PubMed

Nutrients. 2024 Nov 30;16(23):4161. doi: 10.3390/nu16234161.ABSTRACTBackground: Fibromyalgia (FM) is a chronic disorder that causes damage to the neuro-muscular system and alterations in the intestinal microbiota and affects the psychological state of the patient. In our previous study, we showed that 22 women patients subjected to a specific very low-carbohydrate ketogenic therapy (VLCKD) showed an improvement in clinical scores as well as neurotransmission-related and psychological dysfunctions and intestinal dysbiosis. Furthermore, NMR metabolomic data showed that changes induced by VLCKD treatment were evident in all metabolic pathways related to fibromyalgia biomarkers. Methods: Based on this evidence, we extend our investigation into dietary interventions for fibromyalgia by evaluating the impact of transitioning from a VLCKD to a low-glycemic insulinemic (LOGI) diet over an additional 45-day period. Therefore, participants initially following a VLCKD were transitioned to the LOGI diet after 45 days to determine whether the improvements in FM symptoms and metabolic dysfunctions achieved through VLCKD could be sustained with LOGI. Results: Our findings suggested that while VLCKD serves as an effective initial intervention for correcting metabolic imbalances and alleviating FM symptoms, transitioning to a LOGI diet offers a practical and sustainable dietary strategy. This transition preserves clinical improvements and supports long-term adherence and quality of life, underscoring the importance of adaptable nutritional therapies in chronic disease management. Control patients who adhered only to the LOGI diet for 90 days showed only modest improvement in clinical and psychological conditions, but not elimination of fibromyalgia symptoms. Conclusions: In conclusion the LOGI diet is an excellent alternative to maintain the results obtained from the regime VLCKD.PMID:39683556 | DOI:10.3390/nu16234161

Nutrients. 2024 Nov 28;16(23):4096. doi: 10.3390/nu16234096.ABSTRACTObjectives: This study investigates the effectiveness of an herbal formulation, STRESSLESS (ST-65), which combines ashwagandha (Withania somnifera) and bacopa (Bacopa monnieri), on SH-SY5Y human neuroblastoma cells. Given the rising interest in natural compounds for neuroprotection and stress alleviation, we aimed to explore the cellular and molecular effects of this formulation. Methods: Utilizing a nuclear magnetic resonance (NMR) metabolomic approach and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), we identified key bioactive compounds in ST-65, including withanolides from ashwagandha and bacosides from bacopa. Results: Our findings indicate that ST-65 treatment significantly alters the metabolic profile of SH-SY5Y cells. Key changes included increased levels of metabolites linked to neuroprotection, energy metabolism, and antioxidant defense. Notable enhancements were observed in specific amino acids and neuroprotective compounds, suggesting activation of neuroprotective mechanisms and mitigation of stress-induced damage. Conclusions: The study reveals a complex phyto-chemical profile of ST-65 and underscores its potential as a natural active agent for addressing stress-related neurodegenerative conditions. These insights into neuronal mechanisms provide a foundation for further exploration of herbal formulations in neuroprotection.PMID:39683490 | DOI:10.3390/nu16234096

Commun Med (Lond). 2024 Dec 16;4(1):265. doi: 10.1038/s43856-024-00637-1.ABSTRACTBACKGROUND: Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.METHODS: Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics.RESULTS: Clinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology.CONCLUSIONS: These may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.PMID:39681608 | DOI:10.1038/s43856-024-00637-1

Zhonghua Xin Xue Guan Bing Za Zhi. 2024 Dec 24;52(12):1446-1451. doi: 10.3760/cma.j.cn112148-20240922-00561.ABSTRACT肥厚型心肌病是最常见的遗传性心脏病，是青少年和运动员心脏性猝死的主要病因。梗阻性肥厚型心肌病是肥厚型心肌病的重要类型，多项研究显示，与非梗阻性肥厚型心肌病患者及正常人群相比，梗阻性肥厚型心肌病患者机体及心肌细胞存在代谢改变，且与患者不良临床症状与临床结局密切相关。同时，应用代谢组学研究结果可对梗阻性肥厚型心肌病发病机制与通路进行探究。该文就梗阻性肥厚型心肌病能量代谢改变进行综述，总结与梗阻性肥厚型心肌病有关的发病机制及通路，归纳有效的治疗靶点或评估预后的科学指标。.PMID:39681452 | DOI:10.3760/cma.j.cn112148-20240922-00561

