PubMed

Front Microbiol. 2024 Nov 29;15:1474071. doi: 10.3389/fmicb.2024.1474071. eCollection 2024.ABSTRACTINTRODUCTION: Tuberculosis (TB) treatment typically involves a tailored combination of four antibiotics based on the drug resistance profile of the infecting strain. The increasing drug resistance of Mycobacterium tuberculosis (Mtb) requires the development of novel antibiotics to ensure effective treatment regimens. Gallium (Ga) is being explored as a repurposed drug against TB due to its ability to inhibit Mtb growth and disrupt iron metabolism. Given the potential interactions between Ga and established antibiotics, we investigated how a combination of Ga with levofloxacin (Lfx) or linezolid (Lzd) affects the growth and metabolome of a multidrug-resistant (MDR) Mtb clinical strain.METHODS: Mtb was cultured using a BACTEC 960 system with concentrations of Ga ranging from 125 to 1,000 μM and with 250 to 500 μM of Ga combined with 0.125 mg/L of Lfx or Lzd. For metabolome analysis, the antibacterials were used at concentrations that inhibited the growth of bacteria without causing cell death. Metabolites were extracted from Mtb cells and analyzed using chromatography-mass spectrometry.RESULTS: The MDR Mtb strain exhibited a dose-dependent response to Ga. Notably, the enhancement in growth inhibition was statistically significant for the Ga/Lfx combination compared to Ga alone, while no such significance was observed for Ga/Lzd. Moreover, exposure to Ga/Lfx or Ga/Lzd resulted in distinct metabolite profiles. Ga treatment increased the level of aconitate, fumarate, and glucose in the cells, suggesting the inhibition of iron-dependent aconitase and fumarate hydratase, as well as disruption of the pentose phosphate pathway. The levels of glucose, succinic acid, citric acid, and hexadecanoic acid followed a similar pattern in cells exposed to Ga and Ga/Lfx at 500 μM Ga but exhibited different trends at 250 μM Ga.DISCUSSION: In the presence of Lfx, the Mtb metabolome changes induced by Ga are more pronounced compared to those observed with Lzd. Lfx affects nucleic acids and transcription, which may enhance Ga-dependent growth inhibition by preventing the metabolic redirection that bacteria typically use to bypass iron-dependent enzymes.PMID:39697659 | PMC:PMC11654424 | DOI:10.3389/fmicb.2024.1474071

J Circ Biomark. 2024 Dec 16;13:36-44. doi: 10.33393/jcb.2024.3146. eCollection 2024 Jan-Dec.ABSTRACTINTRODUCTION: Prostate cancer (PCa) management presents a multifaceted clinical challenge, intricately linking oncological considerations with cardiovascular health. Despite the recognized importance of lipid metabolism and hypertension in this interwoven relationship, their involvement in PCa development remains partially understood. This study aimed to explore variations in plasma metabolome among Sudanese PCa patients and their associated comorbidities.METHODS: Plasma samples were collected from 50 patients across four hospitals in Sudan and profiled by nuclear magnetic resonance (NMR) spectroscopy. One-dimensional proton NMR spectra were acquired for each sample using standard nuclear Overhauser effect spectroscopy pulse sequence presat on a 500 MHz Bruker Avance III HD NMR spectrometer. Metabolite concentrations were quantified using R scripts developed in-house. Univariate and multivariate analyses were generated in the R software.RESULTS: Patients were categorized into four distinct metabotypes based on their metabolic profiles, and statistical analyses were conducted to evaluate the significance of observed differences. Our findings revealed high levels of fatty acids, phospholipids, cholesterol, valine, leucine, and isoleucine associated with non-hypertensive patients. In contrast, hypertensive patients were associated with high GlycA and GlycB levels and altered amino acid metabolism.CONCLUSION: These findings underscore the intricate interplay between metabolic dysregulation and hypertension in PCa patients. Further research is warranted to elucidate the precise molecular pathways underlying lipid metabolism in PCa and to explore the therapeutic potential of targeting these pathways. In conclusion, our study contributes to a deeper understanding of the metabolic landscape of PCa in Sudanese patients, emphasizing the importance of personalized approaches in cancer management.PMID:39697480 | PMC:PMC11653783 | DOI:10.33393/jcb.2024.3146

