PubMed

J Hepatol. 2023 Jun 9:S0168-8278(23)00405-1. doi: 10.1016/j.jhep.2023.05.031. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Hepatoblastoma (HB) is the most frequent childhood liver cancer. Patients with aggressive tumors have limited therapeutic options; therefore, a better understanding of HB pathogenesis is needed to improve treatment. HB have a very low mutational burden; however, epigenetic alterations are increasingly recognized. We aimed to identify epigenetic regulators consistently dysregulated in HB and to evaluate the therapeutic efficacy of their targeting in clinically relevant models.METHODS: We performed a comprehensive transcriptomic analysis of 180 epigenetic genes. Data from fetal, pediatric, adult, peritumoral (n=72) and tumoral (n=91) tissues were integrated. Selected epigenetic drugs were tested in HB cells. The most relevant epigenetic target identified was validated in primary HB cells, HB organoids, a PDX model, and a genetic mouse model. Transcriptomic, proteomic and metabolomic mechanistic analyses were implemented.RESULTS: Altered expression of genes regulating DNA methylation and histones modifications was consistently observed in association with molecular and clinical features of poor prognosis. The histone methyl-transferase G9a was markedly upregulated in tumors with epigenetic and transcriptomic traits of increased malignancy. Pharmacological targeting of G9a significantly inhibited HB cells, organoids and PDX's growth. Development of HB induced by oncogenic forms of β-catenin and YAP1 was ablated in mice with hepatocyte-specific deletion of G9a. We observed that HB undergo significant transcriptional rewiring in genes involved in amino acids metabolism and ribosomal biogenesis. G9a inhibition counteracted these pro-tumorigenic adaptations. Mechanistically, G9a targeting potently repressed the expression of c-MYC and ATF4, master regulators of HB metabolic reprogramming.CONCLUSIONS: HB display a profound dysregulation of the epigenetic machinery. Pharmacological targeting of key epigenetic effectors exposes metabolic vulnerabilities that can be leveraged to improve the treatment of these patients.IMPACT AND IMPLICATIONS: In spite of recent advances in the management of hepatoblastoma (HB) patients, therapy resistance and drug toxicity are still major concerns. This systematic study reveals the remarkable dysregulation in the expression of epigenetic genes in HB tissues. Through pharmacological and genetic experimental approaches, we demonstrate that the histone-lysine-methyltransferase G9a is an excellent drug target in HB, which also can be harnessed to enhance the efficacy of chemotherapy. Furthermore, our study highlights the profound pro-tumorigenic metabolic rewiring of HB cells orchestrated by G9a in coordination with the c-MYC oncogene. With a broader perspective, our findings suggest that anti-G9a therapies may also be effective in other c-MYC-dependent tumors.PMID:37302584 | DOI:10.1016/j.jhep.2023.05.031

Plant Physiol Biochem. 2023 May 24;201:107797. doi: 10.1016/j.plaphy.2023.107797. Online ahead of print.ABSTRACTCucurbitaceae species are used in traditional medicine around the world. Cucurbitacins are highly oxygenated triterpenoids found in Cucurbitaceae species and exhibit potent anticancer activity alone and in combination with other existing chemotherapeutic drugs. Therefore, increasing production of these specialized metabolites is of great relevance. We recently showed that hairy roots of Cucurbita pepo can be used as a platform for metabolic engineering of cucurbitacins to modify their structure and increase their production. To study the changes in cucurbitacin accumulation upon formation of hairy roots, an empty vector (EV) control and Cucurbitacin inducing bHLH transcription factor 1 (CpCUCbH1)-overexpressing hairy roots of C. pepo were compared to untransformed (WT) roots. Whilst CpCUCbH1-overexpression increased production of cucurbitacins I and B by 5-fold, and cucurbitacin E by 3-fold when compared to EV lines, this increase was not significantly different when compared to WT roots. This indicated that Rhizobium rhizogenes transformation lowered the cucurbitacins levels in hairy roots, but that increasing expression of cucurbitacin biosynthetic genes by CpCUCbH1-overexpression restored cucurbitacin production to WT levels. Subsequent metabolomic and RNA-seq analysis indicated that the metabolic profile and transcriptome of hairy roots was significantly changed when compared to WT roots. Interestingly, it was observed that 11% of the differentially expressed genes were transcription factors. It was noteworthy that the majority of transcripts showing highest Pearson correlation coefficients to the Rhizobium rhizogenes genes rolB, rolC and ORF13a, were predicted to be transcription factors. In summary, hairy roots are an excellent platform for metabolic engineering of plant specialized metabolites, but these extensive transcriptome and metabolic profile changes should be considered in subsequent studies.PMID:37302255 | DOI:10.1016/j.plaphy.2023.107797