Am J Physiol Endocrinol Metab. 2024 Dec 16. doi: 10.1152/ajpendo.00248.2024. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids are significantly changed after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on db/db mice to observe the beneficial effects of the surgery on the kidneys, and performed bile acid targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in db/db mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury, inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Further in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in db/db mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.PMID:39681344 | DOI:10.1152/ajpendo.00248.2024

Respirology. 2024 Dec 16. doi: 10.1111/resp.14866. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is often the fatal complication of idiopathic pulmonary fibrosis (IPF). Emerging evidence indicates that metabolic reprogramming and dysregulation of lipid metabolism are distinctive characteristics of IPF. However, the lipid metabolic mechanisms that underlie the pathophysiology of AE-IPF remain elusive.METHODS: Serum samples for pilot study were collected from 34 Controls, 37 stable IPF (S-IPF) cases and 41 AE-IPF patients. UHPLC-MS/MS was utilized to investigate metabolic variations and identify lipid biomarkers in serum. ELISA, quantitative PCR and western blot were employed to validate the identified biomarkers.RESULTS: There were 32 lipid metabolites and 5 lipid metabolism pathways enriched in all IPF patients compared to Controls. In AE-IPF versus S-IPF, 19 lipid metabolites and 12 pathways were identified, with 5-hydroxyeicosatetraenoic Acid (5-HETE) significantly elevated in AE-IPF. Both in internal and external validation cohorts, the serum levels of 5-HETE were significantly elevated in AE-IPF patients compared to S-IPF subjects. Consequently, the indicators related to 5-HETE in lipid metabolic pathway were significantly changed in AE-IPF patients compared with S-IPF cases in the lung tissues. The serum level of 5-HETE was significantly correlated with the disease severity (CT score and PaO2/FiO2 ratio) and survival time. Importantly, the receiver operating characteristic (ROC) curve, Kaplan-Meier analysis and Multivariate Cox regression analysis demonstrated that 5-HETE represents a promising lipid biomarker for the diagnosis and prognosis of AE-IPF.CONCLUSION: Our study highlights lipid reprogramming as a novel therapeutic approach for IPF, and 5-HETE may be a potential biomarker of AE-IPF patients.PMID:39681341 | DOI:10.1111/resp.14866

Ann Pharm Fr. 2024 Dec 14:S0003-4509(24)00179-2. doi: 10.1016/j.pharma.2024.12.008. Online ahead of print.ABSTRACTIncreasingly, molecular chemistry and pharmacology are complementing classical studies in the field of archaeology. In this case, we present the results of the chemical study of pipe residues found in the context of an archaeological mission (AROMA mission: Archaeology of the Exercise of Royal and Magico-Religious Power) in the royal palaces of Abomey (Benin), dating from the 17th-19th century. The search for many products was carried out (mainly tobacco, cannabis) but surprisingly only highlighted the presence of caffeine residues. This result is discussed and compared with field notions and in particular with ethnological surveys where coffee was consumed in the old way, smoked in a pipe (peripheral part or shell, and not the bean itself or the leaves).PMID:39681307 | DOI:10.1016/j.pharma.2024.12.008

J Steroid Biochem Mol Biol. 2024 Dec 14:106663. doi: 10.1016/j.jsbmb.2024.106663. Online ahead of print.ABSTRACTBACKGROUND: This study investigates the protective effects and potential mechanisms of 1,25(OH)2D3 against high-altitude pulmonary edema (HAPE).METHODS: Hypoxia-induced rats were administered 1,25(OH)2D3 for 24, 48, and 72hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25(OH)2D3 in type II alveolar epithelial cells induced by hypoxia.RESULTS: Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48hours of hypoxi. Treatment with 1,25(OH)2D3 improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25(OH)2D3 significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25(OH)2D3 treatment, these levels exhibited a significant reduction.CONCLUSION: In hypoxic type II alveolar epithelial cells, 1,25(OH)2D3 improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25(OH)2D3 mitigated the deleterious effects of hypoxia on pulmonary function.PMID:39681240 | DOI:10.1016/j.jsbmb.2024.106663

