Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy

Wed, 10/07/2024 - 12:00
Nat Biomed Eng. 2024 Jul 10. doi: 10.1038/s41551-024-01217-3. Online ahead of print.ABSTRACTThe most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.PMID:38987630 | DOI:10.1038/s41551-024-01217-3

Screening for oncogenic AF1q expression predicts disease recurrence in gastric cancer patients

Wed, 10/07/2024 - 12:00
Sci Rep. 2024 Jul 10;14(1):15988. doi: 10.1038/s41598-024-67058-x.ABSTRACTAF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients. Immunohistochemical marker expression was analyzed and data were processed to correlation and survival analysis. Out of 182 GC samples, 178 (97.8%) showed moderate to high AF1q expression (p < 0.001), these samples correlated with positive lymph node stage (p = 0.036). In a subgroup analysis of patients with nodal-positive GC (n = 129, 70.9%), enhanced tumoral AF1q expression resulted in impaired recurrence-free survival (RFS, p = 0.030). Enhanced tumoral CD44 expression resulted in impaired disease-specific survival (DSS) in the subgroup of patients with nodal-positive GC (p = 0.031) as well as in the overall GC group (p = 0.005). AF1q demonstrated as an independent prognostic marker for RFS (p = 0.035) and CD44 for DSS (p = 0.036). AF1q has shown potential for prognostication of RFS in GC patients and is predominantly expressed in nodal-positive GC. Testing AF1q provides a possibility of identifying patients with locoregional (and advanced) disease, particularly at risk for disease recurrence. Implementing AF1q into the diagnostic process may facilitate screening, prognosis estimation as well as consideration of preoperative multimodal treatment in patients qualifying for elective upfront surgery.PMID:38987552 | DOI:10.1038/s41598-024-67058-x

Author Correction: Deciphering Aphanomyces euteiches-pea-biocontrol bacterium interactions through untargeted metabolomics

Wed, 10/07/2024 - 12:00
Sci Rep. 2024 Jul 10;14(1):15929. doi: 10.1038/s41598-024-66737-z.NO ABSTRACTPMID:38987548 | DOI:10.1038/s41598-024-66737-z

Primordial aqueous alteration recorded in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu

Wed, 10/07/2024 - 12:00
Nat Commun. 2024 Jul 10;15(1):5708. doi: 10.1038/s41467-024-49237-6.ABSTRACTWe report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu by the Hayabusa2 spacecraft of JAXA. Newly identified low-molecular-weight hydroxy acids (HO-R-COOH) and dicarboxylic acids (HOOC-R-COOH), such as glycolic acid, lactic acid, glyceric acid, oxalic acid, and succinic acid, are predominant in samples from the two touchdown locations at Ryugu. The quantitative and qualitative profiles for the hydrophilic molecules between the two sampling locations shows similar trends within the order of ppb (parts per billion) to ppm (parts per million). A wide variety of structural isomers, including α- and β-hydroxy acids, are observed among the hydrophilic molecules. We also identify pyruvic acid and dihydroxy and tricarboxylic acids, which are biochemically important intermediates relevant to molecular evolution, such as the primordial TCA (tricarboxylic acid) cycle. Here, we find evidence that the asteroid Ryugu samples underwent substantial aqueous alteration, as revealed by the presence of malonic acid during keto-enol tautomerism in the dicarboxylic acid profile. The comprehensive data suggest the presence of a series for water-soluble organic molecules in the regolith of Ryugu and evidence of signatures in coevolutionary aqueous alteration between water and organics in this carbonaceous asteroid.PMID:38987536 | DOI:10.1038/s41467-024-49237-6

Transcriptome and metabolome analyses reveal regulatory networks associated with nutrition synthesis in sorghum seeds

