PubMed

J Hazard Mater. 2023 Apr 12;453:131404. doi: 10.1016/j.jhazmat.2023.131404. Online ahead of print.ABSTRACTApplication of bioremediation in petroleum-contaminated soils is limited by its low efficiency. Although biochar and urea are commonly used soil additives, their potential beneficial effect on the bioremediation of petroleum contamination have rarely been discussed. In this study, biochar and urea were combined to test their effects on the phytoremediation of petroleum-contaminated soil in pot experiments. Our results showed that the degradation rate of total petroleum hydrocarbons reached 49.6%, 38.3%, 42.5%, and 77.9% when the soil was treated with biochar, urea, ryegrass, and their integrated application treatment (PBCN), respectively. A number of soil physicochemical properties (e.g., pH, elements, aggregate distribution, and organic matter composition) altered by the treatments were found to be linked to the accelerated degradation of petroleum hydrocarbons. The activities of soil dehydrogenase, lipase, and urease, and the abundances of 16 s rRNA gene and alkane degradation-related genes could be increased simultaneously when biochar, urea, and ryegrass were co-applied. Furthermore, urea significantly reduced soil bacterial α-diversity, while soil bacterial community dissimilation was mainly driven by urea and ryegrass. Lysobacter, xanthomonadaceae, and longimicrobia could be biomarker species in the PBCN group. Soil bacterial network analysis showed that biochar and urea application decreased the network complexity and robustness, while ryegrass behaved inversely. Lastly, soil metabolomic analysis revealed that root soil metabolites were greatly affected by urea-addition during phytoremediation, and co-application of biochar and urea could activate the putative metabolism pathway of petroleum hydrocarbons in root soil (e.g., naphthalene and anthracene degradation, and pyruvate metabolism). In summary, this study confirmed the enhancement of biochar and urea application in the phytoremediation of petroleum-contaminated soil and explored the internal mechanism of the interactive effect, which can potentially improve the development of eco-friendly and cost-effective in-situ bioremediation technology for petroleum-contaminated soils.PMID:37080026 | DOI:10.1016/j.jhazmat.2023.131404

Pediatr Rheumatol Online J. 2023 Apr 12;21(1):32. doi: 10.1186/s12969-023-00813-y.ABSTRACTOBJECTIVE: To evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Etanercept ®]) therapy on adrenal activity in juvenile idiopathic arthritis (JIA) .METHOD: Eleven JIA patients aged 12 ± 6.2 years with a disease duration of 6.3 ± 5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3 ± 2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy controls.RESULTS: The levels of 21 of the 31 metabolites were low before etanercept treatment. Those 21 metabolites included 4 C19 steroids (androgens), 5 C C21 steroid hormone intermediates, 10 cortisol metabolites, and 2 corticosterone metabolites. One day after treatment, only 5 of the 21 metabolite levels remained low. They included 2 C19 metabolites, 2 C21 steroid metabolites and 1 cortisol metabolite β -Cortol (β-Cl). Three days after treatment, the only metabolites levels that continued to be low were 2 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite α-Cortol (a-Cl), while the remaining 15 metabolites had already normalized after 1 day. Dehydroepiandrosterone-sulfate and 17-hydroxypregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting cytochrome P450 CYP21A2 (21-hydroxylase) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzymatic activitieswere lower in JIA patients than in controls, although significant was not reached.CONCLUSION: Almost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day after treatment. The therapeutic effect of anti-TNFα treatment in JIA may be related to its effect on the restoration of adrenal function and cortisol levels.PMID:37046333 | DOI:10.1186/s12969-023-00813-y

BMC Genomics. 2023 Apr 12;24(1):194. doi: 10.1186/s12864-023-09272-x.ABSTRACTBACKGROUND: Maize has many kernel colors, from white to dark black. However, research on the color and nutritional quality of the different varieties is limited. The color of the maize grain is an important characteristic. Colored maize is rich in nutrients, which have received attention for their role in diet-related chronic diseases and have different degrees of anti-stress protection for animal and human health.METHODS: A comprehensive metabolome (LC-MS/MS) and transcriptome analysis was performed in this study to compare different colored maize varieties from the perspective of multiple recombination in order to study the nutritional value of maize with different colors and the molecular mechanism of color formation.RESULTS: Maize kernels with diverse colors contain different types of health-promoting compounds, highlighting that different maize varieties can be used as functional foods according to human needs. Among them, red-purple and purple-black maize contain more flavonoids than white and yellow kernels. Purple-black kernels have a high content of amino acids and nucleotides, while red-purple kernels significantly accumulate sugar alcohols and lipids.CONCLUSION: Our study can provide insights for improving people's diets and provide a theoretical basis for the study of food structure for chronic diseases.PMID:37046216 | DOI:10.1186/s12864-023-09272-x

