PubMed

J Econ Entomol. 2023 Jul 17:toad132. doi: 10.1093/jee/toad132. Online ahead of print.ABSTRACTDetection of sex pheromones of insects relies on the antennae. The female pheromone signal transmission in the male antennae ultimately initiates the courtship and mating behaviors of males. To investigate the proteins and metabolites involved in this neural transduction, integrative proteomics and metabolomics analysis including tandem mass tag (TMT) proteomic quantification and liquid chromatography tandem mass spectrometry (LC/MS)-based metabolomics was adopted for comparing proteomic and metabolic changes between the antennae of male moths following stimulation by females and the non-stimulated males of Antheraea pernyi (Guérin-Méneville, Lepidoptera: Saturniidae) in this study. A total of 92 differentially expressed proteins (DEPs) containing 52 upregulated and 40 downregulated proteins and 545 differentially expressed metabolites (DEMs) including 218 upregulated and 327 downregulated metabolites were identified from the antennae of female-stimulated male moths based on the proteome and metabolome data, respectively. Bioinformatics analysis was performed for the 45 DEPs and 160 DEMs, including Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encylopaedia of Genes and Genomes (KEGG) enrichment analysis and Human Metabolome Database (HMDB) annotation. A number of DEPs and DEMs related to neural transmission of female pheromone signals in the male antennae of A. pernyi were screened, including tyrosine hydroxylase, cryptochrome-1, tachykinin, arylalkylamine N-acetyltransferase, cadherin-23, glutathione S-transferase delta 3, tyramine, tryptamine, n-oleoyl dopamine, n-stearoyl dopamine, and n-stearoyl tyrosine. The altered expression levels of those proteins or metabolites were speculated involved in regulating the neuron activity for enhanced transmission of neural impulses and continuous perception, reception, and transduction of female pheromone signals. Our findings yielded novel insights into the potential mechanisms in the antennae of male A. pernyi responding to female attraction.PMID:37459048 | DOI:10.1093/jee/toad132

Eur J Nutr. 2023 Jul 17. doi: 10.1007/s00394-023-03181-1. Online ahead of print.ABSTRACTPURPOSE: The influence of vitamin D status on exercise-induced immune dysfunction remains unclear. The aim of this study was to investigate the effects of vitamin D status (circulating 25(OH)D) on innate immune responses and metabolomic profiles to prolonged exercise.METHODS: Twenty three healthy, recreationally active males (age 25 ± 7 years; maximal oxygen uptake [[Formula: see text]max] 56 ± 9 mL·kg-1·min-1), classified as being deficient (n = 7) or non-deficient n = 16) according to plasma concentrations of 25(OH)D, completed 2.5 h of cycling at 15% Δ (~ 55-60% [Formula: see text]max). Venous blood and unstimulated saliva samples were obtained before and after exercise.RESULTS: Participants with deficient plasma 25(OH)D on average had lower total lymphocyte count (mean difference [95% confidence interval], 0.5 cells × 109 L [0.1, 0.9]), p = 0.013) and greater neutrophil:lymphocyte ratio (1.3 cells × 109 L, [0.1, 2.5], p = 0.033). The deficient group experienced reductions from pre-exercise to 1 h post-exercise (- 43% [- 70, - 15], p = 0.003) in bacterial stimulated elastase in blood neutrophils compared to non-deficient participants (1% [- 20, 21], p = 1.000) Multivariate analyses of plasma metabolomic profiles showed a clear separation of participants according to vitamin D status. Prominent sources of variation between groups were purine/pyrimidine catabolites, inflammatory markers (linoleic acid pathway), lactate and tyrosine/adrenaline.CONCLUSION: These findings provide evidence of the influence of vitamin D status on exercise-induced changes in parameters of innate immune defence and metabolomic signatures such as markers of inflammation and metabolic stress.PMID:37458775 | DOI:10.1007/s00394-023-03181-1