Wed, 10/07/2024 - 12:00
Commun Biol. 2024 Jul 10;7(1):841. doi: 10.1038/s42003-024-06525-7.ABSTRACTCereal seeds are vital for food, feed, and agricultural sustainability because they store and provide essential nutrients to human and animal food and feed systems. Unraveling molecular processes in seed development is crucial for enhancing cereal grain yield and quality. We analyze spatiotemporal transcriptome and metabolome profiles during sorghum seed development in the inbred line 'BTx623'. Morphological and molecular analyses identify the key stages of seed maturation, specifying starch biosynthesis onset at 5 days post-anthesis (dpa) and protein at 10 dpa. Transcriptome profiling from 1 to 25 dpa reveal dynamic gene expression pathways, shifting from cellular growth and embryo development (1-5 dpa) to cell division, fatty acid biosynthesis (5-25 dpa), and seed storage compounds synthesis in the endosperm (5-25 dpa). Network analysis identifies 361 and 207 hub genes linked to starch and protein synthesis in the endosperm, respectively, which will help breeders enhance sorghum grain quality. The availability of this data in the sorghum reference genome line establishes a baseline for future studies as new pangenomes emerge, which will consider copy number and presence-absence variation in functional food traits.PMID:38987396 | DOI:10.1038/s42003-024-06525-7

PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks

Wed, 10/07/2024 - 12:00
Nat Commun. 2024 Jul 11;15(1):5822. doi: 10.1038/s41467-024-50158-7.ABSTRACTDNA polymerase theta (Polθ)-mediated end-joining (TMEJ) repairs DNA double-strand breaks and confers resistance to genotoxic agents. How Polθ is regulated at the molecular level to exert TMEJ remains poorly characterized. We find that Polθ interacts with and is PARylated by PARP1 in a HPF1-independent manner. PARP1 recruits Polθ to the vicinity of DNA damage via PARylation dependent liquid demixing, however, PARylated Polθ cannot perform TMEJ due to its inability to bind DNA. PARG-mediated de-PARylation of Polθ reactivates its DNA binding and end-joining activities. Consistent with this, PARG is essential for TMEJ and the temporal recruitment of PARG to DNA damage corresponds with TMEJ activation and dissipation of PARP1 and PAR. In conclusion, we show a two-step spatiotemporal mechanism of TMEJ regulation. First, PARP1 PARylates Polθ and facilitates its recruitment to DNA damage sites in an inactivated state. PARG subsequently activates TMEJ by removing repressive PAR marks on Polθ.PMID:38987289 | DOI:10.1038/s41467-024-50158-7

A diverse proteome is present and enzymatically active in metabolite extracts

Wed, 10/07/2024 - 12:00
Nat Commun. 2024 Jul 10;15(1):5796. doi: 10.1038/s41467-024-50128-z.ABSTRACTMetabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types. By combining post-resuspension stable isotope addition and enzyme inhibitors, we demonstrate in-extract metabolite interconversions due to residual transaminase activity. We extend these findings with untargeted metabolomics where we observe extensive protein-mediated metabolite changes, including in-extract formation of glutamate dipeptide and depletion of total glutathione. Finally, we present a simple extraction workflow that integrates 3 kDa filtration for protein removal as a superior method for polar metabolomics. In this work, we uncover a previously unrecognized, protein-mediated source of observer effects in metabolomics experiments with broad-reaching implications across all research fields using metabolomics and molecular metabolism.PMID:38987243 | DOI:10.1038/s41467-024-50128-z

Loss of ERBB2 and ERBB3 receptors impacts epidermal differentiation in mice

Wed, 10/07/2024 - 12:00
J Invest Dermatol. 2024 Jul 8:S0022-202X(24)01877-3. doi: 10.1016/j.jid.2024.06.1278. Online ahead of print.NO ABSTRACTPMID:38987017 | DOI:10.1016/j.jid.2024.06.1278

Transcriptomic and metabolomic correlates of increased colonic permeability in post-infection irritable bowel syndrome