Nat Commun. 2023 Apr 12;14(1):1927. doi: 10.1038/s41467-023-37501-0.ABSTRACTCancer cells exhibit elevated lipid synthesis. In breast and other cancer types, genes involved in lipid production are highly upregulated, but the mechanisms that control their expression remain poorly understood. Using integrated transcriptomic, lipidomic, and molecular studies, here we report that DAXX is a regulator of oncogenic lipogenesis. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipogenesis, and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and DAXX mutants unable to bind SREBP1/2 have weakened activity in promoting lipogenesis and tumor growth. Remarkably, a DAXX mutant deficient of SUMO-binding fails to activate SREBP1/2 and lipogenesis due to impaired SREBP binding and chromatin recruitment and is defective of stimulating tumorigenesis. Hence, DAXX's SUMO-binding activity is critical to oncogenic lipogenesis. Notably, a peptide corresponding to DAXX's C-terminal SUMO-interacting motif (SIM2) is cell-membrane permeable, disrupts the DAXX-SREBP1/2 interactions, and inhibits lipogenesis and tumor growth. These results establish DAXX as a regulator of lipogenesis and a potential therapeutic target for cancer therapy.PMID:37045819 | DOI:10.1038/s41467-023-37501-0

J Psychiatry Neurosci. 2023 Apr 12;48(2):E117-E125. doi: 10.1503/jpn.220139. Print 2023 Mar-Apr.ABSTRACTBACKGROUND: Signatures from the metabolome and microbiome have already been introduced as candidates for diagnostic and treatment support. The aim of this study was to investigate the utility of volatile organic compounds (VOCs) from the breath for detection of schizophrenia and depression.METHODS: Patients with a diagnosis of major depressive disorder (MDD) or schizophrenia, as well as healthy controls, were recruited to participate. After being clinically assessed and receiving instruction, each participant independently collected breath samples for subsequent examination by proton transfer-reaction mass spectrometry.RESULTS: The sample consisted of 104 participants: 36 patients with MDD, 34 patients with schizophrenia and 34 healthy controls. Through mixed-model and deep learning analyses, 5 VOCs contained in the participants' breath samples were detected that significantly differentiated between diagnostic groups and healthy controls, namely VOCs with mass-to-charge ratios (m/z) 60, 69, 74, 88 and 90, which had classification accuracy of 76.8% to distinguish participants with MDD from healthy controls, 83.6% to distinguish participants with schizophrenia from healthy controls and 80.9% to distinguish participants with MDD from those with schizophrenia. No significant associations with medication, illness duration, age of onset or time in hospital were detected for these VOCs.LIMITATIONS: The sample size did not allow generalization, and confounders such as nutrition and medication need to be tested.CONCLUSION: This study established promising results for the use of human breath gas for detection of schizophrenia and MDD. Two VOCs, 1 with m/z 60 (identified as trimethylamine) and 1 with m/z 90 (identified as butyric acid) could then be further connected to the interworking of the microbiota-gut-brain axis.PMID:37045476 | DOI:10.1503/jpn.220139

Bioresour Technol. 2023 Apr 10:129045. doi: 10.1016/j.biortech.2023.129045. Online ahead of print.ABSTRACTLignin, a highly heterogeneous polymer of lignocellulosic biomass, is intricately associated with cellulose and hemicellulose, responsible for its strength and rigidity. Lignin decomposition is carried out through certain enzymes derived from microorganisms to promote the hydrolysis of lignin. Analyzing multi-omics data helps to emphasize the probable value of fungal-produced enzymes to degrade the lignocellulosic material, which provides them an advantage in their ecological niches. This review focuses on lignin biodegrading microorganisms and associated ligninolytic enzymes, including lignin peroxidase, manganese peroxidase, versatile peroxidase, laccase, and dye-decolorizing peroxidase. Further, enzymatic catalysis, lignin biodegradation mechanisms, vital factors responsible for lignin modification and degradation, and the design and selection of practical metabolic pathways are also discussed. Highlights were made on metabolic pathway engineering, different aspects of omics analyses, and its scope and applications to ligninase enzymes. Finally, the advantages and essential steps of successfully applying metabolic engineering and its path forward have been addressed.PMID:37044152 | DOI:10.1016/j.biortech.2023.129045