Tob Induc Dis. 2024 Dec 18;22. doi: 10.18332/tid/196677. eCollection 2024.ABSTRACTINTRODUCTION: This study aimed to evaluate the metabolomic profiles of urine samples obtained from smokers who smoked cigarettes with low and high nicotine content.METHODS: Three smokers participated in this study. They were given low-nicotine (LN) cigarettes, and urine was collected at the end of the third day for the LN group. After 1 week of not smoking, they were given high-nicotine (HN) cigarettes, and urine was collected for the HN group. Untargeted metabolomics and bioinformatic analysis methods were used for urine analysis.RESULTS: PCA showed a high degree of similarity between samples within the group and a large distance between samples between groups, indicating a significant difference between the two groups. A total of 1150 significantly differential metabolites were selected between the HN and LN groups, such as cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol-N-glucuronide. Two-way hierarchical clustering analysis also suggested noticeable differences between the two comparison groups Enrichment analysis indicates that the differential metabolites between the two groups were mainly enriched in 19 pathways, such as the protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, adenosine monophosphate (AMP)-activated protein kinase signaling pathway, mammalian target of rapamycin signaling pathway, and Parkinson's disease.CONCLUSIONS: Cigarettes with different nicotine content may alter the metabolism of smokers. A total of 1150 significantly different metabolites were identified between the HN and LN groups, which were mainly enriched in ABC transporters, protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, caffeine metabolism, and arginine biosynthesis pathways.PMID:39697303 | PMC:PMC11653067 | DOI:10.18332/tid/196677

Crit Rev Clin Lab Sci. 2024 Dec 19:1-28. doi: 10.1080/10408363.2024.2430775. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a complex multifactorial endocrinopathy affecting reproductive aged women globally, whose presentation is strongly influenced by genetic makeup, ethnic, and geographic diversity leaving these affected women substantially predisposed to reproductive and metabolic perturbations. Sophisticated techniques spanning genomics, proteomics, epigenomics, and transcriptomics have been harnessed to comprehensively understand the enigmatic pathophysiology of PCOS, however, conclusive markers for PCOS are still lacking today. Metabolomics represents a paradigm shift in biotechnological advances enabling the simultaneous identification and quantification of metabolites and the use of this approach has added yet another dimension to help unravel the strong metabolic component of PCOS. Reports dissecting the metabolic signature of PCOS have revealed disparate levels of metabolites such as pyruvate, lactate, triglycerides, free fatty acids, carnitines, branched chain and essential amino acids, and steroid intermediates in major biological compartments. These metabolites have been shown to be altered in women with PCOS overall, after phenotypic subgrouping, in animal models of PCOS, and also following therapeutic intervention. This review seeks to supplement previous reviews by highlighting the aforementioned aspects and to provide easy, coherent and elementary access to significant findings and emerging trends. This will in turn help to delineate the metabolic plot in women with PCOS in various biological compartments including plasma, urine, follicular microenvironment, and gut. This may pave the way to design additional studies on the quest of unraveling the etiology of PCOS and delving into novel biomarkers for its diagnosis, prognosis and management.PMID:39697160 | DOI:10.1080/10408363.2024.2430775

Plant Physiol. 2024 Dec 19:kiae615. doi: 10.1093/plphys/kiae615. Online ahead of print.ABSTRACTCollections of insertional mutants have been instrumental for characterizing the functional relevance of genes in different model organisms, including Arabidopsis (Arabidopsis thaliana). However, mutations may often result in subtle phenotypes, rendering it difficult to pinpoint the function of a knocked-out gene. Here, we present a data-integrative modeling approach that enables predicting the effects of mutations on metabolic traits and plant growth. To test the approach, we gathered lipidomics data and physiological read-outs for a set of 64 Arabidopsis lines with mutations in lipid metabolism. Use of flux sums as a proxy for metabolite concentrations allowed us to integrate the relative abundance of lipids and facilitated accurate predictions of growth and biochemical phenotype in approximately 73% and 76% of the mutants, respectively, for which phenotypic data were available. Likewise, we showed that this approach can pinpoint alterations in metabolic pathways related to silent mutations. Therefore, our study paves the way for coupling model-driven characterization of mutant lines from different mutagenesis approaches with metabolomic technologies, as well as for validating knowledge structured in large-scale metabolic networks of plants and other species.PMID:39696931 | DOI:10.1093/plphys/kiae615

