SARS-CoV-2 Causes Acute Kidney Injury by Directly Infecting Renal Tubules.

Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient's condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.

Author Correction: Biomarkers of myocardial injury in rats after cantharidin poisoning: Application for postmortem diagnosis and estimation of postmortem interval.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biomarkers of myocardial injury in rats after cantharidin poisoning: Application for postmortem diagnosis and estimation of postmortem interval.

Postmortem diagnosis of cantharidin-induced myocardial injury and postmortem interval estimation (PMI) are the challenges in forensic science. Cardiac biomarkers play an important role in the prediction and diagnosis of myocardial injury and can be used to determine the PMI. Based on the evidence, we aimed to explore the biomarkers which may be used for the postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation using the study of the proteins expression of TN-T, VEGF and HIF-1α by ELISA. Results of this study suggested that postmortem pathological changes were difficult to identify due to the autolysis of myocardium 72 h after death in cantharidin poisoning group. The plasma levels of TN-T and HIF-1α/TN-T are cardiac biomarkers with higher diagnostic accuracy for postmortem diagnosis of cantharidin-induced myocardial injury, VEGF/HIF-1α promises to be a biomarker for PMI estimation. Further studies are needed to verify these biomarkers, based on population, for being a useful tool in postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation.

Cantharidin-induced acute hepatotoxicity: the role of TNF-α, IKK-α, Bcl-2, Bax and caspase3.

Cantharidin is of high medicinal value but has strong toxicity. Nowadays, multiple research has focused on the mechanism of its antitumor activity while research on toxicological profiles associated with cantharidin poisoning is still limited. Its hepatotoxicity has attracted attention recently for the crucial role of the liver in detoxification. Here, we aim to find a potential mechanism for cantharidin-induced acute hepatotoxicity with a view to assisting subsequent research or clinical use or detoxification. Twenty-one male Sprague-Dawley rats were randomly divided into control, low-dose (1.34 mg/kg) and high-dose (2.67 mg/kg) cantharidin exposure groups. We used hematoxylin-eosin to observe pathological changes and used immunofluorescent staining, western blotting and real-time quantitative polymerase chain reaction to detect the expression of the markers. The main pathological changes in livers of cantharidin-treated rats were necrosis, inflammatory infiltration and hemorrhage. We found coexpression of tumor necrosis factor alpha (TNF-α), IkappaB kinase-alpha (IKK-α) and caspase3 by immunofluorescent staining in livers of cantharidin-treated rats. Compared with the control, the levels of TNF-α, IKK-α and caspase3 increased significantly in the experimental groups (P < .05). The ratio of B-cell lymphoma-2 (Bcl-2)/Bax increased in the low-dose group but decreased in the high-dose group (P < .05). Cantharidin exposure raised IKK-α mRNA and caspase3 mRNA levels (P < .05). In conclusion, the participation of TNF-α, IKK-α, Bcl-2, Bax and caspase3 uncovered a novel mechanism underlying cantharidin-induced acute hepatotoxicity, and the mechanism needs to be studied further.

Cantharides poisoning: A retrospective analysis from 1996 to 2016 in China.

Cantharides poisoning may cause serious adverse reactions or even death.We attempt to retrieval articles automatically and manually with the key words of "cantharides" and " poisoning " or " side effects ", then summarized and analyzed the cases of cantharides poisoning from 1996 to 2016 in China, to provide some reference for clinical drug use and forensic identification. Finally, 91 cases were conformance to require; general data, clinical data, prognosis, autopsy results were analyzed.We found that the health education of cantharides in primary doctors and people is lackable, the case fatality rate was 18.68% . The death patients of cantharides poisoning had cardiomyocyte necrosis and neuronal apoptosis in the histopathological examination of autopsy , but the toxicological mechanism was unclear. There may be redistribution of cantharidin in vivo after death. Collectively, we hope that an anthropological database for cantharides poisoning established by multicenter cooperation, include medical institutions and forensic identified centers, and conduct more further studies on its cardiotoxicity and neurotoxicity.