Anal Chem. 2023 Jul 17. doi: 10.1021/acs.analchem.3c01358. Online ahead of print.ABSTRACTGastric cancer is one of the most common malignant digestive cancers, and its diagnostic has still faced challenges based on metabolic analysis due to complex sample pretreatment and low metabolite abundance. In this study, inspired by the structure of bovine omasum, we in situ synthesized a novel interfacial carbon-based nanocomposite of graphene supported nickel nanoparticles-encapsulated in the nitrogen-doped carbon nanotube (Ni/N-CNT/rGO), which was served as a novel matrix with enhanced ionization efficiency for the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) saliva metabolic analysis of gastric cancer. Benefiting from its high sp2 graphitic degree, large surface area, strong UV absorption, and rich active sites, Ni/N-CNT/rGO matrix exhibited excellent performances of reproducibility, coverage, salt-tolerance, sensitivity, and adsorption ability in MALDI-TOF MS. The differential scanning calorimetry (DSC) and thermal conversion behaviors explained the highly efficient LDI mechanism. Based on saliva metabolic fingerprints, Ni/N-CNT/rGO assisted LDI MS with cross-validation analysis could successfully distinguish gastric cancer patients from healthy controls through the screening of four potential biomarkers with an accuracy of 92.50%, specificity of 88.03%, and sensitivity of 97.12%. This work provided a fast and sensitive MS sensing platform for the metabolomics characterization of gastric cancer and might have potential value for precision medicine in the future.PMID:37458487 | DOI:10.1021/acs.analchem.3c01358

mSystems. 2023 Jul 17:e0015123. doi: 10.1128/msystems.00151-23. Online ahead of print.ABSTRACTColon cancer onset is strongly associated with the differences in microbial taxa in the gastrointestinal tract. Although recent studies highlight the role of individual taxa, the effect of a complex gut microbiome (GM) on the metabolome and host transcriptome is still unknown. We used a multi-omics approach to determine how differences in the GM affect the susceptibility to adenoma development in a rat model of human colon cancer. Ultra-high performance liquid chromatography mass spectrometry of feces collected prior to observable disease onset identified putative metabolite profiles that likely predict future disease severity. Transcriptome analyses performed after disease onset from normal colonic epithelium and tumor tissues show a correlation between GM and host gene expression. Integrated pathway analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis is enriched in rats with high tumors along with increased fatty acid metabolism and mucin biosynthesis. Targeted pyrosequencing of the Pirc allele indicates that the GM alters the mechanism of adenoma development and may drive an epigenetic pathway of tumor suppressor silencing. This study reveals how untargeted metabolomics identifies signatures of susceptibility and integrated analyses uncover pathways of differential mechanisms of loss of tumor suppressor gene function and for potential prevention and therapeutic intervention. IMPORTANCE The association between the gut microbiome and colon cancer is significant but difficult to test in model systems. This study highlights the association of differences in the pathogen-free gut microbiome to changes in the host transcriptome and metabolome that correlate with colon adenoma initiation and development in a rat genetic model of early colon cancer. The utilization of a multi-omics approach integrating metabolomics and transcriptomics reveals differences in pathways including bile acid biosynthesis and fatty acid metabolism. The study also shows that differences in gut microbiomes significantly alter the mechanism of adenoma formation, shifting from genetic changes to epigenetic changes that initiate the early loss of tumor suppressor function. These findings enhance our understanding of the gut microbiome's role in colon cancer susceptibility, offer insights into potential biomarkers and therapeutic targets, and may pave the way for future prevention and intervention strategies.PMID:37458451 | DOI:10.1128/msystems.00151-23