Oncoimmunology. 2025 Dec;14(1):2432726. doi: 10.1080/2162402X.2024.2432726. Epub 2024 Dec 18.ABSTRACTOver the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer. Herein, we report on the topics developed by key-opinion leaders during the 7th Immunorad Conference held in Paris-Les Cordeliers (France) from September 27th to 29th 2023, and set the stage for the 8th edition of Immunorad which will be held at Weill Cornell Medical College (New-York, USA) in October 2024.PMID:39696783 | DOI:10.1080/2162402X.2024.2432726

Environ Microbiome. 2024 Dec 18;19(1):103. doi: 10.1186/s40793-024-00656-4.ABSTRACTBACKGROUND: Pollen is a crucial source of nutrients and energy for pollinators. It also provides a unique habitat and resource for microbiota. Previous research on the microbiome of pollen has largely focused on angiosperm systems, with limited research into coniferous gymnosperms. This study characterises the pollen microbiome and metabolome associated with one of the world's most widely grown tree species, Pinus radiata. Trees were sampled from locations across Canterbury, New Zealand. Repeated collections were undertaken in 2020 and 2021.RESULTS: Metabolomic analysis revealed the main compounds present on P. radiata pollen to be amino acids (principally proline), and carbohydrates (fructose, glucose, and sucrose). Although phenolic compounds such as ρ-coumaric acid and catechin, and terpenoids such as dehydroabietic acid, were present at low concentrations, their strong bioactive natures mean they may be important in ecological filtering of microbiome communities on pollen. The P. radiata pollen microbiome was richer in fungal taxa compared with bacteria, which differs from many angiosperm species. Geographic range and annual variation were evaluated as drivers of microbiome assembly. Neither sampling location (geographic range) nor annual variation significantly influenced the fungal community which exhibited remarkable conservation across samples. However, some bacterial taxa exhibited sensitivity to geographic distances and yearly variations, suggesting a secondary role of these factors for some taxa. A core microbiome was identified in P. radiata pollen, characterized by a consistent presence of specific fungal and bacterial taxa across samples. While the dominant phyla, Proteobacteria and Ascomycota, align with findings from other pollen microbiome studies, unique core members were unidentified at genus level.CONCLUSION: This tree species-specific microbiome assembly emphasizes the crucial role of the host plant in shaping the pollen microbiome. These findings contribute to a deeper understanding of pollen microbiomes in gymnosperms, shedding light on the need to look further at their ecological and functional roles.PMID:39696657 | DOI:10.1186/s40793-024-00656-4

Stem Cell Res Ther. 2024 Dec 18;15(1):467. doi: 10.1186/s13287-024-04109-0.ABSTRACTBACKGROUND: Mesenchymal stem cells (MSCs) are widely applied in the treatment of various clinical diseases and in the field of medical aesthetics. However, MSCs exhibit greater heterogeneity limited stability, and more complex molecular and mechanistic characteristics compared to conventional drugs, making rapid and precise monitoring more challenging.METHODS: Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive, tractable and low-cost fingerprinting technique capable of identifying a wide range of molecules related to biological processes. Here, we employed SERS for reproducible quantification of ultralow concentrations of molecules and utilized spectral sets, termed SERSomes, for robust and comprehensive intracellular multi-metabolite profiling.RESULTS: We revealed that with increasing passage number, there is a gradual decline in cell expansion efficiency, accompanied by significant changes in intracellular amino acids, purines, and pyrimidines. By integrating these metabolic features detected by SERS with transcriptomic data, we established a correlation between SERS signals and biological changes, as well as differentially expressed genes.CONCLUSION: In this study, we explore the application of SERS technique to provide robust metabolic characteristics of MSCs across different passages and donors. These results demonstrate the effectiveness of SERSome in reflecting biological characteristics. Due to its sensitivity, adaptability, low cost, and feasibility for miniaturized instrumentation throughout pretreatment, measurement, and analysis, the label-free SERSome technique is suitable for monitoring MSC expansion and offers significant advantages for large-scale MSC manufacturing.PMID:39696645 | DOI:10.1186/s13287-024-04109-0

