PubMed

J Microbiol Biotechnol. 2024 Jul 30;34(9):1-8. doi: 10.4014/jmb.2402.02039. Online ahead of print.ABSTRACTFermentation has been identified as an effective strategy to alter the chemical makeup of tobacco, thereby enhancing its quality. The deliberate introduction of microorganisms can hasten the fermentation process. In this research, microbial consortia harvested from the tobacco surface were utilized to enhance the tobacco quality. This enhancement also elevated several sensory attributes of HnB cigarettes, such as aroma richness, moisture, strength, and reduced irritation, achieving a sensory quality rating of 84.5. This marks a notable improvement compared to the 82 rating of the original, unfermented cigarettes. Untargeted metabolomics analysis revealed a decrease in total polyphenols and unsaturated fatty acids, while the levels of polyacids, alcohols, ketones, furans, and other compounds increased in the fermented tobacco. Additionally, KEGG pathway enrichment analysis indicated that the enhancement in tobacco quality through microbial consortia fermentation is linked to various biological pathways, with pathways related to fatty acid and amino acid degradation playing pivotal roles. The findings of this study will serve as a reference for the commercial production of HnB cigarettes, and the elucidated mechanism offers a theoretical basis for exploring microbial fermentation as a means to improve tobacco quality.PMID:39187455 | DOI:10.4014/jmb.2402.02039

J Microbiol Biotechnol. 2024 Jul 15;34(9):1-9. doi: 10.4014/jmb.2403.03044. Online ahead of print.ABSTRACTChemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after cisplatin injection. KT5720 treatment alleviated cisplatin-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by cisplatin in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the cisplatin-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.PMID:39187454 | DOI:10.4014/jmb.2403.03044

Zhonghua Fu Chan Ke Za Zhi. 2024 Aug 25;59(8):628-635. doi: 10.3760/cma.j.cn112141-20240222-00109.ABSTRACTObjective: To screen plasma metabolic markers in patients with unexplained recurrent spontaneous abortion (URSA) by non-target metabolomics approach. Methods: From September 2022 to May 2023, the plasma of 23 URSA pregnant women with threatened abortion who visited the outpatient clinic of Gansu Provincial Maternity and Child-care Hospital in the first trimester (URSA group) was collected, and the plasma of 22 healthy pregnant women in the first trimester who underwent prenatal examination during the same period (normal control group) was collected. Plasma metabolomics was analyzed by ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS), fold change analysis, principal component analysis and partial least square discriminant analysis were applied to screen for differential metabolites, and the metabolites and their pathways associated with URSA were screened using receiver operating characteristic (ROC) curve and pathway enrichment analysis. Results: There were no significant differences in age, body mass index and gestational weeks between URSA and normal control group(all P<0.05). Metabolomics analysis using UPLC-MS showed that a total of 526 metabolites were detected from plasma, of which 33 were found to be differential metabolites associated with URSA based on the screening standards. Six potential metabolites with large area under the curve (AUC) were identified by ROC curve analysis, including phosphatidylethanolamine (AUC=0.972, 95%CI: 0.920-1.000), santene hydrate (AUC=0.902, 95%CI: 0.786-0.982), L-leucine (AUC=0.884, 95%CI: 0.772-0.960), cembrene (AUC=0.881, 95%CI: 0.758-0.956), caffeine (AUC=0.875, 95%CI: 0.756-0.962), and 4-hydroxybenzoic acid propyl ester (AUC=0.864, 95%CI: 0.732-0.946). The AUC for the combined diagnosis of URSA by the six metabolites was 0.983 (95%CI: 0.929-1.000). Pathway enrichment analysis of the differential metabolites showed that the pathogenesis of URSA was associated with a variety of metabolic pathways including caffeine metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. Conclusion: The plasma metabolic profiles of pregnant women with normal pregnancies versus URSA differ in early pregnancy, and six potential metabolites such as phosphatidylethanolamine, santene hydrate, L-leucine, cembrene, caffeine, 4-hydroxybenzoic acid propyl ester, and their metabolic pathways may be involved in the pathogenesis of URSA.PMID:39187410 | DOI:10.3760/cma.j.cn112141-20240222-00109