J Chromatogr A. 2023 Jun 7;1704:464135. doi: 10.1016/j.chroma.2023.464135. Online ahead of print.ABSTRACTIn chromatography, pressure can affect the retention factors of compounds significantly. In liquid chromatography, this effect is primarily related to the change in the molecular volume of solute during adsorption that is remarkably high for large biomolecules such as peptides and proteins. As a result, the migration velocities of chromatographic bands vary spatially through the column affecting the degree of band broadening. In this work, based on theoretical considerations, chromatographic efficiencies are studied under pressure-induced gradient conditions. The retention factor and migration velocity of different components are examined, and it is shown that components with the same retention time can have different migration patterns. The width of the initial band after injection is affected by the pressure gradient, providing significantly thinner initial bands for compounds with higher pressure sensitivity. In addition to classical band broadening phenomena, the influence of pressure gradients on band broadening is remarkable. The positive velocity gradient leads to extra band broadening. Our results clearly demonstrate that the zones are significantly wider at the end of the column if the change of molar volume of solute during adsorption is large. If the pressure drop is increasing, this effect becomes more significant. In the same time, the high release velocity of the bands somewhat counteracts the extra band broadening effect, however, it can not offset it perfectly. As a result, the separation efficiency of large biomolecules is decreased significantly due to the chromatographic pressure gradient. Under UHPLC conditions, the extent of apparent efficiency loss can reach up to 50% compared to the intrinsic efficiency of the column.PMID:37302250 | DOI:10.1016/j.chroma.2023.464135

Clin Investig Arterioscler. 2023 Jun 9:S0214-9168(23)00047-5. doi: 10.1016/j.arteri.2023.05.003. Online ahead of print.ABSTRACTPrimary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.PMID:37302939 | DOI:10.1016/j.arteri.2023.05.003

New Phytol. 2023 Jun 11. doi: 10.1111/nph.19059. Online ahead of print.ABSTRACTPollen tubes have dynamic tubular vacuoles. Functional loss of AP-3, a regulator of one vacuolar trafficking route, reduces pollen tube growth. However, the role of canonical Rab5 GTPases that are responsible for two other vacuolar trafficking routes in Arabidopsis pollen tubes is obscure. By using genomic editing, confocal microscopy, pollen tube growth assays, and transmission electron microscopy, we demonstrate that functional loss of canonical Rab5s in Arabidopsis, RHA1 and ARA7, causes the failure of pollen tubes to grow through style and thus impairs male transmission. Functional loss of canonical Rab5s compromises vacuolar trafficking of tonoplast proteins, vacuolar biogenesis, and turgor regulation. However, rha1;ara7 pollen tubes are comparable to those of wild-type in growing through narrow passages by microfluidic assays. We demonstrate that functional loss of canonical Rab5s compromises endocytic and secretory trafficking at the plasma membrane (PM), whereas the targeting of PM-associated ATPases is largely unaffected. Despite that, rha1;ara7 pollen tubes contain a reduced cytosolic pH and disrupted actin microfilaments, correlating with the mis-targeting of vacuolar ATPases (VHA). These results imply a key role of vacuoles in maintaining cytoplasmic proton homeostasis and in pollen tube penetrative growth through style.PMID:37301984 | DOI:10.1111/nph.19059

Transl Psychiatry. 2023 Jun 10;13(1):198. doi: 10.1038/s41398-023-02484-5.ABSTRACTDepression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an "atypical/energy-related" symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An 'AES profile' score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = -0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature-commonly linked to cardiometabolic disorders-associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression's detrimental impact on health.PMID:37301859 | DOI:10.1038/s41398-023-02484-5

