PubMed

Metabolomics. 2024 Nov 13;20(6):131. doi: 10.1007/s11306-024-02196-x.ABSTRACTINTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory dermatosis. However, the exact molecular mechanism underlying the development of AD remain largely unclear.OBJECTIVE: To investigate comprehensive metabolomic alterations in serum and skin tissue between 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice and healthy controls, aiming to identify the potential disease biomarkers and explore the molecular mechanisms of AD.METHODS: In this study, Untargeted metabolomics analysis was used to investigate both skin and serum metabolic abnormalities of 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice. Then, the metabolic differences among the groups were determined through the application of multivariate analysis. Additionally, the selection of predictive biomarkers was accomplished using the receiver operating characteristic (ROC) module.RESULTS: Our findings showed that levels of 220 metabolites in the skin and 94 metabolites in the serum were different in AD-like mice that were treated with DNFB compared to control mice. Uracil, N-Acetyl-L-methionine, deoxyadenosine monophoosphate, 2-acetyl-l-alkyl-sn-glycero-3-phosphcholine, and prostaglandin D2 are considered potential biomarkers of AD as obtained by integrating skin and serum differential metabolite results. Metabolomic data analysis showed that the metabolic pathways in which skin and serum are involved together include histidine metabolism, pyrimidine metabolism, alanine, aspartate, and glutamate metabolism.CONCLUSION: Our research explained the possible molecular mechanism of AD at the metabolite level and provided potential targets for the development of clinical drugs for AD.PMID:39537935 | DOI:10.1007/s11306-024-02196-x

Sci Rep. 2024 Nov 13;14(1):27891. doi: 10.1038/s41598-024-78721-8.ABSTRACTThis study presents a comprehensive multimodal analytical study of an Egyptian ritual Bes-vase, of the 2nd century BCE employing cutting-edge proteomics, metabolomics, genetics techniques, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues of its content. We successfully identified the presence of various functional, bioactive, psychotropic, and medicinal substances, shedding light on the diverse components of a liquid concoction used for ritual practices in Ptolemaic Egypt. Using LC-MS/MS with a new methodological approach, we identified key proteins and metabolites, enabling the identification of botanical sources, confirmed by genetic sequences. Our analyses revealed traces of Peganum harmala, Nimphaea nouchali var. caerulea, and a plant of the Cleome genus, all of which are traditionally proven to have psychotropic and medicinal properties. Additionally, the identification of human fluids suggests their direct involvement in these rituals. Furthermore, metabolomics and SR µ-FTIR analyses also revealed the presence of fermented fruit-based liquid and other ingredients such as honey or royal jelly. The identification of specific chemical compounds, such as alkaloids and flavonoids, provides insight into the psychoactive and therapeutic uses of these in ancient ritual practices. This multidisciplinary study highlights the complexity of ancient cultures and their interactions with psychoactive, medicinal, and bioactive substances. These findings contribute to our understanding of ancient belief systems, cultural practices, and the utilization of natural resources, ultimately enhancing our knowledge of past societies and their connection to the natural world.PMID:39537764 | DOI:10.1038/s41598-024-78721-8

Nat Commun. 2024 Nov 13;15(1):9791. doi: 10.1038/s41467-024-54072-w.ABSTRACTDrug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in the katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities in isoniazid-resistant katG mutants, providing potential pathway targets to combat isoniazid resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used to generate a genome-wide map of cellular vulnerabilities in an isoniazid-resistant katG mutant strain of M. tuberculosis. Here, we show that metabolic and transcriptional remodelling compensates for the loss of KatG but in doing so generates vulnerabilities in respiration, ribosome biogenesis, and nucleotide and amino acid metabolism. Importantly, these vulnerabilities are more sensitive to inhibition in an isoniazid-resistant katG mutant and translated to clinical isolates. This work highlights how changes in the physiology of drug-resistant strains generates druggable vulnerabilities that can be exploited to improve clinical outcomes.PMID:39537607 | DOI:10.1038/s41467-024-54072-w

