PubMed

Insects. 2024 Jul 6;15(7):507. doi: 10.3390/insects15070507.ABSTRACTThis study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.PMID:39057240 | DOI:10.3390/insects15070507

Curr Issues Mol Biol. 2024 Jul 4;46(7):6960. doi: 10.3390/cimb46070415.ABSTRACTAfiq Adham Abd Rasib and Roohaida Othman were not included as authors in the original publication [...].PMID:39057102 | DOI:10.3390/cimb46070415

Curr Issues Mol Biol. 2024 Jul 13;46(7):7430-7446. doi: 10.3390/cimb46070441.ABSTRACTObesity is marked by excessive fat accumulation in the adipose tissue, which disrupts metabolic processes and causes chronic systemic inflammation. Commonly, body mass index (BMI) is used to assess obesity-related risks, predicting potential metabolic disorders. However, for a better clustering of obese patients, we must consider molecular and epigenetic changes which may be responsible for inflammation and metabolic changes. Our study involved two groups of patients, obese and healthy donors, on which routine analysis were performed, focused on BMI, leukocytes count, and C-reactive protein (CRP) and completed with global DNA methylation and gene expression analysis for genes involved in inflammation and adipogenesis. Our results indicate that obese patients exhibited elevated leukocytes levels, along with increased BMI and CRP. The obese group revealed a global hypomethylation and upregulation of proinflammatory genes, with adipogenesis genes following the same trend of being overexpressed. The study confirms that obesity is linked to systematic inflammation and metabolic dysfunction through epigenetic and molecular alterations. The CRP was correlated with the hypomethylation status in obese patients, and this fact may contribute to a better understanding of the roles of specific genes in adipogenesis and inflammation, leading to a better personalized therapy.PMID:39057082 | DOI:10.3390/cimb46070441

Curr Issues Mol Biol. 2024 Jun 26;46(7):6390-6406. doi: 10.3390/cimb46070382.ABSTRACTAmidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.PMID:39057024 | DOI:10.3390/cimb46070382

Environ Toxicol Chem. 2024 Jul 26. doi: 10.1002/etc.5960. Online ahead of print.ABSTRACTTraditional approaches for monitoring aquatic pollution primarily rely on chemical analysis and the detection of pollutants in the aqueous environments. However, these methods lack realism and mechanistic insight and, thus, are increasingly supported by effect-based methods, which offer sensitive endpoints. In this context, daphnids, a freshwater species used extensively in molecular ecotoxicology, offer fast and noninvasive approaches to assess the impact of pollutants. Among the phenotypic endpoints used, feeding rate is a highly sensitive approach because it provides evidence of physiological alterations even in sublethal concentrations. However, there has been no standardized method for measuring feeding rate in daphnids, and several approaches follow different protocols. There is a diversity among tests employing large volumes, extensive incubation times, and high animal densities, which in turn utilize measurements of algae via fluorescence, radiolabeling, or counting ingested cells. These tests are challenging and laborious and sometimes require cumbersome instrumentation. In the present study, we optimized the conditions of a miniaturized fast, sensitive, and high-throughput assay to assess the feeding rate based on the ingestion of fluorescent microparticles. The protocol was optimized in neonates in relation to the concentration of microplastic and the number of animals to increase reproducibility. Daphnids, following exposures to nonlethal concentrations, were incubated with microplastics; and, as filter feeders, they ingest microparticles. The new approach revealed differences in the physiology of daphnids in concentrations below the toxicity limits for a range of pollutants of different modes of action, thus proving feeding to be a more sensitive and noninvasive endpoint in pollution assessment. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.PMID:39056977 | DOI:10.1002/etc.5960

Cells. 2024 Jul 19;13(14):1220. doi: 10.3390/cells13141220.ABSTRACTThe MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma's response to MEK inhibition.PMID:39056801 | DOI:10.3390/cells13141220

Biology (Basel). 2024 Jul 9;13(7):511. doi: 10.3390/biology13070511.ABSTRACTThe aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.PMID:39056704 | DOI:10.3390/biology13070511

