PubMed

Virulence. 2024 Dec;15(1):2367647. doi: 10.1080/21505594.2024.2367647. Epub 2024 Jun 17.ABSTRACTThe global surge in multidrug-resistant bacteria owing to antibiotic misuse and overuse poses considerable risks to human and animal health. With existing antibiotics losing their effectiveness and the protracted process of developing new antibiotics, urgent alternatives are imperative to curb disease spread. Notably, improving the bactericidal effect of antibiotics by using non-antibiotic substances has emerged as a viable strategy. Although reduced nicotinamide adenine dinucleotide (NADH) may play a crucial role in regulating bacterial resistance, studies examining how the change of metabolic profile and bacterial resistance following by exogenous administration are scarce. Therefore, this study aimed to elucidate the metabolic changes that occur in Edwardsiella tarda (E. tarda), which exhibits resistance to various antibiotics, following the exogenous addition of NADH using metabolomics. The effects of these alterations on the bactericidal activity of neomycin were investigated. NADH enhanced the effectiveness of aminoglycoside antibiotics against E. tarda ATCC15947, achieving bacterial eradication at low doses. Metabolomic analysis revealed that NADH reprogrammed the ATCC15947 metabolic profile by promoting purine metabolism and energy metabolism, yielding increased adenosine triphosphate (ATP) levels. Increased ATP levels played a crucial role in enhancing the bactericidal effects of neomycin. Moreover, exogenous NADH promoted the bactericidal efficacy of tetracyclines and chloramphenicols. NADH in combination with neomycin was effective against other clinically resistant bacteria, including Aeromonas hydrophila, Vibrio parahaemolyticus, methicillin-resistant Staphylococcus aureus, and Listeria monocytogenes. These results may facilitate the development of effective approaches for preventing and managing E. tarda-induced infections and multidrug resistance in aquaculture and clinical settings.PMID:38884466 | DOI:10.1080/21505594.2024.2367647

Food Chem X. 2024 May 20;22:101470. doi: 10.1016/j.fochx.2024.101470. eCollection 2024 Jun 30.ABSTRACTThe sensory quality of black tea (BT) influenced by various factors, among which tree age is particularly significant. People prefer BT produced by fresh leaves from old tea trees, yet the correlation between tree age and tea quality has not been thoroughly investigated. In this study, we analyzed the quality of BT from young trees (H-JYH) and old trees (H-OJYH) using e-tongue technology and sensory evaluation. Our findings revealed that H-OJYH had stronger sweetness and sourness, richer flavor, and diminished bitter-astringency compared to H-JYH. 1231 non-volatile metabolites and 504 volatile metabolites were discovered by ultra-performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS). L-tartaric acid and trans-citridic acid were found to contribute to increase acidity, and 7,8-dihydroxy-6-methoxycoumarin and d-fructose 6-phosphate were associated with enhanced sweetness in H-OJYH. Additionally, lower levels of octyl gallate and vanillic acid in H-OJYH contributed to the diminished bitter-astringency. β-ionone, 2-phenylethanol and phenylacetaldehyde merged as characteristic compounds of older tree BT with stronger floral and sweet aroma. Our study serves as a guideline to explore the relationship between tree age and tea quality.PMID:38883921 | PMC:PMC11176668 | DOI:10.1016/j.fochx.2024.101470

medRxiv [Preprint]. 2024 Jun 6:2024.06.05.24308502. doi: 10.1101/2024.06.05.24308502.ABSTRACTSerum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.PMID:38883716 | PMC:PMC11178010 | DOI:10.1101/2024.06.05.24308502

Front Endocrinol (Lausanne). 2024 May 31;15:1384115. doi: 10.3389/fendo.2024.1384115. eCollection 2024.ABSTRACTBACKGROUND: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from menopause, ovariectomy or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood.METHODS: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function.RESULTS: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance.CONCLUSION: This study, for the first time, depicts the metabolic landscape of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by menopause.PMID:38883607 | PMC:PMC11176512 | DOI:10.3389/fendo.2024.1384115