J Ethnopharmacol. 2024 Dec 14:119246. doi: 10.1016/j.jep.2024.119246. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD) exerts its anti-cerebral ischemia effects through multiple pathways and targets, although its specific mechanisms remain unclear AIM OF THE STUDY: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) metabolomics and other methods were employed to investigate the role of BYHWD in inhibiting neuronal apoptosis following cerebral ischemia-reperfusion by modulating the RhoA/Rock2 pathway.METHODS: A rat model of exhaustion swimming combined with middle cerebral artery occlusion (ES+I/R) was established to evaluate the intervention effects of Buyang Huanwu Decoction on cerebral ischemia-reperfusion. This was assessed using neurological function scores, Qi deficiency and blood stasis syndrome scores, HE staining, Nissl staining and TT staining. Differential metabolites and metabolic pathways associated with cerebral ischemia-reperfusion were identified using UPLC-QTOF-MS metabolomics, with key differential metabolites validated through ELISA. Molecular docking techniques were employed to predict interactions between the key differential metabolite, hippuric acid, and its primary downstream pathways. Finally, the levels of neurocellular apoptosis, as well as key molecules in the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway, were measured.RESULTS: The results indicated that the primary differential metabolites associated with BYHWD's protective effects against ischemia-reperfusion injury were hippuric acid, lysophosphatidic acid, and lysophosphatidylethanolamine, with the main metabolic pathway being phenylalanine metabolism. Molecular docking studies demonstrated that malonic acid exhibited a strong affinity for proteins related to the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway.Furthermore, we found that BYHWD treatment significantly decreased the apoptosis rate of cells following cerebral ischemia-reperfusion and inhibited the expression of key molecules in both the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway in brain tissue.CONCLUSION: BYHWD ameliorated brain tissue injury after cerebral ischemia/reperfusion in rats with qi deficiency and blood stasis. The underlying mechanism may involve BYHWD's inhibition of the RhoA/Rock2 signaling pathway activation through modulation of the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis mediated by the mitochondrial apoptosis pathway.PMID:39681201 | DOI:10.1016/j.jep.2024.119246

Anal Chem. 2024 Dec 16. doi: 10.1021/acs.analchem.4c03229. Online ahead of print.ABSTRACTApplications of advanced omics methodologies are increasingly popular in biomedicine. However, large-scale studies aiming at clinical translation are typically siloed to single technologies. Here, we present the first comprehensive large-scale population data combining 209 lipoprotein measures from a quantitative NMR spectroscopy platform and 809 lipid classes and species from a quantitative LC-MS/MS platform. These data with 1018 molecular measures were analyzed in two population cohorts totaling 7830 participants. The association and cluster analyses revealed excellent coherence between the methodologically independent data domains and confirmed their quantitative compatibility and suitability for large-scale studies. The analyses elucidated the detailed molecular characteristics of the heterogeneous circulatory macromolecular lipid transport system and the underlying structural and compositional relationships. Unsupervised neural network analysis─the so-called self-organizing maps (SOMs)─revealed that these deep molecular and metabolic data are inherently related to key physiological and clinical population characteristics. The data-driven population subgroups uncovered marked differences in the population distribution of multiple cardiometabolic risk factors. These include, e.g., multiple lipoprotein lipids, apolipoprotein B, ceramides, and oxidized lipids. All 79 structurally unique triglyceride species showed similar associations over the entire lipoprotein cascade and indicated systematically increased risk for carotid intima media thickening and other atherosclerosis risk factors, including obesity and inflammation. The metabolic attributes for 27 individual cholesteryl ester species, which formed six distinct clusters, were more intricate with associations both with higher─e.g., CE(16:1)─and lower─e.g., CE(20:4)─cardiometabolic risk. The molecular details provided by these combined data are unprecedented for molecular epidemiology and demonstrate a new potential avenue for population studies.PMID:39680883 | DOI:10.1021/acs.analchem.4c03229