J Am Heart Assoc. 2023 Jun 10:e028022. doi: 10.1161/JAHA.122.028022. Online ahead of print.ABSTRACTBackground The American Heart Association's framework "ideal cardiovascular health" (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). Methods and Results We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole-3-proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable-adjusted models. Conclusions Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.PMID:37301766 | DOI:10.1161/JAHA.122.028022

Am J Pathol. 2023 Jun 8:S0002-9440(23)00202-X. doi: 10.1016/j.ajpath.2023.05.010. Online ahead of print.ABSTRACTInvasive micropapillary carcinoma (IMPC) of the breast is a special histopathological type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Based on previous spatial transcriptome studies, our team found extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. We performed endogenous metabolite-targeted metabolomic analysis on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry (LC-MS). We found an IMPC-like state, which is an intermediate transitional morphological phenotype between IMPC and IDC-NOS. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High PRMT1 expression was an independent factor related to the poor prognosis of IMPC patients in terms of disease-free survival (DFS). PRMT1 promotes H4R3me2a, which induces tumor cell proliferation via cell cycle regulation and facilitates tumor cell metastasis via the TNF signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC, and the identification of potential targets of PRMT1 is expected to provide a basis for the precise diagnosis and treatment of breast IMPC.PMID:37301537 | DOI:10.1016/j.ajpath.2023.05.010

Environ Pollut. 2023 Jun 8:121951. doi: 10.1016/j.envpol.2023.121951. Online ahead of print.ABSTRACTMultiple epidemics of chronic kidney disease of an unknown etiology (CKDu) have emerged in agricultural communities around the world. Many factors have been posited as potential contributors, but a primary cause has yet to be identified and the disease is considered likely multifactorial. Sugarcane workers are largely impacted by disease leading to the hypothesis that exposure to sugarcane ash produced during the burning and harvest of sugarcane could contribute to CKDu. Estimated exposure levels of particles under 10 μm (PM10) have been found to be exceptionally high during this process, exceeding 100 μg/m3 during sugarcane cutting and averaging ∼1800 μg/m3 during pre-harvest burns. Sugarcane stalks consist of ∼80% amorphous silica and generate nano-sized silica particles (∼200 nm) following burning. A human proximal convoluted tubule (PCT) cell line was subjected to treatments ranging in concentration from 0.025 μg/mL to 25 μg/mL of sugarcane ash, desilicated sugarcane ash, sugarcane ash-derived silica nanoparticles (SAD SiNPs) or manufactured pristine 200 nm silica nanoparticles. The combination of heat stress and sugarcane ash exposure on PCT cell responses was also assessed. Following 6-48 h of exposure, mitochondrial activity and viability were found to be significantly reduced when exposed to SAD SiNPs at concentrations 2.5 μg/mL or higher. Oxygen consumption rate (OCR) and pH changes suggested significant alteration to cellular metabolism across treatments as early as 6 h following exposure. SAD SiNPs were found to inhibit mitochondrial function, reduce ATP generation, increase reliance on glycolysis, and reduce glycolytic reserve. Metabolomic analysis revealed several cellular energetics pathways (e.g., fatty acid metabolism, glycolysis, and TCA cycle) are significantly altered across ash-based treatments. Heat stress did not influence these responses. Such changes indicate that exposure to sugarcane ash and its derivatives can promote mitochondrial dysfunction and disrupt metabolic activity of human PCT cells.PMID:37301454 | DOI:10.1016/j.envpol.2023.121951

Sci Total Environ. 2023 Jun 8:164682. doi: 10.1016/j.scitotenv.2023.164682. Online ahead of print.ABSTRACTIncreasing nanoplastics (NPs) pollution may lead to unknown environmental risks when considered together with climate change, which has the potential to become an increasingly important environmental issue in the coming decades. In this context, the present study aimed to evaluate the stressor modelling of polystyrene nanoplastic (PS-NPs) combined with temperature increase in zebrafish. For this purpose, changes in gill, liver and muscle tissues of zebrafish exposed to PS-NPs (25 ppm) and/or different temperatures (28, 29 and 30 °C) for 96 h under static conditions were evaluated. The results obtained emphasize that exposure to PS-NPs stressors under controlled conditions with temperature increase induces DNA damage through stress-induced responses accompanied by degeneration, necrosis and hyperaemia in zebrafish liver and adhesion of lamellae, desquamation and inflammation in lamellar epithelium in gills. Metabolomic analyses also supported changes indicating protein and lipid oxidation, especially PS-NPs-mediated. These findings will contribute to the literature as key data on the effects of PS-NPs presence on protein/lipid oxidation and fillet quality in muscle tissues.PMID:37301397 | DOI:10.1016/j.scitotenv.2023.164682

