MicroRNA-9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome.

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.

Multimodal Rehabilitation Program Promotes Motor Function Recovery of Rats After Ischemic Stroke by Upregulating Expressions of GAP-43, SYN, HSP70, and C-MYC.

BACKGROUND: Despite the intense efforts devoted to preventing and treating cerebral ischemia, some individuals will continue to have completed infarctions. Failure of prevention or intervention does not, however, preclude therapeutic approaches to enhance recovery. Our study aims to explore the effect of multimodal rehabilitation program on the motor function recovery of rats with ischemic stroke. METHODS: Rat models of ischemic stroke were established using clean-grade adult male Sprague-Dawley rats. Motor function of rats was scored by the Bederson neurological function, balance beam test, and screen test. Nissl staining was conducted for morphological and structural changes of nerve cells in the arteriae cerebri anterior zone. Immunohistochemistry was applied to detect the expressions of growth-associated protein (GAP-43), synaptophysin (SYN) and Caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was carried out in the corpus striatum 21 days after operation; reverse transcription quantitative polymerase chain reaction and Western blot analysis were conducted for testing messager RNA (mRNA) and protein expressions of heat shock protein 70 (Hsp70) and MYC proto-oncogene (c-Myc). RESULTS: Rats receiving multimodal rehabilitation program had lower Bederson neurological function, balance beam, and screen test scores on the 7th, 14th and 21st days after operation; more number of neurons surviving in the arteriae cerebri anterior zone at each time point after operation, higher GAP-43 expression on the 7th and 14th days after operation, and higher SYN expression on the 14th and 21st days after operation, on the 7th, 14th and 21st days after operation, higher mRNA and protein expressions of HSP70 and C-MYC, lower Caspase-3 positive expression and TUNEL positive stained cells. CONCLUSIONS: Multimodal rehabilitation program could promote motor function recovery of rats after ischemic stroke by upregulating GAP-43 and SYN expressions at arteriae cerebri anterior zone and upregulating HSP70 and C-MYC expressions in the brain tissues.

Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice.

BACKGROUND: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. METHODS: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 µl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. RESULTS: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1ß and TNF-α. In addition, NLRP3, Caspase-1 and IL-1ß, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. CONCLUSIONS: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.