Chem Rev. 2024 Dec 16. doi: 10.1021/acs.chemrev.3c00520. Online ahead of print.ABSTRACTThe octadecanoids are a broad class of lipids consisting of the oxygenated products of 18-carbon fatty acids. Originally referring to production of the phytohormone jasmonic acid, the octadecanoid pathway has been expanded to include products of all 18-carbon fatty acids. Octadecanoids are formed biosynthetically in mammals via cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) activity, as well as nonenzymatically by photo- and autoxidation mechanisms. While octadecanoids are well-known mediators in plants, their role in the regulation of mammalian biological processes has been generally neglected. However, there have been significant advancements in recognizing the importance of these compounds in mammals and their involvement in the mediation of inflammation, nociception, and cell proliferation, as well as in immuno- and tissue modulation, coagulation processes, hormone regulation, and skin barrier formation. More recently, the gut microbiome has been shown to be a significant source of octadecanoid biosynthesis, providing additional biosynthetic routes including hydratase activity (e.g., CLA-HY, FA-HY1, FA-HY2). In this review, we summarize the current field of octadecanoids, propose standardized nomenclature, provide details of octadecanoid preparation and measurement, summarize the phase-I metabolic pathway of octadecanoid formation in mammals, bacteria, and fungi, and describe their biological activity in relation to mammalian pathophysiology as well as their potential use as biomarkers of health and disease.PMID:39680864 | DOI:10.1021/acs.chemrev.3c00520

J Agric Food Chem. 2024 Dec 16. doi: 10.1021/acs.jafc.4c03818. Online ahead of print.ABSTRACTLactobacillus reuteri is a well-known probiotic with beneficial effects, such as anti-insulin resistance, anti-inflammatory, and improvement of the intestinal barrier. However, the underlying mechanisms remain unclear. Here, we found that gavage of L. reuteri improved the intestinal barrier and glucose homeostasis in HFD-fed mice. Analysis of lipid metabolomics reveals a significant increase in eicosatrienoic acid (ETA) levels in mouse feces after L. reuteri gavage. We found that ETA maintain intestinal barrier integrity and improve glucose homeostasis by promoting GLP-1 secretion. Mechanistically, by using CD36 inhibitor in vivo and CD36 knockdown STC-1 cells in vitro, we elucidate that ETA activates intestinal CD36-activated PLC/IP3R/Ca2+ signaling to promote GLP-1 secretion. In vivo administration of GLP-1R inhibitor and in vitro intestinal organoid experiments demonstrate that GLP-1 upregulates the PI3K/AKT/HIF-1α pathway by GLP-1R and increases intestinal tight junction protein expressions, which in turn enhance the intestinal barrier integrity, reduce serum LPS level, attenuate inflammation in white adipose tissue (WAT), and ultimately improve glucose homeostasis in HFD and db/db mice. Our study elucidates for the first time the mechanism by which L. reuteri and its enriched metabolite ETA inhibit WAT inflammation by ameliorating the intestinal barrier, ultimately improving glucose homeostasis, and provides a new treatment strategy for T2D.PMID:39680859 | DOI:10.1021/acs.jafc.4c03818