Wed, 10/07/2024 - 12:00
Clin Gastroenterol Hepatol. 2024 Jul 8:S1542-3565(24)00603-7. doi: 10.1016/j.cgh.2024.06.028. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Post-infection irritable bowel syndrome (PI-IBS) is well-known epidemiologically; however, its physiological and molecular characteristics are not well studied. We aimed to determine the physiological phenotypes, colonic transcriptome, fecal microbiome, and metabolome in PI-IBS.METHODS: Fifty-one Rome III Campylobacter PI-IBS patients and 39 healthy volunteers (HV) were enrolled. Participants completed questionnaires, in vivo intestinal permeability, gastrointestinal transit, and rectal sensation. Fecal samples were collected for shotgun metagenomics, untargeted metabolomics, and sigmoid colonic biopsies for bulk RNAseq. Differential gene expression, differences in microbiota composition and metabolite abundance were determined. Gene and metabolite clusters were identified via weighted gene correlation network analysis and correlations with clinical and physiological parameters determined.RESULTS: PI-IBS (59% F, 46±2 yrs.) and HV (64% F, 42±2 yrs.) demographics were comparable. Mean IBS-symptom severity score was 227; 94% were non-constipation. 2-24h lactulose excretion was increased in PI-IBS, suggesting increased colonic permeability (4.4±0.5 mg vs. 2.6±0.3 mg, p=0.01). Colonic transit and sensory thresholds were similar between the two groups. Overall, expression of 2036 mucosal genes and 223 fecal metabolites were different, with changes more prominent in females. Fecal N-acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of Collinsella aerofaciens. Histamine and N-acetyl histamine positively associated with 2-24 hr lactulose excretion. Eight weighted gene coexpression modules significantly correlated with phenotypes (sex, stool frequency, colonic permeability, transit).CONCLUSIONS: Campylobacter PI-IBS patients demonstrate higher colonic permeability which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.PMID:38987012 | DOI:10.1016/j.cgh.2024.06.028

Advancing personalized medicine: Integrating statistical algorithms with omics and nano-omics for enhanced diagnostic accuracy and treatment efficacy

Wed, 10/07/2024 - 12:00
Biochim Biophys Acta Mol Basis Dis. 2024 Jul 8:167339. doi: 10.1016/j.bbadis.2024.167339. Online ahead of print.ABSTRACTMedical laboratory services enable precise measurement of thousands of biomolecules and have become an inseparable part of high-quality healthcare services, exerting a profound influence on global health outcomes. The integration of omics technologies into laboratory medicine has transformed healthcare, enabling personalized treatments and interventions based on individuals' distinct genetic and metabolic profiles. Interpreting laboratory data relies on reliable reference values. Presently, population-derived references are used for individuals, risking misinterpretation due to population heterogeneity, and leading to medical errors. Thus, personalized references are crucial for precise interpretation of individual laboratory results, and the interpretation of omics data should be based on individualized reference values. We reviewed recent advancements in personalized laboratory medicine, focusing on personalized omics, and discussed strategies for implementing personalized statistical approaches in omics technologies to improve global health and concluded that personalized statistical algorithms for interpretation of omics data have great potential to enhance global health. Finally, we demonstrated that the convergence of nanotechnology and omics sciences is transforming personalized laboratory medicine by providing unparalleled diagnostic precision and innovative therapeutic strategies.PMID:38986819 | DOI:10.1016/j.bbadis.2024.167339

Reveal the mechanism of hepatic oxidative stress in mice induced by photo-oxidation milk using multi-omics analysis techniques

