Inhibition of TLR4 Signalling-Induced Inflammation Attenuates Secondary Injury after Diffuse Axonal Injury in Rats

Increasing evidence suggests that secondary injury after diffuse axonal injury (DAI) damages more axons than the initial insult, but the underlying mechanisms of this phenomenon are not fully understood. Recent studies show that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and have been shown to be associated with brain damage. The purpose of this study was to investigate the role of the TLR4 signalling pathway in secondary axonal injury in the cortices of DAI rats. TLR4 was mainly localized in microglial cells and neurons, and the levels of TLR4 downstream signalling molecules, including TLR4, myeloid differentiation primary response gene 88, toll/IR-1-(TIR-) domain-containing adaptor protein inducing interferon-beta, interferon regulatory factor 3, interferon β, nuclear factor κB (NF-κB) p65, and phospho-NF-κB p65, significantly increased and peaked at 1 d after DAI. Inhibition of TLR4 by TAK-242 attenuated apoptosis, neuronal and axonal injury, and glial responses. The neuroprotective effects of TLR4 inhibition were associated with decreases in the levels of TLR4 downstream signalling molecules and inflammatory factors, including interleukin-1β, interleukin-6, and tumour necrosis factor-α. These results suggest that the TLR4 signalling pathway plays an important role in secondary injury and may be an important therapeutic target following DAI

Involvement of Toll Like Receptor 2 Signaling in Secondary Injury during Experimental Diffuse Axonal Injury in Rats

Treatment of diffuse axonal injury (DAI) remains challenging in clinical practice due to the unclear pathophysiological mechanism. Uncontrolled, excessive inflammation is one of the most recognized mechanisms that contribute to the secondary injury after DAI. Toll like receptor 2 (TLR2) is highlighted for the initiation of a vicious self-propagating inflammatory circle. However, the role and detailed mechanism of TLR2 in secondary injury is yet mostly unknown. In this study, we demonstrated the expression of TLR2 levels in cortex, corpus callosum, and internal capsule and the localization of TLR2 in neurons and glial cells in rat DAI models. Intracerebral knockdown of TLR2 significantly downregulated TLR2 expression, attenuated cortical apoptosis, lessened glial response, and reduced the secondary axonal and neuronal injury in the cortex by inhibiting phosphorylation of mitogen-activated protein kinases (MAPK) including Erk, JNK, and p38, translocation of NF-κB p65 from the cytoplasm to the nucleus, and decreasing levels of proinflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. On the contrary, administration of TLR2 agonist to DAI rats achieved an opposite effect. Collectively, we demonstrated that TLR2 was involved in mediating secondary injury after DAI by inducing inflammation via the MAPK and NF-κB pathways

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

Background/Aims: Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. Methods: RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. Results: LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. Conclusions: LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC

A Study on Spatial Distribution of Commercial Housing Prices in Xiangtan City

ArcGIS technology is used to study the spatial pattern of housing prices in Xiangtan City, and it is found that the spatial pattern of housing prices shows primary and secondary two-center rings. In Hedong Jianshe Road and near Hexi Jijianying, there are primary and secondary polar nuclei, respectively; the secondary housing price area is located near the east-west and south-north trunk road in the urban area; there are significant regional differences in housing price changes (fastest reduction of prices in the Hedong main center-southwest direction; slow reduction of prices in the main center-northwest, southeast direction; slowest reduction of prices in the main center-northeast direction). In Hexi sub-center, except slow reduction of prices in the Xiangjiang River direction, the prices decline rapidly in other directions. The housing prices exhibit an obvious overall decreasing trend from primary and secondary centers to the suburbs, but there are also exceptions. On this basis, this paper analyzes the driving factors for spatial pattern of housing prices in Xiangtan City, and finds that the spatial pattern of housing prices is mainly influenced by commercial centers, residential environmental conditions, traffic conditions, and urban land layout differences