Chem Biodivers. 2024 Dec 16:e202401676. doi: 10.1002/cbdv.202401676. Online ahead of print.ABSTRACTThe few current metabolomic studies on ferns are mostly restricted to a single species or focused on specific compounds. We performed an untargeted metabolomic study on six of the most common fern species from the cloud forest, followed by a targeted analysis of 64 phenolic compounds, many of which have been associated with herbivore defense. The untargeted analysis revealed a total of 232 putatively identified metabolites from 463 to 1427 signals per fern species, each with its proper chemical signature but not necessarily correlated to their phylogenetic relationship. The flavonoid, flavone, and flavonol biosynthesis were the most expressed pathways in all species except for Marattia laxa. Fern species also differed strongly in the concentrations of the 10 detected phenolic compounds. Our results show that ferns, including the most ancestral species, such as M. laxa, display a high metabolomic diversity comparable to seed plants. Each fern species held a different combination of defensive phenolic compounds. Further research is needed to explore the metabolic diversity, to identify the biochemical defenses of ferns, and, in particular, to detect the chemical compounds that act against their specific herbivorous insects in the cloud forest ecosystem.PMID:39680754 | DOI:10.1002/cbdv.202401676

Plant Biol (Stuttg). 2024 Dec 16. doi: 10.1111/plb.13753. Online ahead of print.ABSTRACTInterspecific hybridization plays an important role in plant evolution, contributing to taxonomic uncertainty through intermediate phenotypes or the emergence of novel traits. The characterization of hybridization is important to elucidate systematic relationships and its role in the diversification of lineages. The genus Cenostigma comprises neotropical legume trees with phylogenetic inconsistencies, and individuals showing intermediate morphology between sympatric species, suggesting natural hybridization. We tested this hypothesis by investigating two endemic species from the Caatinga dry forest in northeast Brazil (C. microphyllum and C. pyramidale) using molecular markers (nuclear and plastid SSRs), geometric morphometrics, non-targeted metabolomics, and ecological analyses. We detected a high plastidial genetic structure among populations, not related to species boundaries but to their geographic distribution. The geometric morphometric analysis showed a clustering of pure individuals of both species with hybrids in an intermediate position, demonstrating the hybridization of these species in Caatinga. Nuclear DNA and metabolite diversity supported the separation of the two species into three clusters, with a subdivision of C. pyramidale in populations from the north (Pernambuco) and south (Bahia). Metabolomics revealed a fourth group formed mostly by hybrids. Later generation hybrids were detected as intermediate morphological forms, and gene flow was assumed as asymmetric among species and populations, being higher from C. pyramidale to C. microphyllum in populations from Bahia State. Ecological data indicated niche overlap. Hence, interspecific gene flow occurs among Cenostigma tree species, contributing to the evolution of the dry forest. Given the karyotypic and genomic similarity among species, as well as molecular and ecological evidence, we infer that the hybrids are fertile, allowing introgression and contributing to systematic complexity in Cenostigma. Hybridization did not significantly increase chemodiversity in terms of novel compounds but differentiated hybrids from parental species. In summary, we highlight the importance of multiple evidence, particularly genetic, morphological, and metabolomic traits, in the identification of hybrids and its evolutionary impact in natural environments.PMID:39680475 | DOI:10.1111/plb.13753

Mol Biol Rep. 2024 Dec 16;52(1):52. doi: 10.1007/s11033-024-10175-7.ABSTRACTBACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) stands out as a critical health issue due to its high mortality and morbidity rates. This study aimed to comprehensively investigate the biochemical and metabolic alterations induced by lipopolysaccharide (LPS) in human embryonic kidney cells (HEK-293) using an in vitro model.METHODS AND RESULTS: The study investigated the impact of LPS on HEK-293 cells by evaluating cytotoxicity using the MTT assay, analyzing apoptosis, cell cycle progression, and oxidative stress via flow cytometry, measuring TNF-α levels through ELISA, and assessing amino acid metabolism with LC-MS/MS. The findings demonstrated that LPS significantly reduced cell viability in a dose-dependent manner, increased apoptotic cell populations, induced DNA damage by arresting the cell cycle in the Sub-G1 phase, and activated oxidative stress pathways. Notably, elevated reactive oxygen species (ROS) production and increased secretion of the pro-inflammatory cytokine TNF-α highlighted LPS's inflammatory and cytotoxic effects. Furthermore, systematic analysis revealed LPS-induced disruptions in amino acid metabolism, including marked reductions in alanine, arginine, and aspartic acid levels. KEGG pathway analysis identified significant metabolic alterations in pathways such as the urea cycle, TCA cycle, and glutathione metabolism. Interestingly, elevated citrulline levels suggested a potential adaptive mechanism to counteract LPS-induced inflammation and oxidative stress. Additionally, ROC analysis identified cystine as a highly reliable biomarker, with an AUC value of 1.00, emphasizing its critical role in metabolic reprogramming associated with SA-AKI.CONCLUSIONS: This study provides critical insights into the molecular pathophysiology of SA-AKI and emphasizes the promise of metabolomic approaches in the early diagnosis of sepsis-related complications and the development of targeted therapies.PMID:39680269 | DOI:10.1007/s11033-024-10175-7