BMC Vet Res. 2024 Dec 18;20(1):563. doi: 10.1186/s12917-024-04417-w.ABSTRACTMarbling is a key indicator of the meat quality of ruminants. Gastrointestinal microbiota may regulate the formation of marbling by influencing the nutritional metabolism of animals. This study analyzed the composition and functional differences of microbiota in the rumen and cecum, the differences in volatile fatty acids (VFAs) content in the longissimus thoracis muscle, and the differences in protein abundance in the longissimus thoracis muscle of ruminants with different marbling grades through microbiome-proteome analysis. The results showed that the diversity of gastrointestinal microbiota in high-marbling ruminants was significantly higher than that in low-marbling ruminants. The relative abundance of Firmicutes and Akkermansia in the gastrointestinal of high-marbling ruminants was higher than that in low-marbling ruminants, while the relative abundance of Bacteroidetes and Prevotella was lower. In addition, PICRUST2 functional prediction results of the microbiota revealed that the gastrointestinal microbiota of high-marbling ruminants was mainly involved in the biosynthesis pathways of fat and lipids. The metabolomics results showed that the content of VFAs (acetic acid, propionic acid, butyric acid, isovaleric acid, valeric acid, and hexanoic acid) in the rumen of high-marbling ruminants was significantly higher than that in low-marbling ruminants. The proteome analysis results indicated that the differential proteins in the longissimus thoracis muscle of high-marbling ruminants were mainly involved in lipid transport and metabolism compared to low-marbling ruminants. In summary, the differences in the composition and function of the gastrointestinal microbiota led to higher levels of VFAs in the gastrointestinal tract of high-marbling ruminants, which provides the basis for lipid/fat synthesis. The proteome results of the longissimus thoracis muscle support the view that high-marbling ruminants have richer lipid transport and metabolic functions in their muscle.PMID:39696486 | DOI:10.1186/s12917-024-04417-w

Stem Cell Res Ther. 2024 Dec 18;15(1):485. doi: 10.1186/s13287-024-04072-w.ABSTRACTBACKGROUND: Adipose-derived stem cells (ADSCs) are widely used in the field of regenerative medicine because of their various functions, including anti-inflammatory effects. ADSCs are considered to exert their anti-inflammatory effects by secreting anti-inflammatory cytokines and extracellular vesicles. Although recent studies have reported that metabolites have a variety of physiological activities, whether those secreted by ADSCs have anti-inflammatory properties remains unclear. Here, we performed multiomics analyses to examine the effect of ADSC-derived metabolites on M1-like macrophages, which play an important role in inflammatory responses.METHODS: The concentration of metabolites in the culture supernatant of ADSCs was quantified using capillary electrophoresis time-of-flight mass spectrometry. To evaluate their effects on inflammatory responses, M1-like macrophages were exposed to the conditioned ADSC medium or their metabolites, and RNA sequencing was used to detect gene expression changes. Immunoblotting was performed to examine how the metabolite suppresses inflammatory processes. To clarify the contribution of the metabolite in the conditioned medium to its anti-inflammatory effects, metabolite uptake was pharmacologically inhibited, and gene expression and the tumor necrosis factor-α concentration were measured by quantitative PCR and enzyme-linked immunosorbent assay, respectively.RESULTS: Metabolomic analysis showed large amounts of lactate in the culture supernatant. The conditioned medium and lactate significantly suppressed or increased the pro-inflammatory and anti-inflammatory gene expressions. However, sequencing and immunoblotting analysis revealed that lactate did not induce polarization from M1- to M2-like macrophages. Based on a recent report that the immunosuppressive effect of lactate depends on epigenetic reprogramming, histone acetylation was investigated, and H3K27ac expression was upregulated. In addition, 7ACC2, which specifically inhibits the monocarboxylate transporter 1, significantly inhibited the anti-inflammatory effect of the conditioned ADSC medium on M1-like macrophages.CONCLUSIONS: Our results showed that ADSCs suppress pro-inflammatory effects of M1-like macrophages by secreting lactate. This study adds to our understanding of the importance of metabolites and is also expected to elucidate new mechanisms of ADSC treatments.PMID:39696485 | DOI:10.1186/s13287-024-04072-w