Matrix Biol. 2024 Aug 24:S0945-053X(24)00109-4. doi: 10.1016/j.matbio.2024.08.007. Online ahead of print.ABSTRACTBACKGROUND: Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal barrier integrity and the protective effects of small molecular weight (35 kDa) hyaluronan on epithelial barrier function.METHODS: Intestinal organoids derived from mouse colon were grown in normal glucose media (5 mM) or high glucose media (25 mM) to study the impact of hyperglycemic stress on the intestinal barrier. Additionally, organoids were pretreated with 35 kDa hyaluronan (HA35) to investigate the effect of hyaluronan on epithelial barrier under high glucose stress. Immunoblotting as well as confocal imaging was used to understand changes in barrier proteins, quantitative as well as spatial distribution, respectively. Alterations in barrier function were measured using trans-epithelial electrical resistance and fluorescein isothiocyanate flux assays. Untargeted proteomics analysis was performed to elucidate mechanisms by which HA35 exerts a protective effect on the barrier. Intestinal organoids derived from receptor knockout mice specific to various HA receptors were utilized to understand the role of HA receptors in barrier protection under high glucose conditions.RESULTS: We found that high glucose stress decreased the protein expression as well as spatial distribution of two key barrier proteins, zona occludens-1 (ZO-1) and occludin. HA35 prevented the degradation or loss of ZO-1 and maintained the spatial distribution of both ZO-1 and occludin under hyperglycemic stress. Functionally, we also observed a protective effect of HA35 on the epithelial barrier under high glucose conditions. We found that HA receptor, layilin, was involved in preventing barrier protein loss (ZO-1) as well as maintaining spatial distribution of ZO-1 and occludin. Additionally, proteomics analysis showed that cell death and survival was the primary pathway upregulated in organoids treated with HA35 under high glucose stress. We found that XIAP associated factor 1 (Xaf1) was modulated by HA35 thereby regulating apoptotic cell death in the intestinal organoid system. Finally, we observed that spatial organization of both focal adhesion kinase (FAK) as well as F-actin was mediated by HA35 via layilin.CONCLUSION: Our results highlight the impact of hyperglycemic stress on the intestinal barrier function. This is of clinical relevance, as impaired barrier function has been observed in individuals with metabolic syndrome. Additionally, we demonstrate barrier protective effects of HA35 through its receptor layilin and modulation of cellular apoptosis under high glucose stress.PMID:39187208 | DOI:10.1016/j.matbio.2024.08.007

J Sport Health Sci. 2024 Aug 24:100968. doi: 10.1016/j.jshs.2024.100968. Online ahead of print.ABSTRACTBACKGROUND: Resistance exercise leads to improved muscle function and metabolic homeostasis. Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.METHODS: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin. Based on rhythmicity of Fibronectin type III domain containing 5 (FNDC5/irisin), we trained wild type and FNDC5 knockout mice at late active phase (high FNDC5/irisin level) or late rest phase (low FNDC5/irisin level) to analyze exercise benefits on muscle function and metabolic homeostasis. Molecular analysis was performed to understand the regulatory mechanisms of FNDC5 rhythmicity and downstream signaling transduction in skeletal muscle.RESULTS: In this study, we showed that regular resistance exercises performed at different times of day resulted in distinct training outcomes in humans, including exercise benefits and altered plasma metabolomics. We found that muscle FNDC5/irisin levels exhibit rhythmicity. Consistent with human data, compared to late rest phase (low irisin level), mice trained chronically at late active phase (high irisin level) gained more muscle capacity along with improved metabolic fitness and metabolomics/lipidomics profiles under a high-fat diet, whereas these differences were lost in FNDC5 knockout mice. Mechanistically, Basic helix-loop-helix ARNT like 1 (BMAL1) and Peroxisome proliferative activated receptor, gamma, coactivator 1 alpha 4 (PGC1α4) induce FNDC5/irisin transcription and rhythmicity, and the signaling is transduced via αV integrin in muscle.CONCLUSION: Together, our results offered novel insights that exercise performed at distinct times of day determines training outcomes and metabolic benefits through the rhythmic regulation of the BMAL1/PGC1α4-FNDC5/irisin axis.PMID:39187065 | DOI:10.1016/j.jshs.2024.100968

