Molecular omics最新文献

Due to their self-renewal and differentiation capabilities, pluripotent stem cells hold immense potential for advancing our understanding of human disease and developing cell-based or pharmacological interventions. Realizing this potential, however, requires a thorough understanding of the basal cellular mechanisms which occur during differentiation. Lipids are critical molecules that define the morphological, biochemical, and functional role of cells. This, combined with emerging evidence linking lipids to neurodegeneration, cardiovascular health, and other diseases, makes lipids a critical class of analytes to assess normal and abnormal cellular processes. While previous work has examined the lipid composition of stem cells, uncertainties remain about which changes are conserved and which are unique across distinct cell types. In this study, we investigated lipid alterations of induced pluripotent stem cells (iPSCs) at critical stages of differentiation toward neural or mesodermal fates. Lipidomic analyses of distinct differentiation stages were completed using a platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) separations. Results illustrated a shared triacylglyceride and free fatty acid accumulation in early iPSCs that were utilized at different stages of differentiation. Unique fluctuations through differentiation were also observed for certain phospholipid classes, sphingomyelins, and ceramides. These insights into lipid fluctuations across iPSC differentiation enhance our fundamental understanding of lipid metabolism within pluripotent stem cells and during differentiation, while also paving the way for a more precise and effective application of pluripotent stem cells in human disease interventions.

The occurrence and distribution of new and re-emerging fungal pathogens, along with rates of antifungal resistance, are rising across the globe, and correspondingly, so are our awareness and call for action to address this public health concern. To effectively detect, monitor, and treat fungal infections, biological insights into the mechanisms that regulate pathogenesis, influence survival, and promote resistance are urgently needed. Mass spectrometry-based proteomics is a high-resolution technique that enables the identification and quantification of proteins across diverse biological systems to better understand the biology driving phenotypes. In this review, we highlight dynamic and innovative applications of proteomics to characterize three critical fungal pathogens (i.e., Candida spp., Cryptococcus spp., and Aspergillus spp.) causing disease in humans. We present strategies to investigate the host-pathogen interface, virulence factor production, and protein-level drivers of antifungal resistance. Through these studies, new opportunities for biomarker development, drug target discovery, and immune system remodeling are discussed, supporting the use of proteomics to combat a plethora of fungal diseases threatening global health.

Oral squamous cell carcinoma (OSCC) is frequently the outcome of oral submucous fibrosis (OSMF), a common possibly premalignant disease. In our study, a cohort of 50 patients with OSCC and OSMF, along with 50 healthy controls, was analyzed to identify significant metabolic differences between the patient and control groups through multivariate statistical analysis using NMR-based metabolomics in saliva samples. The 2D scatter plot of PC1 versus PC2 scores clearly show a distinction between the groups, with the principal component analysis (PCA) explaining 24.6% of the variance. Partial least-squares discriminant analysis (PLS-DA) demonstrated R² and Q² values of 0.94 and 0.90, respectively, indicating a robust model fit. A total of 20 distinct metabolites were identified, including 5 that were up-regulated and 5 that were down-regulated. Univariate ROC curve analysis identified nine salivary metabolites with AUC values exceeding 0.70, including acetone, tryptophan, 5-aminopentanoic acid, betaine, aspartic acid, ethanol, acetoacetate, adipic acid, and citrate. Notably, the distinct presence of three metabolites-acetone, tryptophan, and 5-aminopentanoic acid-yielded AUC values of 0.98123, 0.95358, and 0.91506, respectively. The refined statistical model was subjected to metabolic pathway analysis, revealing interconnected pathways. We were also able to predict the severity of the disease, specifically distinguishing between stage I and stage II OSCC. This differentiation was highlighted by the PCA score plot, which explained 28.6% of the variance. These results were further confirmed by PLS-DA. These insights pave the way for early diagnosis and predicting severity in patients with oral cancer, which will enable better management of the disease.