Biology (Basel). 2024 Jun 30;13(7):488. doi: 10.3390/biology13070488.ABSTRACTThe rapid development of the mariculture industry has been hindered by limited coastal aquaculture space. To utilize the abundant inland saline-alkaline water, we studied the physiological effects of high carbonate alkalinity stress and high pH stress on Fenneropenaeus chinensis. The study employed quantitative proteomics by tandem mass tag (TMT) and non-targeted metabolomics analysis using a liquid chromatograph mass spectrometer (LC-MS) to understand the physiological and biochemical adaptive mechanisms of the hepatopancreas of F. chinensis in response to saline-alkaline stress at the molecular level. We designed two stress groups as follows: a high carbonate alkalinity (CA) group and a combined high carbonate alkalinity and high pH (CP) group. The study found that the protein and metabolic profiles of the two stress groups were changed, and the CP group, which was exposed to dual stresses, incurred more severe damage to the hepatopancreas compared to that of the CA group. After exposure to CA and CP, the hepatopancreas of F. chinensis showed significant alterations in 455 proteins and 50 metabolites, and 1988 proteins and 272 metabolites, respectively. In addition, F. chinensis upregulated the level of energy metabolism in the hepatopancreas to defend against osmotic imbalance caused by CA or CP stress, which was demonstrated by the significant upregulation of important proteins and metabolites in glycolysis, pyruvate metabolism, TCA cycle, and fatty acid oxidation. Additionally, pattern recognition receptors, the phenol oxidase system, and various immune-related metabolic enzymes and metabolites were also affected. The immune homeostasis of F. chinensis was affected by the alteration of the antioxidant system following exposure to CA or CP. These findings provide valuable information for F. chinensis saline-alkaline water cultivation practices.PMID:39056683 | DOI:10.3390/biology13070488

Pharm Biol. 2024 Dec;62(1):621-633. doi: 10.1080/13880209.2024.2378011. Epub 2024 Jul 26.ABSTRACTCONTEXT: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking.OBJECTIVE: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities.MATERIALS AND METHODS: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'-O-β-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h.RESULTS: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 μM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1).CONCLUSIONS: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.PMID:39056547 | DOI:10.1080/13880209.2024.2378011

Anal Chem. 2024 Jul 26. doi: 10.1021/acs.analchem.4c01630. Online ahead of print.ABSTRACTTraditionally, chemical exposure has been assessed by low-resolution mass spectrometry via targeted approaches due to the typically extremely low concentration of such compounds in biological samples. Nevertheless, untargeted approaches are now becoming a promising tool for a broader investigation of the exposome, covering additional compounds, their biotransformation products, and possible metabolic alterations (metabolomics). However, despite broad compound coverage, untargeted metabolomics still underperforms in ultratrace biomonitoring analysis. To overcome these analytical limitations, we present the development of the first combined targeted/untargeted LC-MS method, merging MRM-HR and SWATH experiments in one analytical run, making use of Zeno technology for improved sensitivity. Multiple reaction monitoring transitions were optimized for 135 highly diverse toxicants including mycotoxins, plasticizers, PFAS, personal care products ingredients, and industrial side products as well as potentially beneficial xenobiotics such as phytohormones. As a proof of concept, standard reference materials of human plasma (SRM 1950) and serum (SRM 1958) were analyzed with both Zeno MRM-HR + SWATH and SWATH-only methodologies. Results demonstrated a significant increase in sensitivity represented by the detection of lower concentration levels in spiked SRM materials (mean value: 2.2 and 3 times lower concentrations for SRMs 1950 and 1958, respectively). Overall, the detection frequency was increased by 68% (19 to 32 positive detections) in the MRM-HR + SWATH mode compared to the SWATH-only. This work presents a promising avenue for addressing the outstanding key challenge in the small-molecule omics field: finding a balance between high sensitivity and broad chemical coverage. It was demonstrated for exposomic applications but might be transferred to lipidomics and metabolomics workflows.PMID:39056508 | DOI:10.1021/acs.analchem.4c01630

