PubMed

Plant Physiol Biochem. 2024 May 25;212:108773. doi: 10.1016/j.plaphy.2024.108773. Online ahead of print.ABSTRACTThe mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.PMID:38820912 | DOI:10.1016/j.plaphy.2024.108773

Poult Sci. 2024 May 16;103(8):103867. doi: 10.1016/j.psj.2024.103867. Online ahead of print.ABSTRACTThe chicken comb is an essential secondary sexual characteristic to measure sexual maturity and is closely related to reproductive performance. Pendulous comb (PC) and upright comb (UC) are 2 common comb phenotypes in hens, which have been highly associated with egg production performance. However, the reasons for the formation of PC remain undetermined. In this study, we first characterized the PC and UC chicken at start (at 175 d age), peak (at 217 d age), and postlaying (at 300 d age) and found that PC and UC could transform for each other. Furthermore, we suggested that PC chicken demonstrated better egg production performance than UC chicken, especially characterizing comb type in the start-laying period. Moreover, we performed histological evaluation of PC and UC tissue, which suggested that the low density of collagen fibers and acid mucopolysaccharides might lead to the formation of PC. To further explore the possible reasons for PC formation, we performed an untargeted metabolomic analysis of serum between PC and UC chicken in the start, peak, and postlaying periods. The enrichment analysis of period-unique differentially expressed metabolites (DEMs) between PC and UC showed that the different metabolic pathways and nutritional levels might contribute to the formation of PC in the different laying periods. Our research provided critical insights into the phenotypic diversity of chicken comb, establishing a foundation for early selection of chicken egg production performance.PMID:38820880 | DOI:10.1016/j.psj.2024.103867

J Pharm Biomed Anal. 2024 May 26;247:116240. doi: 10.1016/j.jpba.2024.116240. Online ahead of print.ABSTRACTSerum 1H NMR metabolomics has been used as a diagnostic tool for screening type 2 diabetes (T2D) with chronic kidney disease (CKD) as comorbidity. This work aimed to evaluate 1H NMR data to detect the initial kidney damage and CKD in T2D subjects, through multivariate statistical analysis. Clinical data and biochemical parameters were obtained for classifying five experimental groups using KDIGO guidelines: Control (healthy subjects), T2D, T2D-CKD-mild, T2D-CKD-moderate, and T2D-CKD-severe. Serum 1H NMR spectra were recorded to follow two strategies: one based on metabolite-to-creatinine (Met/Cr) ratios as targeted metabolomics, and the second one based on untargeted metabolomics from the 1H NMR profile. A prospective biomarkers panel of the early stage of T2D-CKD based in metabolite-to-creatinine ratio (ornithine/Cr, serine/Cr, mannose/Cr, acetate/Cr, acetoacetate/Cr, formate/Cr, and glutamate/Cr) was proposed. Later, a statistical model based on non-targeted metabolomics was used to predict initial CKD, and its metabolic pathway analysis allowed identifying the most affected pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine degradation; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and histidine metabolism. Nonetheless, further studies with a larger cohort are advised to precise ranges in metabolite-to-creatinine ratios and evaluate the prediction pertinency to detect initial CKD in T2D patients in both statistical models proposed.PMID:38820837 | DOI:10.1016/j.jpba.2024.116240

J Pharm Biomed Anal. 2024 May 29;247:116262. doi: 10.1016/j.jpba.2024.116262. Online ahead of print.ABSTRACTPoria cocos (Schw.) Wolf (PCW) are the dried sclerotia of Poaceae fungus Poria cocos that contain many biological activity ingredients such as polysaccharides and triterpenoids. The carbohydrates from Poria cocos have been proven to possess anti-inflammatory and antioxidant effects. This study aimed to investigate the impact and mechanism of Poria cocos oligosaccharides (PCO) protecting mice against acute lung injury (ALI). We examined the histopathological analysis of lung injury, inflammatory, and edema levels to evaluate the benefits of PCO during ALI. As a result, PCO improved the lipopolysaccharide (LPS) induced lung injury and decreased the inflammatory cytokines of lung tissue. Simultaneously, PCO alleviated lung edema by regulating the expression of aquaporin5 (AQP5) and epithelial Na+ channel protein (ENaC-α). Additionally, untargeted metabolomics was performed on the plasma of ALI mice via HUPLC-Triple-TOF/MS. The results indicated that linoleic acid, linolenic acid, arachidonic acid, carnosine, glutamic acid, and 1-methylhistamine were the biomarkers in ALI mice. Besides, metabolic pathway analysis suggested PCO affected the histidine and fatty acid metabolism, which were closely associated with inflammation and oxidative reaction of the host. Consequently, the effects of PCO inhibiting inflammation and edema might relate to the reducing pro-inflammatory mediators and the reverse of abnormal metabolic pathways.PMID:38820835 | DOI:10.1016/j.jpba.2024.116262