Leydig cells rely on lipids and fatty acids (FA) for essential functions like maintaining structural integrity, energy metabolism, and steroid hormone synthesis, including testosterone production. Carbamazepine (CBZ), a common anticonvulsant medication, can influence lipid metabolism and profiles, potentially impacting Leydig cell function and testosterone levels. Understanding this interplay is crucial to optimize treatment strategies for individuals requiring CBZ therapy while mitigating any adverse effects on male reproductive health. This study focuses on evaluating the effects of selected CBZ concentrations on the lipid homeostasis of BLTK-1 murine Leydig cells. By employing liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), we aimed to uncover the specific changes in lipid profiles induced by CBZ exposure (25 and 200 μM). FA analysis demonstrated a significant decrease in FA 22:6 n-3 with increasing CBZ concentration and an increase in the n-6/n-3 ratio. Furthermore, changes in the lipidome, particularly in lipid species belonging to phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylglycerol (PG), and sphingomyelin (SM) classes were observed. PE and PC lipid species were significantly elevated in Leydig cells exposed to 200 μM CBZ, whereas PG and SM species were downregulated. CBZ treatment significantly altered the Leydig cell phospholipidome, suggesting specific phospholipids such as PG 40:4, PG 34:1, PC O-32:1, PC 32:2, and PE P-38:6, which exhibited the lowest p-values, as potential biomarkers for clinical assessment of CBZ's impact on Leydig cells. These findings underscore the intricate relationship between CBZ exposure and alterations in lipid profiles, offering potential insights for monitoring and mitigating the drug's effects on male reproductive health.

Metabolic associated steatohepatitis characterized by lipid accumulation, inflammation and fibrosis, is a growing global health issue, contributing to severe liver-related mortality. With limited effective treatments available, there is an urgent need for novel therapeutic strategies. Moringa oleifera, rich in antioxidants, offers potential for combating steatohepatitis, but its cytotoxicity presents challenges. Aloe vera, renowned for its cytocompatibility and anti-inflammatory effects, shows promise in mitigating these risks. Using infrared spectrometry and mass spectrometry, we identified 1586 metabolites from both plants across 84 chemical classes. By encapsulating these phytochemicals in nanoparticles, we achieved increased solubility, cytocompatibility, and gene modulation to hepatic stellate cells affected by steatohepatitis. Chemoinformatic analysis revealed bioactive metabolites, including hesperetin analogs, known to inhibit TGF-β. Our results demonstrate that these nanoparticles not only improved gene expression modulation related to metabolic associated steatohepatitis, particularly TGF-β and COL1A1, but also outperformed free compounds, highlighting their potential as a novel therapeutic approach.

Hydrogels, three-dimensional polymeric networks capable of absorbing and retaining significant amounts of aqueous solution, offer a promising platform for controlled release of desired compounds. In this study, we explored the effects of urea delivery through galactoxyloglucan-sodium alginate hydrogels on the phenotypic and metabolic responses of Brassica juncea, a vital oilseed and vegetable crop. The experiments were conducted with four treatments: control (without hydrogel beads and urea), direct urea supplementation (U), hydrogel beads with urea (HBWU), and hydrogel beads without urea (HBWOU). Our findings revealed that HBWU-treated plants exhibited commendable plant growth with significantly higher chlorophyll content (11.06 mg/0.1 g) compared to the control (3.67 mg/0.1 g) and U-treated group (6.41 mg/0.1 g). Metabolic analysis identified 17 major intra-cellular metabolites involved in nitrogen metabolism. HBWU treatment significantly boosted nitrogen assimilation in plants, as evidenced by the upregulation of 9 metabolites. Furthermore, a proposed schematic diagram illustrates the HBWU induced-metabolic pathways and nitrogen metabolism in B. juncea. These findings demonstrate the potential of hydrogel-based controlled-release systems to enhance plant growth and nitrogen assimilation.

Lung cancer remains the leading cause of cancer-related deaths worldwide due to its poor prognosis. Despite significant advancements in the understanding of cancer development, improvements in diagnostic methods, and multimodal therapeutic regimens, the prognosis of lung cancer has still not improved. Therefore, it is reasonable to look for newer and alternative medicines for treatment. Bhallataka nut extract, derived from the seeds of Semecarpus anacardium, is known for its anti-inflammatory and antioxidant properties, suggesting potential as a treatment for cancer. In this study, we investigated the molecular networks associated with the Bhallataka taila-mediated inhibition of lung adenocarcinoma. Treating lung cancer cell lines with Bhallataka taila resulted in decreased colony formation, proliferation, and migration, and increased apoptosis. Using a tandem mass tag (TMT)-based temporal quantitative proteomic analysis, we identified 173 overexpressed and 249 downregulated proteins among a total of 2879 proteins. Significantly altered proteins are associated with lung cancer progression, metastasis, invasion, migration, and epithelial–mesenchymal transition (EMT). The analysis of these altered proteins revealed molecular networks underlying the anticancer mechanisms of Bhallataka taila. Validation of these proteins and pathways affected by Bhallataka taila confirmed its utility in cancer treatment.

