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

Conditioned medium-enriched umbilical cord mesenchymal stem cells: a potential therapeutic strategy for spinal cord injury, unveiling transcriptomic and secretomic insights

Wed, 24/04/2024 - 12:00
Mol Biol Rep. 2024 Apr 24;51(1):570. doi: 10.1007/s11033-024-09503-8.ABSTRACTINTRODUCTION: Spinal cord injury (SCI) leads to significant destruction of nerve tissue, causing the degeneration of axons and the formation of cystic cavities. This study aimed to examine the characteristics of human umbilical cord-derived mesenchymal stem cells (HUCMSCs) cultured in a serum-free conditioned medium (CM) and assess their effectiveness in a well-established hemitransection SCI model.MATERIALS AND METHODS: In this study, HUCMSCs cultured medium was collected and characterized by measuring IL-10 and identifying proteomics using mass spectroscopy. This collected serum-free CM was further used in the experiments to culture and characterize the HUMSCs. Later, neuronal cells derived from CM-enriched HUCMSC were tested sequentially using an injectable caffeic acid-bioconjugated gelatin (CBG), which was further transplanted in a hemitransection SCI model. In vitro, characterization of CM-enriched HUCMSCs and differentiated neuronal cells was performed using flow cytometry, immunofluorescence, electron microscopy, and post-transplant analysis using immunohistology analysis, qPCR, in vivo bioluminescence imaging, and behavioral analysis using an infrared actimeter.RESULTS: The cells that were cultured in the conditioned media produced a pro-inflammatory cytokine called IL-10. Upon examining the secretome of the conditioned media, the Kruppel-like family of KRAB and zinc-finger proteins (C2H2 and C4) were found to be activated. Transcriptome analysis also revealed an increased expression of ELK-1, HOXD8, OTX2, YY1, STAT1, ETV7, and PATZ1 in the conditioned media. Furthermore, the expression of Human Stem-101 confirmed proliferation during the first 3 weeks after transplantation, along with the migration of CBG-UCNSC cells within the transplanted area. The gene analysis showed increased expression of Nestin, NeuN, Calb-2, Msi1, and Msi2. The group that received CBG-UCNSC therapy showed a smooth recovery by the end of week 2, with most rats regaining their walking abilities similar to those before the spinal cord injury by week 5.CONCLUSIONS: In conclusion, the CBG-UCNSC method effectively preserved the integrity of the transplanted neuronal-like cells and improved locomotor function. Thus, CM-enriched cells can potentially reduce biosafety risks associated with animal content, making them a promising option for clinical applications in treating spinal cord injuries.PMID:38658405 | DOI:10.1007/s11033-024-09503-8

Prioritization of therapeutic targets for cancers using integrative multi-omics analysis

Wed, 24/04/2024 - 12:00
Hum Genomics. 2024 Apr 24;18(1):42. doi: 10.1186/s40246-024-00571-2.ABSTRACTBACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression.METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis to investigate metabolic pathways related to cancers.RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors.CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.PMID:38659038 | DOI:10.1186/s40246-024-00571-2

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma

Wed, 24/04/2024 - 12:00
BMC Cancer. 2024 Apr 25;24(1):521. doi: 10.1186/s12885-024-12283-w.ABSTRACTBACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches.METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients.RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly.CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.PMID:38658858 | DOI:10.1186/s12885-024-12283-w

OmicNavigator: open-source software for the exploration, visualization, and archival of omic studies

Wed, 24/04/2024 - 12:00
BMC Bioinformatics. 2024 Apr 24;25(1):162. doi: 10.1186/s12859-024-05743-4.ABSTRACTBACKGROUND: The results of high-throughput biology ('omic') experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival. However, an opportunity remains for open-source software that can archive and present the results of omic analyses with broad accommodation of study-specific analytical approaches and visualizations with useful exploration features.RESULTS: We present OmicNavigator, an R package for the archival, visualization and interactive exploration of omic studies. OmicNavigator enables bioinformaticians to create web applications that interactively display their custom visualizations and analysis results linked with app-derived analytical tools, graphics, and tables. Studies created with OmicNavigator can be viewed within an interactive R session or hosted on a server for shared access.CONCLUSIONS: OmicNavigator can be found at https://github.com/abbvie-external/OmicNavigator.PMID:38658834 | DOI:10.1186/s12859-024-05743-4