Anal Biochem. 2024 Aug 24:115654. doi: 10.1016/j.ab.2024.115654. Online ahead of print.ABSTRACTMetabolomics has been widely applied in human diseases and environmental science to study the systematic changes of metabolites over diverse types of stimuli. NMR-based metabolomics has been widely used, but the peak overlap problems in the one-dimensional (1D) NMR spectrum could limit the accuracy of quantitative analysis for metabolomics applications. Two-dimensional (2D) NMR has been applied to solve the 1D NMR overlap problem, but the data processing is still challenging. In this study, we built an automatic approach to process the 2D NMR data for quantitative applications using machine learning approaches. Partial least square discriminant analysis (PLS-DA), artificial neural network classification (ANN-DA), gradient boosted trees classification (XGBoost-DA), and artificial deep learning neural network classification (ANNDL-DA) were applied in combination with an automatic peak selection approach. Standard mixtures, sea anemone extracts, and mouse fecal samples were tested to demonstrate the approach. Our results showed that ANN-DA and ANNDL-DA have high accuracy in selecting 2D NMR peaks (around 90%), which have a high potential application in 2D NMR-based metabolomics quantitively study, while PLS-DA and XGBoost-DA showed limitations in either data variation or overfitting. Our study built an automatic approach to applying 2D NMR data to routine quantitative analysis in metabolomics.PMID:39187053 | DOI:10.1016/j.ab.2024.115654

Genomics. 2024 Aug 24:110927. doi: 10.1016/j.ygeno.2024.110927. Online ahead of print.ABSTRACTKetosis-a metabolic state characterized by elevated levels of ketone bodies in the blood or urine-reduces the performance and health of dairy cows and causes substantial economic losses for the dairy industry. Currently, beta-hydroxybutyric acid is the gold standard for determining ketosis in cows; however, as this method is only applicable postpartum, it is not conducive to the early intervention of ketosis in dairy cows. In this study, the sera of dry, periparturient, postpartum ketotic, and healthy cows were analyzed by both transcriptomics and metabolomics techniques. Moreover, changes of gene expression and metabolites were observed, and serum physiological and biochemical indexes were detected by ELISA. The purpose was to screen biomarkers that can be used to detect the incidence of dry or periparturient ketosis in cows. The results showed that ketotic cows had increased levels of glycolipid metabolism indexes, oxidizing factors, and inflammatory factors during dry periods and liver damage, which could be used as early biomarkers to predict the onset of ketosis. Transcriptomic results yielded 20 differentially expressed genes (DEGs) between ketotic and healthy cows during dry, peripartum, and postpartum periods. GO and KEGG enrichment analyses indicated that these DEGs were involved in amino acid metabolism, energy metabolism, and disease-related signaling pathways. The metabolomics sequencing results showed that ketotic cows mainly showed enrichment in tricarboxylic acid cycle, butyric acid metabolism, carbon metabolism, lysine degradation, fatty acid degradation, and other signaling pathways. Metabolites differed between ketotic and healthy cows in dry, pre-parturition, and post-parturition periods. Combined transcriptomics and metabolomics analyses identified significant enrichment in the glucagon signaling pathway and the lysine degradation signaling pathway in dry, periparturient, and postpartum ketotic cows. PRKAB2 and SETMAR-key DEGs of the glucagon signaling pathway and lysine degradation signaling pathway, respectively-can be used as key marker genes for determining the early onset of ketosis in dairy cows.PMID:39187030 | DOI:10.1016/j.ygeno.2024.110927

J Ethnopharmacol. 2024 Aug 24:118736. doi: 10.1016/j.jep.2024.118736. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined.AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation.MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods.RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. with a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species.CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.PMID:39186991 | DOI:10.1016/j.jep.2024.118736