Environ Sci Technol. 2024 Dec 16. doi: 10.1021/acs.est.4c09592. Online ahead of print.ABSTRACTExisting air pollution metabolomics studies showed inconsistent results, often limited by small sample size and individual air pollutants effects. We conducted a metabolome-wide association study among 1096 women (68.2 ± 5.7 years) who provided blood samples (1998-2001) within the Cancer Prevention Study-II Nutrition Cohort. Annual average individual exposures to particulate matter, nitrogen dioxide, ozone, sulfur dioxide, and carbon monoxide in the year of blood draw were used. Metabolomics profiling was conducted on serum samples by Metabolon. We evaluated the individual air pollutants effects using multiple linear regression and the mixture effect using quantile g-computation, adjusting for confounders and false discovery rate (FDR). Ninety-five metabolites were significantly associated with at least one air pollutant or mixture (FDR < 0.05). These metabolites were enriched in pathways related to oxidative stress, systemic inflammation, energy metabolism, signals transduction, nucleic acid damage and repair, and xenobiotics. Sixty metabolites were confirmed with level 1 or 2 evidence, among which 21 have been previously linked to air pollution exposure, including taurine, creatinine, and sebacate. Overall, our results replicate prior findings in a large sample and provide novel insights into biological responses to long-term air pollution exposure using mixture analysis.PMID:39680091 | DOI:10.1021/acs.est.4c09592

J Exp Bot. 2024 Dec 16:erae481. doi: 10.1093/jxb/erae481. Online ahead of print.ABSTRACTSterols are produced via complex, multistep biosynthetic pathways involving similar enzymatic conversions in plants, animals and fungi, yielding a variety of sterol metabolites with slightly different chemical properties to exert diverse and specific functions. A tremendously diverse landscape of sterols, and sterol-derived compounds, can be found across the plant kingdom, determining a wide spectrum of functions. Resolving the underlying biosynthetic pathways is thus instrumental to understanding the function and use of these molecules. In only a few plants, sterol biosynthesis has been studied using mutants. In non-model species a pharmacological approach is required. However, this relies on only a few inhibitors. Here, we probed a collection of inhibitors of mammalian cholesterol biosynthesis to identify new inhibitors of plant sterol biosynthesis. We show that imidazole-type fungicides, bifonazole, clotrimazole and econazole inhibit the obtusifoliol 14α-demethylase CYP51 in plants. Moreover, we found that the selective estrogen receptor modulator, clomiphene, inhibits sterol biosynthesis in part by inhibiting the plant-specific cyclopropyl-cycloisomerase CPI1. These results demonstrate that rescreening of inhibitors animal sterol biosynthesis is an easy approach for identifying novel inhibitors of plant sterol biosynthesis. These molecules expand the toolkit for studying and manipulating sterol biosynthesis in the plant kingdom.PMID:39680055 | DOI:10.1093/jxb/erae481