J Food Sci. 2023 Jul 17. doi: 10.1111/1750-3841.16701. Online ahead of print.ABSTRACTThe nutritional and volatile profiles of pulp and flavedo samples from four distinct local pummelo landraces ("Siji," "Pingshan," "Wendan," and "Guanxi") cultivated in Fujian province of China were investigated. "Guanxi" pummelo exhibited relatively high contents of vitamin C (42.01 mg/100 mL) and phenols (360.61 mg/L) and displayed a robust antioxidant capacity (41.15 mg/100 mL). Conversely, the red pulp from "Pingshan" demonstrated relatively high values of carotenoids (55.96 µg/g) and flavonoids (79.79 mg/L). Considerable differences were observed in volatile compositions between the two fruit tissues and among the four genotypes. A total of 166 and 255 volatile compounds were detected in the pulp and flavedo samples, respectively. Notably, limonene and β-myrcene were identified as the principal volatile compounds in flavedo, whereas hexanal was highly abundant in the pulp of "Siji," "Pingshan," and "Guanxi." "Wendan" displayed distinct separation from the other three pummelo cultivars in principal component analysis based on the pulp volatile compositions. This distinction was attributed to the higher number and content of volatile compounds in "Wendan" pulp, particularly the remarkable enrichment of β-myrcene. The newly characterized pummelo landraces and genotype/tissue-dependent variations in volatiles provide essential information for the genetic improvement of pummelo aroma, as well as for fruit processing and utilization.PMID:37458289 | DOI:10.1111/1750-3841.16701

J Food Sci. 2023 Jul 17. doi: 10.1111/1750-3841.16698. Online ahead of print.ABSTRACTBambara groundnut (BG) (Vigna subterranean) is an underutilized, indigenous crop in South Africa that has nutritional and associated health benefits. Decreasing the antinutrients in food sources can potentially increase the digestibility of proteins and mineral absorption. To determine the effect of traditional processing (cooking) on the antinutrient content and metabolome of this crop, BG was sampled from 12 rural farms in three districts of the Mpumalanga province, South Africa. The four main colors that were identified (cream, orange, brown, and purple) were pooled together according to the district they were obtained from. One-half of each color sample obtained from each of the three districts was dehulled, color sorted, milled, and subjected to subsequent antinutrient and metabolome analyses, while the other half was cooked, air-dried, and milled prior to analyses. Samples were analyzed for phytate and tannins (antinutrients) by hydrochloric acid extraction methods as well as metabolome constituents by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Phytate, tannins, as well as other metabolomic constituents, namely, catechin, epicatechin, procyanidin, as well as citric acid, were identified in all raw and cooked BG samples. The cooking process resulted in a significant decrease (p < 0.05) in the phytate and tannin content as well as an increase in the health-associated phenolic compounds.PMID:37458285 | DOI:10.1111/1750-3841.16698

Eur J Clin Invest. 2023 Jul 17:e14063. doi: 10.1111/eci.14063. Online ahead of print.ABSTRACTBACKGROUND: H-type hypertension (HHT) is a disease combined with hyperhomocysteinaemia and hypertension (HT). This study aims to find specific metabolic changes and reveal the pathophysiological mechanism of HHT, which provide the theoretical basis for the early prevention and treatment of HHT.METHODS: Serum samples from three groups including 53 HHT patients, 36 HT patients and 46 healthy controls (HC) were collected. The targeted and untargeted metabolomics analyses were performed to determine the metabolic changes. Based on multivariate statistical analysis, the serum potential metabolites were screened and different metabolic pathways were explored.RESULTS: Our results demonstrated that there were 28 important potential metabolites for distinguishing HT from HHT patients. Metabolic pathway analysis showed that the different metabolic pathways between HHT and HC group were arginine biosynthesis, arginine and proline metabolism, and tyrosine metabolism. The changed metabolic pathway of HT and HC group included linoleic acid metabolism. The specific metabolic pathways of HT-HHT comparison group had phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; glycine, serine and threonine metabolism.CONCLUSIONS: Metabolomics analysis by mass spectrometry multi-platform revealed the differences of metabolic profiles between HHT and HT subjects. This work laid the groundwork for understanding the aetiology of HHT, and these findings may provide the useful information for explaining the HHT metabolic alterations and try to prevent HHT.PMID:37458276 | DOI:10.1111/eci.14063