Sci Total Environ. 2024 Nov 11:176313. doi: 10.1016/j.scitotenv.2024.176313. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants known to pose significant risks to human and wildlife health. Freshwater turtles (Emydura macquarii macquarii), as long-lived species inhabiting aquatic ecosystems, are particularly vulnerable to PFAS bioaccumulation. This study investigated the multifaceted impact of PFAS contamination on these turtles, focusing on metabolic disruptions, reproductive success, hatchling health, and population impacts. Comprehensive analyses, including proteomics, lipidomics, metabolomics, and histopathology, were conducted on turtles from PFAS-impacted, control, and reference sites. The findings reveal significant metabolic disruptions in PFAS-exposed turtles, with alterations in amino acid and lipid metabolism, energy production, and oxidative stress responses. Proteomic analysis identified several health biomarkers indicative of early disease progression. Despite high levels of PFAS in tissues and organs, no gross or histopathological phenotypical abnormalities were directly linked to PFAS exposure. Gravid females from contaminated sites exhibited altered egg composition, particularly in magnesium to calcium ratios, potentially affecting eggshell strength. Biochemical profiles of egg albumin and yolk indicated significant differences in metabolites and lipids between contaminated and reference sites, suggesting potential impacts on embryo development. Hatchling deformities were notably higher and with increased frequency in terms of the types of deformities at the PFAS-impacted sites, with common defects including abnormal intergular scale shapes and marginal scale counts. Furthermore, the demographic profile of the turtle population showed a lack of juvenile turtles at contaminated sites, indicating reduced recruitment and potential long-term population declines. This indicates a field-based demonstration of an Adverse Outcome Pathway, from elevated levels of PFAS in the turtles, to biochemical perturbations within the animals, and finally population effects. These findings underscore the urgent need for regulatory measures to address PFAS contamination and its detrimental effects on wildlife.PMID:39537477 | DOI:10.1016/j.scitotenv.2024.176313

J Proteome Res. 2024 Nov 13. doi: 10.1021/acs.jproteome.4c00538. Online ahead of print.ABSTRACTAntibodies have a key role in the immune system, making their characterization essential to biomedical, biopharmaceutical, and clinical research questions. Antibody effector functions are mainly controlled by quantity, subclass, and Fc glycosylation. We describe an integrated method to measure these three critical dimensions simultaneously. The subclass-specific immunoglobulin G (IgG) Fc glycosylation analysis combines immunosorbance with glycopeptide-centered LC-MS detection. For integrated IgG1-specific quantitation, a commercial, stable isotope labeled IgG1 protein standard was spiked into the immunosorbent eluates. Robust quantitation was achieved, relying on a combination of a proteotypic peptide and the most abundant glycopeptides, generated through proteolytic cleavage from a mixture of natural IgG1 and the recombinant IgG1 standard. Method performance was demonstrated in a large coronavirus vaccination cohort at a throughput of 100 samples/day. LC-MS-derived, anti-SARS-CoV-2 spike protein IgG1 concentrations ranged from 100 to 10000 ng/mL and correlated well with a clinically relevant immunoassay. Technical variation was 200 times lower than biological variation; intermediate precision was 44%. In conclusion, we present a method capable of robustly and simultaneously assessing quantity, subclass, and Fc glycosylation of antigen-specific IgG in large clinical studies. This method will facilitate a broader understanding of immune responses, especially the important interplay among the three dimensions.PMID:39537390 | DOI:10.1021/acs.jproteome.4c00538

