Molecular omics最新文献

The increasing exposure to nanoparticles raises a concern over their toxicity. Incidentally, reactive oxygen species (ROS) are produced as a result of the nanoparticle's physicochemical characteristics and interactions with intracellular elements, primarily enzymes, leading to oxidative stress. In this context, the extent of oxidative stress resulting from the toxicity of titanium dioxide nanoparticles (TiO₂-NPs) on the cardiovascular system has not yet been thoroughly investigated. Initially, the gel/label-free proteomics (nLC-HRMS/MS) method was used to examine human serum protein interaction and corona composition. Furthermore, different oxidative stress assays (superoxide, total ROS, mitochondrial ROS, and lipid peroxidation) and cell stress assays (apoptosis, ER stress, mitochondrial dysfunction, autophagy, and hypertrophy) were performed in conjunction with endothelial (rat aortic cells) and cardiomyoblast (H9c2) cell cultures. In addition, expression studies (RT-qPCR and immunofluorescence), kinase signalling, and siRNA-mediated gene knockout (NOX2 and XO) studies were conducted. Alongside, in ovo effects on the heart's antioxidant enzymes (SOD and CAT) and metabolomic pathways (1H NMR) confirmed the involvement of oxidative stress in cardiotoxicity. The present results demonstrate a dose-dependent increase in cytotoxicity via the activation of caspase 3 and 9. The dose-dependent increase and its synergistic relationship with cardiovascular stress signalling (ET-1 and Ang-II) highlight the significant role of oxidative stress in nanoparticle toxicity. In summary, this study expands our understanding of the precise health risks associated with human exposure by establishing a connection between the role of the redox system and molecular stress pathways in TiO₂-NPs-induced cardiotoxicity.

The incidence of chronic kidney disease (CKD) is increasing globally; however, effective preventive and therapeutic strategies are currently limited. Roxadustat is being clinically used to treat renal anemia in CKD patients to reduce anemia-related complications and improve patients' life quality. Exosomes are small vesicles carrying important information that contribute to cell-to-cell communication and are present in various body fluids. However, little is known about the role of serum exosomes and their association with CKD after roxadustat treatment. Next-generation sequencing approaches have revealed that exosomes are enriched in noncoding RNAs and thus exhibit great potential as sensitive nucleic acid biomarkers in various human diseases. In this study, we aimed to identify the changed mRNAs–lncRNAs after roxadustat treatment as novel biomarkers for assessing the efficiency of the treatment. Through our study using RNA-seq data, we identified 957 mRNAs (626 upregulated and 331 downregulated after roxadustat treatment) and 914 lncRNAs (444 upregulated and 470 downregulated) derived from exosomes that were significantly changed, which was highly correlated to lipid metabolism. Our analysis through whole transcriptome profiling of exosome RNAs encompasses an identified differentially expressed mRNA–lncRNA regulatory axis in a larger patient cohort for the validation of suitable biomarkers for assessing CKD after roxadustat treatment.

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.

Genome architecture in eukaryotes exhibits a high degree of complexity. Amidst the numerous intricacies, the existence of genes as non-continuous stretches composed of exons and introns has garnered significant attention and curiosity among researchers. Accurate identification of exon–intron (EI) boundaries is crucial to decipher the molecular biology governing gene expression and regulation. This includes understanding both normal and aberrant splicing, with aberrant splicing referring to the abnormal processing of pre-mRNA that leads to improper inclusion or exclusion of exons or introns. Such splicing events can result in dysfunctional or non-functional proteins, which are often associated with various diseases. The currently employed frameworks for genomic signals, which aim to identify exons and introns within a genomic segment, need to be revised primarily due to the lack of a robust consensus sequence and the limitations posed by the training on available experimental datasets. To tackle these challenges and capitalize on the understanding that DNA exhibits function-dependent local physicochemical variations, we present ChemEXIN, an innovative novel method for predicting EI boundaries. The method utilizes a deep-learning (DL) architecture alongside tri- and tetra-nucleotide-based structural and energy features. ChemEXIN outperforms existing methods with notable accuracy and precision. It achieves an accuracy of 92.5% for humans, 79.9% for mice, and 92.0% for worms, along with precision values of 92.0%, 79.6%, and 91.8% for the same organisms, respectively. These results represent a significant advancement in EI boundary annotations, with potential implications for understanding gene expression, regulation, and cellular functions.

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.

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.

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.

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.

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.

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.