Analyst. 2023 Jul 17. doi: 10.1039/d3an00599b. Online ahead of print.ABSTRACTMetabolites in biological matrices belong to diverse chemical groups, ranging from non-polar long-chain fatty acids to small polar molecules. The goal of untargeted metabolomic analysis is to measure the highest number of metabolites in the sample. Nevertheless, from an analytical point of view, no single technique can measure such a broad spectrum of analytes. Therefore, we selected a method based on GC-MS and LC-MS with two types of stationary phases for the untargeted profiling of gastrointestinal stromal tumours. The procedure was applied to GIST xenograft samples (n = 71) representing four different mutation models, half of which were treated with imatinib. We aimed to verify the method coverage and advantages of applying each technique. RP-LC-MS measured most metabolites due to a significant fraction of lipid components of the tumour tissue. What is unique and worth noting is that all applied techniques were able to distinguish between different mutation models. However, for detecting imatinib-induced alterations in the GIST metabolome, RP-LC-MS and GC-MS proved to be more relevant than HILIC-LC-MS, resulting in a higher number of significantly changed metabolites in four treated models. Undoubtedly, the inclusion of all mentioned techniques makes the method more comprehensive. Nonetheless, for green chemistry and time and labour saving, we assume that RP-LC-MS and GC-MS analyses are sufficient to cover the global GIST metabolome.PMID:37458061 | DOI:10.1039/d3an00599b

Front Nutr. 2023 Jun 29;10:1168025. doi: 10.3389/fnut.2023.1168025. eCollection 2023.ABSTRACTINTRODUCTION: Low temperature is the most common method used to maintain the freshness of Phlebopus portentosus during long-distance transportation. However, there is no information regarding the nutritional changes that occur in P. portentosus preserved postharvest in low temperature.METHODS: In this study, the changes in flavor quality and bioactive components in fruiting bodies stored at 4 °C for different storage periods were determined through LC/MS and GC/MS analyses. Sampling was performed at 0, 3, 5, 7, and 13 days storage.RESULTS AND DISCUSSION: Based on the results, the metabolites present in caps and stipes were different at the same period and significantly different after 7 days of storage. A total of 583 and 500 different metabolites were detected in caps and stipes, respectively, and were mainly lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds and others. Except for prenol lipids and nucleotides, the expression levels of most metabolites increased with longer storage time. In addition, geosmin was identified as the major contributor to earthy-musty odors, and the level of geosmin was increased when the storage time was short.CONCLUSION: The variations in these metabolites might cause changes in flavor quality and bioactive components in P. portentosus. Variations in these metabolites were thoroughly analyzed, and the results revealed how storage processes affect the postharvest quality of P. portentosus for the first time.PMID:37457983 | PMC:PMC10349180 | DOI:10.3389/fnut.2023.1168025

Int J Bioprint. 2023 Feb 21;9(5):691. doi: 10.18063/ijb.691. eCollection 2023.ABSTRACTEdible bird's nests (EBN)-the nests of swiftlet birds harvested from the wild- are high-end healthcare food in East Asia, while their excessive harvesting poses increasing ecological, environmental, and food safety concerns. Here, we report for the first time a tissue-engineering (TE) approach for fabricating EBNs substitutes by integrating the technologies of three-dimensional (3D) printing and live cell culture. The engineered products, tissue-engineered edible bird's nests (TeeBN), comprise two layers. The first is a feeding layer that encapsulates epithelial cells in 3D-printed biocompatible gelation scaffolds. These cells secrete bioactive ingredients, e.g., sialic acid and epidermal growth factors (EGF), recapitulating the natural production of these substances by birds. The second is a receiving layer, consisting of foodgrade natural polymers, e.g., polysaccharides, which mimics the building blocks of natural EBNs while biologically stabilizing the factors released from the feeding layer. In vitro characterizations demonstrate that the feeding layer facilitates 3D cell growth and functions, and the receiving layer (as the end product) contains the necessary nutrients expected from natural EBNs-while without harmful substances commonly detected in natural EBNs. Further, in vivo metabolomics studies in mice indicate that TeeBN showed a similar profile of serum metabolites as natural EBN, reflecting comparable nutritional effects. In summary, we innovatively developed a tissue engineering-based substitute for EBNs with comparable metabolic functions and minimized safety risks, opening a new avenue for producing delicacy food from laboratorial cell culture with 3D printing technology.PMID:37457942 | PMC:PMC10339468 | DOI:10.18063/ijb.691