ACS Nano. 2024 Jul 26. doi: 10.1021/acsnano.4c05763. Online ahead of print.ABSTRACTMaterial-microbial interfaces offer a promising future in sustainable and efficient chemical-energy conversions, yet the impacts of these artificial interfaces on microbial metabolisms remain unclear. Here, we conducted detailed proteomic and metabolomic analyses to study the regulations of microbial metabolism induced by the photocatalytic material-microbial interfaces, especially the intracellular redox and energy homeostasis, which are vital for sustaining cell activity. First, we learned that the materials have a heavier weight in perturbing microbial metabolism and inducing distinctive biological pathways, like the expression of the metal-resisting system, than light stimulations. Furthermore, we observed that the materials-microbe interfaces can maintain the delicate redox balance and the energetic status of the microbial cells since the intracellular redox cofactors and energy currencies show stable levels as naturally inoculated microbes. These observations ensure the possibility of energizing microbial activities with artificial materials-microbe interfaces for diverse applications and also provide guides for future designs of materials-microbe hybrids to guard microbial activities.PMID:39056348 | DOI:10.1021/acsnano.4c05763

New Phytol. 2024 Jul 26. doi: 10.1111/nph.19981. Online ahead of print.ABSTRACTThe NPR proteins function as salicylic acid (SA) receptors in Arabidopsis thaliana. AtNPR1 plays a central role in SA-induced transcriptional reprogramming whereby positively regulates SA-mediated defense. NPRs are found in the genomes of nearly all land plants. However, we know little about the molecular functions and physiological roles of NPRs in most plant species. We conducted phylogenetic and alignment analyses of NPRs from 68 species covering the significant lineages of land plants. To investigate NPR functions in bryophyte lineages, we generated and characterized NPR loss-of-function mutants in the liverwort Marchantia polymorpha. Brassicaceae NPR1-like proteins have characteristically gained or lost functional residues identified in AtNPRs, pointing to the possibility of a unique evolutionary trajectory for the Brassicaceae NPR1-like proteins. We find that the only NPR in M. polymorpha, MpNPR, is not the master regulator of SA-induced transcriptional reprogramming and negatively regulates bacterial resistance in this species. The Mpnpr transcriptome suggested roles of MpNPR in heat and far-red light responses. We identify both Mpnpr and Atnpr1-1 display enhanced thermomorphogenesis. Interspecies complementation analysis indicated that the molecular properties of AtNPR1 and MpNPR are partially conserved. We further show that MpNPR has SA-binding activity. NPRs and NPR-associated pathways have evolved distinctively in diverged land plant lineages to cope with different terrestrial environments.PMID:39056290 | DOI:10.1111/nph.19981

J Med Virol. 2024 Aug;96(8):e29798. doi: 10.1002/jmv.29798.ABSTRACTAntiretroviral therapy (ART) is an effective treatment for people living with HIV (PLHIVs), requiring an extended period to achieve immune reconstitution. Metabolic alterations induced by ART are crucial for predicting long-term therapeutic responses, yet comprehensive investigation through large-scale clinical studies is still lacking. Here, we collected plasma samples from 108 PLHIVs to the untargeted plasma metabolomics study, based on the longitudinal metabolomics design. Cross-sectional analyzes were performed at pre- and post-ART to explore the metabolic transformation induced by the therapy. Subsequently, delta values between pre- and post-ART measurements were calculated to quantify metabolic alterations. Then, the optimal set of metabolic traits and clinical signatures were further identified and applied to construct random forest model for predicting the future therapeutic responses to ART. We found distinct ART-induced metabolic transformation among PLHIVs. After confounder-adjustments, five metabolites exhibited significant associations with future immune response: tetracosatetraenoic acid (24:4n-6) (pre-ART) (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.955~0.997), 1-(3,4-dihydroxyphenyl)-5-hydroxy-3-decanone (pre-ART) (OR: 1.298, 95% CI: 1.061~1.727), beta-PC-M6 (change) (OR: 0.967, 95% CI: 0.938~0.993), d-Galactaro-1,4-lactone (change) (OR: 1.032, 95% CI: 1.007~1.063), Annuionone C (change) (OR: 1.100, 95% CI: 1.030~1.190). The addition of plasma metabolites to clinical markers accurately predicted immune response to ART with an area under curve of 0.91. Notably, most disrupted metabolites were significantly correlated with blood lipids, suggesting that metabolic transformation might contribute to dyslipidemia among PLHIVs. This study highlights the distinct metabolic transformation post-ART among PLHIVs and reveals the potential role of metabolic transformation as key determinants of ART efficacy.PMID:39056244 | DOI:10.1002/jmv.29798