Neuropsychiatr Dis Treat. 2024 Jun 12;20:1247-1270. doi: 10.2147/NDT.S459891. eCollection 2024.ABSTRACTBACKGROUND: There is growing interest in the role of physical activity in patients with of Alzheimer's disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors.OBJECTIVE: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-β (Aβ).METHODS: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aβ mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aβ mice.RESULTS: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aβ mice. In the hippocampus of Aβ mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3β and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice.CONCLUSION: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aβ mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.PMID:38883414 | PMC:PMC11180438 | DOI:10.2147/NDT.S459891

Hortic Res. 2024 Apr 9;11(6):uhae105. doi: 10.1093/hr/uhae105. eCollection 2024 Jun.ABSTRACTSaposhnikovia divaricata, 2n = 2x = 16, as a perennial species, is widely distributed in China, Mongolia, Russia, etc. It is a traditional Chinese herb used to treat tetanus, rubella pruritus, rheumatic arthralgia, and other diseases. Here, we assembled a 2.07 Gb and N50 scaffold length of 227.67 Mb high-quality chromosome-level genome of S. divaricata based on the PacBio Sequel II sequencing platform. The total number of genes identified was 42 948, and 42 456 of them were functionally annotated. A total of 85.07% of the genome was composed of repeat sequences, comprised mainly of long terminal repeats (LTRs) which represented 73.7% of the genome sequence. The genome size may have been affected by a recent whole-genome duplication event. Transcriptional and metabolic analyses revealed bolting and non-bolting S. divaricata differed in flavonoids, plant hormones, and some pharmacologically active components. The analysis of its genome, transcriptome, and metabolome helped to provide insights into the evolution of bolting and non-bolting phenotypes in wild and cultivated S. divaricata and lays the basis for genetic improvement of the species.PMID:38883332 | PMC:PMC11179723 | DOI:10.1093/hr/uhae105

J Pestic Sci. 2024 May 20;49(2):104-113. doi: 10.1584/jpestics.D23-065.ABSTRACTRice false smut (RFS) caused by Ustilaginoidea virens is widely distributed in major rice-producing regions. Previous studies have shown that treating RFS with chelerythrine can decrease the germination of fungus spores by 86.7% and induce fungal cell apoptosis. In the present study, the effects of chelerythrine on the metabolism of U. virens explored using metabolomics and analyses of differentially accumulated metabolites and altered metabolic pathways. The top 15 metabolites in random forest analysis were significantly different between groups. In positive ion mode, purine, phenylalanine metabolism, phenylalanine, tyrosine, tryptophan biosynthesis, pyrimidine metabolism, and nitrogen metabolism were dominant. Alanine, aspartate, glutamate metabolism, and phenylalanine metabolism were enriched in negative ion mode. Differentially expressed genes and altered metabolic pathways of U. virens were effected by chelerythrine. The findings support future research on the prevention and treatment of RFS by chelerythrine and provide a theoretical basis for targeted drug delivery.PMID:38882710 | PMC:PMC11176050 | DOI:10.1584/jpestics.D23-065

J Pestic Sci. 2024 May 20;49(2):77-86. doi: 10.1584/jpestics.D23-036.ABSTRACTDimesulfazet can control annual and perennial sedges in rice paddies. Here we assessed its mode of action. We performed a phenotype assay of Arabidopsis, conducted a metabolomic analysis of Echinochloa crus-galli, and analyzed the endogenous concentration of very long-chain fatty acids (VLCFAs) in Schoenoplectiella juncoides. Dimesulfazet treatment caused curling and greening symptoms in the leaves and fiddlehead-like symptoms in the inflorescences of Arabidopsis. These symptoms were visually indistinguishable from those caused by flufenacet and benfuresate, which belong to Herbicide Resistance Action Committee (HRAC) Group 15. We performed GC-MS/MS analysis of primary metabolites and LC-MS analysis of lipids in the herbicide-treated E. crus-galli, followed by Orthogonal Partial Least Squares Discriminant Analysis clustering. The results showed that dimesulfazet belongs to the HRAC Group 15 cluster. The endogenous concentrations of C24:0, C26:0, and C28:0 decreased in dimesulfazet-treated plants as compared to those in the control. Overall, the mode of action of dimesulfazet involves the inhibition of VLCFA biosynthesis.PMID:38882707 | PMC:PMC11176045 | DOI:10.1584/jpestics.D23-036