Cancer Metab. 2024 Dec 18;12(1):37. doi: 10.1186/s40170-024-00366-y.ABSTRACTBACKGROUND: The efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.METHODS: Our study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies. We conducted metabolomics to trace glucose rerouting in response to PFKFB3 inhibition during TKI treatment. Live cell imaging and DCFDA oxidation were used to quantify levels of oxidation stress. Immunocytochemistry and Neutral Comet assay were employed to evaluate DNA integrity in response to therapy-driven oxidative stress.RESULTS: Our metabolic profiling revealed that PFKFB3 inhibition significantly alters the metabolic profile of TKI-treated cells. It limited glucose utilization in the polyol pathway, glycolysis, and TCA cycle, leading to a depletion of ATP levels. Furthermore, pharmacological inhibition of PFKFB3 overcome TKI-driven redox capacity by diminishing the expression of glutathione peroxidase 4 (GPX4), thereby exacerbating oxidative stress. Our study also unveiled a novel role of PFKFB3 in DNA oxidation and damage by controlling the expression of DNA-glycosylases involved in base excision repair. Consequently, PFKFB3 inhibition improved the cytotoxicity of EGFR-TKIs by facilitating ROS-dependent cell death.CONCLUSIONS: Our results suggest that PFKFB3 inhibition reduces glucose utilization and DNA damage repair, limiting the adaptivity of the cells to therapy-driven oxidative stress and DNA integrity insults. Inhibiting PFKFB3 can be an effective strategy to eradicate cancer cells surviving under EGFR TKI therapy before they enter the drug-resistant state. These findings may have potential implications in the development of new therapies for drug-resistant cancer treatment.PMID:39696407 | DOI:10.1186/s40170-024-00366-y

Lipids Health Dis. 2024 Dec 18;23(1):402. doi: 10.1186/s12944-024-02380-x.ABSTRACTBACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages.METHODS: We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring.RESULTS: Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH.CONCLUSIONS: Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH.PMID:39696394 | DOI:10.1186/s12944-024-02380-x

J Nanobiotechnology. 2024 Dec 19;22(1):768. doi: 10.1186/s12951-024-03034-x.ABSTRACTBACKGROUND: Sleep disorder is widespread and involves a variety of intricate factors in its development. Sleep deprivation is a manifestation of sleep disorder, can lead to energy metabolism disturbances, weakened immune system, and compromised body functions. In extreme situations, sleep deprivation can cause organ failure, presenting significant risks to human health.PURPOSE: This study aimed to investigate the efficacy and mechanisms of Astragalus Radix vesicles-like nanoparticles (AR-VLNs) in counteracting the deleterious effects of sleep deprivation.METHODS: The ICR mice were divided into control, model, AR-VLNs high dose (equivalent to 20 g/kg crude drug), AR-VLNs low dose (equivalent to 10 g/kg crude drug), AR high dose (equivalent to 20 g/kg crude drug), and AR low dose (equivalent to 10 g/kg crude drug). The REM (rapid eye movement) sleep-deprivation model was established, and evaluations were conducted for motor function, antioxidant capacity, and energy metabolism indices. Moreover, CACO-2 cells damage was induced with lipopolysaccharide to evaluate the repairing ability of AR-VLNs on the intestinal cell mucosa by measuring permeability. Furthermore, metabolomics was employed to elucidate the mechanisms of AR-VLNs action.RESULTS: AR-VLNs were demonstrated to enhance the motor efficiency and antioxidant capacity in REM sleep-deprived mice, while also minimized pathological damage and restored the integrity of the intestinal mucosal barrier. In vitro experiments indicated the anti-inflammatory effect of AR-VLNs against LPS-induced cell damage. Additionally, metabolomic analysis linked these effects with regulation of the amino acid metabolic pathways. Further confirmation from molecular biology experiments revealed that the protective effects of AR-VLNs against the deleterious effects of REM sleep deprivation were associated with the restoration of the intestinal mucosal barrier and the enhancement of amino acid metabolism.CONCLUSION: AR-VLNs administration effectively improved energy metabolism disorders in REM sleep deprived mice, by facilitating the repair of the intestinal mucosal barrier and regulating the amino acid metabolism.PMID:39696385 | DOI:10.1186/s12951-024-03034-x