Endocr J. 2024 Nov 14. doi: 10.1507/endocrj.EJ24-0377. Online ahead of print.ABSTRACTObesity resulting from long-term sedentary a significant threat to human health. This study explores the effects of exercise snack intervention on body composition and plasma metabolomics in sedentary obese adults. Participants in the snack group were subjected to 4 days of sprint exercises by stair-climbing per week for 12 weeks. Systemic and regional fat mass, epicardial adipose tissue (EAT), abdominal visceral (AVFA) and subcutaneous (ASFA) fat area and plasma metabolomics data were measured before and after intervention. A higher improvement of EAT, AVFA and ASFA in the snack group compared to that in the control group, with a significant interaction effect (p < 0.05). The key differential metabolites between the two groups include isoleucine, glycine and serine. The proposed exercise snack effectively reduced the amount of AVFA and EAT. The change in body composition may be associated with the altered pathways of isoleucine, glycine, and serine metabolism.PMID:39537176 | DOI:10.1507/endocrj.EJ24-0377

Fish Shellfish Immunol. 2024 Nov 11:110016. doi: 10.1016/j.fsi.2024.110016. Online ahead of print.ABSTRACTThis study explores the impact of SYNLAC Prime probiotics on the growth performance, health status, and metabolic profile of white shrimp, Penaeus vannamei. Shrimp fed with the experimental diets, including the control diet without probiotic supplementation, and the diets supplemented with SYNLAC Prime probiotics at concentrations of 105 CFU (g diet)-1 (P5) and 106 CFU (g diet)-1 (P6) for 56 days. Results indicated a significant enhancement in growth performance in probiotic-treated shrimp relative to the control group, attributed to structural improvements in the digestive tract, particularly the increased abundances of B cells in the hepatopancreas. The administration of dietary probiotics markedly reduced the severity of Enterocytozoon hepatopenaei (EHP) infection and decreased cumulative mortalities following Vibrio alginolyticus challenge. Shrimp in the P6 group exhibited significant elevations in phenoloxidase activity, respiratory burst, lysozyme activity and phagocytic activity compared to control group. Furthermore, there was an upregulation of several immune-related genes in hepatopancreas, including serine protease (SP), prophenoloxidase (proPO) I, proPO II, and penaeidin 3a. Additionally, the expression of β-1, 3-glucan binding protein and SP mRNA was significantly increased in hemocytes. Untargeted metabolomics analysis using LC-MS/MS revealed significant changes in the hepatopancreas metabolic profile, highlighting alterations in energy metabolisms pathways, such as citrate cycle and nicotinate and nicotinamide metabolism, as well as amino acid metabolisms pathways including arginine and proline metabolism, taurine and hypotaurine metabolism, and histidine metabolism. These findings underscore the potential of SYNLAC Prime probiotics in enhancing shrimp growth, immune function, and metabolic pathways, offering valuable insights for advancing health management strategies in shrimp aquaculture.PMID:39537121 | DOI:10.1016/j.fsi.2024.110016

Life Sci. 2024 Nov 11:123231. doi: 10.1016/j.lfs.2024.123231. Online ahead of print.ABSTRACTMinor ginsenosides have demonstrated notable anti-fatigue capabilities. The aim of this study was to investigate the anti-fatigue mechanisms of total minor ginsenosides (TMGs) derived from a process involving probiotic fermentation and high-pressure steam treatment. The fatigue model was established in BALB/c male mice using weight-bearing swimming and TMGs were administered by orally at a dosage of 200 mg/kg for four weeks. The anti-fatigue mechanisms of TMGs were explored by assessing liver oxidative stress, skeletal muscle inflammation markers, as well as their impact on gut microbiota and serum metabolism. The results indicated that TMGs could significantly increase the levels of SOD, CAT, ATP and Na+-K+-ATPase and enhance the antioxidant capacity by modulating the PGC-1α/KEAP1/NRF2/HO-1 pathway. Meanwhile, TMGs reducing the levels of inflammatory factors TNF-α, IL-1β and IL-6 and inhibited inflammation by modulating the AMPK/TORC2/CREB/PGC-1α pathway. TMGs also regulated the gut microbiota, increasing the abundance of probiotic bacteria and the content of short-chain fatty acids (SCFAs) in the cecum. Serum metabolomics analyses have shown that TMGs can significantly affect the serum metabolic profile of fatigue model mice, regulating metabolic markers through affecting anti-fatigue-related metabolic pathways. In conclusion, TMGs exerted significant anti-fatigue effects through antioxidant and anti-inflammatory effects, and alleviate fatigue by regulating gut microbiota and serum metabolism.PMID:39537101 | DOI:10.1016/j.lfs.2024.123231