Sci Total Environ. 2023 Jun 8:164718. doi: 10.1016/j.scitotenv.2023.164718. Online ahead of print.ABSTRACTAs the herbicide acetochlor (ACT) affects the plankton food web, this study investigated the effects of ACT and exocrine infochemicals from daphnids (after ACT exposure and/or starvation) on Scenedesmus obliquus growth, as well as the effects of ACT and starvation on life-history traits of Daphnia magna. Filtered secretions from daphnids increased algal ACT tolerance, dependent on different ACT exposure histories and food intake. Endogenous and secretory metabolite profiles of daphnids following ACT and/or starvation appear to be regulated by the fatty acid synthesis pathway and sulfotransferases and were related to energy allocation trade-offs. Oleic acid (OA) and octyl sulfate (OS), screened by secreted and somatic metabolomics, affected algal growth and ACT behavior in the algal culture in opposite ways. Trophic and non-trophic interspecific effects caused by ACT were observed in microalgae-daphnid microcosms, including algal growth inhibition, daphnid starvation, OA down-regulation, and OS up-regulation. Based on these findings, risk assessment of ACT on the freshwater plankton communities should take species interactions into account.PMID:37301391 | DOI:10.1016/j.scitotenv.2023.164718

Diabetes Res Clin Pract. 2023 Jun 8:110772. doi: 10.1016/j.diabres.2023.110772. Online ahead of print.ABSTRACTAIMS: The aim of this study was to combine nuclear magnetic resonance-based metabolomics and machine learning to find a glucose-independent molecular signature associated with future type 2 diabetes mellitus development in a subgroup of individuals from the Di@bet.es study.METHODS: The study group included 145 individuals developing type 2 diabetes mellitus during the 8-year follow-up, 145 individuals matched by age, sex and BMI who did not develop diabetes during the follow-up but had equal glucose concentrations to those who did and 145 controls matched by age and sex. A metabolomic analysis of serum was performed to obtain the lipoprotein and glycoprotein profiles and 15 low molecular weight metabolites. Several machine learning-based models were trained.RESULTS: Logistic regression performed the best classification between individuals developing type 2 diabetes during the follow-up and glucose-matched individuals. The area under the curve was 0.628, and its 95% confidence interval was 0.510-0.746. Glycoprotein-related variables, creatinine, creatine, small HDL particles and the Johnson-Neyman intervals of the interaction of Glyc A and Glyc B were statistically significant.CONCLUSIONS: The model highlighted a relevant contribution of inflammation (glycosylation pattern and HDL) and muscle (creatinine and creatine) in the development of type 2 diabetes as independent factors of hyperglycemia.PMID:37301326 | DOI:10.1016/j.diabres.2023.110772

Microbiol Res. 2023 Jun 5;274:127422. doi: 10.1016/j.micres.2023.127422. Online ahead of print.ABSTRACTProdigiosin pigment is a secondary metabolite produced by many bacterial species and is known for its medicinal properties. A few of these prodigiosin-producing bacteria are also reported to be entomopathogenic. It is intriguing to unravel the role of prodigiosin in insecticidal activities and its mode of action. In this study, we have shown the production and characterization of prodigiosin from the Serratia rubidaea MJ 24 isolated from the soil of the Western Ghats, India. Further, we assessed the effect of this pigment on the lepidopteran agricultural pest, Helicoverpa armigera. Prodigiosin-fed H. armigera indicated defective development of insect growth upon treatment. Due to defective early development, about 50% mortality and 40% reduction in body weight were observed in insects fed on a 500 ppm prodigiosin-containing diet. The transcriptomic analysis of these insects indicated significant dysregulation of Juvenile hormone synthesis and response related genes. In addition, dopamine related processes and their resultant melanization and sclerotization processes were also found to be affected. The changes in the expression levels of the key transcripts were further validated using real-time quantitative PCR. The metabolome data confirmed the developmental dysregulation of precursors and products of differentially regulated genes due to prodigiosin. Therefore, the corroborated data suggests that prodigiosin majorly affects H. armigera development through dysregulation of the Juvenile hormone-dopamine system and can be considered as a bioactive scaffold to design insect-pest management compounds. This study provides the first report of in-depth analysis of insecticidal system dynamics in H. armigera insects upon prodigiosin feeding via gene expression and metabolic change via omics approach.PMID:37301080 | DOI:10.1016/j.micres.2023.127422