BMC Vet Res. 2024 Dec 19;20(1):569. doi: 10.1186/s12917-024-04402-3.ABSTRACTBACKGROUND: Infectious bursal disease virus (IBDV) is a highly contagious immunosuppressive virus of chickens. Chickens acquire infection by the oral route under natural conditions. Although the histological and pathological changes after IBDV infection are well described, the alterations in serum metabolome have not been reported. In this study, SPF chickens were infected with attenuated IBDV (atIBDV) strain LM and very virulent IBDV (vvIBDV) strain LX, respectively. On the seventh day after oral infection, serum samples of experimental chickens were identified using ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS). The serum metabolic profiles were analyzed by multivariate statistical methods. KEGG enrichment analysis was performed to evaluate the dysregulated biological pathways.RESULTS: We identified 368 significantly altered metabolites in response to both atIBDV and vvIBDV infection. The metabolic disorder of amino acid and lipid was associated with IBDV infection, especially tryptophan, glycerophospholipid, lysine, and tyrosine metabolism. The differential metabolites enriched in the four metabolic pathways were PC(20:4(5Z,8Z,11Z,14Z)/18:0), PE(16:0/18:2(9Z,12Z)), PE(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(18:0/20:4(5Z,8Z,11Z,14Z)), PE(18:0/20:4(8Z,11Z,14Z,17Z)), PE(18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(20:3(8Z,11Z,14Z)/16:0), PE(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0), PE-NMe(20:5(5Z,8Z,11Z,14Z,17Z)/18:0), PS(20:3(5Z,8Z,11Z)/18:2(9Z,12Z)), 2-aminobenzoic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, N-acetylserotonin, 5-hydroxyindoleacetate, indole-3-acetaldehyde, indole-3-acetate, p-coumaric acid, L-tyrosine, homovanillin, and S-glutaryldihydrolipoamide.CONCLUSION: The atIBDV and vvIBDV infection causes metabolic changes in chicken serum. The differential metabolites and dysregulated metabolic pathways reflect the host response to the IBDV infection.PMID:39696379 | DOI:10.1186/s12917-024-04402-3

Cardiovasc Diabetol. 2024 Dec 18;23(1):439. doi: 10.1186/s12933-024-02535-1.ABSTRACTBACKGROUND: Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and causes vision impairment and blindness. The presence of major risk factors for DR, such as high levels of HbA1c, does not predict all DR pathogenesis in the clinic, which suggests that uncovering the underlying mechanisms and identifying novel markers are needed. Previous evidence has shown that the serum metabolic signature of DR is unique and detectable compared with that of diabetes mellitus (DM). Here, we aimed to identify serum metabolites as reliable biomarkers for the presence of DR in type 2 DM (T2DM) patients.METHODS: We performed untargeted and targeted metabolomic studies using liquid chromatography‒mass spectrometry (LC‒MS) and multiple reaction monitoring (MRM) methods on the serum samples of T2DM patients. For the discovery dataset, 39 DR patients and 39 non-DR (NDR) patients were included. For the validation dataset, 95 DR patients and 95 non-DR (NDR) patients were included. Receiver operating characteristic curve analysis was performed to evaluate the discriminating power of the metabolites. Binary logistic regression models were fit to evaluate the associations of metabolite peak areas or neurotransmitter concentrations with the presence of DR and adjusted for known risk factors.RESULTS: A total of 7123 metabolites were tested. The 39 DR patients had a mean age of 56 years with an average diabetes duration of 12 years, and the 39 NDR patients had a mean age of 57 years with an average diabetes duration of 11 years. Nine serum candidate markers were further identified. Six out of nine markers were associated with DR after we adjusted for covariates, including blood pressure, HbA1c, diabetes duration, fasting blood glucose, triglyceride, eGFR etc. Among them, eicosapentaenoic acid (EPA) and L-tyrosine were validated in an independent, risk factor-matched sample set. The serum L-tyrosine concentration was decreased in DR group by 47% (-0.22 ± 0.87 vs. 0.48 ± 1.05, P < 0.001), of which the cutoff value was 0.10 mg/ml, with 86% sensitivity and 40% specificity (AUC = 0.62, 95% CI = 0.54-0.70, P = 0.005).CONCLUSIONS: Low levels of circulating L-Tyrosine indicate retinopathy occurrence in T2DM population.PMID:39696333 | DOI:10.1186/s12933-024-02535-1

