Ribonuclease attenuates hepatic ischemia reperfusion induced cognitive impairment through the inhibition of inflammatory cytokines in aged mice

Ma, Gang; Chen, Chan; Jiang, Haixia; Qiu, Yanhua; Li, Yansong; Li, Xiao-Qiang; Zhang, Xiyang; Liu, Jin; Zhu, Tao

doi:10.1016/j.biopha.2017.02.094

Cited by 35 publications

(27 citation statements)

References 31 publications

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“…An excess of exRNA is released in hypoxic conditions, and hRNase1 administration was reported to provide cardiac protection in a mouse model ( 76 ). Administration of the protein in vivo reduces the release of pro-inflammatory cytokines and provides a multiple-organ protection in mice ( 29 ).…”

Section: The Rnase a Superfamilymentioning

confidence: 99%

“…Selective cytotoxicity can be mediated by the activation of autophagy or apoptotic pathways ( 72 , 75 ). To facilitate subsequent tissue remodeling, the RNases also function as cytokines and chemokines, displaying anti-inflammatory activities and inducing chemoattraction of innate cells, such as macrophages or DCs ( 29 , 46 – 48 ). Other complementary activities have been reported such as binding to nucleic acids, activation of TLR receptors and removal of exRNA ( 54 , 55 , 76 ).…”

Section: Role In Health and Diseasementioning

confidence: 99%

“…Furthermore, successful results achieved using experimental animal models promise therapeutic applications in the near future. Removal of circulating exRNA shows beneficial anti-inflammatory properties following tissue damage ( 17 , 29 , 76 ). In particular, removal of blood exRNA can protect cardiac tissue in hypoxic conditions ( 29 , 76 ).…”

Section: Role In Health and Diseasementioning

confidence: 99%

“…Removal of circulating exRNA shows beneficial anti-inflammatory properties following tissue damage ( 17 , 29 , 76 ). In particular, removal of blood exRNA can protect cardiac tissue in hypoxic conditions ( 29 , 76 ). Treatment with hRNase1 has been observed to reduce deposits of exRNA and inflammation in a mouse model of atherosclerosis ( 78 ).…”

Section: Role In Health and Diseasementioning

confidence: 99%

“…Hopefully, knowledge on RNases action and trafficking in biological fluids will give path to translational research from academia to pharmaceutical industry. Indeed, recent experimental trials with animal models, such as those on hematopoiesis regulation by human RNase5 ( 28 ) or attenuation of extracellular RNA (exRNA) pro-inflammatory activity by RNaseA ( 29 ), are already offering promising therapeutic results.…”

Section: Introductionmentioning

confidence: 99%

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Immune Modulation by Human Secreted RNases at the Extracellular Space

et al. 2018

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The ribonuclease A superfamily is a vertebrate-specific family of proteins that encompasses eight functional members in humans. The proteins are secreted by diverse innate immune cells, from blood cells to epithelial cells and their levels in our body fluids correlate with infection and inflammation processes. Recent studies ascribe a prominent role to secretory RNases in the extracellular space. Extracellular RNases endowed with immuno-modulatory and antimicrobial properties can participate in a wide variety of host defense tasks, from performing cellular housekeeping to maintaining body fluid sterility. Their expression and secretion are induced in response to a variety of injury stimuli. The secreted proteins can target damaged cells and facilitate their removal from the focus of infection or inflammation. Following tissue damage, RNases can participate in clearing RNA from cellular debris or work as signaling molecules to regulate the host response and contribute to tissue remodeling and repair. We provide here an overall perspective on the current knowledge of human RNases’ biological properties and their role in health and disease. The review also includes a brief description of other vertebrate family members and unrelated extracellular RNases that share common mechanisms of action. A better knowledge of RNase mechanism of actions and an understanding of their physiological roles should facilitate the development of novel therapeutics.

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Section: The Rnase a Superfamilymentioning

confidence: 99%

Section: Role In Health and Diseasementioning

confidence: 99%

Section: Role In Health and Diseasementioning

confidence: 99%

Section: Role In Health and Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune Modulation by Human Secreted RNases at the Extracellular Space

et al. 2018

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Responsive Multi‐Arm PEG‐Modified COF Nanocomposites: Dynamic Photothermal, pH/ROS Dual‐Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment

Ge,

Wang,

Zhao

et al. 2024

Adv Healthcare Materials

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Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast‐like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi‐armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF‐κB p65 protein, and Western blotting confirm its inhibitory effect on NF‐κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant‐induced arthritis (AIA) rats after treatment with RNase A delivered by multi‐armed PEG‐modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.

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Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

Anderberg,

Andersson,

Bucher

et al. 2024

J of Neuroscience Research

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There is a need for new treatments to reduce brain injuries derived from neonatal hypoxia/ischemia. The only viable option used in the clinic today in infants born at term is therapeutic hypothermia, which has a limited efficacy. Treatments with exogenous RNase have shown great promise in a range of different adult animal models including stroke, ischemia/reperfusion injury, or experimental heart transplantation, often by conferring vascular protective and anti‐inflammatory effects. However, any neuroprotective function of RNase treatment in the neonate remains unknown. Using a well‐established model of neonatal hypoxic/ischemic brain injury, we evaluated the influence of RNase treatment on RNase activity, gray and white matter tissue loss, blood–brain barrier function, as well as levels and expression of inflammatory cytokines in the brain up to 6 h after the injury using multiplex immunoassay and RT‐PCR. Intraperitoneal treatment with RNase increased RNase activity in both plasma and cerebropinal fluids. The RNase treatment resulted in a reduction of brain tissue loss but did not affect the blood–brain barrier function and had only a minor modulatory effect on the inflammatory response. It is concluded that RNase treatment may be promising as a neuroprotective regimen, whereas the mechanistic effects of this treatment appear to be different in the neonate compared to the adult and need further investigation.

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Ribonuclease attenuates hepatic ischemia reperfusion induced cognitive impairment through the inhibition of inflammatory cytokines in aged mice

Cited by 35 publications

References 31 publications

Immune Modulation by Human Secreted RNases at the Extracellular Space

Immune Modulation by Human Secreted RNases at the Extracellular Space

Responsive Multi‐Arm PEG‐Modified COF Nanocomposites: Dynamic Photothermal, pH/ROS Dual‐Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

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