybean in response to salt stress, with six pathways standing out prominently: stilbenoid, diarylheptanoid, and gingerol biosynthesis; carotenoid biosynthesis; carbon fixation in photosynthetic organisms; alanine, aspartate, and glutamate metabolism; thiamine metabolism; and pyruvate metabolism. These findings not only offer valuable insights into leveraging multiomics profiling techniques for uncovering salt tolerance mechanisms but also identify candidate genes for soybean improvement.PMID:39769326 | DOI:10.3390/ijms252413559

Int J Mol Sci. 2024 Dec 17;25(24):13502. doi: 10.3390/ijms252413502.ABSTRACTOrgan shortage remains a significant challenge in transplantology, prompting efforts to maximize the use of available organs and expand the donor pool, including through extended criteria donors (ECDs). However, ECD kidney recipients often face poorer outcomes, including a higher incidence of delayed graft function (DGF), which is linked to worse graft performance, reduced long-term survival, and an increased need for interventions like dialysis. This underscores the urgent need for strategies to improve early DGF risk assessment and optimize post-transplant management for high-risk patients. This study conducted multi-time point metabolomic and lipidomic analyses of donor kidney tissue and recipient plasma to identify compounds predicting DGF risk and assess the translational potential of solid-phase microextraction (SPME) for graft evaluation and early complication detection. The SPME-based chemical biopsy enabled a direct kidney analysis, while thin-film microextraction facilitated high-throughput plasma preparation. Following high-performance liquid chromatography coupled with a mass spectrometry analysis, the random forest algorithm was applied to identify compounds with predictive potential for assessing DGF risk before transplantation. Additionally, a comparison of metabolomic and lipidomic profiles of recipient plasma during the early post-operative days identified metabolites that distinguish between DGF and non-DGF patients. The selected compounds primarily included amino acids and their derivatives, nucleotides, organic acids, peptides, and lipids, particularly phospholipids and triacylglycerols. In conclusion, this study highlights the significant translational potential of chemical biopsies and plasma metabolite analyses for risk assessments and the non-invasive monitoring of DGF. The identified metabolites provide a foundation for developing a comprehensive DGF assessment and monitoring method, with potential integration into routine clinical practice.PMID:39769265 | DOI:10.3390/ijms252413502

Int J Mol Sci. 2024 Dec 16;25(24):13483. doi: 10.3390/ijms252413483.ABSTRACTMulberry (Morus spp.) is an economically significant plant in the production of silk through feeding leaves to silkworm larvae. Traditional silkworm rearing is heavily labor-intensive, particularly in leaf collection, which leads to low efficiency and impedes the development of sericulture. Here, to assess the feasibility and effectiveness of a novel low-pruning mulberry cultivar, ZJ1, in the silkworm rearing industry, a comprehensive investigation integrating physiological, proteomic, and metabolomic analyses was conducted in comparison with the traditionally high-pruning cultivar, N14. The low-pruning mulberry variety ZJ1 exhibited a notable increase in annual leaf yield of 43.94%, along with a significant enrichment of serine and isoleucine contents, in contrast to those of the high-pruning variety N14. Through iTRAQ proteomics and LC-MS/MS metabolomics analyses, a total of 561 reduced and 803 increased differentially expressed proteins (DEPs), as well as 332 differential expressed metabolites (DEMs) in positive ions and 192 DEMs in negative ions, were identified in the ZJ1 group relative to the N14 group, respectively. The observed features in amino acid profiles and the enrichment of the sucrose-related metabolic pathway provided interesting insights for future endeavors in mulberry variety improvement and the optimization of silkworm diet formulations. Collectively, the low-pruning cultivar ZJ1, characterized by its rapid growth, high leaf productivity, and suitability for mechanized operations, is expected to be an efficient substitute in improving the future sericultural industry, especially in urbanized and industrialized regions.PMID:39769246 | DOI:10.3390/ijms252413483

Int J Mol Sci. 2024 Dec 16;25(24):13465. doi: 10.3390/ijms252413465.ABSTRACTThere is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses. This study profiled the faecal (n = 221) and plasma (n = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies. Discriminant analysis separated patients with the 'all constipation' group (FC and IBS-C) from the healthy control group and 'all diarrhoea' group (FD and IBS-D) from the healthy control group in both sample types. In plasma, almost all multimodal metabolite analyses separated the 'all constipation' or 'all diarrhoea' group from the healthy controls, and the IBS-C or IBS-D group from the healthy control group. Plasma phospholipids and metabolites linked to several amino acid and nucleoside pathways differed (p < 0.05) between healthy controls and IBS-C. In contrast, metabolites involved in bile acid and amino acid metabolism were the key differentiating classes in the plasma of subjects with IBS-D from healthy controls. Faecal lipids, particularly ceramides, diglycerides, and triglycerides, varied (p < 0.05) between healthy controls and the 'all constipation' group and between healthy controls and 'all diarrhoea' group. The faecal and plasma metabolomes showed perturbations between constipation, diarrhoea and healthy control groups that may reflect processes and mechanisms linked to FGIDs.PMID:39769229 | DOI:10.3390/ijms252413465

