Biology subjects

Thu, N. Q.

Publications and source records attributed to Thu, N. Q..

4 recordsLinked to original sources

bioRxiv2025

The Lipidome Landscape of Amiodarone Toxicity: An in vivo Lipid-centric Multi-Omics Study

Amiodarone is an effective therapy for arrhythmias, its prolonged management may lead to significant adverse drug reactions. Amiodarone-induced hepatoxicity is described by phospholipidosis, hepatic steatosis, cholestatic hepatitis, and cirrhosis. However, the systemic and hepatic lipidome disturbances and underlying toxicological mechanisms remain comprehensively elucidated. Untargeted lipidomics were utilized to analyze serum and liver samples from the rats orally administered a daily dose of amiodarone of either 100 or 300 mg/kg for one week. Changes in the expression of hepatic lipid-related genes were also examined utilizing transcriptomics. We found a higher magnitude of lipidome alterations in the 300 mg/kg than those in the 100 mg/kg groups. Treated animals showed elevated abundances of phosphatidylcholines, ether-linked phosphatidylcholines, sphingomyelins, and ceramides, and decreased levels of triacylglycerols, ether-linked triacylglycerols, and fatty acids. We also found 199 lipid-related differentially expressed hepatic genes between the 300 mg/kg group versus controls, implying lipid metabolism and signaling pathways disturbances. Specifically, elevation of serum phosphatidylcholines and ether-linked phosphatidylcholines, as well as hepatic bismonoacylglycerophosphates were associated with reduced expression of phospholipase genes and elevated expression of glycerophospholipid biosynthesis genes, possibly driving phospholipidosis. Perturbations of sphingolipid metabolism might also be the key events for amiodarone-induced toxicity. Alterations in gene expression levels related to lipid storage and metabolism, mitochondria functions, and energy homeostasis were also found. Collectively, our study characterized the sophisticated perturbations in the lipidome and transcriptome of amiodarone-treated rats and suggested potential mechanisms responsible for amiodarone-induced hepatotoxicity.

pharmacology and toxicology↗

bioRxiv2024

EasyPubPlot: a shiny web application for rapid omics data exploration and visualization

Computational toolkits for data exploration and visualization from widely used omics platforms often lack flexibility and customization. While many tools generate standardized output, advanced programming skills are necessary to create high-quality visualizations. Therefore, user-friendly tools that simplify this crucial yet time-consuming step are essential. We developed EasyPubPlot (Easy Publishable Plotting), a straightforward, easy-to-use, user experience-oriented, open-source, and shiny web application along with its associated R package to streamline data exploration and visualization for functional omics-empowered research. EasyPubPlot generates publishable scores plots, volcano plots, heatmaps, box plots, dot plots, and bubble plots with minimal necessary steps. The tool was designed to guide new users for accurate and efficient navigation. Step-by-step tutorials for each type of plot are also provided. Herein, we demonstrated EasyPubPlots competent functionality and versatility by showcasing metabolomics and transcriptomics data. Collectively, EasyPubPlot reduces the gap between data analysis and stunning visualization, thereby diminishing friction and focusing on science. The app can be downloaded and installed locally (https://github.com/Pharmaco-OmicsLab/EasyPubPlot) or used through a web application (https://pharmaco-omicslab.shinyapps.io/EasyPubPlot).

bioinformatics↗

bioRxiv2024

Endoplasmic reticulum stress inhibition preserves mitochondrial function and cell survival during early onset of isoniazid-induced oxidative stress

A comprehensive understanding of isoniazid (INH)-mediated hepatotoxic effects is essential for developing strategies to predict and prevent severe liver toxicity in tuberculosis treatment. Our study utilized multi-omics profiling to investigate the toxic effects of INH, revealing significant involvement of endoplasmic reticulum (ER) stress, mitochondrial impairment, redox imbalance, and altered metabolism. Followed-up mechanistic studies revealed that INH triggered the generation of cytosolic reactive oxygen species (ROS) and the activation of the Nrf2 signaling pathway prior to mitochondrial ROS accumulation. Subsequently, INH disrupted mitochondrial function by impairing respiratory complexes I-IV and caused mitochondrial membrane proton leaks without affecting ATP synthase activity, together leading to mitochondrial depolarization and reduced ATP production. These disturbances enhanced mitochondrial fission and mitophagy. While much attention has been given to mitochondrial dysfunction and oxidative stress in INH-induced hepatotoxicity, our findings highlight the potential of inhibiting ER stress during early INH exposure to mitigate cytosolic and mitochondrial oxidative stress. We further revealed the critical role of Nrf2 signaling in protecting liver cells under INH-induced oxidative stress by maintaining redox homeostasis and enabling metabolic reprogramming via regulating the expression of antioxidant genes and cellular lipid abundance. We also identified other antioxidant pathways (e.g., selenocompound metabolism, HIF-1 signaling pathway, and pentose phosphate pathway) as potential alternative mechanisms besides Nrf2 signaling in response to INH-induced oxidative stress. In conclusion, our research emphasizes the importance of ER stress, redox imbalance, metabolic changes, and mitochondrial dysfunction underlying INH-induced hepatotoxicity.

pharmacology and toxicology↗

bioRxiv2024

Multi-omics phenotyping characterizes molecular divergence underlying different clinical scenarios of inflammatory bowel disease

Clinically heterogeneous spectrum and molecular phenotypes of inflammatory bowel disease (IBD) remain to be comprehensively elucidated. This study set out to explore the serum molecular profiles (I) of IBD subtypes; in association with (II) elevated fecal calprotectin and (III) disease activity states; (IV) upon treatment escalation; and (V) in patients who needed treatment escalation. The serum proteome, metabolome, and lipidome of 75 treated IBD patients were profiled. Single- and multi-omic data analysis was performed to determine differential analytes and integrative biosignatures. (I) Chronic inflammation, and phosphatidylcholine and bile acid homeostasis disturbances underlined the differences between Crohns disease (CD) and ulcerative colitis. (II) Elevated calprotectin was associated with higher levels of inflammatory proteins and sphingomyelins (SM) and lower levels of bile acids, amino acids, and triacylglycerols (TG). Relative to patient remission, active disease state (III) was characterized by decreased SMs and increased inflammatory proteins and TGs. (IV) Treatment escalation was associated with augmented levels of inflammatory response-related proteins and reduced levels of amino acids. Most TG species increased in the post-treatment escalation. Moreover, needed-treatment-escalation patients had significantly lower levels of TGs (V). They also showed increased SMs and decreased signaling receptor binding proteins. Multi-omics analysis revealed biosignatures that captured the differences between groups of each scenario. Eight analytes, including NFASC, ANGPTL4, and chenodeoxycholate, were found in at least three biosignatures. Collectively, disturbances in immune response, bile acid homeostasis, amino acids, and lipids alteration potentially underlie the clinically heterogeneous spectrum of IBD.

systems biology↗