ROS-mediated M1 polarization-necroptosis crosstalk involved in Di-(2-ethylhexyl) phthalate-induced chicken liver injury
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The widespread use of plasticizers poses a serious threat to the environment and poultry health. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that can cause liver damage with prolonged exposure. Oxidative stress is closely associated with DEHP toxicity. Macrophage polarization plays an important role in many physiological and pathological processes and regulates disease development. This study aims to elucidate the mechanism of chronic DEHP exposure leading to chicken liver injury through oxidative stress-induced M1 polarization-necroptosis. In this study, the DEHP exposure model of chicken liver and the single and co-culture model of LMH and HD11 cells were established. With increasing dose and time, DEHP decreased body weight, increased liver coefficient, raised activities of liver function indicators and caused pathological liver damage in chickens. Further studies revealed the increase of reactive oxygen species (ROS) level and malonaldehyde (MDA) content, and the decrease of total antioxidant capacity (T-AOC) level, total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities, which led to excessive oxidative stress in the liver. In addition, there was increased infiltration of liver macrophages (CD68), upregulation of M1 polarization indicators (CD86, iNOS, IL-1β, TNF-α) and downregulation of M2 polarization indicators (CD163, Arg-1, IL-10, TGF-β) and appearance of necroptosis (RIPK1, RIPK3, MLKL). The vitro experiments confirmed the addition of N-acetylcysteine (NAC) inhibited M1 polarization and necroptosis. Besides, M1 polarization of HD11 cells promoted necroptosis of LMH cells in the HD11-LMH co-culture system. In brief, ROS-mediated M1 polarization-necroptosis is involved in DEHP-induced liver injury. This study provides a reference for environmental toxicant exposure in livestock and poultry farming.Keywords:
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가상현실 헤드셋에 대한 제어는 머리에 착용한 상태에서 손을 사용하기 때문에 조작에 대한 부담감이 발생한다. 본 논문에서는 손을 사용하지 않고 즉각적인 입력신호를 줄 수 있는 안전도(EOG, electro-oculogram)를 이용한 가상현실 헤드셋 입력시스템을 제안하였다. 이는 가상현실 헤드셋의 제어를 위한 입력 신호를 손의 움직임 없이 사용자의 안전도만으로 디스플레이 되는 콘텐츠를 제어할 수 있는 시스템이다. 제안된 시스템은 모바일 폰, 가상현실 헤드셋, 그리고 뇌전도 데이터 획득용 헤드셋으로 구성되어 있으며, 신호처리 및 제어를 위한 Unity3D 엔진을 이용하여 제어 시스템을 구현하였으며, 구현된 시스템을 통해 가상현실 헤드셋의 손쉬운 제어가 가능함을 확인하였다. The most of virtual reality headset have the separated controllers while they put on the headset; so the users may feel the discomfort and burden for the operation. In this paper, a novel virtual reality headset system using the EOG (electro-oculogram) is proposed and it has a distinguished feature that the user does not need to control the virtual reality headset by the hands, but the displayed contents are controllable by the electrical activity of the user's brain. The proposed system consist of the mobile device, a virtual reality headset, and an EOG headset for data acquisition. The system is implemented by using the Unity3D engine for the signal processing and controller, and the concept is confirmed through the implementation that it is more interesting and easier to control the virtual reality headset.
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Necroptosis is a special cell necrosis that is capable of being regulated through particular molecular mechanism.Multiple stimuli could induce necroptosis,complex Ⅰ,complex Ⅱ and RIP1-RIP3 necrosome are critical participants in the necroptosis.Also,necrostatin-1 is a special and potent small-molecular inhibitor of necroptosis.Necroptosis could be an important alternative for cell death in ischemia-reperfusion injury.
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Programmed necrosis, or necroptosis, is a type of specialized cell death with necrotic characteristics, including the loss of membrane integrity and swollen organelles in dying cells. However, unlike simple necrosis, it may be induced as an alternative form of cell death when apoptosis is blocked and it is mediated in an orchestrated manner, similar to apoptosis, by a series of signaling molecules. Necroptosis-associated proteins and their specific small molecules have been extensively identified in order to illuminate the underlying mechanisms by which necroptosis is activated through a novel signaling pathway. However, the biological significance of necroptosis, which is known as a secondary route of apoptosis, remains under debate. Concurrent with these concerns, the clinical application of necroptosis has been cautiously proposed to treat necroptosis-associated diseases, and to overcome resistance to anticancer drugs. Accordingly, the present review will highlight the harnessing of necroptosis for anticancer therapy. To this end, the state-of-the art technique of necroptosis as a cancer therapy will be briefly described, and then its potential for clinical purposes will be delineated. For a further understanding of necroptosis, the present review begins with a basic introduction to necroptosis and its multifaceted physiological consequences.
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Necroptosis is a type of programmed cell death with necrotic morphology, occurring in a variety of biological processes, including inflammation, immune response, embryonic development and metabolic abnormalities. The current nomenclature defines necroptosis as cell death mediated by signal transduction from receptor‑interacting serine/threonine kinase (RIP) 1 to RIP3 (hereafter called RIP1/RIP3). However, RIP3‑dependent cell death would be a more precise definition of necroptosis. RIP3 is indispensable for necroptosis, while RIP1 is not consistently involved in the signal transduction. Notably, deletion of RIP1 even promotes RIP3‑mediated necroptosis under certain conditions. Necroptosis was previously thought as an alternate process of cell death in case of apoptosis inhibition. Currently, necroptosis is recognized to serve a pivotal role in regulating various physiological processes. Of note, it mediates a variety of human diseases, such as ischemic brain injury, immune system disorders and cancer. Targeting and inhibiting necroptosis, therefore, has the potential to be used for therapeutic purposes. To date, research has elucidated the suppression of RIP1/RIP3 via effective inhibitors and highlighted their potential application in disease therapy. The present review focused on the molecular mechanisms of RIP1/RIP3‑mediated necroptosis, explored the functions of RIP1/RIP3 in necroptosis, discussed their potential as a novel therapeutic target for disease therapy, and provided valuable suggestions for further study in this field.
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Cell death is one of the basic life properties. A new type of cell death named necroptosis was discovered and became increasingly noticed attention in recent years. Necroptosis has similar morphological characteristics with cell necrosis and is controlled by special signal pathways. The interaction of the receptor interacting protein 1 (RIP1) and 3 (RIP3) plays a crucial important role in the necroptosis signal pathway. The RIP1 determines whether a cell goes survival and death, and the RIP3 determines the pathway of cell death apoptosis or necrosis. This paper summarizes the knowledge about the necroptosis signal pathways and explores its significance in the organ ischemic injury, inflammation and tumor pathogenesis briefly.
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