JHEP Rep. 2024 Mar 18;6(6):101068. doi: 10.1016/j.jhepr.2024.101068. eCollection 2024 Jun.ABSTRACTBACKGROUND & AIMS: Metabolomic and lipidomic analyses provide an opportunity for novel biological insights. Cholangiocarcinoma (CCA) remains a highly lethal cancer with limited response to systemic, targeted, and immunotherapeutic approaches. Using a global metabolomics and lipidomics platform, this study aimed to discover and characterize metabolomic variations and associated pathway derangements in patients with CCA.METHODS: Leveraging a biospecimen collection, including samples from patients with digestive diseases and normal controls, global serum metabolomic and lipidomic profiling was performed on 213 patients with CCA and 98 healthy controls. The CCA cohort of patients included representation of intrahepatic, perihilar, and distal CCA tumours. Metabolome-wide association studies utilizing multivariable linear regression were used to perform case-control comparisons, followed by pathway enrichment analysis, CCA subtype analysis, and disease stage analysis. The impact of biliary obstruction was evaluated by repeating analyses in subsets of patients only with normal bilirubin levels.RESULTS: Of the 420 metabolites that discriminated patients with CCA from controls, decreased abundance of cysteine-glutathione disulfide was most closely associated with CCA. Additional conjugated bile acid species were found in increased abundance even in the absence of clinically relevant biliary obstruction denoted by elevated serum bilirubin levels. Pathway enrichment analysis also revealed alterations in caffeine metabolism and mitochondrial redox-associated pathways in the serum of patients with CCA.CONCLUSIONS: The presented metabolomic and lipidomic profiling demonstrated multiple alterations in the serum of patients with CCA. These exploratory data highlight novel metabolic pathways in CCA and support future work in therapeutic targeting of these pathways and the development of a precision biomarker panel for diagnosis.IMPACT AND IMPLICATIONS: Cholangiocarcinoma (CCA) is a highly lethal hepatobiliary cancer with limited treatment response, highlighting the need for a better understanding of the disease biology. Using a global metabolomics and lipidomics platform, we characterized distinct changes in the serum of 213 patients with CCA compared with healthy controls. The results of this study elucidate novel metabolic pathways in CCA. These findings benefit stakeholders in both the clinical and research realms by providing a foundation for improved disease diagnostics and identifying novel targets for therapeutic design.PMID:38882601 | PMC:PMC11179355 | DOI:10.1016/j.jhepr.2024.101068

Front Plant Sci. 2024 May 31;15:1379299. doi: 10.3389/fpls.2024.1379299. eCollection 2024.ABSTRACTThe commonly used analytical tools for metabolomics cannot directly probe metabolic activities or distinguish metabolite differences between cells and suborgans in multicellular organisms. These issues can be addressed by in-vivo isotope labeling and mass spectrometry imaging (MSI), respectively, but the combination of the two, a newly emerging technology we call MSIi, has been rarely applied to plant systems. In this study, we explored MSIi of Arabidopsis thaliana with D2O labeling to study and visualize D-labeling in three classes of lipids: arabidopsides, chloroplast lipids, and epicuticular wax. Similar to other stress responses, D2O-induced stress increased arabidopsides in an hour, but it was relatively minor for matured plants and reverted to the normal level in a few hours. The D-labeling isotopologue patterns of arabidopsides matched with those of galactolipid precursors, supporting the currently accepted biosynthesis mechanism. Matrix-assisted laser desorption/ionization (MALDI)-MSI was used to visualize the spatiotemporal distribution of deuterated chloroplast lipids, pheophytin a, MGDGs, and DGDGs, after growing day-after-sowing (DAS) 28 plants in D2O condition for 3-12 days. There was a gradual change of deuteration amount along the leaf tissues and with a longer labeling time, which was attributed to slow respiration leading to low D2O concentration in the tissues. Finally, deuterium incorporation in epicuticular wax was visualized on the surfaces of the stem and flower. The conversion efficiency of newly synthesized C30 aldehyde to C29 ketone was very low in the lower stem but very high at the top of the stem near the flower or on the flower carpel. This study successfully demonstrated that MSIi can unveil spatiotemporal metabolic activities in various tissues of A. thaliana.PMID:38882571 | PMC:PMC11176549 | DOI:10.3389/fpls.2024.1379299