J Endocr Soc. 2023 Jul 1;7(8):bvad091. doi: 10.1210/jendso/bvad091. eCollection 2023 Jul 3.ABSTRACTCONTEXT: Obesity surveillance is scarce in adolescents, and little is known on whether salivary metabolomics data, emerging minimally invasive biomarkers, can characterize metabolic patterns associated with overweight or obesity in adolescents.OBJECTIVE: This pilot study aims to identify the salivary molecular signatures associated with body mass index (BMI) in Italian adolescents.METHODS: Saliva samples and BMI were collected in a subset of n = 74 young adolescents enrolled in the Public Health Impact of Metal Exposure study (2007-2014). A total of 217 untargeted metabolites were identified using liquid chromatography-high resolution mass spectrometry. Robust linear regression was used to cross-sectionally determine associations between metabolomic signatures and sex-specific BMI-for-age z-scores (z-BMI).RESULTS: Nearly 35% of the adolescents (median age: 12 years; 51% females) were either obese or overweight. A higher z-BMI was observed in males compared to females (P = .02). One nucleoside (deoxyadenosine) and 2 lipids (18:0-18:2 phosphatidylcholine and dipalmitoyl-phosphoethanolamine) were negatively related to z-BMI (P < .05), whereas 2 benzenoids (3-hydroxyanthranilic acid and a phthalate metabolite) were positively associated with z-BMI (P < .05). In males, several metabolites including deoxyadenosine, as well as deoxycarnitine, hyodeoxycholic acid, N-methylglutamic acid, bisphenol P, and trigonelline were downregulated, while 3 metabolites (3-hydroxyanthranilic acid, theobromine/theophylline/paraxanthine, and alanine) were upregulated in relation to z-BMI (P < .05). In females, deoxyadenosine and dipalmitoyl-phosphoethanolamine were negatively associated with z-BMI while deoxycarnitine and a phthalate metabolite were positively associated (P < .05). A single energy-related pathway was enriched in the identified associations in females (carnitine synthesis, P = .04).CONCLUSION: Salivary metabolites involved in nucleotide, lipid, and energy metabolism were primarily altered in relation to BMI in adolescents.PMID:37457847 | PMC:PMC10341611 | DOI:10.1210/jendso/bvad091

Front Mol Biosci. 2023 Jun 15;10:1182643. doi: 10.3389/fmolb.2023.1182643. eCollection 2023.ABSTRACTEmerging evidence reveals the fundamental role of the gut microbiome in human health. Among various factors regulating our gut microbiome, diet is one of the most indispensable and prominent one. Inulin is one of the most widely-studied dietary fiber for its beneficial prebiotic effects by positively modulating the gut microbiome and microbial metabolites. Recent research underscores sexual dimorphism and sex-specific disparities in microbiome and also diet-microbiome interactions. However, whether and how the prebiotic effects of dietary fiber differ among sexes remain underexplored. To this end, we herein examine sex-specific differences in the prebiotic effects of inulin on gut microbiome and metabolome in a humanized murine model of aging i.e., aged mice carrying human fecal microbiota. The findings demonstrate that inulin exerts prebiotic effects, but in a sex-dependent manner. Overall, inulin increases the proportion of Bacteroides, Blautia, and glycine, while decreasing Eggerthella, Lactococcus, Streptococcus, trimethylamine, 3-hydroxyisobutyrate, leucine and methionine in both sexes. However, we note sex-specific effects of inulin including suppression of f_Enteroccaceae:_, Odoribacter, bile acids, malonate, thymine, valine, acetoin, and ethanol while promotion of Dubosiella, pyruvate, and glycine in males. Whereas, suppression of Faecalibaculum, Lachnoclostridium, Schaedlerella, phenylalanine and enhancement of Parasutterella, Phocaeicola, f_Lachnospiraceae;_, Barnesiella, Butyricimonas, glycine, propionate, acetate and glutamate are observed in females. Altogether, the study reveals that prebiotic mechanisms of dietary fiber vary in a sex-dependent manner, underscoring the importance of including both sexes in preclinical/clinical studies to comprehend the mechanisms and functional aspects of dietary interventions for effective extrapolation and translation in precision nutrition milieus.PMID:37457834 | PMC:PMC10345844 | DOI:10.3389/fmolb.2023.1182643