Plant Physiol Biochem. 2024 Aug 23;215:109066. doi: 10.1016/j.plaphy.2024.109066. Online ahead of print.ABSTRACTThe study aims to explore the natural variation in the metabolome of different populations of the invasive plant Carpobrotus from different genetic clusters and geographical origins to enhance our comprehension of its involvement in the adaptation process and phenotypic diversity. The metabolomic profile of shoots was analysed in four populations from two different genetic clusters (Cluster A: Cádiz and A Lanzada; Cluster B: La Marina and Samil) and two different biogeographical regions in Spain (Atlantic: Samil and A Lanzada; Mediterranean: Cádiz and La Marina), collected in the field and subsequently grown in the greenhouse. In addition, climatic, and physiological parameters were analysed. The Mediterranean populations (Cádiz and La Marina) showed lower initial weight and length measurements in morphological parameters than the Atlantic populations. On the contrary, only root parameters showed significant differences in growth parameters among populations. The analysis of ion levels revealed a consistent pattern of higher concentrations in shoots compared to roots, with significant differences among populations, particularly in sodium (Na+) and chlorides (Cl-) levels. Regarding metabolomic analysis, clear correlations between the metabolome, genetic and climatic conditions of Carpobrotus sp.pl populations are described. Pairwise comparisons using t-tests and Principal Component Analysis (PCA) indicated that the differences in metabolomic profile between the Samil and La Marina populations, which correspond to the same genetic cluster (cluster B), were smaller than in the rest of the comparisons indicating that populations from the same genetic cluster were more similar metabolically than those from the same climatic region. The study identified key metabolites representative of each cluster, with significant differences in amino acids, organic acids, and sugars contributing to the variation among populations. Pathway analysis highlighted the impact of climatic conditions on metabolic pathways, particularly in populations from Cluster A. In conclusion, the different populations were more similar according to the genetic cluster than to the climatic region of origin when studied at the metabolomic level. Consequently, the metabolites more representative of each cluster were also identified.PMID:39186850 | DOI:10.1016/j.plaphy.2024.109066

Can J Physiol Pharmacol. 2024 Aug 26. doi: 10.1139/cjpp-2024-0201. Online ahead of print.ABSTRACTSarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, and frailty which underscore the complexity. Despite recent advances in metabolomics and other omics data for early detection and treatment, the precise characterization and diagnosis of sarcopenia remains challenging. In the present review we provide an overview of the complex metabolic mechanisms that underlie sarcopenia, with particular emphasis on protein, lipid, carbohydrate, and bone metabolism. The review highlights the importance of leucine and other amino acids in promoting muscle protein synthesis and clarifies the critical role played by amino acid metabolism in preserving muscular health. In addition, the review provides insights regarding lipid metabolism on sarcopenia, with an emphasis on the effects of inflammation and insulin resistance. The review also emphasizes the complex relationship between bone and muscle health by highlighting the interaction between sarcopenia and bone metabolism. Furthermore, the review outlines various therapeutic approaches and potential biomarkers for diagnosing sarcopenia. These include pharmacological strategies such as hormone replacement therapy and anabolic steroids as well as lifestyle modifications such as exercise, nutrition, and dietary changes.PMID:39186818 | DOI:10.1139/cjpp-2024-0201

PLoS One. 2024 Aug 26;19(8):e0308405. doi: 10.1371/journal.pone.0308405. eCollection 2024.ABSTRACTThe archaeal isolate J.3.6.1-F.2.7.3T was obtained from an anaerobic enrichment culture, where it may play an important role in methane production during pyrite formation. The new isolate formed a species-level clade with Methanospirillum hungatei strains GP1 and SK, which is separate from the type strain JF-1T. Cultivation-independent surveys indicate the occurrence of this phylogenetic group in sediments and anaerobic digesters. The abundance of this clade appears to be negatively affected by high nitrogen loads, indicating a sensitivity to certain nitrogen compounds that is not known in M. hungatei JF-1T. The relatively large core genome of this Methanospirillum clade is indicative of niche specialization and efficient control of horizontal gene transfer. Genes for nitrogenase and F420-dependent secondary alcohol dehydrogenase contribute to the metabolic versatility of this lineage. Characteristics of the new isolate such as the ability to utilize 2-propanol as an electron donor or the requirement for acetate as a carbon source are found also in the strains GP1 and SK, but not in the type strain M. hungatei JF-1T. Based on the genomic differences to related species, a new species within the genus Methanospirillum is proposed with the name M. purgamenti sp. nov. The determined phenotypic characteristics support this proposal and indicate a metabolic adaptation to a separate ecological niche.PMID:39186748 | DOI:10.1371/journal.pone.0308405