J Hazard Mater. 2024 May 29;474:134767. doi: 10.1016/j.jhazmat.2024.134767. Online ahead of print.ABSTRACTEcological risk of micro/nano-plastics (MPs/NPs) has become an important environmental issue. Microcystin-leucine-arginine (MC-LR) produced by Microcystis aeruginosa (M. aeruginosa) is the most common and toxic secondary metabolites (SM). However, the influencing mechanism of MPs and NPs exposure on MC-LR synthesis and release have still not been clearly evaluated. In this work, under both acute (4d) and long-term exposure (10d), only high-concentration (10 mg/L) exposure of amino-modified polystyrene NPs (PS-NH2-NPs) promoted MC-LR synthesis (32.94 % and 42.42 %) and release (27.35 % and 31.52 %), respectively. Mechanistically, PS-NH2-NPs inhibited algae cell density, interrupted pigment synthesis, weakened photosynthesis efficiency, and induced oxidative stress, with subsequent enhancing the MC-LR synthesis. Additionally, PS-NH2-NPs exposure up-regulated MC-LR synthesis pathway genes (mcyA, mcyB, mcyD, and mcyG) combined with significantly increased metabolomics (Leucine and Arginine), thereby enhancing MC-LR synthesis. PS-NH2-NPs exposure enhanced the MC-LR release from M. aeruginosa via up-regulated MC-LR transport pathway genes (mcyH) and the shrinkage of plasma membrane. Our results provide new insights into the long-time coexistence of NPs with algae in freshwater systems might pose a potential threat to aquatic environments and human health.PMID:38820757 | DOI:10.1016/j.jhazmat.2024.134767

J Hazard Mater. 2024 May 29;474:134768. doi: 10.1016/j.jhazmat.2024.134768. Online ahead of print.ABSTRACTCadmium (Cd) and microplastics (MPs) gradually increased to be prevalent contaminants in soil, it is important to understand their combined effects on different soil-plant systems. We studied how different doses of polylactic acid (PLA) and polyethylene (PE) affected Cd accumulation, pakchoi growth, soil chemical and microbial properties, and metabolomics in two soil types. We found that high-dose MPs decreased Cd accumulation in plants in red soil, while all MPs decreased Cd bioaccumulation in fluvo-aquic soil. This difference was primarily attributed to the increase in dissolved organic carbon (DOC) and pH in red soil by high-dose MPs, which inhibited Cd uptake by plant roots. In contrast, MPs reduced soil nitrate nitrogen and available phosphorus, and weakened Cd mobilization in fluvo-aquic soil. In addition, high-dose PLA proved detrimental to plant health, manifesting in shortened shoot and root lengths. Co-exposure of Cd and MPs induced the shifts in bacterial populations and metabolites, with specific taxa and metabolites closely linked to Cd accumulation. Overall, co-exposure of Cd and MPs regulated plant growth and Cd accumulation by driving changes in soil bacterial community and metabolic pathways caused by soil chemical properties. Our findings could provide insights into the Cd migration in different soil-plant systems under MPs exposure. ENVIRONMENTAL IMPLICATION: Microplastics (MPs) and cadmium (Cd) are common pollutants in farmland soil. Co-exposure of MPs and Cd can alter Cd accumulation in plants, and pose a potential threat to human health through the food chain. Here, we investigated the effects of different types and doses of MPs on Cd accumulation, plant growth, soil microorganisms, and metabolic pathways in different soil-plant systems. Our results can contribute to our understanding of the migration and transport of Cd by MPs in different soil-plant systems and provide a reference for the control of combined pollution in the future research.PMID:38820749 | DOI:10.1016/j.jhazmat.2024.134768