Front Mol Biosci. 2023 Jun 29;10:1204273. doi: 10.3389/fmolb.2023.1204273. eCollection 2023.ABSTRACTHow the human body reacts to the exposure of HIV-1 is an important research goal. Frequently, HIV exposure leads to infection, but some individuals show natural resistance to this infection; they are known as HIV-1-exposed but seronegative (HESN). Others, although infected but without antiretroviral therapy, control HIV-1 replication and progression to AIDS; they are named controllers, maintaining low viral levels and an adequate count of CD4+ T lymphocytes. Biological mechanisms explaining these phenomena are not precise. In this context, metabolomics emerges as a method to find metabolites in response to pathophysiological stimuli, which can help to establish mechanisms of natural resistance to HIV-1 infection and its progression. We conducted a cross-sectional study including 30 HESN, 14 HIV-1 progressors, 14 controllers and 30 healthy controls. Plasma samples (directly and deproteinized) were analyzed through Nuclear Magnetic Resonance (NMR) metabolomics to find biomarkers and altered metabolic pathways. The metabolic profile analysis of progressors, controllers and HESN demonstrated significant differences with healthy controls when a discriminant analysis (PLS-DA) was applied. In the discriminant models, 13 metabolites associated with HESN, 14 with progressors and 12 with controllers were identified, which presented statistically significant mean differences with healthy controls. In progressors, the metabolites were related to high energy expenditure (creatinine), mood disorders (tyrosine) and immune activation (lipoproteins), phenomena typical of the natural course of the infection. In controllers, they were related to an inflammation-modulating profile (glutamate and pyruvate) and a better adaptive immune system response (acetate) associated with resistance to progression. In the HESN group, with anti-inflammatory (lactate and phosphocholine) and virucidal (lactate) effects which constitute a protective profile in the sexual transmission of HIV. Concerning the significant metabolites of each group, we identified 24 genes involved in HIV-1 replication or virus proteins that were all altered in progressors but only partially in controllers and HESN. In summary, our results indicate that exposure to HIV-1 in HESN, as well as infection in progressors and controllers, affects the metabolism of individuals and that this affectation can be determined using NMR metabolomics.PMID:37457832 | PMC:PMC10339029 | DOI:10.3389/fmolb.2023.1204273

Food Chem (Oxf). 2023 Jul 3;7:100176. doi: 10.1016/j.fochms.2023.100176. eCollection 2023 Dec 30.ABSTRACTAn integrated analysis of the transcriptome and metabolome was conducted to investigate the underlying mechanisms of apple fruit response to impact damage stress. During the post-damage storage, a total of 124 differentially expressed genes (DEGs) were identified, which were mainly annotated in 13 pathways, including phenylpropanoid biosynthesis. Besides, 175 differentially expressed metabolites (DEMs), including 142 up-regulated and 33 down-regulated metabolites, exhibited significant alteration after impact damage. The DEGs and DEMs were simultaneously annotated in 7 metabolic pathways, including flavonoid biosynthesis. Key genes in the volatile esters and flavonoid biosynthesis pathways were revealed, which may play a crucial role in the coping mechanisms of apple fruit under impact damage stress. Moreover, 13 ABC transporters were significantly upregulated, indicating that ABC transporters may contribute to the transportation of secondary metabolites associated with response to impact damage stress. The results may elucidate the comprehension of metabolic networks and molecular mechanisms in apple fruits that have undergone impact damage.PMID:37457816 | PMC:PMC10344661 | DOI:10.1016/j.fochms.2023.100176