Plant Physiol Biochem. 2023 Mar 31;198:107675. doi: 10.1016/j.plaphy.2023.107675. Online ahead of print.ABSTRACTBicolor flower lotus is rare with high ornamental value. During the long history of breeding and artificial selection, a very famous lotus cultivar 'Da Sajin' with red and white picotee bicolor petals were obtained. In order to reveal the mechanism underlying the formation of its picotee bicolor pattern in the petal, an integrative metabolomics and proteomics analyses were conducted between red and white parts of its petals. The results showed that the defect of anthocyanidin 3-O-glucosyltransferases (UFGTs) accumulation resulted in the failure of the glycosylation of anthocyanidin, the last step of anthocyanin biosynthesis in white part of the petals. And proteomic data and biochemical analysis showed that the defect of UFGTs accumulation is not related to their transcription, but because of their degradation. Function of one differentially accumulated NnUFGT were proven being involved in anthocyanin biosynthesis through both in-vitro enzyme assay and in-vivo transgenic analyses. This regulation on the protein accumulation of structural genes in anthocyanin biosynthesis was not explored in any other plants, and hence supposed to be a novel mechanism for the formation of picotee bicolor pattern flower. The results not only provide some new insights into the understanding of lotus flower coloration, but also might assist the breeding of flower lotus.PMID:37043997 | DOI:10.1016/j.plaphy.2023.107675

Food Chem. 2023 Apr 1;420:136068. doi: 10.1016/j.foodchem.2023.136068. Online ahead of print.ABSTRACTVolatile organic compounds produced by bacteria (BVOCs) have been proven to effect the postharvest metabolism of fruits and vegetables. The quality, color and antioxidant capacity of membrane lipids of broccoli in storage were effectively maintained by fumigation with BVOCs produced by Lysinibacillus fusiformis combined with white light emitting diode (LED) technology. An analysis of the transcriptome and metabolome of broccoli treated with the combined LED-BVOCs technology resulted in the identification of 49 differentially expressed genes (DEGs) and 13 differentially abundant metabolites (DAMs) involved in photosynthesis (32/0 DEGs upregulated/downregulated; 0/0 DAMs with increased/decreased abundance), chlorophyll (7/0; 1/2), carotenoid (5/0; 1/4) and flavonoid (3/3; 3/2) metabolism. The maintenance of green color in harvested broccoli treated by LED-BVOCs was associated with DEGs and DAMs that inhibited chlorophyll degradation and carotenoid accumulation. Our study provides a theoretical basis for understanding the delayed senescence of broccoli during storage using BVOCs-LED technology.PMID:37043993 | DOI:10.1016/j.foodchem.2023.136068

J Hazard Mater. 2023 Mar 28;453:131304. doi: 10.1016/j.jhazmat.2023.131304. Online ahead of print.ABSTRACTIndoxacarb is a widely used insecticide in the prevention and control of agricultural pests, whereas its negative effects on non-target organisms remain largely unclear. Herein, we demonstrated the integrated metabolomics and mass spectrometry imaging (MSI) methods to investigate the chronic exposure toxicity of indoxacarb at environmentally relevant concentrations in adult zebrafish (Danio rerio) liver. Results showed that movement behaviors of zebrafish can be affected and catalase (CAT), glutamic oxalacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) activities were significantly increased after indoxacarb exposure for 28 days. Pathological analysis of zebrafish livers also showed that cavitation and pathological reactions occur. Metabolomics results indicated that metabolic pathways of zebrafish liver could be significantly affected by indoxacarb, such as tricarboxylic acid (TCA) cycle and various amino acid metabolisms. MSI results revealed the spatial differentiation of crucial metabolites involved in these metabolic pathways within zebrafish liver. Taken together, these integrated MSI and metabolomics results revealed that the toxicity of indoxacarb arises from metabolic pathways disturbance, which resulted in the decrease of liver detoxification ability. These findings will promote the current understanding of pesticide risks and metabolic disorders in zebrafish liver, which provide new insights into the environmental risk assessment of insecticides on aquatic organisms.PMID:37043861 | DOI:10.1016/j.jhazmat.2023.131304

