Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

实验室用数字图像处理进行三维表面轮廓诊断

表面质量和轮廓精度的测量难是许多工业行业中存在的主要问题,半成品的表面质量直接影响到后续的生产步骤。虽然有许多方法可以获得所需的数据,但根据问题的复杂性所需要的测量硬件,比如二维或三维扫描仪,都比较昂贵。因此,本文提出一种新颖的算法,并在简单的三维扫描仪模型上,以0.1 mm的分辨率的图像处理进行了验证。扫描表面轮廓的方法有很多,但图像处理是目前工业自动化中最热门的课题。最重要的是,为了获得表面图像,使用标准的高分辨率反射相机,以MatLab为软件环境实现后处理。因此,这种解决方案可以替代昂贵的扫描仪,利用单一用途设备的额外功能扩展来实现。

Toxic Potential of Palytoxin

This review briefly describes the origin,chemistry,molecular mechanism of action,pharmacology,toxicology,and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids（i.e. Palythoa）,and Cyanobacteria（Trichodesmium）. Palytoxin is a very large,non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na＋/K＋-ATPase with a Kd of 20 p M and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 p S. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous,intraperitoneal,intramuscular,subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal,yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation,cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals,and currently this toxin is of great concern worldwide.

MicroRNA regulates the toxicological mechanism of four mycotoxins in vivo and in vitro

Mycotoxins can cause body poisoning and induce carcinogenesis,often with a high mortality rate.Therefore,it is of great significance to seek new targets that indicate mycotoxin activity and to diagnose and intervene in mycotoxin-induced diseases in their early stages.MicroRNAs(miRNAs)are physiological regulators whose dysregulation is closely related to the development of diseases.They are thus important markers for the occurrence and development of diseases.In this review,consideration is given to the toxicological mechanisms associated with four major mycotoxins(ochratoxin A,aflatoxin B1,deoxynivalenol,and zearalenone).The roles that miRNAs play in these mechanisms and the interactions between them and their target genes are explained,and summarize the important role of histone modifications in their toxicity.As a result,the ways that miRNAs are regulated in the pathogenicity signaling pathways are revealed which highlights the roles played by miRNAs in preventing and controlling the harmful effects of the mycotoxins.It is hoped that this review will provide a theoretical basis for the prevention and control of the damage caused by these mycotoxins.