Food Chem. 2023 Jun 7;426:136577. doi: 10.1016/j.foodchem.2023.136577. Online ahead of print.ABSTRACTGinger (Zingiber officinale Roscoe) is a high-value food and herb worldwide. The quality of ginger is often related to its production regions. In this study, stable isotopes, multiple elements, and metabolites were investigated together to realize ginger origin traceability. Chemometrics showed that ginger samples could be preliminarily separated, and 4 isotopes (δ13C, δ2H, δ18O, and δ34S), 12 mineral elements (Rb, Mn, V, Na, Sm, K, Ga, Cd, Al, Ti, Mg, and Li), 1 bioelement (%C), and 143 metabolites were the most important variables for discrimination. Furthermore, three algorithms were introduced, and the fused dataset based on VIP features led to the highest accuracies for origin classification, with predictive rates of 98% for K-nearest neighbor and 100% for support vector machine and random forest. The results demonstrated that isotopic, elemental, and metabolic fingerprints were useful indicators for the geographical origins of Chinese ginger.PMID:37301043 | DOI:10.1016/j.foodchem.2023.136577

Food Chem. 2023 Jun 2;426:136503. doi: 10.1016/j.foodchem.2023.136503. Online ahead of print.ABSTRACTThis study examined the phytochemical profiles (mainly phenolics, carotenoids, and organosulfur compounds) and biological effects of hydroalcoholic extracts of Allium flavum (AF), a species of the Allium genus commonly known as small yellow onion. Unsupervised and supervised statistical approaches revealed clear differences between extracts prepared with samples collected from different areas of Romania. Overall, the AFFF (AF flowers collected from Făget) extract was the best source of polyphenols, also showing the highest antioxidant capacity evaluated through both in vitro DPPH, FRAP, and TEAC anti-radical scavenging assays and cell-based OxHLIA and TBARS assays. All the tested extracts exhibited α-glucosidase inhibition potential, while only the AFFF extract exhibited anti-lipase inhibitory activity. The phenolic subclasses annotated were positively correlated with the assessed antioxidant and enzyme inhibitory activities. Our findings suggested that A. flavum has bioactive properties worth exploring further, being a potential edible flower with health-promoting implications.PMID:37301042 | DOI:10.1016/j.foodchem.2023.136503

Food Chem. 2023 Jun 3;425:136538. doi: 10.1016/j.foodchem.2023.136538. Online ahead of print.ABSTRACTThe narrow geographical traceability of green tea is both important and challenging. This study aimed to establish multi-technology metabolomic and chemometric approaches to finely discriminate the geographic origins of green teas. Taiping Houkui green tea samples were analyzed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry and 1H NMR of polar (D2O) and non-polar (CDCl3). Common dimension, low-level and mid-level data fusion approaches were tested to verify if the combination of several analytical sources can improve the classification ability of samples from different origins. In assessments of tea from six origins, the single instrument data test set results in 40.00% to 80.00% accuracy. Data fusion improved single-instrument performance classification with mid-level data fusion to obtain 93.33% accuracy in the test set. These results provide comprehensive metabolomic insights into the origin of TPHK fingerprinting and open up new metabolomic approaches for quality control in the tea industry.PMID:37300997 | DOI:10.1016/j.foodchem.2023.136538