Phytomedicine. 2024 May 23;130:155774. doi: 10.1016/j.phymed.2024.155774. Online ahead of print.ABSTRACTBACKGROUND: Metabolic and alcohol-associated liver disease (MetALD) shows a high prevalence rate in liver patients, but there is currently no effective treatment for MetALD. As a typical edible traditional Chinese medicinal herb, the anti-inflammatory, antioxidant, and hepatoprotective properties of water extract of Chrysanthemum morifolium Ramat. (WECM) has been demonstrated. However, its therapeutic effect on MetALD and the associated mechanisms remain unclear.PURPOSE: To investigate the underlying mechanisms of WECM against MetALD.METHODS: We constructed a MetALD rat model following a high-fat & high-sucrose plus alcohol diet (HFHSAD). MetALD rats were treated with WECM at 2.1, 4.2, and 8.4 g/kg/d for six weeks. Efficacy was determined, and pathways associated with WECM against MetALD were predicted through serum and hepatic biochemical marker measurement, histopathological section analysis, 16S rDNA sequencing of the gut microbiota and untargeted serum metabolomics analyses. Changes in genes and proteins in the peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) signaling pathways were detected by RT‒PCR and Western blotting.RESULTS: WECM treatment significantly attenuated hepatic steatosis, hyperlipidemia and markers of liver injury in MetALD rats. Moreover, WECM improved vascular endothelial function, hypertension, and systematic oxidative stress. Mechanistically, WECM treatment altered the overall structure of the gut microbiota through maintaining Firmicutes/Bacteroidota ratio and reducing harmful bacterial abundances such as Clostridium, Faecalibaculum, and Herminiimonas. Notably, WECM promoted 15-deoxy-△12, 14-prostaglandin J2 (15d-PGJ2) release and further activated the PPARγ to reduce serum TNF-α, IL-1β, and IL-6 levels. Additionally, WECM upregulated PPARα and downregulated the levels of CD36 and FABP4 to improve lipid metabolism.CONCLUSION: Our findings provide the first evidence that WECM treatment significantly improved hepatic steatosis, oxidative stress and inflammation in MetALD rats by regulating the gut microbiota and activating the 15d-PGJ2/PPARγ and PPARα signaling pathway.PMID:38820659 | DOI:10.1016/j.phymed.2024.155774

Food Chem. 2024 May 21;454:139786. doi: 10.1016/j.foodchem.2024.139786. Online ahead of print.ABSTRACTThis study aims to investigate the potential of using advanced spectroscopies for cheese quality monitoring. For this purpose, six semi-hard cheeses manufactured using lactic acid bacteria (LAB) and/or propionic acid bacteria (PAB) were explored using near-infrared spectroscopy (NIRS) and Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. The spectral data were analyzed using principal component analysis for extraction of possible discriminative patterns in quality parameters. The results show that the green analytical, but primarily bulk-sensitive, NIRS method was able to discriminate the cheese varieties primarily due to differences in the first overtone CH stretching region between 1650 and 1720 nm, in particular by the lactate methylene absorption at 1674 nm. A total of 25 metabolites were identified in the 1H NMR spectra of the cheese extracts, several of which were associated with the LAB and PAB metabolic pathways. PAB-associated metabolites include propionate, acetate, and glutamate, while LAB-associated metabolites include lactate and acetoin among others.PMID:38820640 | DOI:10.1016/j.foodchem.2024.139786

J Am Soc Mass Spectrom. 2024 May 31. doi: 10.1021/jasms.4c00042. Online ahead of print.ABSTRACTTracing in vivo isotope-labeled metabolites has been used to study metabolic pathways or flux analysis. However, metabolic differences between the cells have been often ignored in these studies due to the limitation of solvent-based extraction. Here we demonstrate that the mass spectrometry imaging of in vivo isotope-labeled metabolites, referred to as MSIi, can provide important insights into metabolic dynamics with cellular resolution that may supplement the traditional metabolomics and flux analysis. Developing maize root tips are adopted as a model system for MSIi by supplementing 200 mM [U-13C]glucose in 0.1x Hoagland medium. MSIi data sets were acquired for longitudinal sections of newly grown maize root tips after growing 5 days in the medium. A total of 56 metabolite features were determined to have been 13C-labeled based on accurate mass and the number of carbon matching with the metabolite databases. Simple sugars and their derivatives were fully labeled, but some small metabolites were partially labeled with a significant amount of fully unlabeled metabolites still present, suggesting the recycling of "old" metabolites in the newly grown tissues. Some distinct localizations were found, including the low abundance of hexose and its derivatives in the meristem, the high abundance of amino acids in the meristem, and the localization to epidermal and endodermal cells for lipids and their intermediates. Fatty acids and lipids were slow in metabolic turnover and showed various isotopologue distributions with intermediate building blocks, which may provide flux information for their biosynthesis.PMID:38820138 | DOI:10.1021/jasms.4c00042