PLoS One. 2024 Aug 26;19(8):e0309456. doi: 10.1371/journal.pone.0309456. eCollection 2024.ABSTRACTThe metabolomic landscape in myelodysplastic syndrome (MDS) is highly deregulated and presents promising avenues for understanding disease pathogenesis and potential molecular dependencies. Here, we evaluated the transcriptomic landscape in MDS in multiple independent studies focusing more on metabolomics pathways. Identifying molecular dependencies will pave the way for a more precise disease stratification as well as the development of novel personalized treatment strategies. The study adopted a retrospective, cross-sectional approach, utilizing transcriptomic data from multiple MDS studies. The transcriptomic data were then subjected to comprehensive analyses, including differential gene expression, gene enrichment analysis, gene co-expression analysis, protein-protein interaction analyses, and survival analyses. PSAT1 showed a significant upregulation profile in MDS patients. This observed upregulation is correlated with the deregulation of immune-related pathways in MDS samples. This observation suggests a novel role for PSAT1 in immune modulation and potentially in augmenting immune evasion, which may lead to poor prognosis. This was evident in other tumors in the TCGA database, where cancer patients with high PSAT1 expression have a shorter overall survival. This study unveils a novel potential therapeutic avenue in MDS. Identifying the role of the PSAT1 gene sheds light on the disease's intricate biology, highlighting the ongoing cross-talk between metabolism and immune regulation, which may pave the way for innovative treatment modalities.PMID:39186541 | DOI:10.1371/journal.pone.0309456

J Chem Ecol. 2024 Aug 26. doi: 10.1007/s10886-024-01538-2. Online ahead of print.ABSTRACTPlants defend themselves chemically against herbivory through secondary metabolites and phytohormones. Few studies have investigated how constitutive variation in secondary metabolites contributes to systemic herbivory response. We hypothesized that plants with lower constitutive defenses would induce a stronger phytohormone response to spatially separated herbivory than plants with high constitutive defense. We used growth chamber bioassays to investigate how aboveground herbivory by Colorado potato beetle (Leptinotarsa decemlineata, CPB) and belowground herbivory by northern root-knot nematode (Meloidogyne hapla, RKN) altered phytohormones and glycoalkaloids in roots and shoots of two lines of wild potato (Solanum chacoense). These lines had different constitutive levels of chemical defense, particularly leptine glycoalkaloids, which are only present in aboveground tissues. We also determined how these differences influenced the preference and performance of CPB. The susceptible wild potato line responded to aboveground damage by CPB through induction of jasmonic acid (JA) and OPDA. However, when challenged by both RKN and CPB, the susceptible line retained high levels of JA, but not OPDA. Beetles gained more mass after feeding on the susceptible line compared to the resistant line, but were not affected by nematode presence. Belowground, JA, JA-Isoleucine, and OPDA were higher in the resistant line compared to the susceptible line, and some compounds demonstrated response to local herbivory. In contrast, the susceptible line did not induce phytohormone defenses belowground. These findings allow us to predict that constitutive level of defense may influence the threshold of herbivory that may lead to plant-mediated effects on spatially separated herbivores.PMID:39186175 | DOI:10.1007/s10886-024-01538-2

Phytopathology. 2024 Aug 26. doi: 10.1094/PHYTO-04-24-0151-R. Online ahead of print.ABSTRACTIn soil-borne diseases, the plant-pathogen interaction begins as soon as the seed germinates and develops into a seedling. Aphanomyces euteiches, an oomycete, stays dormant in soil and gets activated by sensing the host through chemical signals present in the root exudates. The composition of plant exudates may, thus, play an important role during the early phase of infection. To better understand the role of root exudates in plant resistance, we investigated the interaction between partially resistant lines (PI660736 and PI557500) and susceptible pea cultivars (CDC Meadow and AAC Chrome) against Aphanomyces euteiches during the pre-invasion phase. The root exudates of two sets of cultivars clearly distinguished from each other in inducing oospore germination. PI557500 root exudate not only had diminished induction but also inhibited the oospore germination. The contrast between the root exudates of resistance and susceptible cultivars was reflected in their metabolic profiles. Data from fractionation and oospore germination inhibitory experiments identified a group of saponins that accumulated differentially in susceptible and resistant cultivars. We detected 56 saponins and quantified 44 of them in pea root and 30 from root exudate; the majority of them, especially Soyasaponin I and dehydrosoyasaponin I with potent in vitro inhibitory activities, were present in significantly higher amounts in both roots and root exudates of PI660736 and PI557500 as compared to Meadow and Chrome. Our results provide evidence for saponins as deterrents against Aphanomyces euteiches, which might have contributed to the resistance against root rot in the studied pea cultivars.PMID:39186063 | DOI:10.1094/PHYTO-04-24-0151-R

