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E. M. Peterman C. Sullivan M. F. Goody I. Rodriguez-Nunez J. A. Yoder C. H. Kim 《Infection and immunity》2015,83(1):430-440
Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections. 相似文献
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Maxime Lafond Shin Yoshizawa Shin‐ichiro Umemura 《Journal of ultrasound in medicine》2019,38(3):567-580
Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them. 相似文献
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Sarah E. Sheppard Laura Elizabeth Anderson Cathryn Sibbald Colleen Cotton Elizabeth Bhoj Marissa J. Perman Leslie Castelo‐Soccio 《Pediatric dermatology》2019,36(6):1007-1009
Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease. 相似文献
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Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.