J Clin Endocrinol Metab. 2024 May 31:dgae381. doi: 10.1210/clinem/dgae381. Online ahead of print.ABSTRACTCONTEXT: Given the promising effects of prolonged treatment with beta2-agonist on insulin sensitivity in animals and non-diabetic individuals, the beta2-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta2-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance.OBJECTIVE: To assess the impact of beta2-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects.METHODS AND PARTICIPANTS: In a cross-over design, we assessed the effect of beta2-agonist on insulin-stimulated muscle glucose uptake during a 3-h hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant overweight subjects. Two hours into the clamp, we infused beta2-agonist. We collected muscle biopsies before, two hours into and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques.RESULTS: We establish that beta2-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta2-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. While both beta2-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta2-agonist attenuated incorporation of glucose into glycogen.CONCLUSIONS: Our findings suggest that beta2-agonist inhibits glycogenesis while intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta2-agonist.PMID:38820114 | DOI:10.1210/clinem/dgae381

Anticancer Drugs. 2024 Jun 3. doi: 10.1097/CAD.0000000000001626. Online ahead of print.ABSTRACTOBJECTIVE: To explore the mechanism of anlotinib resistance in thyroid carcinoma.METHODS: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways.RESULTS: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-β, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target.CONCLUSION: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.PMID:38820067 | DOI:10.1097/CAD.0000000000001626

J Parkinsons Dis. 2024 May 24. doi: 10.3233/JPD-240075. Online ahead of print.ABSTRACTBACKGROUND: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.OBJECTIVE: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains.METHODS: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) across ten brain regions. Case-control differences were determined by nonparametric Mann-Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD.RESULTS: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum.CONCLUSIONS: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.PMID:38820022 | DOI:10.3233/JPD-240075

J Agric Food Chem. 2024 May 31. doi: 10.1021/acs.jafc.4c02805. Online ahead of print.ABSTRACTObtaining a microorganism strain with a broad-spectrum resistance property and highly efficient antifungal activity is important to the biocontrol strategy. Herein, a marine Streptomyces sp. HNBCa1 demonstrated a broad-spectrum resistance to 17 tested crop pathogenic fungi and exhibited a high biocontrol efficiency against mango anthracnose and banana fusarium wilt. To uncover the critical bioactive secondary metabolites basis, genome assembly and annotation, metabolomic analysis, and a semipreparative HPLC-based activity-guide method were employed. Finally, geldanamycin and ectoine involved in codifferential secondary metabolites were also found to be related to biosynthetic gene clusters in the genome of HNBCa1. Reblastatin and geldanamycin were uncovered in response to broad-spectrum resistance to the 17 crop pathogenic fungi. Our results suggested that reblastatin and geldanamycin were critical to maintaining the broad-spectrum resistance property and highly efficient antifungal activity of HNBCa1, which could be further developed as a biological control agent to control crop fungal diseases.PMID:38819965 | DOI:10.1021/acs.jafc.4c02805

JAMA Netw Open. 2024 May 1;7(5):e2414322. doi: 10.1001/jamanetworkopen.2024.14322.ABSTRACTIMPORTANCE: Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited.OBJECTIVES: To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction.DESIGN, SETTING, AND PARTICIPANTS: This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023.EXPOSURES: Mediterranean diet score (range, 0-9) was computed based on 9 dietary components.MAIN OUTCOME AND MEASURES: Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association.RESULTS: Among 25 315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24 036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend < .001). Further adjusting for lifestyle factors attenuated the risk reductions, but they remained statistically significant (middle adherence group: HR, 0.92 [95% CI, 0.85-0.99]; upper adherence group: HR, 0.89 [95% CI, 0.82-0.98]; P for trend = .001). Of the biomarkers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk (explaining 14.8% and 13.0%, respectively, of the association), followed by triglyceride-rich lipoproteins (10.2%), body mass index (10.2%), and insulin resistance (7.4%). Other pathways, including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension, had smaller contributions (<3%).CONCLUSIONS AND RELEVANCE: In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors.PMID:38819819 | DOI:10.1001/jamanetworkopen.2024.14322

J Sep Sci. 2024 Jun;47(11):e2400164. doi: 10.1002/jssc.202400164.ABSTRACTOxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.PMID:38819794 | DOI:10.1002/jssc.202400164