J Toxicol Environ Health A. 2024 Aug 26:1-14. doi: 10.1080/15287394.2024.2393770. Online ahead of print.ABSTRACTDry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1β), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.PMID:39185961 | DOI:10.1080/15287394.2024.2393770

Ann Clin Transl Neurol. 2024 Aug 26. doi: 10.1002/acn3.52167. Online ahead of print.ABSTRACTBACKGROUND: Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear.OBJECTIVE: Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing-remitting MS (RRMS).METHODS: Thirty-one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality-of-life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed-effects models.RESULTS: Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p-value <0.001, coefficient: -0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p-value = 0.016, coefficient: -0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e-01, 95% CI: 6.83e-02, 9.09e-01, p-value = 3.15E-02).INTERPRETATION: In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.PMID:39185939 | DOI:10.1002/acn3.52167

Hepatol Commun. 2024 Aug 26;8(9):e0523. doi: 10.1097/HC9.0000000000000523. eCollection 2024 Sep 1.ABSTRACTBACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. Sex and age affect MASLD prevalence and pathophysiology. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex-associated and age-associated mechanisms underlying the pathophysiology remain poorly understood. This knowledge gap limits the development of personalized sex-specific and age-specific drug treatments.METHODS: Young (7 wk) and aged (52 wk) male and female mice were fed a high-fat diet (HFD) or low-fat diet. Liver metabolome (>600 molecules) and transcriptome profiles were analyzed.RESULTS: Male and female mice fed an HFD developed obesity, glucose intolerance, and hepatic steatosis. However, fasting blood glucose, insulin, and serum alanine aminotransferase levels were higher in males fed an HFD, indicating a more severe metabolic disease. In addition, males showed significant increases in liver diacylglycerides and glycosylceramides (known mediators of insulin resistance and fibrosis), and more changes in the transcriptome: extracellular matrix organization and proinflammatory genes were elevated only in males. In contrast, no major increase in damaging lipid classes was observed in females fed an HFD. However, aging affected the liver to a greater extent in females. Acylcarnitine levels were significantly reduced, suggestive of changes in fatty acid oxidation, and broad changes in the transcriptome were observed, including reduced oxidative stress response gene expression and alterations in lipid partitioning genes.CONCLUSIONS: Here, we show distinct responses to an HFD between males and females. Our study underscores the need for using both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals.PMID:39185904 | DOI:10.1097/HC9.0000000000000523

ACS Chem Neurosci. 2024 Aug 26. doi: 10.1021/acschemneuro.4c00231. Online ahead of print.ABSTRACTIn recent years, there has been a drastic surge in neurological disorders with sporadic cases contributing more than ever to their cause. Radiation exposure through diagnostic or therapeutic routes often results in neurological injuries that may lead to neurodegenerative pathogenesis. However, the underlying mechanisms regulating the neurological impact of exposure to near-low doses of ionizing radiation are not known. In particular, the neurological changes caused by metabolomic reprogramming have not yet to be elucidated. Hence, in the present study, C57BL/6 mice were exposed to a single whole-body X-ray dose of 0.5 Gy, and 14 days post-treatment, the hippocampus was subjected to metabolomic analysis. The hippocampus of the IR animals showed significant alterations in 15 metabolites, which aligned with altered tyrosine, phenylalanine, and alpha-linolenic acid metabolism and the biosynthesis of unsaturated fatty acids. Furthermore, a multiomics interaction network comprising metabolomics and RNA sequencing data analysis provided insights into gene-metabolite interactions. Tyrosine metabolism was revealed to be the most altered, which was demonstrated by the interaction of several crucial genes and metabolites. The present study revealed the regulation of low-dose radiation-induced neurotoxicity at the metabolomic level and its implications for the pathogenesis of neurological disorders. Present study provides novel insights into metabolomic pathways altered following near-low-dose IR exposure and its link withneurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.PMID:39185768 | DOI:10.1021/acschemneuro.4c00231