Arthritis Rheumatol. 2023 Apr 12. doi: 10.1002/art.42523. Online ahead of print.ABSTRACTOBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.METHODS: We conducted a pre-diagnostic metabolome-wide analysis among 105,615 UK Biobank participants with NMR metabolomic profiling (N=168 metabolites) from baseline blood samples (2006-2010), without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration of sampling. Potential causal effects were tested with two-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RR) for the association with recurrent flares among incident gout cases.RESULTS: Correcting for multiple testing, 88 metabolites were associated with risk of incident gout (N=1303 cases) before urate adjustment, including glutamine and glycine (inversely), and lipids, branched-chain amino acids, and most prominently, glycoprotein acetyls (GlycA; P=9.17x10-32 ). Only GlycA remained associated following urate adjustment (HR=1.52 [95% CI: 1.22, 1.88] between extreme quintiles); the HR increased progressively with fasting duration, reaching 4.01 (1.36, 11.82) for ≥8 hours' fasting. Corresponding HR per SD was 1.10 (1.04, 1.17) overall and 1.54 (1.21 to 1.96) for ≥8 hours' fasting. GlycA levels were also associated with recurrent gout flares among incident gout cases (RR=1.90; 1.27, 2.85 between extreme quintiles) with larger associations with fasting. Mendelian randomization corroborated a potential causal role for GlycA on gout risk.CONCLUSION: This population-based prospective study implicates GlycA, a stable long-term biomarker reflecting neutrophil overactivity, in incident and recurrent gout flares (central manifestation from neutrophilic synovitis) beyond serum urate. This article is protected by copyright. All rights reserved.PMID:37043280 | DOI:10.1002/art.42523

Metabolomics. 2023 Apr 12;19(4):40. doi: 10.1007/s11306-023-02007-9.ABSTRACTINTRODUCTION: The endocannabinoid system consists of different types of receptors, enzymes and endocannabinoids (ECs), which are involved in several physiological processes, but also play important role in the development and progression of central nervous system disorders.OBJECTIVES: The purpose of this study was to apply precise and sensitive methodology for monitoring of four ECs, namely anandamide (AEA), 2-arachidonoyl glycerol (2-AG), N-arachidonoyl dopamine (NADA), 2-arachidonyl glyceryl ether (2-AGe) in selected brain regions of female and male rats at different stages of development (young, adult and old).METHODS: Biocompatible solid-phase microextraction (SPME) probes were introduced into the intact (non-homogenized) brain structures for isolation of four ECs, and the extracts were subjected to LC-MS/MS analysis. Two chemometric approaches, namely hierarchical cluster analysis (HCA) and Principal Component Analysis (PCA) were applied to provide more information about the levels of 2-AG and AEA in different brain structures.RESULTS: 2-AG and AEA were extracted and could be quantified in each brain region; the level of 2-AG was significantly higher in comparison to the level of AEA. Two highly unstable ECs, NADA and 2-AGe, were captured by SPME probes from intact brain samples for the first time.CONCLUSION: SPME probes were able to isolate highly unstable endogenous compounds from intact tissue, and provided new tools for precise analysis of the level and distribution of ECs in different brain regions. Monitoring of ECs in brain samples is important not only in physiological conditions, but also may contribute to better understanding of the functioning of the endocannabinoid system in various disorders.PMID:37043024 | DOI:10.1007/s11306-023-02007-9

