Enrofloxacin hydrochloride toxicological effects on crucian carp reflected by serological changes and neurotoxicity.

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects.

Downregulation of THRSP Promotes Hepatocellular Carcinoma Progression by Triggering ZEB1 Transcription in an ERK-dependent Manner.

Background: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Thyroid hormone responsive (THRSP) gene is primarily known for regulating responses to thyroid hormones, but its expression has been correlated with differential outcomes in some cancers. To date, however, its role in the progression of HCC remains unknown. Methods: The mRNA and protein expression of THRSP was measured in HCC tissues and cell lines via qPCR and western blot assays. Lentiviral transfection was used to establish stable cell lines overexpressing THRSP and shRNA was used to silence THRSP. The effects of THRSP on cell growth were then determined in vivo and in vitro. Cell migration and invasion of HCC cells were investigated using transwell and wound healing assays. Results: In tissue samples from patients, HCC tissues had decreased THRSP expression relative to adjacent healthy tissues. Further, patients with decreased THRSP protein and mRNA expression had worse outcomes. Knockdown of THRSP led to increased cell growth, migration, and invasion of HCC cells, and THRSP overexpression exerted an anti-tumor effect in vivo and in vitro. We found that increased expression of THRSP inhibited hepatocellular carcinogenesis by inhibiting the process of epithelial-to-mesenchymal transition through acting on the ERK/ZEB1 signaling pathway. Conclusion: THRSP may act as a functional tumor suppressor and was frequently reduced in HCC tissue samples. We identified a novel pathway for the THRSP/ERK/ZEB1-regulated suppression of HCC tumorigenesis and invasion. Restoring THRSP expression may represent a promising approach for HCC therapies.