Cancer remains the second leading cause of death worldwide, surpassed only by cardiovascular disease. From the different types of cancer, pancreatic cancer (PaC) has one of the lowest survival rates, with a survival rate of about 20% after the first year of diagnosis and about 8% after 5 years. The lack of highly sensitive and specific biomarkers, together with the absence of symptoms in the early stages, determines a late diagnosis, which is associated with a decrease in the effectiveness of medical intervention, regardless of its nature – surgery and/or chemotherapy. This review provides an updated overview of recent studies combining multi-OMICs approaches (e.g., proteomics, metabolomics) with analytical tools, highlighting the synergy between high-throughput molecular data generation and precise analytical tools such as LC–MS, GC–MS and MALDI-TOF MS. This combination significantly improves the detection, quantification and identification of biomolecules in complex biological systems and represents the latest advances in understanding PaC management and the search for effective diagnostic tools. Large-scale data analysis coupled with bioinformatics tools enables the identification of specific genetic mutations, gene expression patterns, pathways, networks, protein modifications and metabolic signatures associated with PaC pathogenesis, progression and treatment response through the integration of multi-OMICs data.

Brevetoxins are a type of neurotoxin produced in red tide blooms. Northern quahogs (M. mercenaria) are extensively used in commercial aquaculture farming, and early-stage metabolomics studies can provide early warnings of brevetoxins for farmers. In this study, NMR-based metabolomics was performed to investigate the response of clam gills and digestive glands under a series of sublethal doses of brevetoxins. Our study showed that the brevetoxin PbTx-2 had minimal influence on the physical activities of M. mercenaria for a short exposure time (24 hours). However, major metabolic level perturbations were observed in the clam gill extracts from the 1 ppb treatment. In addition, in the low concentration (0.1 ppb) study, clam gills showed combinational metabolite perturbations, as observed by an OPLS-DA study. The highly disturbed metabolites in the gill samples were the upregulated serine, glucose, hypotaurine, and glycine and the downregulated lactate, leucine, isoleucine, threonine, biotin, taurine, and valine. The results indicated that the brevetoxin PbTx-2 potentially affects glycolysis, glycine, serine, and threonine metabolism, taurine and hypotaurine metabolism, and biotin metabolism. While the digestive gland had less significantly changed metabolites, the potential combinational metabolite changes from PCA were observed from the 5-ppb treatment. Glucose and glycine are the primary metabolites that showed high contributions to the OPLS-DA model, which indicates the potential influence of digestive activities. The study indicated that metabolomic analysis of the gills and digestive glands of M. mercenaria is a feasible method to monitor the toxicity of brevetoxins, especially under sublethal doses in marine water.

The present work aimed to examine the primary mechanisms of liver damage, namely the impact of gut-derived endotoxins along the gut–liver axis and adipose-derived free fatty acids along the adipose–liver axis. These processes are known to play a significant role in the development of hepatic inflammation and steatosis. Although possible overlapping in the pathogenesis was expected, these processes have unique pathophysiological consequences. Therefore, we used HepG2 cells as a model system to investigate the impact of lipopolysaccharides (LPS) and free fatty acid (FFA; albumin conjugated palmitic acid) on the intracellular metabolome. Although both LPS and FFA triggered the expression of nuclear factor κB (NFκB)-dependent inflammation, only LPS treatment was able to trigger a Toll-like receptor 4 (TLR4) dependent response. The intracellular cytoprotective enzymatic levels (catalase, peroxidase, glutathione) were increased due to FFA but lowered due to LPS. The free-radical neutralizing efficacies of cell-free metabolites of FFA-treated cells were better than those of the LPS-treated ones. The use of untargeted metabolomics allowed for the identification of distinct metabolic pathway enrichments, providing further insights into the differential effects of LPS and FFA on the metabolism of hepatocytes. Collectively, the current study highlights the distinct impacts of endotoxemia and lipotoxicity on the metabolome of hepatocytes, hence offering valuable insights into hepatocellular function.