Wed, 10/07/2024 - 12:00
J Adv Res. 2024 Jul 8:S2090-1232(24)00271-6. doi: 10.1016/j.jare.2024.07.005. Online ahead of print.ABSTRACTINTRODUCTION: Photo-oxidation is recognized as a contributor to the deterioration of milk quality, posing potential safety hazards to human health. However, there has been limited investigation into the impact of consuming photo-oxidized milk on health.OBJECTIVES: This study employs multi-omics analysis techniques to elucidate the mechanisms by which photo-oxidized milk induces oxidative stress in the liver.METHODS: Mouse model was used to determine the effect of the gavage administration of milk with varying degrees of photo-oxidation on the mouse liver. The damage degree was established by measuring serum markers indicative of oxidative stress, and with a subsequent histopathological examination of liver tissues. In addition, comprehensive metabolome, lipidome, and transcriptome analyses were conducted to elucidate the underlying molecular mechanisms of hepatic damage caused by photo-oxidized milk.RESULTS: A significant elevation in the oxidative stress levels and the presence of hepatocellular swelling and inflammation subsequent to the gavage administration of photo-oxidized milk to mice. Significant alterations in the levels of metabolites such as lumichrome, all-trans-retinal, L-valine, phosphatidylglycerol, and phosphatidylcholine within the hepatic tissue of mice. Moreover, photo-oxidized milk exerted a pronounced detrimental impact on the glycerophospholipid metabolism of mice liver. The peroxisome proliferator-activated receptors (PPAR) signaling pathway enrichment appreciated in the animals that consumed photo-oxidized milk further supports the substantial negative influence of photo-oxidized milk on hepatic lipid metabolism. Gene set enrichment and interaction analyses revealed that photo-oxidized milk inhibited the cytochrome P450 pathway in mice, while also affecting other pathways associated with cellular stress response and lipid biosynthesis.CONCLUSION: This comprehensive study provides significant evidence regarding the potential health risks associated with photo-oxidized milk, particularly in terms of hepatic oxidative damage. It establishes a scientific foundation for assessing the safety of such milk and ensuring the quality of dairy products.PMID:38986809 | DOI:10.1016/j.jare.2024.07.005

Copper impairs the intestinal barrier integrity in Wilson disease

Wed, 10/07/2024 - 12:00
Metabolism. 2024 Jul 8:155973. doi: 10.1016/j.metabol.2024.155973. Online ahead of print.ABSTRACTIn Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls. We observed gastrointestinal (GI) inflammation in patients, rats and mice lacking ATP7B. Mitochondrial alterations and increased intestinal leakage were observed in WD rats, Atp7b-/- mice and human ATP7B KO Caco-2 cells. Proteome analyses of intestinal WD homogenates revealed profound alterations of energy and lipid metabolism. The intestinal damage in WD animals and human ATP7B KO cells did not correlate with absolute Cu elevations, but likely reflects intracellular Cu mislocalization. Importantly, Cu depletion by the high-affinity Cu chelator methanobactin (MB) restored enterocyte mitochondria, epithelial integrity, and resolved gut inflammation in WD rats and human WD enterocytes, plausibly via autophagy-related mechanisms. Thus, we report here before largely unrecognized intestinal damage in WD, occurring early on and comprising metabolic and structural tissue damage, mitochondrial dysfunction, and compromised intestinal barrier integrity and inflammation, that can be resolved by high-affinity Cu chelation treatment.PMID:38986805 | DOI:10.1016/j.metabol.2024.155973

Combining untargeted and targeted metabolomics to reveal the mechanisms of herb pair Anemarrhena asphodeloides Bunge and Phellodendron chinense C. K. Schneid on benign prostatic hyperplasia

Wed, 10/07/2024 - 12:00
J Ethnopharmacol. 2024 Jul 8:118539. doi: 10.1016/j.jep.2024.118539. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct.AIM OF THE STUDY: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective.MATERIALS AND METHODS: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway.RESULTS: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway.CONCLUSIONS: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment.PMID:38986754 | DOI:10.1016/j.jep.2024.118539

Metabolomic biomarkers of multiple myeloma: A systemati review

Wed, 10/07/2024 - 12:00
Biochim Biophys Acta Rev Cancer. 2024 Jul 8:189151. doi: 10.1016/j.bbcan.2024.189151. Online ahead of print.ABSTRACTMultiple myeloma is an incurable malignancy of clonal plasma cells. Various diagnostic methods are used in parallel to accurately determine stage and severity of the disease. Identifying a biomarker or a panel of biomarkers could enhance the quality of medical care that patients receive by adopting a more personalized approach. Metabolomics utilizes high-throughput analytical platforms to examine the levels and quantities of biochemical compounds in biosamples. The aim of this review was to conduct a systematic literature search for potential metabolic biomarkers that may aid in the diagnosis and prognosis of MM. The review was conducted in accordance with PRISMA recommendations and was registered in PROSPERO. The systematic search in PubMed, CINAHL, SciFinder, Scopus, The Cochrane Library and Google Scholar was performed. Studies were limited to those involving people with clinically diagnosed MM and healthy controls as comparators. Articles had to be published in English and had no restrictions on publication date or sample type. The quality of articles was assessed according to QUADOMICS criteria. A total of 709 articles were collected during the literature search. Of these, 436 were excluded based on their abstract, with 26 more removed after a thorough review of the full text. Finally, 16 articles were deemed relevant and were subjected to further analysis of their data. A number of promising candidate biomarkers was discovered. Follow-up studies with large sample sizes are needed to determine their suitability or clinical applications.PMID:38986721 | DOI:10.1016/j.bbcan.2024.189151

