miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3.

BACKGROUND: MicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied. METHODS: We collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3'-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed. RESULTS: The results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3. CONCLUSIONS: Therefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.

Role of the HIF­1α/SDF­1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury.

The hypoxic state of the brain tissue surrounding craniocerebral injury induces an increase in the secretion of HIF­1α during the healing process. HIF­1α can promote mesenchymal stem cell (MSC) migration to ischemic and hypoxic sites by regulating the expression levels of molecules such as stromal cell­derived factor­1 (SDF­1) in the microenvironment. Stem cells express the SDF­1 receptor C­X­C chemokine receptor type 4 (CXCR4) and serve a key role in tissue repair, as well as a number of physiological and pathological processes. The present study aimed to determine the role of HIF­1α/SDF­1/CXCR4 signaling in the process of accelerated fracture healing during craniocerebral injury. Cultured MSCs underwent HIF­1α knockdown to elucidate its effect on the proliferative ability of MSCs, and the effect of SDF­1 in MSCs was investigated. It was also determined whether HIF­1α could promote osteogenesis via SDF­1/CXCR4 signaling and recruit MSCs. The results indicated that HIF­1α knockdown suppressed MSC proliferation in vitro, and SDF­1 promoted cell migration via binding to CXCR4. Furthermore, HIF­1α knockdown inhibited MSC migration via SDF­1/CXCR4 signaling. Considering the wide distribution and diversity of roles of SDF­1 and CXCR4, the present results may form a basis for the development of novel strategies for the treatment of craniocerebral injury.

Dextromethorphan provides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury.

Traumatic brain injury (TBI) is caused by primary and secondary injury mechanisms. TBI induces a certain amount of inflammatory responses and glutamate excitotoxicity that are believed to participate in the pathogenesis of secondary injury. The non­narcotic anti­tussive drug dextromethorphan (DM) has been reported to have a high safety profile in humans and its neuroprotective against a variety of disorders, including cerebral ischemia, epilepsy and acute brain injury. However, few studies have explored the underlying mechanisms of the neuroprotective effects of DM in animals in the setting of TBI. The aim of the present study was to investigate the neuroprotective effects of DM on TBI and to determine the underlying mechanisms. Rats were subjected to a controlled cortical impact (CCI) injury and randomly divided into three groups: Sham­operated, TBI and DM treatment groups. The DM treatment group was administered DM (30 mg/kg of body weight, intraperitoneally) immediately after injury. It was identified that DM treatment following TBI significantly reduced brain edema and neurological deficits, as well as increased neuronal survival. These effects correlated with a decrease of tumor necrosis factor α, interleukin­1ß (IL­1ß) and IL­6 protein expression and an increase of glutamate/aspartate transporter and glutamate transporter­1 in the cortex of the brain. These results provided in vivo evidence that DM exerts neuroprotective effects via reducing inflammation and excitotoxicity induced following TBI. The present study has shed light on the potential use of DM as a neuroprotective agent in the treatment of cerebral injuries.

Source apportionment of ambient total suspended particulates and coarse particulate matter in urban areas of Jiaozuo, China.

Approximately 750 total suspended particulates (TSPs) and coarse particulate matter (PM10) filter samples from six urban sites and a background site and >210 source samples were collected in Jiaozuo City during January 2002 to April 2003. They were analyzed for mass and abundances of 25 chemical components. Seven contributive sources were identified, and their contributions to ambient TSP/PM10 levels at the seven sites in three seasons (spring, summer, and winter days) and a "whole" year were estimated by a chemical mass balance (CMB) receptor model. The spatial TSP average was high in spring and winter days at a level of approximately 530 microg/m(3) and low in summer days at 456 microg/m(3); however, the spatial PMo0 average exhibited little variation at a level of approximately 325 microg/m(3), and PM10-to-TSP ratios ranged from 0.58 to 0.81, which suggested heavy particulate matter pollution existing in the urban areas. Apportionment results indicated that geological material was the largest contributor to ambient TSP/PM10 concentrations, followed by dust emissions from construction activities, coal combustion, secondary aerosols, vehicle movement, and other industrial sources. In addition, paved road dust and re-entrained dust were also apportioned to the seven source types and found soil, coal combustion, and construction dust to be the major contributors.