Tumor necrosis factor α modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation pathway.

The dorsal horn (DH) of the spinal cord is the integrative center that processes and transmits pain sensation. Abnormal changes in ion channel expression can enhance the excitability of pain-related DH neurons. Sodium-activated potassium (KNa) channels are highly expressed particularly in the central nervous system; however, information about whether rat DH neurons express the SLICK channel protein is lacking, and the direct effects on SLICK in response to inflammation and the potential signaling pathway mediating such effects are yet to be elucidated. Here, using cultured DH neurons, we have shown that tumor necrosis factor-α inhibits the total outward potassium current IK and the KNa current predominantly as well as induces a progressive loss of firing accommodation. However, we found that this change in channel activity is offset by the p38 inhibitor SB202190, thereby suggesting the modulation of SLICK channel activity via the p38 MAPK pathway. Furthermore, we have demonstrated that the tumor necrosis factor-α modulation of KNa channels does not occur at the level of SLICK channel gating but arises from possible posttranslational modification.

Evaluation of transforaminal endoscopic lumbar discectomy in the treatment of lumbar disc herniation.

PURPOSE: The purpose of this study was to evaluate the efficacy of transforaminal endoscopic lumbar discectomy (TELD) in the treatment of lumbar disc herniation (LDH) and to identify the relationship between TELD efficacy and age. METHODS: A total of 207 consecutive LDH patients who had undergone TELD with the THESSYS system from January 2013 to September 2014 were divided into two groups on the basis of their age, with 108 cases in the ≤ 45-year-old age group and 99 cases in the >45-year-old group. The Oswestry Disability Index (ODI) was used to quantify the pain relief. The degree of pain and disability were measured on the basis of the visual analog scale (VAS) and the modified MacNab criteria. Complications, duration of hospital stay, surgical costs, and operation time were recorded and compared between the two groups. Spearman's coefficient of rank correlation was used to assess the learning curves for TELD. RESULTS: The mean pre-operative and postoperative VAS and ODI scores significantly improved in both age ≤ 45 group and age >45 group, with no significant differences between them. In age ≤45 group, 56 % had excellent outcomes, 28 % good, 14 % fair, and 3 % poor. In the age >45 group, 51 % had excellent outcomes, 20 % good, 25 % fair, and 4 % poor. The average lengths of hospital stay for the age ≤ 45 group and age >45 group were 6.8 and 8.4 days, respectively. The mean time to return to work or normal activities was ten days for the age ≤ 45 group and 15 days for the age >45 group. The mean operative time for the age ≤ 45 group was 94 minutes and that for age >45 group was 97 minutes. The surgical cost of age ≤ 45 group was 15,480 RMB, which was lower than the 16,381 RMB of age >45 group. A total of 14 patients in the age ≤ 45 group and 13 patients in age >45 group used analgesic medications. Three and five recurrences were reported in the age ≤ 45 group and age >45, respectively. The steep learning curves of operative time plotted against the number of surgeries conducted suggest that the TELD technique can be mastered quickly in terms of reducing the duration of operation. CONCLUSIONS: The efficacy of TELD is relatively good for the selected young and elderly patients in this study. Therefore, age is not a predictor of TELD surgery-related outcomes.

In vivo and in vitro expression of the RASAL1 gene in human gastric adenocarcinoma and its clinicopathological significance.

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) is a potential tumor suppressor, which is found to be reduced in certain human cancers. Its downregulation is involved in the progression of malignancies. However, whether or not RASAL1 plays a role in the development of gastric cancer remains to be determined. Our study aimed to clarify the role of RASAL1 in the progression of gastric adenocarcinoma. The expression of RASAL1 in primary gastric adenocarcinoma tissue specimens was determined by immunohistochemistry. The expression of RASAL1 mRNA and protein was detected by RT-PCR and western blotting in gastric adenocarcinoma cell lines with varying differentiation statuses, including well-differentiated MKN-28, moderately differentiated SGC-7901 and poorly differentiated BGC-823, respectively. A normal gastric epithelial cell line, GES-l, was used as the control line. The immunohistochemical results revealed that the expression of the RASAL1 protein was mainly observed in the cytoplasm. Among 50 cases of gastric adenocarcinoma tissues, 12 cases were identified as (-), 23 cases (+), 13 cases (++) and 2 cases (+++). Among 50 cases of normal gastric tissues, 16 cases were (++) and 34 cases (+++). The expression of the RASAL1 protein was found to be decreased in the gastric adenocarcinoma tissue compared with normal gastric tissue (p<0.01). Moreover, in the gastric carcinoma tissues, the expression of RASAL1 was correlated with carcinoma diameter, differentiation grades, invasive depth, lymph node metastasis and TNM. Additionally, the RASAL1 mRNA and proteins were decreased in the three gastric adenocarcinoma cell lines compared with the normal gastric epithelial cell line GES-l. In addition, the downregulation of RASAL1 correlated with the differentiation status of cancer cell lines. Based on the above investigation, we conclude that expression of the RASAL1 gene is decreased in gastric carcinoma tissues and cell lines. The results indicate that RASAL1 may be important in the tumorigenesis and development of gastric carcinoma.