J Biomol Struct Dyn. 2023 Apr 12:1-16. doi: 10.1080/07391102.2023.2199076. Online ahead of print.ABSTRACTTribulus terrestris L. (Gokshura) is a medicinal herb used for treating cardiac diseases and several other diseases. However, the active ingredients and the possible mechanism of action for treating cardiac diseases remain unclear. Hence, the study was designed to identify the active ingredients and to explore the potential mechanism of action of Tribulus terrestris L. for treating cardiac diseases by an integrated approach of metabolomics and network pharmacology. We performed HPLC-QTOF-MS/MS analysis to identify putative compounds and network pharmacology approach for predictive key targets and pathways. Using molecular docking and molecular dynamics simulation, we identified the active ingredients in Tribulus terrestris L. that can act as putative lead compounds to treat cardiac diseases. A total of 55 putative compounds were identified using methanolic extract of Tribulus terrestris L. using HPLC-QTOF-MS/MS analysis. Network pharmacology analysis predicted 32 human protein targets from 25 secondary metabolites, which have shown direct interaction with cardiac diseases. Based on the degrees of interaction, the hub targets such as TACR1, F2, F2R, ADRA1B, CHRM5, ADRA1A, ADRA1D, HTR2B, and AVPR1A were identified. In silico molecular docking and simulation resulted in the identification of active ingredients such as Kaempferol 3-rutinoside 7-glucuronide, Keioside, rutin, moupinamide, aurantiamide, quercetin-3-o-α-rhamnoside, tribuloside, and 3'',6''- Di-O-p-coumaroyltrifolin against hub protein targets. Hence, these compounds could be potential lead compounds for treating cardiac diseases. A further assessment of its efficacy can be made based on in vivo and in vitro studies for better understanding and strong assertion.Communicated by Ramaswamy H. Sarma.PMID:37042962 | DOI:10.1080/07391102.2023.2199076

Environ Health Perspect. 2023 Apr;131(4):47009. doi: 10.1289/EHP11896. Epub 2023 Apr 12.ABSTRACTBACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology.OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60-69 years of age to elucidate the underlying mechanisms using a multi-omics approach.METHODS: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations.RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3-kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs.DISCUSSION: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896.PMID:37042841 | DOI:10.1289/EHP11896

Microbiol Spectr. 2023 Apr 12:e0063122. doi: 10.1128/spectrum.00631-22. Online ahead of print.ABSTRACTShigellosis caused by Shigella is one of the most important foodborne illnesses in global health, but little is known about the metabolic cross talk between this bacterial pathogen and its host cells during the different stages of the infection process. A detailed understanding of the metabolism can potentially lead to new drug targets remedying the pressing problem of antibiotic resistance. Here, we use stable isotope-resolved metabolomics as an unbiased and fast method to investigate how Shigella metabolizes 13C-glucose in three different environments: inside the host cells, adhering to the host cells, and alone in suspension. We find that especially formate metabolism by bacteria is sensitive to these different environments. The role of formate in pathogen metabolism is sparsely described in the literature compared to the roles of acetate and butyrate. However, its metabolic pathway is regarded as a potential drug target due to its production in microorganisms and its absence in humans. Our study provides new knowledge about the regulatory effect of formate. Bacterial metabolism of formate is pH dependent when studied alone in culture medium, whereas this effect is less pronounced when the bacteria adhere to the host cells. Once the bacteria are inside the host cells, we find that formate accumulation is reduced. Formate also affects the host cells resulting in a reduced infection rate. This was correlated to an increased immune response. Thus, intriguingly formate plays a double role in pathogenesis by increasing the virulence of Shigella and at the same time stimulating the immune response of the host. IMPORTANCE Bacterial infection is a pressing societal concern due to development of resistance toward known antibiotics. Central carbon metabolism has been suggested as a potential new target for drug development, but metabolic changes upon infection remain incompletely understood. Here, we used a cellular infection model to study how the bacterial pathogen Shigella adapts its metabolism depending on the environment starting from the extracellular medium until Shigella successfully invaded and proliferated inside host cells. The mixed-acid fermentation of Shigella was the major metabolic pathway during the infectious process, and the glucose-derived metabolite formate surprisingly played a divergent role in the pathogen and in the host cell. Our data show reduced infection rate when both host cells and bacteria were treated with formate, which correlated with an upregulated immune response in the host cells. The formate metabolism in Shigella thus potentially provides a route toward alternative treatment strategies for Shigella prevention.PMID:37042762 | DOI:10.1128/spectrum.00631-22

J Am Heart Assoc. 2023 Apr 12:e027736. doi: 10.1161/JAHA.122.027736. Online ahead of print.NO ABSTRACTPMID:37042260 | DOI:10.1161/JAHA.122.027736