Imeta. 2024 Jan 25;3(2):e166. doi: 10.1002/imt2.166. eCollection 2024 Apr.ABSTRACTAsthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.PMID:38882497 | PMC:PMC11170967 | DOI:10.1002/imt2.166

Imeta. 2024 Feb 19;3(2):e176. doi: 10.1002/imt2.176. eCollection 2024 Apr.ABSTRACTMalaria continues to pose a serious global health threat, and artemisinin remains the core drug for global malaria control. However, the situation of malaria resistance has become increasingly severe due to the emergence and spread of artemisinin resistance. In recent years, significant progress has been made in understanding the mechanism of action (MoA) of artemisinin. Prior research on the MoA of artemisinin mainly focused on covalently bound targets that are alkylated by artemisinin-free radicals. However, less attention has been given to the reversible noncovalent binding targets, and there is a paucity of information regarding artemisinin targets at different life cycle stages of the parasite. In this study, we identified the protein targets of artemisinin at different stages of the parasite's intraerythrocytic developmental cycle using a photoaffinity probe. Our findings demonstrate that artemisinin interacts with parasite proteins in vivo through both covalent and noncovalent modes. Extensive mechanistic studies were then conducted by integrating target validation, phenotypic studies, and untargeted metabolomics. The results suggest that protein synthesis, glycolysis, and oxidative homeostasis are critically involved in the antimalarial activities of artemisinin. In summary, this study provides fresh insights into the mechanisms underlying artemisinin's antimalarial effects and its protein targets.PMID:38882489 | PMC:PMC11170969 | DOI:10.1002/imt2.176

Heliyon. 2024 May 23;10(11):e31667. doi: 10.1016/j.heliyon.2024.e31667. eCollection 2024 Jun 15.ABSTRACTOBJECTIVE: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model.METHODS: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis.RESULTS: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered.CONCLUSION: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.PMID:38882385 | PMC:PMC11177062 | DOI:10.1016/j.heliyon.2024.e31667

Plant Environ Interact. 2024 Jun 15;5(3):e10155. doi: 10.1002/pei3.10155. eCollection 2024 Jun.ABSTRACTTo better understand the salt tolerance of the wild rice, Oryza coarctata, root tissue-specific untargeted comparative metabolomic profiling was performed against the salt-sensitive Oryza sativa. Under control, O. coarctata exhibited abundant levels of most metabolites, while salt caused their downregulation in contrast to metabolites in O. sativa. Under control conditions, itaconate, vanillic acid, threonic acid, eicosanoids, and a group of xanthin compounds were comparatively abundant in O. coarctata. Similarly, eight amino acids showed constitutive abundance in O. coarctata. In contrast, under control, glycerolipid abundances were lower in O. coarctata and salt stress further reduced their abundance. Most phospholipids also showed a distribution similar to the glycerolipids. Fatty acyls were however significantly induced in O. coarctata but organic acids were prominently induced in O. sativa. Changes in metabolite levels suggest that there was upregulation of the arachidonic acid metabolism in O. coarctata. In addition, the phenylpropanoid biosynthesis as well as cutin, suberin, and wax biosynthesis were also more enriched in O. coarctata, likely contributing to its anatomical traits responsible for salt tolerance. The comparative variation in the number of metabolites like gelsemine, allantoin, benzyl alcohol, specific phospholipids, and glycerolipids may play a role in maintaining the superior growth of O. coarctata in salt. Collectively, our results offer a comprehensive analysis of the metabolite profile in the roots of salt-tolerant O. coarctata and salt-sensitive O. sativa, which confirm potential targets for metabolic engineering to improve salt tolerance and resilience in commercial rice genotypes.PMID:38882243 | PMC:PMC11179383 | DOI:10.1002/pei3.10155

Drug Des Devel Ther. 2024 Jun 12;18:2227-2248. doi: 10.2147/DDDT.S458983. eCollection 2024.ABSTRACTPURPOSE: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.METHODS: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.RESULTS: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.CONCLUSION: BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.PMID:38882046 | PMC:PMC11180446 | DOI:10.2147/DDDT.S458983