Substitution of One Meat-Based Meal With Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial

Wed, 10/07/2024 - 12:00
Clin Transl Gastroenterol. 2024 Jun 1;15(6):e1. doi: 10.14309/ctg.0000000000000707.ABSTRACTINTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet.METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups.RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups.DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.PMID:38986526 | DOI:10.14309/ctg.0000000000000707

Comprehensive multi-layered analyses of genotype-dependent proteo-metabolic networks reveal organellar crosstalk and biochemical pathways regulating aroma formation in rice

Wed, 10/07/2024 - 12:00
Food Chem. 2024 Jun 4;459:139949. doi: 10.1016/j.foodchem.2024.139949. Online ahead of print.ABSTRACTMolecular basis of rice aroma formation is sparsely known and developmental programs driving biochemical pathways towards aroma is in infancy. Here, discovery and targeted proteo-metabolome of non-aromatic and aromatic rice seeds across developmental stages identified a total of 442 aroma-responsive proteins (ARPs) and 824 aroma-responsive metabolites (ARMs) involved in metabolism, calcium and G-protein signaling. Biochemical examination revealed ARM/Ps were linked to 2-acetylpyrrolidine, γ-aminobutyrate, anthocyanin, tannins, flavonoids and related enzymes. Pairwise correlation and clustering showed positive correlation among ARM/Ps. Consistent with aroma-related QTLs, ARPs were mapped on chromosomes 3,4,5,8 and were mainly compartmentalized in cytoplasm and mitochondria. ARM/P-correlation network identified associations related to metabolism and signaling. Multiple reaction monitoring (MRM) confirmed role of catechins, quinic acid and quercetin in aroma formation. Pathway enrichment, multivariate analysis and qRT-PCR validated that calcium and G-protein signaling, aromatic/branched-chain aminoacid, 2-acetylpyrrolidine, oxylipin, melvonate and prenylpyrophosphate pathways, indole, phenylacetate, flavonoid, cinnamoic ester govern aroma formation in rice.PMID:38986209 | DOI:10.1016/j.foodchem.2024.139949

Metabolomics analysis of rice fermented by medicinal fungi providing insights into the preparation of functional food

Wed, 10/07/2024 - 12:00
Food Chem. 2024 Jul 6;459:140372. doi: 10.1016/j.foodchem.2024.140372. Online ahead of print.ABSTRACTRice, a primary staple food, may be improved in value via fermentation. Here, ten medicinal basidiomycetous fungi were separately applied for rice fermentation. After preliminary screening, Ganoderma boninense, Phylloporia pulla, Sanghuangporus sanghuang and Sanghuangporus weigelae were selected for further LC-MS based determination of the changes in metabolic profile after their fermentation with rice, and a total of 261, 296, 312, and 355 differential compounds were identified, respectively. Most of these compounds were up-regulated and involved in the metabolic pathways of amino acid metabolism, lipid metabolism, carbohydrate metabolism and the biosynthesis of other secondary metabolites. Sanghuangporus weigelae endowed the rice with the highest nutritional and bioactive values. The metabolic network of the identified differential compounds in rice fermented by S. weigelae illustrated their close relationships. In summary, this study provides insights into the preparation and application of potential functional food via the fermentation of rice with medicinal fungi.PMID:38986207 | DOI:10.1016/j.foodchem.2024.140372

Field isolates of Beauveria bassiana exhibit biological heterogeneity in multitrophic interactions of agricultural importance

