Abstract. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine synthesized by several cell types, e.g

Abstract-The atherogenic effect of the renin-angiotensin system can be explained, in part, by the influence of its effector, angiotensin II (Ang II), on vascular smooth muscle cell (VSMC) growth. There is evidence that reactive oxygen species (ROS) play a role in the atherogenesis and activation of mitogen-activating protein (MAP) kinases, which are involved in proliferation and differentiation. The study was performed to further characterize the role of ROS in Ang II-mediated MAP kinase activation and the regulation of the transcription factor activator protein-1 (AP-1). Rat VSMCs were stimulated with Ang II. The activities of MAP kinases were assessed by Western blot analysis or by immunocomplex kinase assay. AP-1 binding was determined by using an electrophoretic mobility shift assay. Rat VSMCs were treated with Ang II-activated MAP kinases, extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK), p38 MAP kinase (p38 MAPK), and their downstream effector, AP-1. Interestingly, only the activation of ERK1/2, but not JNK or p38 MAPK, was tyrosine kinase, protein kinase C, and MEK1/2 dependent. Ang II also induced the rapid formation of ROS, which could be inhibited by a specific antibody as well as by antisense against the p22phox subunit of the NAD(P)H oxidase. JNK and p38 MAPK, but not ERK, activation was inhibited by an inhibitor of NAD(P)H oxidase. Antisense against p22phox also solely inhibited p38 MAPK but did not affect ERK. The results indicate that in VSMCs, Ang II activates MAP kinases and AP-1 through different pathways; the results further suggest that ROS, generated by p22phox, mediate Ang II-induced JNK and p38 MAPK activation, which may contribute to the pathogenesis of atherosclerosis. Key Words: angiotensin II Ⅲ atherosclerosis Ⅲ reactive oxygen species Ⅲ mitogen-activated protein kinase Ⅲ activator protein-1 A ngiotensin II (Ang II), the main peptide hormone of the renin-angiotensin system, plays an important role in the pathogenesis of cardiovascular diseases, including atherosclerosis, myocardial infarction, and hypertension. 1 Ang II exerts hypertrophic and hyperplastic effects by activating a number of intracellular signal transduction pathways through a 7-transmembrane heterotrimeric G protein-coupled receptor called the Ang II type 1 (AT 1 ) receptor. 2 New data indicate that Ang II plays an important role in the generation of reactive oxygen species (ROS) by activation of NAD(P)H oxidase, a plasma membrane-bound protein. 3,4

Recently, deepfake videos, generated by deep learning algorithms, have attracted widespread attention. Deepfake technology can be used to perform face manipulation with high realism. So far, there have been a large amount of deepfake videos circulating on the Internet, most of which target at celebrities or politicians. These videos are often used to damage the reputation of celebrities and guide public opinion, greatly threatening social stability. Although the deepfake algorithm itself has no attributes of good or evil, this technology has been widely used for negative purposes. To prevent it from threatening human society, a series of research have been launched, including developing detection methods and building large-scale benchmarks. This review aims to demonstrate the current research status of deepfake video detection, especially, generation process, several detection methods and existing benchmarks. It has been revealed that current detection methods are still insufficient to be applied in real scenes, and further research should pay more attention to the generalization and robustness.This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.

Abstract-Endothelin-1 (ET-1) has been proposed to contribute to atherogenesis and plaque rupture in coronary heart disease through activation of mitogen-activated protein kinases (MAPKs) in smooth muscle cells (SMCs). Reactive oxygen species (ROS) have been shown to be important signal transduction molecules in SMCs. Thus, the present study aimed to assess the role of ROS in ET-1-mediated activation of c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2. Rat SMCs were exposed to ET-1 over time at concentrations from 10 Ϫ6 to 10 Ϫ10 mol/L, and MAPK activity was quantified. Activation of JNK and ERK was observed with a maximum stimulation at 10 Ϫ7 mol/L ET-1. JNK and ERK were activated by ET-1 binding to a single receptor (ET-1A) but differed in their downstream mechanisms: only JNK activation was sensitive to the radical scavenger N-acetylcysteine and diphenylene iodonium, an inhibitor of NADPH oxidase, indicating a role for ROS. The downstream MAPK effector and proinflammatory transcription factor, the activator protein-1 complex, was maximally activated 2 hours after the addition of ET-1. It was mainly composed of the JNK substrate c-Jun, and activation was also dependent on ROS formation. We suggest that plaque activation by ET-1 can be mediated through ROS. It can be hypothesized that the clinical benefit of antioxidants in the treatment of atherogenesis may partially depend on neutralization of ET-1-mediated ROS production. Key Words: endothelin-1 Ⅲ atherosclerosis Ⅲ reactive oxygen species Ⅲ mitogen-activated protein kinase Ⅲ smooth muscle S everal lines of evidence suggest a role for endothelin-1 (ET-1) in the pathogenesis of atherosclerosis, including immunohistochemical studies demonstrating an increased accumulation of ET-1 in human atheroma. 1 Furthermore, a direct correlation could be shown between the amount of ET-1 present in human coronary artery lesions and unstable angina. 2 In animal experiments, endothelin antagonists had a protective effect against atherosclerosis. 3,4 A release of endothelin, in vitro, by smooth muscle cells (SMCs) themselves was also demonstrated. 5 The proatherogenic properties of endothelin are attributed to its vasoconstrictive action, 2,6,7 and more recently, ET-1 has been reported to activate SMCs. 8,9 As shown by numerous studies, activation of SMCs can be an important step in the inflammatory response of the vessel wall. 10 The inflammatory response of SMCs involves a number of proteins of the signal cascade, including the inducible transcription factors c-Jun and c-Fos. 11 These are expressed at very low levels in quiescent SMCs but can be induced by stimulating SMCs with different agents, such as angiotensin II 12 or platelet-derived growth factor. 13 When activated, c-Jun and c-Fos can dimerize to form activator protein-1 (AP-1), a transcription factor complex. 14 Expression and activation of AP-1 proteins is tightly controlled by mitogen-activated protein (MAP) kinases, such as the c-Jun amino-terminal kinase (JNK) and extracellul...

The terminal complement complex C5b-9 is known to participate in inflammatory processes including atherosclerosis. Inflammation appears to be a direct consequence of C5b-9-mediated cell stimulation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors may exert anti-inflammatory effects on vascular cells independent of lowering plasma cholesterol. Thus, we studied activation of vascular smooth muscle cells (VSMCs) by C5b-9 focusing on whether inhibition of the HMG-CoA reductase can reduce the proinflammatory effects of C5b-9.C5b-9 in sublytic concentrations increased the proliferation of human VSMCs and induced a time-dependent activation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK). Proliferation and ERK1/2 activation could be inhibited by the specific ERK inhibitor PD98059. HMG-CoA inhibition with cerivastatin-reduced VSMC proliferation and C5b-9-induced ERK1/2 activation. Cerivastatin also reduced the C5b-9-induced synthesis of the proinflammatory interleukin-6 (IL-6). Furthermore, C5b-9 induced activation of the transcription factors activator protein- 1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which could be inhibited by pretreatment of VSMCs with cerivastatin. L-mevalonate and geranylgeranylpyrophosphate reversed the inhibitory effects of cerivastatin. The present study in VSMCs shows that cerivastatin inhibits IL-6 synthesis and cell proliferation induced by the terminal complement complex C5b-9. This may be an important mechanism contributing to the beneficial effects of HMG-CoA reductase inhibitors beyond lowering of plasma cholesterol.