Life Sci. 2024 Nov 11:123238. doi: 10.1016/j.lfs.2024.123238. Online ahead of print.ABSTRACTMetabolomics is an emerging field involving the systematic identification and quantification of numerous metabolites in biological samples. Precision medicine applies multiomics systems biology to individual patients for reliable diagnostic classification, disease monitoring, and treatment. Multiomics systems biology encompasses genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Therefore, metabolomic techniques could be highly valuable for future clinical decision-making. This review provides a technical overview of two commonly used techniques for metabolomics measurements: mass spectrometry (MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy. We also discuss recent clinical advances in these techniques. Individuals with inflammatory bowel disease (IBD) exhibit significant variability in prognosis and response to treatment. Since both genetic predisposition and environmental factors contribute to this condition, targeting the metabolome may provide key insights for distinguishing and profiling patients with different clinical needs. Additionally, the considerable overlap in the clinical presentation of various disease subtypes emphasizes the need for enhanced diagnostic methods to improve patient care.PMID:39537099 | DOI:10.1016/j.lfs.2024.123238

J Nutr. 2024 Nov 11:S0022-3166(24)01171-4. doi: 10.1016/j.tjnut.2024.11.004. Online ahead of print.ABSTRACTBACKGROUND: Epidemiological evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. We characterized objective 24-hr urinary metabolites and a derived metabolite score associated with fruit and vegetable intake and assessed their associations with BP and body mass index (BMI), with validation across cohorts.METHODS: We used untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) of two timed repeated 24-hr urine collections from free-living participants from the US (n=2,032) and the UK (n=449) of the cross-sectional International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). We evaluated correlations between fruit and vegetable intake assessed by 24-hr dietary recalls with 7,100 1H NMR features, adjusted for confounders and multiple testing. We related identified metabolites and a metabolite score with BP and BMI using extensively adjusted multiple linear regression models.RESULTS: We characterized eleven 1H NMR-derived 24-hr urinary metabolites related to fruit and vegetable intake, reproducible across multiple 24-hr urine collections of both cohorts. Proline betaine, citrate, N-methylproline, scyllo-inositol, 2-hydroxy-2-(4-methyl cyclohex-3-en-1-yl) propoxyglucuronide, and proline were associated with fruit intake, specifically with Rutaceae intake, while S-methyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide metabolite were associated with Brassicacea intake. The metabolite score, explaining 39.8% of fruit and vegetable intake, was inversely associated with systolic BP (-1.65 mmHg; 95% confidence interval (CI): -2.68,-0.62, P<0.002) and BMI (-1.21 kg/m2; 95% CI: -1.62,-0.78, P<0.0001). These associations were to a large extent explained by urinary citrate excretion.CONCLUSION: We identified 1H NMR-derived urinary metabolites associated with fruit and vegetable consumption, consistent and reproducible between urine collections and across populations. A higher fruit and vegetable-related metabolite score showed associations with lower systolic BP and BMI, mainly mediated by citrate, but would need confirmation in further studies.STUDY REGISTRATION: This study was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT00005271?term=NCT00005271&rank=1) as NCT00005271.PMID:39536968 | DOI:10.1016/j.tjnut.2024.11.004