Front Immunol. 2024 May 31;15:1393802. doi: 10.3389/fimmu.2024.1393802. eCollection 2024.ABSTRACTBACKGROUND: Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast cells are heterogeneous, and mast cells from different anatomical sites have been shown to respond differently to certain stimuli and drugs. The origin of the mast cells is therefore of importance when setting up a model system, and human lung mast cells are highly relevant cells to study in the context of asthma. We therefore set out to optimize a protocol of IgE-mediated activation of human lung mast cells.METHODS: Human lung mast cells were extracted from lung tissue obtained from patients undergoing pulmonary resection by enzyme digestion and mechanical disruption followed by CD117 magnetic-activated cell sorting (MACS) enrichment. Different culturing media and conditions for the IgE-mediated degranulation were tested to obtain an optimized method.RESULTS: IgE crosslinking of human lung mast cells cultured in serum-free media gave a stronger response compared to cells cultured with 10% serum. The addition of stem cell factor (SCF) did not enhance the degranulation. However, when the cells were put in fresh serum-free media 30 minutes prior to the addition of anti-IgE antibodies, the cells responded more vigorously. Maximum degranulation was reached 10 minutes after the addition of anti-IgE. Both CD63 and CD164 were identified as stable markers for the detection of degranulated mast cells over time, while the staining with anti-CD107a and avidin started to decline 10 minutes after activation. The levels of CD203c and CD13 did not change in activated cells and therefore cannot be used as degranulation markers of human lung mast cells.CONCLUSIONS: For an optimal degranulation response, human lung mast cells should be cultured and activated in serum-free media. With this method, a very strong and consistent degranulation response with a low donor-to-donor variation is obtained. Therefore, this model is useful for further investigations of IgE-mediated mast cell activation and exploring drugs that target human lung mast cells, for instance, in the context of asthma.PMID:38881896 | PMC:PMC11179429 | DOI:10.3389/fimmu.2024.1393802

Front Microbiol. 2024 May 31;15:1408622. doi: 10.3389/fmicb.2024.1408622. eCollection 2024.ABSTRACTSalt stress is a major abiotic stress that affects the growth of Reaumuria soongorica and many psammophytes in the desert areas of Northwest China. However, various Plant Growth-Promoting Rhizobacteria (PGPR) have been known to play an important role in promoting plant growth and alleviating the damaging effects of salt stress. In this study, three PGPR strains belonging to Bacillaceae were isolated from the rhizosphere of Reaumuria soongorica by morphological and molecular identification. All isolated strains exhibited capabilities of producing IAA, solubilizing phosphate, and fixing nitrogen, and were able to tolerate high levels of NaCl stress, up to 8-12%. The results of the pot-based experiment showed that salt (400 mM NaCl) stress inhibited Reaumuria soongorica seedlings' growth performance as well as biomass production, but after inoculation with strains P2, S37, and S40, the plant's height significantly increased by 26.87, 17.59, and 13.36%, respectively (p < 0.05), and both aboveground and root fresh weight significantly increased by more than 2 times compared to NaCl treatment. Additionally, inoculation with P2, S37, and S40 strains increased the content of photosynthetic pigments, proline, and soluble protein in Reaumuria soongorica seedlings under NaCl stress, while reducing the content of malondialdehyde and soluble sugars. Metabolomic analysis showed that strain S40 induces Reaumuria soongorica seedling leaves metabolome reprogramming to regulate cell metabolism, including plant hormone signal transduction and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Under NaCl stress, inoculation with strain S40 upregulated differential metabolites in plant hormone signal transduction pathways including plant hormones such as auxins (IAA), cytokinins, and jasmonic acid. The results indicate that inoculation with Bacillaceae can promote the growth of Reaumuria soongorica seedlings under NaCl stress and enhance salt tolerance by increasing the content of photosynthetic pigments, accumulating osmoregulatory substances, regulating plant hormone levels This study contributes to the enrichment of PGPR strains capable of promoting the growth of desert plants and has significant implications for the psammophytes growth and development in desert regions, as well as the effective utilization and transformation of saline-alkali lands.PMID:38881656 | PMC:PMC11176432 | DOI:10.3389/fmicb.2024.1408622

