scholarly journals Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hua Tao ◽  
Jianghao Zhao ◽  
Tingting Liu ◽  
Yujie Cai ◽  
Xu Zhou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Target ◽  
Hippocampal Damage ◽  
Intranasal Delivery ◽  
Seizure Onset ◽  
Time Points ◽  
Novel Treatments ◽  
Anti Inflammatory ◽  
Pilocarpine Injection

Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments.

scholarly journals Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors

2012 ◽  
Vol 8 (4) ◽  
pp. 693-704 ◽  
Author(s):  
Fernanda da Rocha Lapa ◽  
Morgana Duarte da Silva ◽  
Daniela de Almeida Cabrini ◽  
Adair R. S. Santos
Keyword(s):  
Mouse Model ◽  
Anti Inflammatory ◽  
A2 Receptors

scholarly journals Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Bruno Alexandre Quadros Gomes ◽  
João Paulo Bastos Silva ◽  
Camila Fernanda Rodrigues Romeiro ◽  
Sávio Monteiro dos Santos ◽  
Caroline Azulay Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Hippocampal Damage ◽  
Neuroprotective Effects ◽  
Amyloid A ◽  
Silent Information Regulator 1 ◽  
Anti Inflammatory

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence ofβ-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβpeptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβpeptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

Abstract 590: Loss of Myeloid Cell Prostaglandin E Receptor 4 Does Not Alter Diabetes-Accelerated Atherosclerosis in a Murine Model of Type 1 Diabetes

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Sara N Vallerie ◽  
Farah Kramer ◽  
Jenny E Kanter ◽  
Shelley Barnhart ◽  
Richard M Breyer ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mouse Model ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Prostaglandin E ◽  
Lesion Area ◽  
Accelerated Atherosclerosis ◽  
Anti Inflammatory

Diabetes is associated with an increased risk of cardiovascular disease, largely due to increased atherosclerosis. Our studies have suggested myeloid cell prostaglandin E 2 (PGE 2 ) production as a possible mediator of diabetes-accelerated atherosclerosis in a virally-induced mouse model of type 1 diabetes. Prostaglandin E Receptor 4 (EP4; Ptger4 ) is a major PGE 2 receptor in myeloid cells. We hypothesized that generation of a mouse model of myeloid cell-targeted EP4-deficiency would allow us to test the role of myeloid EP4 in diabetes-accelerated atherosclerosis. Thus, we generated a Ptger4 flox/flox LysM-Cre tg/tg mouse model. Peritoneal macrophages isolated from these myeloid cell EP4-deficient (EP4 M-/- ) mice expressed <90% Ptger4 mRNA compared to LysM-Cre tg/tg controls (n=10; p<0.0001). To analyze the role of myeloid cell EP4 in diabetes-accelerated atherosclerosis, we transplanted bone marrow from EP4 M-/- mice and littermate controls into lethally irradiated Ldlr -/- RIP-LCMV mice (the model of type 1 diabetes) and, after 7 weeks of recovery, induced diabetes by viral infection and fed the mice a low-fat semi-purified diet for an additional 12 weeks. Diabetic EP4 M-/- mice had similar blood glucose (568 ± 15 vs. 569 ± 15 mg/dl), blood cholesterol (531 ± 29 vs. 510 ± 37 mg/dl), and plasma triglycerides (249 ± 49 vs. 247 ± 44 mg/dl) as diabetic controls (n=15 all groups; mean ± SEM). At the endpoint, aortas were harvested for lesion area quantification. Diabetic EP4 M-/- and diabetic wild type mice had similar lesion area (1.9% ± 0.2 vs. 1.7% ± 0.2), which were both increased (p < 0.01; n=9-15) as compared to their non-diabetic controls. Additionally, we analyzed the role of EP4 in inflammatory activation of myeloid cells ex vivo. EP4-deficiency had no significant effect on basal or lipopolysaccharide (LPS)-induced inflammatory gene expression in the absence of PGE 2 . Pretreatment of the cells with PGE 2 (10 nM) followed by LPS stimulation resulted in a significant reduction of Tnfa and Il6 mRNA compared to LPS alone, and this anti-inflammatory effect of PGE 2 was completely blocked in EP4-deficient cells. These results suggest that myeloid cell EP4 mediates anti-inflammatory actions of PGE 2 but that it is not involved in diabetes-accelerated atherosclerosis.

scholarly journals Anti-inflammatory Role of Mesenchymal Stem Cells in an Acute Lung Injury Mouse Model

2018 ◽  
Vol 33 (3) ◽  
pp. 154-161 ◽  
Author(s):  
Jin Won Huh ◽  
Won Young Kim ◽  
Yun Young Park ◽  
Chae-Man Lim ◽  
Younsuck Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Anti Inflammatory

scholarly journals ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL-2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaohui Pan ◽  
Jingxue Tan ◽  
Xiaokun Weng ◽  
Rui Du ◽  
Yuqing Jiang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bone Tumor ◽  
Molecular Target ◽  
Osteosarcoma Cell ◽  
Malignant Bone Tumor ◽  
Novel Treatments ◽  
Mitochondrial Ribosomes ◽  
And Function ◽  
Insight Into

Osteosarcoma (OS) is a familiar malignant bone tumor that occurs mainly in adolescents. Immature colon carcinoma transcript-1 (ICT1) is an important member of the large mitoribosomal subunit in mitochondrial ribosomes, which has been shown to be closely related to tumorigenesis. Its expression and function in OS, however, remained unclear. Here, we showed that ICT1 was significantly upregulated in OS and promoted the growth of OS cells. Mechanistically, ICT1 acted as an oncogene in OS and promoted proliferation and inhibited apoptosis of OS cells through the STAT3/BCL-2 axis. These results reveal a novel insight into the role of the ICT1/STAT3/BCL-2 axis in OS and therefore may represent a novel molecular target for novel treatments.

scholarly journals Protective Role of the Cholinergic Anti-Inflammatory Pathway in a Mouse Model of Viral Myocarditis

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112719 ◽  
Author(s):  
Zheng Cheng ◽  
Ge Li-Sha ◽  
Zhao Jing-Lin ◽  
Zhang Wen-Wu ◽  
Chen Xue-Si ◽  
...  
Keyword(s):  
Mouse Model ◽  
Viral Myocarditis ◽  
Protective Role ◽  
Inflammatory Pathway ◽  
Anti Inflammatory
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