Arch Biochem Biophys. 2024 Nov 11:110202. doi: 10.1016/j.abb.2024.110202. Online ahead of print.ABSTRACTMagnesium (Mg2+), the second most abundant intracellular cation, plays a crucial role in cellular functions. In this study, we investigate the interaction between Mg2+ and coenzyme A (CoA), a thiol-containing cofactor central to cellular metabolism also involved in protein modifications. Isothermal titration calorimetry revealed a 1:1 binding stoichiometry between Mg2+ and free CoA under biologically relevant conditions. Association constants of (537 ± 20) M-1 and (312 ± 7) M-1 were determined at 25°C and pH 7.2 and 7.8, respectively, suggesting that a significant fraction of CoA is likely bound to Mg2+ both in the cytosol and in the mitochondrial matrix. Additionally, the process is entropically-driven, and our results support that the origin of the entropy gain is solvent-related. On the other hand, the combination of 1- and 2-dimensional nuclear magnetic resonance spectroscopy with molecular dynamics simulations and unsupervised learning demonstrate a direct coordination between Mg2+ and the phosphate groups of the 4-phosphopantothenate unit and bound to position 5' of the adenosine ring. Interestingly, the phosphate in position 3' only indirectly contributes to Mg2+ coordination. Finally, we discuss how the binding of Mg2+ to CoA perturbates the chemical environment of different CoA atoms, regardless of their apparent proximity to the coordination site, through the modulation of the CoA conformational landscape. This insight holds implications for understanding the impact on both CoA and Mg2+ functions in physiological and pathological processes.PMID:39536960 | DOI:10.1016/j.abb.2024.110202

Clin Chim Acta. 2024 Nov 11:120038. doi: 10.1016/j.cca.2024.120038. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide, affecting one-fourth of the world's population. With more than half of the world's population, the Asia-Pacific region contributed 62.6 % of liver-related fatal incidents in 2015. Currently, liver imaging techniques such as computed tomography (CT), nuclear magnetic resonance (NMR) spectroscopy, and ultrasound are non-invasive imaging methods to diagnose the disease. A liver biopsy is the gold standard test for establishing the definite diagnosis of non-alcoholic steatohepatitis (NASH). However, there are still significant problems with sample variability and the procedure's invasiveness. Numerous studies have indicated various non-invasive biomarkers for both fibrosis and steatosis to counter the invasiveness of diagnostic procedures. Metabolomics could be a promising method for detecting early liver diseases, investigating pathophysiology, and developing drugs. Metabolomics, when utilized with other omics technologies, can result in a deeper understanding of biological systems. Metabolomics has emerged as a prominent research topic, offering extensive opportunities to investigate biomarkers for liver diseases that are both sensitive and specific. In this review, we have described the recent studies involving the use of a metabolomics approach in the diagnosis of liver diseases, which would be beneficial for the early detection and treatment of liver diseases.PMID:39536895 | DOI:10.1016/j.cca.2024.120038

Microb Pathog. 2024 Nov 11:107030. doi: 10.1016/j.micpath.2024.107030. Online ahead of print.ABSTRACTAcute pancreatitis (AP) is influenced by interactions between gut microbiota and metabolic products, though the mechanisms remain unclear. This study investigates variations in gut microbiota and metabolites between severe (SAP) and mild acute pancreatitis (MAP) patients to assess their impact on disease progression. Using a cross-sectional cohort design, gut microbiota and metabolite profiles were compared in SAP and MAP patients over two weeks post-diagnosis. 16S rRNA gene sequencing and metabolomic analyses, including KEGG pathway assessments and Spearman correlation, were employed, along with Mendelian Randomization (MR) to assess the influence of specific microbiota on AP. Results showed that SAP patients had significantly reduced gut microbiota diversity, which further declined in the second week. This was marked by increases in pathogenic bacteria like Stenotrophomonas and Enterobacter and decreases in beneficial bacteria such as Blautia. Key changes included a rise in Proteobacteria and a decline in Ruminococcaceae, Enterococcus, and Faecalicatena. Metabolic shifts included lipid metabolite upregulation and antioxidant downregulation. Correlation analysis linked Stenotrophomonas to short-chain fatty acid and amino acid metabolism, highlighting its role in disease progression. MR analysis confirmed negative causal relationships between Enterococcus B, Faecalicatena torques, and AP, suggesting protective effects. Variations in Blautia species indicated differing influences on AP. This study underscores the critical role of gut microbiota and metabolites in AP progression and suggests the need for further research to confirm these findings and explore targeted therapeutic interventions.PMID:39536839 | DOI:10.1016/j.micpath.2024.107030