J Sep Sci. 2024 Jun;47(11):e2400090. doi: 10.1002/jssc.202400090.ABSTRACTEphedra herb (EH), an important medicine prescribed in herbal formulas by Traditional Chinese Medicine practitioners, has been widely used in the treatment of viral pneumonia in China. However, the molecular basis of EH in viral pneumonia remains unclear. In this study, a ternary correlation multi-symptom network strategy was established based on in vivo chemical profile identification and metabolomics to explore the molecular basis of EH against viral pneumonia. Results showed that 143 compounds of EH and 70 prototype components were identified in vivo. EH could reduce alveolar-capillary barrier disruption in rats with viral pneumonia and significantly downregulate the expression of inflammatory factors and bronchoalveolar lavage fluid. Plasma metabolomics revealed that EH may be involved in the regulation of arachidonic acid, tryptophan, tyrosine, nicotinate, and nicotinamide metabolism. The multi-symptom network showed that 12 compounds have an integral function in the treatment of viral pneumonia by intervening in many pathways related to viruses, immunity and inflammation, and lung injury. Further verification demonstrated that sinapic acid and frambinone can regulate the expression of related genes. It has been shown to be a promising representative of the pharmacological constituents of ephedra.PMID:38819782 | DOI:10.1002/jssc.202400090

Parasitol Res. 2024 May 31;123(6):229. doi: 10.1007/s00436-024-08244-8.ABSTRACTThe intricate relationships between parasites and hosts encompass a wide range of levels, from molecular interactions to population dynamics. Parasites influence not only the physiological processes in the host organism, but also the entire ecosystem, affecting mortality of individuals, the number of offspring through parasitic castration, and matter and energy cycles. Understanding the molecular mechanisms that govern host-parasite relationships and their impact on host physiology and environment remains challenging. In this study, we analyzed how infection with Microphallus trematodes affects the metabolome of two Littorina snail species inhabiting different intertidal zone shore levels. We applied non-targeted GC-MS-based metabolomics to analyze biochemical shifts induced by trematode infection in a host organism. We have identified changes in energy, amino acid, sugar, and lipid metabolism. In particular, we observed intensified amino acid catabolism and nitrogenous catabolites (glutamine, urea) production. These changes primarily correlated with infection and interspecies differences of the hosts rather than shore level. The changes detected in the host metabolism indicate that other aspects of life may have been affected, both within the host organism and at a supra-organismal level. Therefore, we explored changes in microbiota composition, deviations in the host molluscs behavior, and acetylcholinesterase activity (ACE, an enzyme involved in neuromuscular transmission) in relation to infection. Infected snails displayed changes in their microbiome composition. Decreased ACE activity in snails was associated with reduced mobility, but whether it is associated with trematode infection remains unclear. The authors suggest a connection between the identified biochemical changes and the deformation of the shell of molluscs, changes in their behavior, and the associated microbiome. The role of parasitic systems formed by microphallid trematodes and Littorina snails in the nitrogen cycle at the ecosystem level is also assumed.PMID:38819740 | DOI:10.1007/s00436-024-08244-8

Plant Cell Rep. 2024 May 31;43(6):157. doi: 10.1007/s00299-024-03244-5.ABSTRACTCmMYB308 was identified as a key regulator in chrysanthemum flower color variation from purple to pink by conducting transcriptome and metabolome analysis. CmMYB308 can inhibit anthocyanin biosynthesis by suppressing the expression of CmPAL, CmC4H, and Cm4CL. Flower color variation is a widespread natural occurrence that plays a significant role in floral breeding. We discovered a variation in the flower of the chrysanthemum cultivar 'Dante Purple' (abbreviated as 'DP'), where the flower color shifted from purple to pink. We successfully propagated these pink flowers through tissue culture and designated them as DPM. By conducting transcriptome and metabolome analysis, we identified a reduction in the expression of critical genes involved in anthocyanin biosynthesis-CmPAL, CmC4H, and Cm4CL-in the DPM. This downregulation led to an accumulation of phenylalanine and cinnamic acid within the general phenylpropanoid pathway (GPP), which prevented their conversion into cyanidin and cyanidin 3-glucoside. As a result, the flowers turned pink. Additional transformation and biochemical experiments confirmed that the upregulation of CmMYB308 gene expression in the DPM directly suppressed CmPAL-1 and CmC4H genes, which indirectly affected Cm4CL-3 expression and ultimately inhibited anthocyanin biosynthesis in the DPM. This study offers a preliminary insight into the molecular mechanism underlying chrysanthemum flower color mutation, paving the way for genetic improvements in chrysanthemum flower color breeding.PMID:38819475 | DOI:10.1007/s00299-024-03244-5