Food Funct. 2024 Jul 26. doi: 10.1039/d4fo00210e. Online ahead of print.ABSTRACTBackground: A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods: Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results: The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions: In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.PMID:39056112 | DOI:10.1039/d4fo00210e

Front Mol Biosci. 2024 Jul 11;11:1420664. doi: 10.3389/fmolb.2024.1420664. eCollection 2024.ABSTRACTGestational diabetes mellitus (GDM) is a common metabolic disorder affecting approximately 16.5% of pregnancies worldwide and causing significant health concerns. GDM is a serious pregnancy complication caused by chronic insulin resistance in the mother and has been associated with the development of neurodevelopmental disorders in offspring. Emerging data support the notion that GDM affects both the maternal and fetal microbiome, altering the composition and function of the gut microbiota, resulting in dysbiosis. The observed dysregulation of microbial presence in GDM pregnancies has been connected to fetal neurodevelopmental problems. Several reviews have focused on the intricate development of maternal dysbiosis affecting the fetal microbiome. Omics data have been instrumental in deciphering the underlying relationship among GDM, gut dysbiosis, and fetal neurodevelopment, paving the way for precision medicine. Microbiome-associated omics analyses help elucidate how dysbiosis contributes to metabolic disturbances and inflammation, linking microbial changes to adverse pregnancy outcomes such as those seen in GDM. Integrating omics data across these different layers-genomics, transcriptomics, proteomics, metabolomics, and microbiomics-offers a comprehensive view of the molecular landscape underlying GDM. This review outlines the affected pathways and proposes future developments and possible personalized therapeutic interventions by integrating omics data on the maternal microbiome, genetics, lifestyle factors, and other relevant biomarkers aimed at identifying women at high risk of developing GDM. For example, machine learning tools have emerged with powerful capabilities to extract meaningful insights from large datasets.PMID:39055983 | PMC:PMC11269231 | DOI:10.3389/fmolb.2024.1420664

iScience. 2024 Jun 17;27(7):110295. doi: 10.1016/j.isci.2024.110295. eCollection 2024 Jul 19.ABSTRACTLong-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervention influenced 80 serum metabolites over two years, with 17 metabolites continuing to be affected after eight years. The intervention primarily impacted fatty amides, including palmitic amide, linoleamide, oleamide, and others, as well as unsaturated fatty acids, acylcarnitines, phospholipids, sterols, gut microbiota-derived metabolites, amino acids, and purine metabolites. Particularly noteworthy were the pronounced changes in serum fatty amides. These serum metabolite alterations could represent molecular mechanisms responsible for the observed benefits of long-term lifestyle interventions on cardiometabolic and overall health since childhood. Understanding these metabolic changes may provide valuable insights into the prevention of cardiometabolic and other non-communicable diseases since childhood.PMID:39055945 | PMC:PMC11269805 | DOI:10.1016/j.isci.2024.110295

iScience. 2024 Jun 22;27(7):110357. doi: 10.1016/j.isci.2024.110357. eCollection 2024 Jul 19.ABSTRACTVon Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.PMID:39055909 | PMC:PMC11269943 | DOI:10.1016/j.isci.2024.110357