Mol Metab. 2024 Nov 11:102064. doi: 10.1016/j.molmet.2024.102064. Online ahead of print.ABSTRACTOBJECTIVE: The study aimed to investigate the effects of glucagon on metabolic pathways in mouse models of obesity, fatty liver disease, and type 2 diabetes (T2D) to determine the extent and variability of hepatic glucagon resistance in these conditions.METHODS: We investigated glucagon's effects in mouse models of fatty liver disease, obesity, and type 2 diabetes (T2D), including male BKS-db/db, high-fat diet-fed, and western diet-fed C57Bl/6 mice. Glucagon tolerance tests were performed using the selective glucagon receptor agonist acyl-glucagon (IUB288). Blood glucose, serum and liver metabolites include lipids and amino acids were measured. Additionally, liver protein expression related to glucagon signalling and a comprehensive liver metabolomics were performed.RESULTS: Western diet-fed mice displayed impaired glucagon response, with reduced blood glucose and PKA activation. In contrast, high-fat diet-fed and db/db mice maintained normal glucagon sensitivity, showing significant elevations in blood glucose and phospho-PKA motif protein expression. Acyl-glucagon treatment also lowered liver alanine and histidine levels in high-fat diet-fed mice, but not in western diet-fed mice. Additionally, some amino acids, such as methionine, were increased by acyl-glucagon only in chow diet control mice. Despite normal glucagon sensitivity in PKA signalling, db/db mice had a distinct metabolomic response, with acyl-glucagon significantly altering 90 metabolites in db/+ mice but only 42 in db/db mice, and classic glucagon-regulated metabolites, such as cyclic adenosine monophosphate (cAMP), being less responsive in db/db mice.CONCLUSIONS: The study reveals that hepatic glucagon resistance in obesity and T2D is complex and not uniform across metabolic pathways, underscoring the complexity of glucagon action in these conditions.PMID:39536823 | DOI:10.1016/j.molmet.2024.102064

Cell. 2024 Nov 7:S0092-8674(24)01214-5. doi: 10.1016/j.cell.2024.10.032. Online ahead of print.ABSTRACTβ-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit increased food intake and body weight following exogenous ketone ester supplementation or a ketogenic diet. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, enzymatic amino acid BHB-ylation defines a ketone shunt pathway and bioactive ketone metabolites linked to energy balance.PMID:39536746 | DOI:10.1016/j.cell.2024.10.032

Med Princ Pract. 2024 Nov 13:1-21. doi: 10.1159/000542557. Online ahead of print.ABSTRACTAging is an inevitable life process which is accelerated by lifestyle and environmental factors. It is an irreversible accretion of molecular and cellular damage associated with changes in the body composition and deterioration in physiological functions. Each cell (other than stem cells), reaches the limit of its ability to replicate, known as cellular or replicative senescence and consequently, the organs lose their physiological functions resulting in overall impairment. Other factors that promote aging include smoking, alcohol, UV rays, sleep habits, food, stress, sedentary life style and genetic abnormalities. These stress factors, can alter our endogenous clock (the circadian rhythm) and the microbial commensals. As a result of effect of these stressors, the microorganisms that generally support human physiological processes become baleful. The disturbance of natural physiology instigates many age-related pathologies, such as cardiovascular diseases, chronic obstructive pulmonary disorder, cerebrovascular diseases, opportunistic infections, high blood pressure, cancer, diabetes, kidney diseases, dementia, and Alzheimer's disease. The present review covers the three most essential processes of the circadian clock; the circadian gene mechanism and regulation, the mitotic clock (which plays a vital role in the telomere's attrition) and gut microbiota and their metabolome that drive aging and lead to age-related pathologies. In conclusion, maintaining a synchronized circadian rhythm, a healthy gut microbiome and telomere integrity is essential for mitigating the effects of aging and promoting longevity. The interplay among these factors underscores the importance of lifestyle choices in enhancing overall health and lifespan.PMID:39536739 | DOI:10.1159/000542557