Food Chem. 2023 May 2;425:135946. doi: 10.1016/j.foodchem.2023.135946. Online ahead of print.ABSTRACTThe differences between dry- and flood-cultivated rice and the reason behind low-quality dry-cultivated rice were clarified. The physiological traits, starch synthase activity, and grain metabolomics of 'Longdao 18' were measured and analyzed at four growth stages. The brown, milled, and whole-milled rice rates and AGPase, SSS, and SBE activity were lower after drought treatment than during flood cultivation, while the chalkiness, chalky grain rate, amylose (16.57-20.999%), protein (7.99-12.09%), and GBSS activity were higher. Related enzymatic gene expression showed significant differences. Metabolic results showed pyruvate, glycine, and methionine upregulation at 8DAF and higher citric, pyruvic, and α-ketoglutaric acid content at 15DAF. Therefore, 8DAF-15DAF represented the crucial quality formation period for dry-cultivated rice. At 8DAF, the respiratory pathways used amino acids as signaling molecules and alternative substrates to adapt to energy shortages, arid environments and rapid protein accumulation and synthesis. Excessive amylose synthesis at 15DAF accelerated reproductive growth, promoting rapid premature aging.PMID:37300996 | DOI:10.1016/j.foodchem.2023.135946

Metab Brain Dis. 2023 Jun 10. doi: 10.1007/s11011-023-01244-0. Online ahead of print.ABSTRACTDepression is a serious mental illness, but the molecular mechanisms of depression remain unclear. Previous research has reported metabolomic changes in the blood of patients with depression, while integrated analysis based on these altered metabolites was still lacking. The objective of this study was to integrate metabolomic changes to reveal the underlying molecular alternations of depression. We retrieved altered metabolites in the blood of patients with depression from the MENDA database. Pathway analysis was conducted to explore enriched pathways based on candidate metabolites. Pathway crosstalk analysis was performed to explore potential correlations of these enriched pathways, based on their shared candidate metabolites. Moreover, potential interactions of candidate metabolites with other biomolecules such as proteins were assessed by network analysis. A total of 854 differential metabolite entries were retrieved in peripheral blood of patients with depression, including 555 unique candidate metabolites. Pathway analysis identified 215 significantly enriched pathways, then pathway crosstalk analysis revealed that these pathways were clustered into four modules, including amino acid metabolism, nucleotide metabolism, energy metabolism and others. Additionally, eight molecular networks were identified in the molecular network analysis. The main functions of these networks involved amino acid metabolism, molecular transport, inflammatory responses and others. Based on integrated analysis, our study revealed pathway-based modules and molecular networks associated with depression. These results will contribute to the underlying knowledge of the molecular mechanisms in depression.PMID:37300637 | DOI:10.1007/s11011-023-01244-0

Nutrients. 2023 Jun 5;15(11):2638. doi: 10.3390/nu15112638.ABSTRACTBACKGROUND: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort.METHODS: In the ZOE PREDICT 1 study (n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated.RESULTS: Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate.CONCLUSIONS: In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.PMID:37299601 | DOI:10.3390/nu15112638

Nutrients. 2023 May 25;15(11):2457. doi: 10.3390/nu15112457.ABSTRACTTogether with its comorbidities, nonalcoholic fatty liver disease (NAFLD) is likely to rise further with the obesity epidemic. However, the literature's evidence shows how its progression can be reduced by the administration of calorie-restrictive dietary interventions and physical activity regimens. The liver function and the gut microbiota have been demonstrated to be closely related. With the aim of ascertaining the impact of a treatment based on the combination of diet and physical activity (versus physical activity alone), we recruited 46 NAFLD patients who were divided into two groups. As a result, we traced the connection between volatile organic compounds (VOCs) from fecal metabolomics and a set of statistically filtered clinical variables. Additionally, we identified the relative abundances of gut microbiota taxa obtained from 16S rRNA gene sequencing. Statistically significant correlations emerged between VOCs and clinical parameters, as well as between VOCs and gut microbiota taxa. In comparison with a physical activity regimen alone, we disclose how ethyl valerate and pentanoic acid butyl ester, methyl valerate, and 5-hepten-2-one, 6-methyl changed because of the positive synergistic effect exerted by the combination of the Mediterranean diet and physical activity regimens. Moreover, 5-hepten-2-one, 6-methyl positively correlated with Sanguinobacteroides, as well as the two genera Oscillospiraceae-UCG002 and Ruminococcaceae UCG010 genera.PMID:37299420 | DOI:10.3390/nu15112457