Non-Farm Employment, Farmland Renting and Farming Ability: Evidence from China

In the process of China’s urbanization, non-farm employment and farmland rental activity are closely correlated. Using data from a survey on rural households in three Chinese provinces, this article examines the relationship between farmland renting activity and non-farm employment with simultaneous equations that consider the farming ability of farmers. Our results are fourfold. First, farmland renting-out promotes non-farm employment, while farmland renting-in reduces non-farm employment. Second, non-farm employment encourages farmland renting-out and decreases farmland renting-in. Third, farming ability increases farmland renting-in but decreases non-farm employment. Fourth, non-farm employment decreases the farming ability of farmers. Based on our empirical findings, we would suggest that the Chinese government further reforms its land system in rural areas, which could better facilitate land-use-right transfer and promote farmland rental market

Intraspinal primitive neuroectodermal tumors: Report of four cases and review of the literature

Intraspinal primitive neuroectodermal tumors (PNETs) are extremely rare and are aggressive with poor outcomes. Till date only 41 cases of intraspinal PNET have been reported. Here we report four new cases. Total excision of the tumor was done in three patients and partial excision in one patient. The unusual clinical features were vertebral metasis in one patient and short history of symptoms for four dasy. All had surgical excision, total excision in three patients and gross partial excision in one patient. Three patients were treated with craniospinal radiotherapy and chemotherapy. All the four patients are alive and asymptomatic at 6 to 25 months of followup

Effect of Coal Mining Subsidence on Soil Enzyme Activity in Mining Areas with High Underground Water Levels

In order to investigate the changes in soil enzyme activity and their influencing factors in coal mining subsidence areas with high underground water levels, in this study, we collected soil samples at different depths (SL: 0–20 cm; ML: 20–40 cm; DL: 40–60 cm) in a deep coal seam subsidence area (T1), a shallow coal seam subsidence area (T2), and control non-subsidence areas (W1 and W2) in eastern China. Soil physicochemical properties and enzyme activities were determined, and the mechanism of the latter’s response to coal mining subsidence was investigated based on correlation analysis, redundancy analysis, and structural equation modeling. The results show the following: (1) In the coal mining subsidence areas, the soil pH value (pH), soil available nitrogen (AN), available phosphorus (AP), available potassium (AK), and soil organic matter (SOM) contents were lower than those in the non-subsidence areas, while the soil water content (SWC) and bulk density (BD) were higher than those in the non-subsidence areas and increased with depth. (2) The activities of soil urease (URE), sucrase (SUC), alkaline phosphatase (ALP), and catalase (CAT) gradually decreased with depth and were all lower than those in the non-subsidence areas; the largest decreases with respect to the latter were 24.33%, 18.73%, 38.89%, and 5.88%, respectively. (3) The soil nutrient environment had a highly significant and direct positive effect on enzyme activity, with AN, AP, and SOM contents having the greatest impact. (4) Soil BD had a highly significant and direct negative effect and an indirect negative effect (by affecting nutrients) on enzyme activity. The results of this study on the effects of soil physicochemical properties on enzyme activity provide a basis for the ecological restoration of mines

Comparison of Outcomes between Early Fascial Closure and Delayed Abdominal Closure in Patients with Open Abdomen: A Systematic Review and Meta-Analysis

Up to the present, the optimal time to close an open abdomen remains controversial. This study was designed to evaluate whether early fascial abdominal closure had advantages over delayed approach for open abdomen populations. Medline, Embase, and Cochrane Library were searched until April 2013. Search terms included “open abdomen,” “abdominal compartment syndrome,” “laparostomy,” “celiotomy,” “abdominal closure,” “primary,” “delayed,” “permanent,” “fascial closure,” and “definitive closure.” Open abdomen was defined as “fail to close abdominal fascia after a laparotomy.” Mortality, complications, and length of stay were compared between early and delayed fascial closure. In total, 3125 patients were included for final analysis, and 1942 (62%) patients successfully achieved early fascial closure. Vacuum assisted fascial closure had no impact on pooled fascial closure rate. Compared with delayed abdominal closure, early fascial closure significantly reduced mortality (12.3% versus 24.8%, RR, 0.53, P<0.0001) and complication incidence (RR, 0.68, P<0.0001). The mean interval from open abdomen to definitive closure ranged from 2.2 to 14.6 days in early fascial closure groups, but from 32.5 to 300 days in delayed closure groups. This study confirmed clinical advantages of early fascial closure over delayed approach in treatment of patients with open abdomen