NAR Genom Bioinform. 2024 Jun 14;6(2):lqae071. doi: 10.1093/nargab/lqae071. eCollection 2024 Jun.ABSTRACTMass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in mass spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address this pressing need, we developed omicsMIC (mass spectrometry-based omics with Missing values Imputation methods Comparison platform), an interactive platform that provides researchers with a versatile framework to evaluate the performance of 28 diverse imputation methods. omicsMIC offers a nuanced perspective, acknowledging the inherent heterogeneity in biological data and the unique attributes of each dataset. Our platform empowers researchers to make data-driven decisions in imputation method selection based on real-time visualizations of the outcomes associated with different imputation strategies. The comprehensive benchmarking and versatility of omicsMIC make it a valuable tool for the scientific community engaged in mass spectrometry-based omics research. omicsMIC is freely available at https://github.com/WQLin8/omicsMIC.PMID:38881578 | PMC:PMC11177553 | DOI:10.1093/nargab/lqae071

Am J Physiol Regul Integr Comp Physiol. 2024 Jun 17. doi: 10.1152/ajpregu.00056.2024. Online ahead of print.ABSTRACTCentral administration of valine has been shown to cause hyperphagia in fish. Although mechanistic target of rapamycin (mTOR) is involved in this response, the contributions on feed intake of central and peripheral metabolite changes due to excess valine are unknown. Here we investigated whether intracerebroventricular (ICV) injection of valine modulates central and peripheral metabolite profiles and may provide insights into feeding response in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were administered an ICV injection of valine (10 µg · µL-1 at 1 μL·100 g-1 body weight) and the metabolite profile in plasma, hypothalamus, and rest of the brain (comprising of telencephalon, optic tectum, cerebellum, and medulla oblongata) was carried out by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. Valine administration led to a spatially distinct metabolite profile at 1 h post-injection in the brain: enrichment of amino acid metabolism and energy production pathways in the rest of the brain but not in hypothalamus. This suggests a role for extrahypothalamic input in the regulation of feed intake. Also, there was enrichment of several amino acids, including tyrosine, proline, valine, phenylalanine, and methionine, in plasma in response to valine. Changes in liver transcript abundance and protein expression reflect an increased metabolic capacity, including energy production from glucose and fatty acids, and a lower protein kinase B (Akt) phosphorylation in the valine group. Altogether, valine ICV administration affects central and peripheral metabolism in rainbow trout, and we propose a role for the altered metabolite profile in modulating the feeding response to this branched-chain amino acid.PMID:38881412 | DOI:10.1152/ajpregu.00056.2024

Food Funct. 2024 Jun 17. doi: 10.1039/d4fo01070a. Online ahead of print.ABSTRACTAlcoholic liver injury has become a leading threat to human health, with complicated pathogenesis and limited therapeutic options. Our previous study showed that Musculus senhousei peptides (MSPs) exhibit protective potential against early-stage alcoholic liver injury, although the underlying mechanism is not yet clear. In this study, histopathological analysis, mRNA abundance of injury-associated biomarkers, the gut microbiota, and faecal metabolome were evaluated using a mouse model subjected to acute alcohol exposure, aiming to identify the mechanism by which MSP can alleviate alcoholic hepatotoxicity. The results showed that MSP intervention significantly ameliorated symptoms of liver injury (suppressed serum ALT increment, hepatic lipid accumulation, and neutrophil infiltration in liver tissue), and reversed the abnormal mRNA abundance of biomarkers associated with oxidative stress (iNOS), inflammation (TNF-α, IL-1β, MCP-1, TNF-R1, and TLR4), and apoptosis (Bax and Casp. 3) in the liver. Moreover, MSP improved intestinal barrier function by increasing the expression of tight junction proteins (Claudin-1 and Claudin-3). Further analysis of faecal microbiota and metabolome revealed that MSP promoted the growth of tryptophan-metabolizing bacteria (Clostridiales, Alistipes, and Odoribacter), leading to increased production of indole derivatives (indole-3-lactic acid and N-acetyltryptophan). These results suggested that MSPs may alleviate alcohol-induced liver injury targeting the gut-liver axis, and could be an effective option for the prevention of alcoholic liver injury.PMID:38881239 | DOI:10.1039/d4fo01070a