Cell Commun Signal. 2024 Dec 18;22(1):597. doi: 10.1186/s12964-024-01951-w.ABSTRACTOne of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked reduction in glycolytic and TCA cycle metabolites in M-I-treated cells. M-I treatment significantly downregulated mRNA and protein expression of essential enzymes involved in de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, and SCD1. Using shotgun lipidomics, we found a significant increase in lysophosphatidylcholine and phosphatidylcholine loss in M-I treated cells. Subsequently, we observed dysregulation of mitochondrial membrane potential and significant reduction of mitochondrial oxygen consumption after M-I treatment. We further observed M-I treatment induced autophagy, activated AMPK and inhibited mTOR and Akt signaling pathways and leading to apoptosis. However, blocking autophagy did not rescue the M-I-mediated alterations in lipogenesis, suggesting an independent mechanism of action. M-I treated mouse HNC MOC2 cell tumors displayed reduced Hk1, Pdk3, Fasn, and Acly expression. In conclusion, our study revealed that M-I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells and reduces tumor volume in mice. Therefore, M-I-mediated metabolic reprogramming of HNC has the potential for important therapeutic implications.PMID:39696286 | DOI:10.1186/s12964-024-01951-w

BMC Psychiatry. 2024 Dec 18;24(1):907. doi: 10.1186/s12888-024-06369-9.ABSTRACTBACKGROUND: The psychosocial factors play an important role in the development of depression in adolescents. we used metabolomics techniques to explore the links among childhood trauma, rumination, resilience, and adolescent depression.METHODS: We selected 57 adolescent depression patients and 53 healthy adolescents. The Childhood Trauma Questionnaire (CTQ), Hamilton Depression Scale (HAMD), Resilience Scale (CD-RISC), and Redundant Thinking Response Scale (RRS) were employed for the purpose of psychological assessment. The patients were regrouped according to their scores using the 27% high-low grouping method. Blood specimens were collected from all adolescents and metabolic data were obtained using LC-MS.RESULTS: We found no statistically significant difference between the groups in terms of age, gender, and body mass index (BMI). HAMD, CTQ, and RRS scores were significantly higher in the adolescent depression group (MDD) than in the adolescent healthy control group (HC), and CD-RISP scores were significantly lower than in the HC group (P < 0.001). There were significant differences between the low childhood trauma group (LCT) and high childhood trauma group (HCT), the low rumination group (LRR) and high rumination group (HRR), and the low resilience group (LPR) and high resilience group (HPR) (P < 0.001). RRS, CTQ and HAMD scores were positively correlated, RRS and CTQ scores were positively correlated, CD-RIS was negatively correlated with HAMD, RRS and CTQ scores (P < 0.01). More importantly, we found that DHEAS and LPA (22:6) were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood trauma groups. N-Acetyl-L-aspartic acid and DHEAS were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood rumination groups. Pseudouridine and LPA(22:6) were identified as significant differential metabolites in both the depressed and normal groups, as well as in the high and low childhood resilience groups.CONCLUSION: Psychological factors (childhood trauma, rumination, resilience) are biologically linked to the development of depression in adolescents. The impact of rumination on adolescent depression may be associated with DHEA. The impact of childhood trauma and resilience on adolescent depression may be associated with LPA (22:6).PMID:39696147 | DOI:10.1186/s12888-024-06369-9