Front Immunol. 2023 Jun 29;14:1158455. doi: 10.3389/fimmu.2023.1158455. eCollection 2023.ABSTRACTINTRODUCTION: Severe COVID-19 results initially in pulmonary infection and inflammation. Symptoms can persist beyond the period of acute infection, and patients with Post-Acute Sequelae of COVID (PASC) often exhibit a variety of symptoms weeks or months following acute phase resolution including continued pulmonary dysfunction, fatigue, and neurocognitive abnormalities. We hypothesized that dysregulated NAD metabolism contributes to these abnormalities.METHODS: RNAsequencing of lungs from transgenic mice expressing human ACE2 (K18-hACE2) challenged with SARS-CoV-2 revealed upregulation of NAD biosynthetic enzymes, including NAPRT1, NMNAT1, NAMPT, and IDO1 6 days post-infection.RESULTS: Our data also demonstrate increased gene expression of NAD consuming enzymes: PARP 9,10,14 and CD38. At the same time, SIRT1, a protein deacetylase (requiring NAD as a cofactor and involved in control of inflammation) is downregulated. We confirmed our findings by mining sequencing data from lungs of patients that died from SARS-CoV-2 infection. Our validated findings demonstrating increased NAD turnover in SARS-CoV-2 infection suggested that modulating NAD pathways may alter disease progression and may offer therapeutic benefits. Specifically, we hypothesized that treating K18-hACE2 mice with nicotinamide riboside (NR), a potent NAD precursor, may mitigate lethality and improve recovery from SARS-CoV-2 infection. We also tested the therapeutic potential of an anti- monomeric NAMPT antibody using the same infection model. Treatment with high dose anti-NAMPT antibody resulted in significantly decreased body weight compared to control, which was mitigated by combining HD anti-NAMPT antibody with NR. We observed a significant increase in lipid metabolites, including eicosadienoic acid, oleic acid, and palmitoyl carnitine in the low dose antibody + NR group. We also observed significantly increased nicotinamide related metabolites in NR treated animals.DISCUSSION: Our data suggest that infection perturbs NAD pathways, identify novel mechanisms that may explain some pathophysiology of CoVID-19 and suggest novel strategies for both treatment and prevention.PMID:37457744 | PMC:PMC10344451 | DOI:10.3389/fimmu.2023.1158455

Front Plant Sci. 2023 Jun 29;14:1201486. doi: 10.3389/fpls.2023.1201486. eCollection 2023.ABSTRACTPogostemon cablin is a well-known protected species widely used in medicine and spices, however the underlying molecular mechanisms and metabolite dynamics of P. cablin flower development remain unclear due to the difficulty in achieving flowering in this species. A comparison of the transcriptome and widely targeted metabolome during P. cablin flower development was first performed in this study. Results showed that a total of 13,469 differentially expressed unigenes (DEGs) and 371 differentially accumulated metabolites (DAMs) were identified. Transcriptomic analysis revealed that the DEGs were associated with starch and sucrose metabolism, terpenoid biosynthesis and phenylpropanoid biosynthesis. Among these DEGs, 75 MIKC-MADS unigenes were associated with the development of floral organs. Gibberellins (GAs), auxin, and aging signaling might form a cross-regulatory network to regulate flower development in P. cablin. According to the metabolic profile, the predominant DAMs were amino acids, flavonoids, terpenes, phenols, and their derivatives. The accumulation patterns of these predominant DAMs were closely associated with the flower developmental stage. The integration analysis of DEGs and DAMs indicated that phenylpropanoids, flavonoids, and amino acids might be accumulated due to the activation of starch and sucrose metabolism. Our results provide some important insights for elucidating the reproductive process, floral organ, and color formation of P. cablin flowers at the molecular level. These results will improve our understanding of the molecular and genetic mechanisms involved in the floral development of P. cablin.PMID:37457333 | PMC:PMC10340533 | DOI:10.3389/fpls.2023.1201486

Front Public Health. 2023 Jun 28;11:1188673. doi: 10.3389/fpubh.2023.1188673. eCollection 2023.NO ABSTRACTPMID:37457250 | PMC:PMC10338829 | DOI:10.3389/fpubh.2023.1188673