Anal Chem. 2023 Apr 12. doi: 10.1021/acs.analchem.2c05079. Online ahead of print.ABSTRACTLiquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics provides comprehensive and quantitative profiling of metabolites in clinical investigations. The use of whole metabolome profiles is a promising strategy for disease diagnosis but technically challenging. Here, we developed an approach, namely MetImage, to encode LC-MS-based untargeted metabolomics data into multi-channel digital images. Then, the images that represent the comprehensive metabolome profiles can be employed for developing deep learning-based AI models toward clinical diagnosis. In this work, we demonstrated the application of MetImage for clinical screening of esophageal squamous cell carcinoma (ESCC) in a clinical cohort with 1104 participants. A convolutional neuronal network-based AI model was trained to distinguish ESCC screening positive and negative subjects using their serum metabolomics data. Superior performances such as sensitivity (85%), specificity (92%), and area under curve (0.95) were validated in an independent testing cohort (N = 442). Importantly, we demonstrated that our AI-based ESCC screening model is not a "black box". The encoded images reserved the characteristics of mass spectra from the raw LC-MS data; therefore, metabolite identifications in key image features were readily achieved. Altogether, MetImage is a unique approach that encodes raw LC-MS-based untargeted metabolomics data into images and facilitates the utilization of whole metabolome profiles for AI-based clinical applications with improved interpretability.PMID:37042095 | DOI:10.1021/acs.analchem.2c05079

Cancer. 2023 Apr 11. doi: 10.1002/cncr.34730. Online ahead of print.ABSTRACTBACKGROUND: Combination BRAF and MEK inhibitor therapy is an active regimen in patients who have BRAF V600E-mutated tumors; however, the clinical efficacy of this therapy is limited by resistance. Preclinically, the addition of heat shock protein 90 (HSP90) inhibition improves the efficacy of BRAF inhibitor therapy in both BRAF inhibitor-sensitive and BRAF inhibitor-resistant mutant cell lines.METHODS: Cancer Therapy Evaluation Program study 9557 (ClinicalTrials.gov identifier NCT02097225) is a phase 1 study that was designed to assess the safety and efficacy of the small-molecule HSP90 inhibitor, AT13387, in combination with dabrafenib and trametinib in BRAF V600E/K-mutant solid tumors. Correlative analyses evaluated the expression of HSP90 client proteins and chaperones.RESULTS: Twenty-two patients with metastatic, BRAF V600E-mutant solid tumors were enrolled using a 3 + 3 design at four dose levels, and 21 patients were evaluable for efficacy assessment. The most common tumor type was colorectal cancer (N = 12). Dose-limiting toxicities occurred in one patient at dose level 3 and in one patient at dose level 4; specifically, myelosuppression and fatigue, respectively. The maximum tolerated dose was oral dabafenib 150 mg twice daily, oral trametinib 2 mg once daily, and intravenous AT13387 260 mg/m2 on days 1, 8, and 15. The best response was a partial response in two patients and stable disease in eight patients, with an overall response rate of 9.5% (90% exact confidence interval [CI], 2%-27%), a disease control rate of 47.6% (90% CI, 29%-67%), and a median overall survival of 5.1 months (90% CI, 3.4-7.6 months). There were no consistent proteomic changes associated with response or resistance, although responders did have reductions in BRAF expression, and epidermal growth factor receptor downregulation using HSP90 inhibition was observed in one patient who had colorectal cancer.CONCLUSIONS: HSP90 inhibition combined with BRAF/MEK inhibition was safe and produced evidence of modest disease control in a heavily pretreated population. Additional translational work may identify tumor types and resistance mechanisms that are most sensitive to this approach.PMID:37042037 | DOI:10.1002/cncr.34730