BMC Genomics. 2024 Dec 18;25(1):1194. doi: 10.1186/s12864-024-11093-5.ABSTRACTBACKGROUND: Meat quality in yak is influenced by the fluctuation of nutritional composition in different grazing seasons on the Qinghai-Tibetan Plateau. However, the molecular mechanism underlying in yak meat remains unknown. Therefore, this study aimed to investigate the seasonal dynamics of meat quality in yak by transcriptomics and metabolomics techniques. Twelve healthy female yaks with a similar weight were divided into two groups, including the warm season group (WS) and cold season group (CS). After slaughter, samples of longissimus lumborum were collected and subjected to transcriptomics and metabolomics to explore the effects of different seasons on meat quality.RESULTS: Yak in the WS group had higher contents of n-3 Polyunsaturated fatty acid (PUFA), n-6 PUFA, threonine, and valine compared to the CS group, but the pH45min and b* values were lower. A total of 75 differentially expressed metabolites in the longissimus lumborum muscle were identified, with 23 metabolites upregulated and 52 metabolites downregulated in the WS group. These metabolites were mainly enriched in the pathway of glycine, serine and threonine metabolism, tryptophan metabolism, and carbohydrate digestion and absorption. In comparison, the WS group exhibited 262 upregulated genes in the longissimus lumborum muscle and 81 downregulated genes relatives to the CS group, which were enriched in the fat deposition of TGF-beta, ECM-receptor interaction, MAPK, and PPAR signaling pathway.CONCLUSIONS: Among these, downregulated genes NPNT, GADL1, SESN3, and CPXM1 were associated with lipid metabolism and fat deposition in grazing yaks. It was found that DDC, DHTKD1, CCBL1, GCDH, and AOC1 involved in the tryptophan metabolism played an important role in the regulation of energy metabolism in yak.PMID:39695977 | DOI:10.1186/s12864-024-11093-5

BMC Plant Biol. 2024 Dec 18;24(1):1186. doi: 10.1186/s12870-024-05923-7.ABSTRACTBACKGROUND: Lotus (Nelumbo nucifera) is a significant aquatic ornamental genus widely utilized in horticulture for its decorative, culinary, medicinal, and other practical uses. It presents a variety of flower shapes, including few-petalled, semi-double-petalled, double-petalled and thousand-petalled flowers, making it an ideal candidate for studying the flower development of aquatic plants. However, the molecular mechanism of floral development in lotus remains elusive.RESULTS: In this study, two APETALA2 (AP2) homologues, NnAP2a and NnAP2b, were identified in lotus. Interestingly, both NnAP2a and NnAP2b proteins contained two conserved AP2 domains and were verified to be located primarily in the nucleus. Both NnAP2a and NnAP2b showed high expression levels in the floral buds and petals. Ectopic expression of NnAP2a and NnAP2b in Arabidopsis led to an increase in the number of petals and sepals compared to the wild type (WT). Meanwhile, each of the two NnAP2 genes was able to rescue the sepal and petal defective phenotype of the ap2-6 mutant in Arabidopsis. Furthermore, protein-protein interaction assays indicated that NnAP2s could form a protein complex with other proteins involved in floral organ development, such as AP3, PISTILLATA (PI), and SEPALLATA3 (SEP3).CONCLUSIONS: These results suggest that NnAP2s could influence sepal and petal development in N. nucifera. Our findings not only provide some insights into molecular mechanism underlying sepal and petal development and formation of lotus, but also might help its breeding in improving flower morphology.PMID:39695956 | DOI:10.1186/s12870-024-05923-7

BMC Plant Biol. 2024 Dec 18;24(1):1182. doi: 10.1186/s12870-024-05924-6.ABSTRACTAs a significant fruit and timber tree species among conifers, Pinus koraiensis remains it evergreen status throughout the harsh winters of the north, a testament to its intricate and prolonged evolutionary adaptation. This study delves into the annual trends of physiological indicators, gene expression levels, and metabolite accumulation to dissect the seasonal adaptability of P. koraiensis needles. Chlorophyll content reaches its zenith primarily between July and September, whereas carotenoids persist until spring. Additionally, notable seasonal variations are observed in the levels of soluble sugar and protein. Transcriptome data is categorized into four distinct stages: spring (S2), summer (S3-S4), autumn (S5), and winter (S6-S1). The differential expression of transcription factor genes, including bHLH, MYB-related, AP2/ERF, C3H, and NAC, provides insights into the needles' seasonal adaptations. Analysis of chlorophyll and carotenoid metabolism, sugar metabolism, and the MAPK signaling pathway identifies PSY5 (Cluster-50735.3), AMY13 (Cluster-37114.0), pgm1 (Cluster-46022.0), and MEKK1-1 (Cluster-33069.0) may as potential key genes involved in sustaining the needle's evergreen nature and cold resistance. Ultimately, a comprehensive annual adaptability map for P. koraiensis is proposed, enhancing understanding of its responses to seasonal variations.PMID:39695949 | DOI:10.1186/s12870-024-05924-6