Study of cabbage antioxidant system response on early infection stage of Xanthomonas campestris pv. campestris

Wed, 24/04/2024 - 12:00
BMC Plant Biol. 2024 Apr 24;24(1):324. doi: 10.1186/s12870-024-04994-w.ABSTRACTBlack rot, caused by Xanthomonas campestris pv. campestris (Xcc) significantly affects the production of cabbage and other cruciferous vegetables. Plant antioxidant system plays an important role in pathogen invasion and is one of the main mechanisms underlying resistance to biological stress. Therefore, it is important to study the resistance mechanisms of the cabbage antioxidant system during the early stages of Xcc. In this study, 108 CFU/mL (OD600 = 0.1) Xcc race1 was inoculated on "zhonggan 11" cabbage using the spraying method. The effects of Xcc infection on the antioxidant system before and after Xcc inoculation (0, 1, 3, and 5 d) were studied by physiological indexes determination, transcriptome and metabolome analyses. We concluded that early Xcc infection can destroy the balance of the active oxygen metabolism system, increase the generation of free radicals, and decrease the scavenging ability, leading to membrane lipid peroxidation, resulting in the destruction of the biofilm system and metabolic disorders. In response to Xcc infection, cabbage clears a series of reactive oxygen species (ROS) produced during Xcc infection via various antioxidant pathways. The activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased after Xcc infection, and the ROS scavenging rate increased. The biosynthesis of non-obligate antioxidants, such as ascorbic acid (AsA) and glutathione (GSH), is also enhanced after Xcc infection. Moreover, the alkaloid and vitamin contents increased significantly after Xcc infection. We concluded that cabbage could resist Xcc invasion by maintaining the stability of the cell membrane system and improving the biosynthesis of antioxidant substances and enzymes after infection by Xcc. Our results provide theoretical basis and data support for subsequent research on the cruciferous vegetables resistance mechanism and breeding to Xcc.PMID:38658831 | DOI:10.1186/s12870-024-04994-w

Multimodal joint deconvolution and integrative signature selection in proteomics

Wed, 24/04/2024 - 12:00
Commun Biol. 2024 Apr 24;7(1):493. doi: 10.1038/s42003-024-06155-z.ABSTRACTDeconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .PMID:38658803 | DOI:10.1038/s42003-024-06155-z

Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models

Wed, 24/04/2024 - 12:00
Sci Rep. 2024 Apr 24;14(1):9432. doi: 10.1038/s41598-024-60045-2.ABSTRACTNovel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.PMID:38658766 | DOI:10.1038/s41598-024-60045-2

Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development

Wed, 24/04/2024 - 12:00
Nat Commun. 2024 Apr 24;15(1):3468. doi: 10.1038/s41467-024-47437-8.ABSTRACTMetabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.PMID:38658571 | DOI:10.1038/s41467-024-47437-8

Metabolic coupling between soil aerobic methanotrophs and denitrifiers in rice paddy fields

Wed, 24/04/2024 - 12:00
Nat Commun. 2024 Apr 24;15(1):3471. doi: 10.1038/s41467-024-47827-y.ABSTRACTPaddy fields are hotspots of microbial denitrification, which is typically linked to the oxidation of electron donors such as methane (CH4) under anoxic and hypoxic conditions. While several anaerobic methanotrophs can facilitate denitrification intracellularly, whether and how aerobic CH4 oxidation couples with denitrification in hypoxic paddy fields remains virtually unknown. Here we combine a ~3300 km field study across main rice-producing areas of China and 13CH4-DNA-stable isotope probing (SIP) experiments to investigate the role of soil aerobic CH4 oxidation in supporting denitrification. Our results reveal positive relationships between CH4 oxidation and denitrification activities and genes across various climatic regions. Microcosm experiments confirm that CH4 and methanotroph addition promote gene expression involved in denitrification and increase nitrous oxide emissions. Moreover, 13CH4-DNA-SIP analyses identify over 70 phylotypes harboring genes associated with denitrification and assimilating 13C, which are mostly belonged to Rubrivivax, Magnetospirillum, and Bradyrhizobium. Combined analyses of 13C-metagenome-assembled genomes and 13C-metabolomics highlight the importance of intermediates such as acetate, propionate and lactate, released during aerobic CH4 oxidation, for the coupling of CH4 oxidation with denitrification. Our work identifies key microbial taxa and pathways driving coupled aerobic CH4 oxidation and denitrification, with important implications for nitrogen management and greenhouse gas regulation in agroecosystems.PMID:38658559 | DOI:10.1038/s41467-024-47827-y

Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats

Wed, 24/04/2024 - 12:00
Transl Psychiatry. 2024 Apr 24;14(1):195. doi: 10.1038/s41398-024-02904-0.ABSTRACTLifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer's disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.PMID:38658547 | DOI:10.1038/s41398-024-02904-0

The era of panomics-driven gene discovery in plants

Wed, 24/04/2024 - 12:00
Trends Plant Sci. 2024 Apr 23:S1360-1385(24)00063-3. doi: 10.1016/j.tplants.2024.03.007. Online ahead of print.ABSTRACTPanomics is an approach to integrate multiple 'omics' datasets, generated using different individuals or natural variations. Considering their diverse phenotypic spectrum, the phenome is inherently associated with panomics-based science, which is further combined with genomics, transcriptomics, metabolomics, and other omics techniques, either independently or collectively. Panomics has been accelerated through recent technological advancements in the field of genomics that enable the detection of population-wide structural variations (SVs) and hence offer unprecedented insights into the genetic variations contributing to important agronomic traits. The present review provides the recent trends of panomics-driven gene discovery toward various traits related to plant development, stress tolerance, accumulation of specialized metabolites, and domestication/dedomestication. In addition, the success stories are highlighted in the broader context of enhancing crop productivity.PMID:38658292 | DOI:10.1016/j.tplants.2024.03.007

Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study

Wed, 24/04/2024 - 12:00
Allergol Int. 2024 Apr 23:S1323-8930(24)00047-9. doi: 10.1016/j.alit.2024.04.003. Online ahead of print.ABSTRACTBACKGROUND: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma.METHODS: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS).RESULTS: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1-5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR.CONCLUSIONS: Exhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.PMID:38658257 | DOI:10.1016/j.alit.2024.04.003

Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

Wed, 24/04/2024 - 12:00
Chin J Nat Med. 2024 Apr;22(4):375-384. doi: 10.1016/S1875-5364(24)60614-X.ABSTRACTThe aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.PMID:38658100 | DOI:10.1016/S1875-5364(24)60614-X

Reverse metabolomics as a novel strategy to annotate the human metabolome

Wed, 24/04/2024 - 12:00
Chin J Nat Med. 2024 Apr;22(4):289-290. doi: 10.1016/S1875-5364(24)60589-3.NO ABSTRACTPMID:38658091 | DOI:10.1016/S1875-5364(24)60589-3

Unraveling the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) complex on alga Raphidocelis subcapitata

Wed, 24/04/2024 - 12:00
Sci Total Environ. 2024 Apr 22:172034. doi: 10.1016/j.scitotenv.2024.172034. Online ahead of print.ABSTRACTDue to their assembly properties and variable molecular weights, the potential biological toxicity effects of macromolecular organic ligand heavy metal complexes are more difficult to predict and their mechanisms are more complex. This study unraveled the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) (TA-Cr(III)) complex on alga Raphidocelis subcapitata using multi-omics approaches. Results showed TA-Cr(III) complex caused oxidative damage and photosystem disruption, destroying the cell morphology and inhibiting algal growth by >80 % at high exposure levels. TA-Cr(III) complex stress down-regulated proteins linked to proliferation, photosynthesis and antioxidation while upregulating carbon fixation, TCA cycle and amino acid metabolism. The increase of fumarate, citrate, isocitrate and semialdehyde succinate was validated by metabolomics analysis, which improved the TCA cycle, amino acid metabolism and carbon fixation. Activation of the above cellular processes somewhat compensated for the inhibition of algal photosynthesis by TA-Cr(III) complex exposure. In conclusion, physiological toxicity coupled with downstream metabolic compensation in response to Cr(III) complex of macromolecular was characterized in Raphidocelis subcapitata, unveiling the adaptive mechanism of algae under the stress of heavy metal complexes with macromolecular organic ligands.PMID:38657806 | DOI:10.1016/j.scitotenv.2024.172034