Wed, 10/07/2024 - 12:00
Microbiol Res. 2024 Jun 29;286:127819. doi: 10.1016/j.micres.2024.127819. Online ahead of print.ABSTRACTBeauveria bassiana (Bb) is a widespread entomopathogenic fungus widely used in agriculture for crop protection. Other than pest control, fungi belonging to the B. bassiana complex represent an important microbial resource in agroecosystems, considering their multiple interactions with other microorganisms as antagonists of phytopathogens, or with plants as endophytic colonizers and growth promoters. Here, we characterised field collected or commercial isolates of B. bassiana relative to the environmental factors that affect their growth. We further compared the metabolome, the entomopathogenic potential and biocontrol activity of the tested isolates respectively on the insect pest Spodoptera littoralis or against the fungal plant pathogen Fusarium oxysporum. Our analysis revealed that the B. bassiana complex is characterised by a high level of inter-isolate heterogeneity in terms of nutritional requirements, establishment of intra- or inter-kingdom interactions, and the nature of metabolites produced. Interestingly, certain B. bassiana isolates demonstrated a preference for low nutrient plant-derived media, which hints at their adaptation towards an endophytic lifestyle over a saprophytic one. In addition, there was a noticeable variation among different B. bassiana isolates in their capacity to kill S. littoralis larvae in a contact infection test, but not in an intrahaemocoelic injection experiment, suggesting a unique level of adaptability specific to the host. On the other hand, most B. bassiana isolates exhibited similar biocontrol efficacy against the soil-dwelling ascomycete F. oxysporum f. sp. lycopersici, a pathogen responsible for vascular wilt disease in tomato plants, effectively averting wilting. Overall, we show that the effectiveness of B. bassiana isolates can greatly vary, emphasising the importance of isolate selection and nutritional adaptability consideration for their use in sustainable agriculture.PMID:38986181 | DOI:10.1016/j.micres.2024.127819

Sepsis Research Using Omics Technology in the European Union and the United Kingdom: Maps, Trends, and Future Implications

Wed, 10/07/2024 - 12:00
OMICS. 2024 Jul;28(7):357-366. doi: 10.1089/omi.2024.0089.ABSTRACTHigh-throughput omics technologies have become valuable tools for systems science research and clinical management of sepsis. This article analyzes sepsis research using omics technologies in the European Union (EU) and the United Kingdom from 1990 to May 2023 using bibliometric data from the Web of Science database. Using VOSviewer for network analysis, we examined the distribution patterns, funding characteristics, and collaborations among the states, noting trends of convergence and divergence. The analysis included 2078 articles, revealing an increasing rate of publications on sepsis research using omics approaches. The United Kingdom's research output is notably high, contributing 28.3% of the total research from the EU and United Kingdom combined. Germany, France, the Netherlands, and Italy together account for 56.9% of the publications from the EU member states. The United States is the leading international collaborator, particularly with the United Kingdom, followed by Germany and France. The EU-15 countries have significantly more publication outputs in this domain with growing but limited inclusion of the newer members of the EU. We suggest that the role of EU member states and the United Kingdom in sepsis research using omics technologies can be advanced by facilitating high-value, technology-driven health research, fostering collaboration, convergence, and equity in global health and biomedical research.PMID:38986085 | DOI:10.1089/omi.2024.0089

Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis

Wed, 10/07/2024 - 12:00
J Proteome Res. 2024 Jul 10. doi: 10.1021/acs.jproteome.4c00153. Online ahead of print.ABSTRACTDupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment. At v10 versus v2, the percentages of CD4+ interleukin-producing cells showed a decreasing trend in ISF L and NL, unbound IL-4 levels in plasma were increased, IL-5 levels in ISF L reduced, and levels of factors involved in anti-inflammatory pathways and re-epithelization increased. At v2, ISF L showed that AD lesions might have altered amino acid pathways and lipid signaling compared to ISF NL. At v10, ISF L exhibited raised levels of long- and very-long-chain fatty acids and lipids compared to v2. Furthermore, dupilumab administration caused reduced expression of miR-155-5p and miR-378a-3p in ISF L. In conclusion, results from the present study provided novel knowledge by linking local immune and metabolic alterations to AD pathogenesis and treatment response.PMID:38986055 | DOI:10.1021/acs.jproteome.4c00153

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