Ecotoxicol Environ Saf. 2024 Nov 12;287:117335. doi: 10.1016/j.ecoenv.2024.117335. Online ahead of print.ABSTRACTPesticide residues, resulting from agricultural practices, pose significant health and environmental risks. This review synthesizes the current understanding of pesticide impacts on the immune system, highlighting their role in chronic diseases such as asthma, diabetes, Parkinson's disease (PD) and cancer. We emphasize the significant role of omics technologies in the study of pesticide toxicity mechanisms. The integration of genomics, proteomics, metabolomics, and epigenomics offers a multidimensional strategy for a comprehensive assessment of pesticide effects, facilitating personalized risk management and policy formulation. We advocate for stringent regulatory policies, public education, and global cooperation to enhance food safety and environmental sustainability. By adopting a unified approach, we aim to mitigate the risks of pesticide residues, ensuring human health and ecological balance are preserved.PMID:39536570 | DOI:10.1016/j.ecoenv.2024.117335

Ecotoxicol Environ Saf. 2024 Nov 12;287:117319. doi: 10.1016/j.ecoenv.2024.117319. Online ahead of print.ABSTRACTGiven the reduction of freshwater resources, saline-alkaline aquaculture has emerged as an effective approach to expand the fishery's accessible space. High carbonate alkalinity (CA) is a major stressor for aquatic organisms in saline-alkaline environments. Paramisgurnus dabryanus is a potential species for culture in saline-alkaline water, making it an ideal model for investigating the physiological responses and tolerance mechanisms to CA exposure in freshwater fishes. In the current study, P. dabryanus were exposed to 15 and 30 mmol/L NaHCO3, combining blood biochemical, gill histological, transcriptomic, and metabolomic methods for conjoint analysis of response mechanisms. After 28-d exposure, the gill ventilation frequency of P. dabryanus decreased significantly, gill lamellae twisted and atrophied, and gill filament epithelial cells proliferated, potentially limiting gas exchange, whereas the accessory air-breathing frequency increased significantly, possibly for greater oxygen uptake. Serum osmolality and blood pH remained relatively steady, while serum ammonia levels rose significantly. A total of 3718 differentially expressed genes (DEGs) and 205 differential metabolites (DMs) were identified between the control group and 30 mmol/L NaHCO3 group, involved in ion transport (Na+/K+-ATPase, V-type ATPase, carbonic anhydrase, and ABC transporters), ammonia transport (Rh glycoproteins and Aquaporins), amino acid metabolism, carbohydrate metabolism, and fatty acid metabolism. Furthermore, DEGs were significantly associated with cell-cell/ extracellular matrix interaction and protein synthesis. An integrated multi-omics analysis revealed the activation of carbon metabolism and TCA cycle. These results indicate that in response to CA exposure, P. dabryanus may facilitate carrier-mediated ion and ammonia transport to maintain the internal osmotic equilibrium and lessen the deleterious effects of blocked ammonia excretion. Meanwhile, amino acid metabolism and protein synthesis are disturbed, P. dabryanus can modulate carbohydrate catabolism to maintain energy homeostasis. The above findings provide novel insights into saline-alkaline adaptation in freshwater fishes, paving the way for future research and development of saline-alkaline-tolerant Cobitidae strains.PMID:39536569 | DOI:10.1016/j.ecoenv.2024.117319