Appl Microbiol Biotechnol. 2024 May 31;108(1):352. doi: 10.1007/s00253-024-13199-y.ABSTRACTFucoxanthin is a versatile substance in the food and pharmaceutical industries owing to its excellent antioxidant and anti-obesity properties. Several microalgae, including the haptophyte Pavlova spp., can produce fucoxanthin and are potential industrial fucoxanthin producers, as they lack rigid cell walls, which facilitates fucoxanthin extraction. However, the commercial application of Pavlova spp. is limited owing to insufficient biomass production. In this study, we aimed to develop a mixotrophic cultivation method to increase biomass and fucoxanthin production in Pavlova gyrans OPMS 30543X. The effects of culturing OPMS 30543X with different organic carbon sources, glycerol concentrations, mixed-nutrient conditions, and light intensities on the consumption of organic carbon sources, biomass production, and fucoxanthin accumulation were analyzed. Several organic carbon sources, such as glycerol, glucose, sucrose, and acetate, were examined, revealing that glycerol was well-consumed by the microalgae. Biomass and fucoxanthin production by OPMS 30543X increased in the presence of 10 mM glycerol compared to that observed without glycerol. Metabolomic analysis revealed higher levels of the metabolites related to the glycolytic, Calvin-Benson-Bassham, and tricarboxylic acid cycles under mixotrophic conditions than under autotrophic conditions. Cultures grown under mixotrophic conditions with a light intensity of 100 µmol photons m-2 s-1 produced more fucoxanthin than autotrophic cultures. Notably, the amount of fucoxanthin produced (18.9 mg/L) was the highest reported thus far for Pavlova species. In conclusion, the use of mixotrophic culture is a promising strategy for increasing fucoxanthin production in Pavlova species. KEY POINTS: • Glycerol enhances biomass and fucoxanthin production in Pavlova gyrans • Metabolite levels increase under mixotrophic conditions • Mixotrophic conditions and medium-light intensity are appropriate for P. gyrans.PMID:38819468 | DOI:10.1007/s00253-024-13199-y

J Bacteriol. 2024 May 31:e0005224. doi: 10.1128/jb.00052-24. Online ahead of print.ABSTRACTMicrobes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux. Here, we demonstrate that deletion of the Bacillus subtilis yqgC-sodA (YS) complex operon, but not deletion of the individual genes, causes hypersensitivity to manganese (Mn). YqgC is an integral membrane protein of unknown function, and SodA is a Mn-dependent superoxide dismutase (MnSOD). The YS strain has reduced expression of two Mn efflux proteins, MneP and MneS, consistent with the observed Mn sensitivity. The YS strain accumulated high levels of Mn, had increased reactive radical species (RRS), and had broad metabolic alterations that can be partially explained by the inhibition of Mg-dependent enzymes. Although the YS operon deletion strain and an efflux-deficient mneP mneS double mutant both accumulate Mn and have similar metabolic perturbations, they also display phenotypic differences. Several mutations that suppressed Mn intoxication of the mneP mneS efflux mutant did not benefit the YS mutant. Further, Mn intoxication in the YS mutant, but not the mneP mneS strain, was alleviated by expression of Mg-dependent, chorismate-utilizing enzymes of the menaquinone, siderophore, and tryptophan (MST) family. Therefore, despite their phenotypic similarities, the Mn sensitivity in the mneP mneS and the YS deletion mutants results from distinct enzymatic vulnerabilities.IMPORTANCEBacteria require multiple trace metal ions for survival. Metal homeostasis relies on the tightly regulated expression of metal uptake, storage, and efflux proteins. Metal intoxication occurs when metal homeostasis is perturbed and often results from enzyme mis-metalation. In Bacillus subtilis, Mn-dependent superoxide dismutase (MnSOD) is the most abundant Mn-containing protein and is important for oxidative stress resistance. Here, we report novel roles for MnSOD and a co-regulated membrane protein, YqgC, in Mn homeostasis. Loss of both MnSOD and YqgC (but not the individual proteins) prevents the efficient expression of Mn efflux proteins and leads to a large-scale perturbation of the metabolome due to inhibition of Mg-dependent enzymes, including key chorismate-utilizing MST (menaquinone, siderophore, and tryptophan) family enzymes.PMID:38819154 | DOI:10.1128/jb.00052-24