Plasma steroid profiling combined with machine learning for the differential diagnosis in mild autonomous cortisol secretion from nonfunctioning adenoma in patients with adrenal incidentalomas

Wed, 24/04/2024 - 12:00
Endocr Pract. 2024 Apr 22:S1530-891X(24)00498-1. doi: 10.1016/j.eprac.2024.04.008. Online ahead of print.ABSTRACTBACKGROUND: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas.METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting (XGBoost) was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model.RESULTS: 76 patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among five ML models evaluated, XGBoost demonstrated superior performance with an AUC of 0.77 using 24 steroid hormones. The SHAP method identified five steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone (DHEA), 11-deoxycortisol, 11β-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate (DHEAS). Upon incorporating clinical features into the model, the AUC increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, DHEA, LDL-c, BMI, and ACTH along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model.CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these two entities through a single blood collection.PMID:38657794 | DOI:10.1016/j.eprac.2024.04.008

Metabolomic Profiling of the Aqueous Humor in Patients with Pediatric Cataract

Wed, 24/04/2024 - 12:00
Exp Eye Res. 2024 Apr 22:109906. doi: 10.1016/j.exer.2024.109906. Online ahead of print.ABSTRACTPediatric cataract, including congenital and developmental cataract, is a kind of pediatric vision-threatening disease with extensive phenotypic heterogeneity and multiple mechanisms. We aimed to investigate the metabolite profile of aqueous humor (AH) in patients with pediatric cataracts, and identify underlying mutual correlations between differential metabolites. Metabolomic profiles of AH were analyzed and compared between pediatric cataract patients (n=33) and age-related cataract patients without metabolic diseases (n=29), using global untargeted metabolomics with ultra-high-performance liquid chromatography tandem mass spectrometry. Principal component analysis, partial least squares discriminant analysis and heat map were applied. Enriched pathway analysis was conducted using Kyoto Encyclopedia of Genes and Genomes. Receiver-operating characteristic (ROC) analyses were employed to select potential biomarkers. A total of 318 metabolites were identified, of which 54 differential metabolites (25 upregulated and 29 downregulated) were detected in pediatric cataract group compared with controls (variable importance of projection > 1.0, fold change ≥ 1.5 or ≤ 0.667 and P < 0.05). A significant accumulation of N-Acetyl-Dl-glutamic acid was observed in pediatric cataract group. The differential metabolites were mainly enriched in histidine metabolism (increased L-Histidine and decreased 1-Methylhistamine) and the tryptophan metabolism (increased N-Formylkynurenine and L-Kynurenine). 5-Aminosalicylic acid showed strong positive mutual inter-correlation with L-Tyrosinemethylester and N,N-Diethylethanolamine, both of which were down-regulated in pediatric cataract group. The ROC analysis implied 11 metabolites served as potential biomarkers for pediatric cataract patients (all area under the ROC curve ≥ 0.900). These results illustrated novel potential metabolites and metabolic pathways in pediatric cataract, which provides new insights into the pathophysiology of pediatric cataract.PMID:38657786 | DOI:10.1016/j.exer.2024.109906

Delineating molecular regulatory network of meat quality of longissimus dorsi indicated by transcriptomic, proteomic, and metabolomics analysis in rabbit