Front Physiol. 2023 Jun 30;14:1082953. doi: 10.3389/fphys.2023.1082953. eCollection 2023.ABSTRACTAltered mito-ribosomal fidelity is an important and insufficiently understood causative agent of mitochondrial dysfunction. Its pathogenic effects are particularly well-known in the case of mitochondrially induced deafness, due to the existence of the, so called, ototoxic variants at positions 847C (m.1494C) and 908A (m.1555A) of 12S mitochondrial (mt-) rRNA. It was shown long ago that the deleterious effects of these variants could remain dormant until an external stimulus triggered their pathogenicity. Yet, the link from the fidelity defect at the mito-ribosomal level to its phenotypic manifestation remained obscure. Recent work with fidelity-impaired mito-ribosomes, carrying error-prone and hyper-accurate mutations in mito-ribosomal proteins, have started to reveal the complexities of the phenotypic manifestation of mito-ribosomal fidelity defects, leading to a new understanding of mtDNA disease. While much needs to be done to arrive to a clear picture of how defects at the level of mito-ribosomal translation eventually result in the complex patterns of disease observed in patients, the current evidence indicates that altered mito-ribosome function, even at very low levels, may become highly pathogenic. The aims of this review are three-fold. First, we compare the molecular details associated with mito-ribosomal fidelity to those of general ribosomal fidelity. Second, we gather information on the cellular and organismal phenotypes associated with defective translational fidelity in order to provide the necessary grounds for an understanding of the phenotypic manifestation of defective mito-ribosomal fidelity. Finally, the results of recent experiments directly tackling mito-ribosomal fidelity are reviewed and future paths of investigation are discussed.PMID:37457031 | PMC:PMC10349377 | DOI:10.3389/fphys.2023.1082953

iScience. 2023 Jun 14;26(7):107127. doi: 10.1016/j.isci.2023.107127. eCollection 2023 Jul 21.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease with no specific drug therapy. High-throughput metabolomics present an unprecedented opportunity to identify biomarkers and potentially causal risk factors for NAFLD. Here, we determined the impact of 21 circulating metabolites, 17 lipids, and 132 lipoprotein particle characteristics on NAFLD combining prospective observational and two-sample Mendelian randomization (MR) analyses in 121,032 UK Biobank participants. We identified several metabolic factors associated with NAFLD risk in observational and MR analyses including triglyceride-rich and high-density lipoprotein particles composition, as well as the ratio of polyunsaturated fatty acids to total fatty acids. This study, is one of the largest to investigate incident NAFLD, provides concordant observational and genetic evidence that therapies aimed at reducing circulating triglycerides and increasing large HDL particles, as well as interventions aimed at increasing polyunsaturated fatty acid content may warrant further investigation into NAFLD prevention and treatment.PMID:37456853 | PMC:PMC10339047 | DOI:10.1016/j.isci.2023.107127

Front Oncol. 2023 Jun 30;13:1142838. doi: 10.3389/fonc.2023.1142838. eCollection 2023.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically 'non-inflamed' tumor microenvironment in PDACs has proven to be challenging. Indolamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the catabolic pathway of L-Tryptophan, an essential amino acid, that gives rise to the immunosuppressive metabolite Kynurenine. IDO1, Indolamine 2,3-dioxygenase 2 (IDO2), and Tryptophan 2,3-dioxygenase (TDO) are the key enzymes in the tryptophan catabolic pathway but we focus on the role of the predominant enzyme form IDO1 in this review. Nicotinamide phosphoribosyl transferase (iNAMPT) regulates the intracellular concentration of NAD and is upregulated in the tumor. In light of the potential role of IDO1 as a driver of hostile TME in PDAC and NAD+ as a key coenzyme in anti-tumor immune response, this review urges focus on extensive research and initiation of clinical trials using IDO1 and NAMPT inhibitors in pancreatic cancer in the future.PMID:37456260 | PMC:PMC10348419 | DOI:10.3389/fonc.2023.1142838