Project description:Diquat is one of the most commonly used pesticides in recent years, and its improper use can lead to acute poisoning and loss of life. This study employed single-cell and single-cell nucleus transcriptome sequencing on mouse lung, liver, and kidney tissues induced by diquat to unveil the molecular pathophysiology of multi-organ damage caused by diquat exposure. In this research, we emphasize a novel hepatic cell subpopulation associated with detoxification and metabolic dysregulation following diquat exposure in the liver. Furthermore, a robust and intricate immune-inflammatory response is a prominent feature in the lungs, while a time-dependent shift from glomerular infiltration to tubular injury pattern is the main characteristic in the kidneys. This study underscores distinct injury features in multiple organs, significantly enhancing our understanding of diquat-induced multi-organ damage. Relevant molecules and pathways identified may serve as potential novel molecular targets.
Project description:Paraquat and diquat are viologen herbicides used in commercial agriculture and for residential outdoor weed control. They are related structurally, each containing multiple aromatic rings and two quaternary ammonium cations. Paraquat is one of the most widely used herbicides in the world; however, due to recent toxicity studies and its association with Parkinson’s disease, it is now available only to commercially licensed users in the United States. In contrast, diquat has not been associated with Parkinson’s disease and is available for both commercial and residential applications in the United States. In general, the proposed mechanism by which toxicity occurs following exposure to either herbicide is similar. Both are readily converted to free radicals via the superoxide anion radical and react with molecular oxygen to generate additional redox products that promote oxidative stress and potentially cell death. Diquat is generally considered a safer alternative to paraquat based on its lower incidence of poisoning reports; however, recent work in our lab suggests diquat is significantly more hepatotoxic than paraquat. Studies reporting direct comparisons of paraquat and diquat, especially regarding their potential impact on liver injury, are definitely lacking. The goal of this project is to address this knowledge gap by exposing an in vitro hepatocellular model (TGF-alpha transgenic mouse hepatocytes; TAMH) with each viologen herbicide to further elucidate toxicologic mechanisms and outcomes. The microarray data identified MAPK as an important contributor to diquat-induced toxicity and offers a new generalized approach for broader gene expression-level investigations.
Project description:Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage and fatal outcomes. MicroRNAs (miRNAs) are detectable in blood, reflecting cell activation and tissue injury. We performed small RNA-Seq in healthy controls (N=11), non-severe (N=18) and severe (N=16) COVID-19 patients
Project description:<p>The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has established the Drug-Induced Liver Injury Network (DILIN) to collect and analyze cases of severe liver injury caused by prescription drugs, over-the-counter drugs, and alternative medicines, such as herbal products and supplements.</p>
Project description:We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.
Project description:Oxaliplatin has been used as the first choice for the adjuvant chemotherapy of colorectal cancer and it has significantly improved the outcomes in patients with colorectal cancer. However, hepatotoxicity is the potentially problematic adverse effect of oxaliplatin. The pathological evaluation of non-tumoral liver from patients with advanced colorectal cancer undergoing neoadjuvant oxaliplatin-based treatment has provided histological evidence of hepatic sinusoidal injury. Oxaliplatin-induced sinusoidal injury can persist for more than 1 year after the completion of chemotherapy, and the increase in splenic volume may be a predictor of irreversible sinusoidal damage. In this current study, the investigators aim to evaluate the values of potential biomarkers in diagnosing patients with oxaliplatin-induced gastroesophageal varices after colorectal cancer surgery.
Project description:Oxaliplatin has been used as the first choice for the adjuvant chemotherapy of colorectal cancer and it has significantly improved the outcomes in patients with colorectal cancer. However, hepatotoxicity is the potentially problematic adverse effect of oxaliplatin. The pathological evaluation of non-tumoral liver from patients with advanced colorectal cancer undergoing neoadjuvant oxaliplatin-based treatment has provided histological evidence of hepatic sinusoidal injury. Oxaliplatin-induced sinusoidal injury can persist for more than 1 year after the completion of chemotherapy, and the increase in splenic volume may be a predictor of irreversible sinusoidal damage. In this current study, we aim to evaluate the efficacy of individualized treatment in patients with oxaliplatin-induced gastroesophageal varices after colorectal cancer surgery.
Project description:In the present study, the proteomics approach identified potential protein signatures with high discriminative ability in TB patients with and without drug-induced liver injury which might play a crucial role in developing Anti-tubercular drug-induced liver injury.