Int J Mol Sci. 2024 Dec 13;25(24):13386. doi: 10.3390/ijms252413386.ABSTRACTThe gut-liver axis and its interactions are essential for host physiology. Thus, we examined the jejunal microbiota, fermentation parameters, digestive enzymes, morphology, and liver metabolic profiles in different growth development lambs to investigate the liver-gut axis's role in their development. One hundred male Hu lambs of similar birth weight and age were raised under the same conditions until they reached 180 days of age. Subsequently, the eight lambs with the highest (HADG) and lowest (LADG) average daily weight gains were slaughtered for index assessment. The study indicates that the body weight, carcass weight, propanoic acid, butyric acid, propanoic acid ratio, butyric acid ratio, and digestive enzymes (beta-glucosidase, microcrystalline cellulase, xylanase, and carboxymethyl cellulase) were significantly higher in HDAG lambs than in LADG lambs (p < 0.05). Additionally, there were no significant differences in the jejunal microbiota's structure and function among lambs at different growth development stages (p > 0.05). Overall, our analysis revealed that HADG lambs compared to LADG lambs exhibited an up-regulation of metabolites (such as spermine, cholic acid, succinic acid, betaine, etc.) that were positively correlated with the butyric acid ratio, propanoic acid ratio, propanoic acid, xylanase, microcrystalline cellulase, beta-glucosidase, amylase, carboxymethyl cellulase, carcass weight, and body weight, while these metabolites were negatively correlated with the kidney, acetic acid, acetic acid/ propanoic acid, and acetic acid ratio. Furthermore, there was a significant correlation between liver metabolism and jejunal microbiota. This study revealed significant differences in hepatic metabolites and jejunal fermentation among lambs at different growth stages, which may inform targeted regulation strategies to enhance lamb productivity.PMID:39769152 | DOI:10.3390/ijms252413386

Int J Mol Sci. 2024 Dec 13;25(24):13372. doi: 10.3390/ijms252413372.ABSTRACTCold stress during overwintering is considered a bottleneck problem limiting the development of the red tilapia (Oreochromis spp.) industry, and the regulation mechanism is currently not well understood. In this study, the fish (initial weight: 72.71 ± 1.32 g) were divided into the cold stress group (cold) and the control (normal) group. In the control group, the water temperature was maintained at 20 °C, which is basically consistent with the overwintering water temperature in greenhouses of local areas. In the cold group, the water temperature decreased from 20 °C to 8 °C by 2 °C per day during the experiment. At the end of the experiment, the levels of fish serum urea nitrogen, glucose, norepinephrine, alkaline phosphatase, total bilirubin, and total cholesterol in the cold group changed significantly compared with that in the control group (P < 0.05). Then transcriptome sequencing and LC-MS metabolome of brain tissue were further employed to obtain the mRNA and metabolite datasets. We found that the FoxO signaling pathway and ABC transporters played an important role by transcriptome-metabolome association analysis. In the FoxO signaling pathway, the differentially expressed genes were related to cell cycle regulation, apoptosis and immune-regulation, and oxidative stress resistance and DNA repair. In the ABC transporters pathway, the ATP-binding cassette (ABC) subfamily abca, abcb, and abcc gene expression levels, and the deoxycytidine, L-lysine, L-glutamic acid, L-threonine, ornithine, and uridine metabolite contents changed. Our results suggested that the cold stress may promote apoptosis through regulation of the FoxO signaling pathway. The ABC transporters may respond to cold stress by regulating amino acid metabolism. The results provided a comprehensive understanding of fish cold stress during overwintering, which will facilitate the breeding of new cold-resistant varieties of red tilapia in the future.PMID:39769137 | DOI:10.3390/ijms252413372

Int J Mol Sci. 2024 Dec 12;25(24):13325. doi: 10.3390/ijms252413325.ABSTRACTThe color variation of the leaves in autumn is a significant ornamental feature of Acer truncatum Bunge, especially when the leaves gradually become redder. Many studies focused on leaf color changes; however, less research has been conducted on the mechanism by which A. truncatum's autumn leaves turn red. Red, middle and green leaves of Acer truncatum were used as the study materials to evaluate their flavonoid-related metabolites and infer gene and metabolite expression patterns in conjunction with transcriptome expression. For a start, phenotypic and leaf color parameters analyses showed that red leaves had the highest color redness and greenness (a*). In addition, a total of 23 flavonoid-related metabolites were identified through the metabolome, including five anthocyanins. Of them, cyanidin 3-O-β-D-sambubioside, cyanidin 3-O rutinoside, pelargonidin 3-O-3″,6″-O-dimalonylglucoside, delphinidin 3,7-di-O-β-D-glucoside and 3-O-β-D-sambubioside would help the leaves turn red in A. truncatum. Similarly, combined transcriptomics and metabolomics analyses showed that most genes in the flavonoid and anthocyanin biosynthetic pathways were differentially expressed in both types of leaves. Chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and anthocyanin synthase (ANS) could affect flavonoid synthesis during leaf color change. This study could provide data for the genetic improvement of maple plants by exploring valuable metabolites and genes in flavonoid synthesis, and enhance the understanding of different developmental stages.PMID:39769090 | DOI:10.3390/ijms252413325