Plant Cell Environ. 2024 Dec 16. doi: 10.1111/pce.15333. Online ahead of print.ABSTRACTLunar farming, often regarded as a myth, is regularly practiced in many places around the world (e.g., India) where framers organized their agricultural activities according to moon phases. Early and recent work showed that exposure to moonlight affects the life cycle of plants, from seed germination and vegetative growth to fruit maturation and dispersal. Here we addressed the long-term effect of short exposure to full moonlight (FML) on cellular activities in Brassica juncea by analyzing protein and metabolite profiles immediately after 3-night-exposure (3NE) or 7 and 15 days after exposure (DAE) to FML. This study shows an increase in nuclear size following 3NE to FML, which was accompanied by changes in protein and metabolite profiles. We identified significant alterations in protein and metabolite profiles between FML and dark-treated plants in conjunction with developmental stages, which persisted long after exposure to FML. Most notable are the changes in composition of metabolite interconversion enzymes (MIEs) at various developmental stages which were intensified in FML-treated plants. Changes in MIEs were accompanied by significant alterations in metabolite composition and level, particularly at 15DAE, including branched-chain amino acids (e.g., valine, leucine), multiple sugars (raffinose, glucose, sucrose) as well as the tricarboxylic acid (TCA) cycle intermediates malic acid and citric acid. Thus, our results show that short-term exposure to FML triggers a developmental switch resulting in a long-term impact on plant performance that brings about an increase in cell activities and consequently enhanced growth. Our results call for meticulous research on this lunar phenomenon and its potential to enhance crop plant growth and development.PMID:39679718 | DOI:10.1111/pce.15333

Gut Microbes. 2024 Jan-Dec;16(1):2405547. doi: 10.1080/19490976.2024.2405547. Epub 2024 Oct 7.ABSTRACTThe intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption, warrants further investigation to determine its microbiota composition and functions. Here, we conducted a clinical research project in 30 age- and sex-matched participants with (n = 15) and without (n = 15) obesity. Duodenojejunal fluid was obtained by aspiration during endoscopy. Phenotyping included clinical variables related to metabolic status, lifestyle, and psychosocial factors using validated questionnaires. We performed metagenomic analyses of the oral, duodenojejunal, and fecal microbiome, alongside metabolomic data from duodenojejunal fluid and feces, integrating these data with clinical and lifestyle information. Our results highlight significant associations between duodenojejunal microbiota composition and usual dietary intake, as well as clinical phenotypes, with larger effect sizes than the associations between these variables and fecal microbiota. Notably, we found that the duodenojejunal microbiota of patients with obesity exhibited higher diversity and showed distinct differences in the abundance of several duodenojejunal microbiota species compared with individuals without obesity. Our findings support the relevance of studying the role of the small intestinal microbiota in the pathogenesis of nutrition-related diseases.PMID:39679619 | DOI:10.1080/19490976.2024.2405547

Front Pharmacol. 2024 Nov 28;15:1429960. doi: 10.3389/fphar.2024.1429960. eCollection 2024.ABSTRACTIschemic stroke (IS) is a highly lethal type of cardiovascular and cerebrovascular disease. Improving survival rates and promoting recovery in patients with IS pose significant challenges, however, recent research has identified the gut-brain axis as a therapeutic target. In this study, we evaluated the regulatory effect of Periplaneta americana (L.) extract (PAS840), which has established anti-inflammatory, antioxidant, and neuroprotective effects, on the gut microbiota using a rat model of temporary middle cerebral artery occlusion (tMCAO). We evaluated the protective effects of PAS840 on brain damage in IS rats through TTC (triphenyltetrazolium chloride), Nissl staining, and pathological section analysis. Additionally, we investigated the impact of PAS840 on the gut microbiota and metabolites using 16S rRNA sequencing, untargeted metabolomics of gut contents, and transcriptomics analyses of brain tissues to explore its mechanism of action. PAS840 intervention resulted in significant changes in the gut microbiota, including an increase in the abundance of probiotic flora, decrease in the abundance of harmful flora, and significant changes in metabolite profiles. It also attenuated brain damage, decreased platelet activity, inhibited oxidative stress and genes related to inflammation, and improved neurological function in rats. These findings suggest that PAS840 has preventive and therapeutic effects against IS via the gut-brain axis by regulating the gut microbiota and related metabolites. Accordingly, PAS840 is a candidate therapeutic drug for further research.PMID:39679371 | PMC:PMC11638836 | DOI:10.3389/fphar.2024.1429960