Rapid Commun Mass Spectrom. 2024 Oct 30;38(20):e9893. doi: 10.1002/rcm.9893.ABSTRACTRATIONALE: Anemarrhenae Rhizoma (AR) has been a frequently utilized traditional Chinese medicine (TCM) for an extended period, with its salt-processed variant being a prevalent application form. Contemporary pharmacological investigations have demonstrated that the salt-processed iteration exhibits a multitude of markedly augmented pharmacological properties. However, whether the pharmacodynamic material basis of this change is related to volatile substances remains unclear. The aim of this study was to develop a strategy to screen volatile pharmacodynamic substances in AR and salt-processed AR (SAR).METHODS: A comprehensive approach was developed to identify volatile pharmacodynamic compounds by integrating plant metabolomics, target network pharmacology, and molecular docking technology. Plant metabolomics using GC-MS analysis was conducted to identify volatile chemical markers distinguishing between AR and SAR. Subsequently, network pharmacology was utilized to investigate the correlation between chemical markers and associated diseases. Following this, molecular docking technology was utilized to explore the correlation between chemical markers and disease targets, resulting in the discovery of potential quality control markers.RESULTS: Fifty volatile compounds were isolated and identified in the salt of AR and SAR. The findings from plant metabolomics analysis demonstrated a distinct differentiation, revealing 13 volatile chemical markers that distinguish between AR and SAR. A target (PPARG) associated with diabetes was identified through target network pharmacology analysis. Thirteen volatile components were subsequently chosen as potential quality markers, taking into account their hypoglycemic activity.CONCLUSIONS: The method developed provides a novel strategy for the identification of pharmacophores in AR and SAR, as well as establishing a foundation for the exploration of the volatile differential components and pharmacodynamics in various processed products of TCMs. Additionally, the findings of this study can serve as a theoretical framework for the development and utilization of volatile components in AR and its processed derivatives.PMID:39185578 | DOI:10.1002/rcm.9893

Front Pharmacol. 2024 Aug 9;15:1434136. doi: 10.3389/fphar.2024.1434136. eCollection 2024.ABSTRACTINTRODUCTION: Overexposure to ultraviolet (UV) light is known to cause damage to the skin, leading to sunburn and photo-aging. Chemical sunscreen products may give rise to health risks including phototoxicity, photosensitivity, and photosensitivity. Natural polysaccharides have attracted considerable interests due to diverse biological activities.METHODS: A novel polysaccharide isolated was purified and structurally characterized using chemical methods followed by HPLC, GLC-MS, as well as 1D and 2D NMR spectroscopy. The photoprotective effect of the EPS on UVB-induced damage was assessed in vitro using cultured keratinocytes and in vivo using C57BL/6 mouse models.RESULTS: The average molecular weight of the EPS was 5.48 × 106 Da, composed of glucose, mannose and galactose residues at a ratio of 2:2:1. The repeating units of the EPS were →3)-β-D-Glcp (1→3) [β-D-Galp (1→2)-α-D-Glcp (1→2)]-α-D-Manp (1→3)-α-D-Manp (1→. In cultured keratinocytes, the EPS reduced cytotoxicity and excessive ROS production induced by UVB irradiation. The EPS also exhibits an inhibitory effect on oxidative stress, inflammation, and collagen degradation found in the photodamage in mice. 1H NMR-based metabolomics analysis for skin suggested that the EPS partly reversed the shifts of metabolic profiles of the skin in UVB-exposed mice.CONCLUSION: The EPS exhibits skin photoprotective effects through regulating oxidative stress both in vivo and in vitro. Our findings highlight that the EPS is a potential candidate in sunscreen formulations for an efficient solution to UVB radiation.PMID:39185320 | PMC:PMC11341463 | DOI:10.3389/fphar.2024.1434136