Compr Rev Food Sci Food Saf. 2023 Apr 11. doi: 10.1111/1541-4337.13151. Online ahead of print.ABSTRACTPostharvest diseases and quality degradation are the major factors causing food losses in the fresh produce supply chain. Hence, detecting diseases and quality deterioration at the asymptomatic stage of produce enables growers to treat the diseases earlier, maintain quality and reduce postharvest food losses. With the emergence of numerous technologies to detect diseases early and monitor the quality of fresh produce, such as polymerase chain reaction, gas chromatography-mass spectrophotometry, and near-infrared spectroscopy, electronic nose (EN) has also gained acknowledgement and popularity in the past decade as a robust and non-invasive analysis tool to detect odor profile and establish volatile biomarkers for metabolomics databases. However, literature reviewing the EN research on the early detection of diseases in produce after harvest is scarce. The fundamental concept of EN working principles (odor sampling, gas detection, and data acquisition method), as well as the application of EN as a whole, are covered in the first section of the review. An in-depth discussion of the application of EN analysis in the early identification of postharvest diseases and quality monitoring is provided in the subsequent sections, which is the key objective of this comprehensive review. The prospect, limitations, and likely future developments of EN in the postharvest sector are further highlighted in the last section.PMID:37042021 | DOI:10.1111/1541-4337.13151

PeerJ. 2023 Apr 6;11:e15167. doi: 10.7717/peerj.15167. eCollection 2023.ABSTRACTBACKGROUND: Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease with multiple and complex pathogenic mechanisms. Currently, renal biopsy is considered the gold standard for diagnosing membranous nephropathy. However, there were limitations to the renal puncture biopsy, such as the relatively high cost, longer time consuming, and the risk of invasive procedures. We investigated the profile of serum metabolites in IMN patients based on the UHPLC-QE-MS metabolomics technique for exploring the potential disease biomarkers and clinical implementation.METHODS: In our research, we collected serum samples from healthy control (n = 15) and IMN patients (n = 25) to perform metabolomics analysis based on the UHPLC-QE-MS technique.RESULT: We identified 215 differentially expressed metabolites (DEMs) between the IMN and healthy control (HC) groups. Furthermore, these DEMs were significantly identified in histidine metabolism, arginine and proline metabolism, pyrimidine metabolism, purine metabolism, and steroid hormone biosynthesis. Several key DEMs were significantly correlated with the level of clinical parameters, such as serum albumin, IgG, UTP, and cholesterol. Among them, dehydroepiandrosterone sulfate (DHEAS) was considered the reliable diagnostic biomarker in the IMN group. There was an increased abundance of actinobacteria, phylum proteobacteria, and class gammaproteobacterial in IMN patients for host-microbiome origin analysis.CONCLUSION: Our study revealed the profiles of DEMs from the IMN and HC groups. The result demonstrated that there were disorders of amino acids, nucleotides, and steroids hormones metabolism in IMN patients. The down-regulation of DHEAS may be associated with the imbalance of the immune environment in IMN patients. In host-microbiome origin analysis, the gut microbiota and metabolite disturbances were present in IMN patients.PMID:37041975 | PMC:PMC10083006 | DOI:10.7717/peerj.15167

Diabetes Obes Metab. 2023 Apr 11. doi: 10.1111/dom.15084. Online ahead of print.ABSTRACTAIM: The lack of longitudinal metabolomics data and the statistical techniques to analyze them has limited the understanding of the metabolite levels related to type 2 diabetes (T2D) onset. Thus, we carried out logistic regression analysis and simultaneously proposed new approaches based on residuals of multiple logistic regression and geometric angle-based clustering for the analysis in T2D onset-specific metabolic changes.METHODS: We used the 6th, 7th, and 8th follow-up data from 2013, 2015, and 2017 among the Korea Association REsource (KARE) cohort data. Semi-targeted metabolite analysis was performed using ultra performance liquid chromatography/triple quadrupole-mass spectrometry (UPLC/TQ-MS) systems.RESULTS: Since the results from the multiple logistic regression and a single metabolite in a logistic regression analysis varied dramatically, we recommend using models that consider potential multicollinearity among metabolites. The residual-based approach particularly identified neurotransmitters or related precursors as T2D onset-specific metabolites. By using geometric angle-based pattern clustering studies, ketone bodies and carnitines are observed as disease onset specific metabolites and separated from others.CONCLUSIONS: To treat patients with early-stage insulin resistance and dyslipidemia when metabolic disorders are still reversible, our findings may contribute to a greater understanding of how metabolomics could be used in disease intervention strategies in the early stages of T2D. This article is protected by copyright. All rights reserved.PMID:37041660 | DOI:10.1111/dom.15084