Wed, 24/04/2024 - 12:00
J Proteomics. 2024 Apr 22:105179. doi: 10.1016/j.jprot.2024.105179. Online ahead of print.ABSTRACTThis study aims to investigate the potential regulatory network responsible for the meat quality using multi-omics to help developing better varieties. Slaughter performance and meat quality of Shuxing No.1 rabbit outperformed IRA rabbit according to the tested rabbit parameters. Differentially expressed genes (DEGs) and differentially abundance proteins (DAPs) were involved in meat quality-related pathways, such as PI3K - Akt and MAPK signaling pathway. Only SMTNL1 and PM20D2 shared between DEGs and DAPs. Olfactory-sensitive undecanal, a differentially abundant metabolite (DAM) in volatilomics (vDAMs), correlated with all of the remaining 11 vDAMs, and most of 12 vDAMs were associated with amino acid metabolism. Integration revealed that 829 DEGs/DAPs were associated with 15 DAMs in four KEGG pathways, such as melatonin (a DAM in widely targeted metabolomics) was significantly positively correlated with ALDH and negatively correlated with RAB3D and CAT in tryptophan metabolism pathway. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor. SIGNIFICANCE: Shuxing No.1 rabbit is a new breed of meat rabbit in the Chinese market. In meat marketing, meat quality usually determines the purchase intention of consumers. Determining the biological and molecular mechanisms of meat quality in meat rabbit is essential for developing strategies to improve meat quality. According to the tested rabbit parameters, this study ascertained that the slaughter performance and meat quality of Shuxing No.1 rabbit surpasses that of IRA rabbit. The present study profiled the transcriptome, proteome, widely targeted metabolome, and volatilome of longissimus dorsi from Shuxing No.1 rabbit and IRA rabbit. The study found that meat quality and flavor-related tryptophan metabolism pathway is enriched with many DEGs/DAPs (including ALDH, RAB3D, and CAT), as well as a DAM, melatonin. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor.PMID:38657733 | DOI:10.1016/j.jprot.2024.105179

Metabolomics analysis of larval secretions reveals a caste-driven nutritional shift in a social wasp colony

Wed, 24/04/2024 - 12:00
Insect Biochem Mol Biol. 2024 Apr 22:104128. doi: 10.1016/j.ibmb.2024.104128. Online ahead of print.ABSTRACTSocial wasps exhibit a unique nutritional cycle in which adults feed larvae with prey, and larvae provide adults with larval secretions (LS). LS serves as a vital nutritional source for adults, contributing to the colony's health and reproductive success. The LS nutrient composition has been previously reported in various wasp species, yet these analyses focused solely on worker-destined larvae, overlooking the potential caste designation effects on LS composition. Using metabolomics techniques, we analysed and compared the metabolite and nutrient composition in LS of queen- and worker-destined larvae of the Oriental hornet. We found that queen-destined LS (QLS) contain greater amounts of most metabolites, including amino acids, and smaller amounts of sugars compared to worker-destined LS (WLS). The amino acid-to-sugar ratio in QLS was approximately tenfold higher than in WLS. Thus, as the colony transitions from the production of workers to the production of reproductives, it gradually experiences a nutritional shift that may influence the behaviour and physiology of the adult nest population. This caste-specific metabolite profile and nutrient composition of LS reflect the differences in the diet and physiological requirements of worker- and queen-destined larvae and may play a critical role in caste determination in social wasps.PMID:38657707 | DOI:10.1016/j.ibmb.2024.104128

Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology

Wed, 24/04/2024 - 12:00
Cell Host Microbe. 2024 Apr 22:S1931-3128(24)00121-5. doi: 10.1016/j.chom.2024.04.004. Online ahead of print.ABSTRACTThe intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the responsible microbes/genes, we developed a metabolomics-based assay to screen 104 commensals and identified candidates that efficiently utilize aa. Using genetics, we identified multiple responsible metabolic genes in phylogenetically diverse microbes. By colonizing germ-free mice with the wild-type strain and their isogenic mutant deficient in individual aa-metabolizing genes, we found that these genes regulate the availability of gut and circulatory aa. Notably, microbiota genes for branched-chain amino acids (BCAAs) and tryptophan metabolism indirectly affect host glucose homeostasis via peripheral serotonin. Collectively, at single-gene level, this work characterizes a microbiota-encoded metabolic activity that affects host nutrient homeostasis and provides a roadmap to interrogate microbiota-dependent activity to improve human health.PMID:38657606 | DOI:10.1016/j.chom.2024.04.004

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