Ecotoxicol Environ Saf. 2024 Nov 12;287:117275. doi: 10.1016/j.ecoenv.2024.117275. Online ahead of print.ABSTRACTBisphenol A (BPA) exposure is linked to multiple adverse health outcomes, prompting the rise of "BPA-free" products. However, substitutes like Bisphenol S (BPS) and Bisphenol F (BPF) are equally prevalent, with detection frequencies and concentrations rivaling BPA. Our research previously identified BPA as an endocrine disruptor affecting reproductive and developmental systems. This study explores the impact of BPA, BPS, and BPF on endometrial decidualization and receptivity. We detected these bisphenols in serum samples from infertile women undergoing assisted reproductive technology (ART) treatment whose average age was 31.58 years. Human endometrial stromal cells were exposed to varying concentrations (0, 1 nM, 10 nM, 100 nM, and 1 µM) of BPA, BPS, and BPF, following hormonal induction of decidualization (10 nM E2 (Estradiol) + 0.5 mM cAMP (Cyclic adenosine monophosphate) + 1 µM MPA (Medroxyprogesterone acetate) for 6 days). Methods including CCK-8, RT-qPCR, untargeted metabolomics, and transcriptome sequencing assessed cell proliferation, molecular markers, gene expression, and metabolites. BPS levels in the serum of infertile patients were significantly higher than BPA (14.52 vs. 2.58 ng/mL) and even more pronounced in the recurrent implantation failure (RIF) group compared to the Control group (23.46 vs. 5.57 ng/mL). Findings revealed that BPA and its substitutes inhibited endometrial stromal cell proliferation and reduced decidualization markers. Differential metabolites (25, 66, 104) and gene expressions (3260, 9686, 10357) were observed with BPA, BPF, and BPS exposure, respectively. Enriched pathways included glutathione metabolism, arginine biosynthesis, ABC transporters, cAMP signaling, and glucagon signaling. Metabolomics and transcriptome analyses unveiled the reproductive toxic effects of BPA and its substitutes, suggesting significant impacts on endometrial decidualization through diverse signaling pathways.PMID:39536566 | DOI:10.1016/j.ecoenv.2024.117275

Microbiol Res. 2024 Nov 9;290:127968. doi: 10.1016/j.micres.2024.127968. Online ahead of print.ABSTRACTDrought is a significant abiotic stress that adversely affects the physiological and biochemical processes in crops, posing a considerable challenge to agricultural productivity. The present study explored the efficacy of plant-derived biostimulant (PDB) and plant growth-promoting rhizobacteria (PGPR) strains Pseudomonas putida (RA) and Paenibacillus lentimorbus CHM12) in the management of negative impacts of drought stress in Zea mays (maize). Adathoda vasica leaf extracts (ADLE) emerged as the most potent biostimulant of the seven evaluated medicinal plant extracts. The synergetic effect of ADLE and RA enhances plant vegetative growth (root length, shoot length, fresh weight and dry weight) as well as significantly modulates drought-induced oxidative stress, as indicated by higher chlorophyll content and increased sugar and phenolic levels and reduction of proline level. The expression of defence-related (ZmAPX, ZmSOD, and ZmCAT) and transcription factor (ZmNAC, ZmWRKY, and ZmMYB) genes further supported the beneficial effects of this synergism under drought conditions. Furthermore, metabolite profiling through GC-MS analysis showed significant alterations in metabolites such as glucose, galactose, mannose, hexopyranose, linolenic acid, hexadecenoic acid, and butanedioic acid when PDB and PGPR were applied together. Overall, the findings of the present study affirm that the combined application of plant-derived biostimulant ADLE and plant-beneficial rhizobacteria RA can effectively alleviate the adverse effects of drought on maize, providing an eco-friendly and sustainable solution for improving productivity under stress.PMID:39536514 | DOI:10.1016/j.micres.2024.127968