iScience. 2024 Jun 21;27(7):110345. doi: 10.1016/j.isci.2024.110345. eCollection 2024 Jul 19.ABSTRACTBreast cancer (BC) is currently the most prevalent malignancy worldwide, and finding effective non-invasive biomarkers for routine clinical detection of BC remains a significant challenge. Here, we performed non-targeted and targeted metabolomics analysis on the screening, training and validation cohorts of serum samples from 1,947 participants. A metabolite biomarker model including glutamate, erythronate, docosahexaenoate, propionylcarnitine, and patient's age was established for detecting BC. This model demonstrated better diagnostic performance than carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) alone in discriminating BC from healthy controls both in the training and validation cohorts [area under the curve (AUC), 0.954; sensitivity, 87.1% and specificity, 93.5% for the training cohort and 0.834, 68.3%, and 85.2%, respectively, for the validation cohort 1]. This study has established a noninvasive approach for the detection of BC, which shows potential as a suitable supplement to the clinical screening methods currently employed for BC.PMID:39055906 | PMC:PMC11269948 | DOI:10.1016/j.isci.2024.110345

Front Vet Sci. 2024 Jul 11;11:1442931. doi: 10.3389/fvets.2024.1442931. eCollection 2024.ABSTRACTINTRODUCTION: Gonadotropin-releasing hormone (GnRH) is widely used in the timed artificial insemination protocol for sheep. However, there remains a debate regarding its impact on pregnancy rates during artificial insemination. This study aims to evaluate the effect of GnRH on the pregnancy rates in Huyang ewes, analyze the pre-implantation metabolite changes caused by GnRH using metabolomics, and elucidate the mechanism effect on pregnancy rates.METHODS: All ewes were administered a vaginal progesterone sponge containing 45 mg of flurogestone acetate for 12 days and received 330 units of equine chorionic gonadotropin (eCG) intramuscularly after sponge removal. The experimental group (n = 69) received an intramuscular treatment of 17 μg GnRH agonist triptorelin 48 h after sponge removal on Day 0, while the control group (n = 41) received 1 mL of sterile saline solution. All ewes underwent a single vaginal insemination 58 h after the withdrawal of the progesterone sponge. The difference in pregnancy rates between the two groups was calculated. Metabolomic analysis was performed on plasma samples collected on Day 7 after the treatment of GnRH agonist.RESULTS: Gonadotropin-releasing hormone (GnRH) treatment significantly reduced the pregnancy rate in the experimental group compared with the control group (72.2 vs. 82.9%, p < 0.05). Metabolomic analysis indicated that GnRH treatment affected metabolites involved in collagen synthesis and prostaglandin synthesis in the endometrial tissue, which includes a marked decrease in hydroxyproline amino acid content and a significant increase in corticosterone and prostaglandin D2 lipids and unsaturated fatty acids.CONCLUSION: In summary, the injection of GnRH agonist Triptorelin 48 h after progesterone sponges removal reduces the pregnancy rate of Huyang ewe following artificial insemination. It also affects the metabolite levels related to endometrial collagen and prostaglandin synthesis, harming embryo implantation.PMID:39055862 | PMC:PMC11270128 | DOI:10.3389/fvets.2024.1442931

Food Sci Nutr. 2024 Apr 22;12(7):5100-5110. doi: 10.1002/fsn3.4159. eCollection 2024 Jul.ABSTRACTOur previous clinical metabolomics study illustrated that energy metabolism disorder is an underlying pathogenesis mechanism for the development of alcoholic liver disease (ALD). Supplementation of nicotinamide (NAM), the precursor of nicotinamide adenine dinucleotide (NAD+), may restore the energy metabolism homeostasis of ALD and thus serves as potential therapeutics to treat ALD. In this bedside-to-bench study, the protective effect of NAM against ALD was investigated by using the NIAAA mice model (chronic-plus-binge ethanol), and the liver regeneration boosting capability of NAM was evaluated by the partial hepatectomy mice model. Our results showed that NAM supplements not only protected the liver from alcohol-induced injury and improved alcohol-induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content. These findings suggested that NAM, a water-soluble form of vitamin B3, can promote liver regeneration and improves liver function by alleviating alcohol-induced energy metabolism disorder.PMID:39055233 | PMC:PMC11266918 | DOI:10.1002/fsn3.4159