Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway.

Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo.

Contralateral C7 Nerve Root Transfer for Function Recovery in Adults: A Meta-analysis.

BACKGROUND: Root avulsion to all 5 roots of the brachial plexus is a common presentation and keeps a major reconstructive challenge. The contralateral C7 (CC7) nerve transfer has been used in treating brachial plexus avulsion injury (BPAI) since 1986. However, the effectiveness of the procedure remains a subject of controversy. The aim of this meta-analysis was to study surgical outcomes regarding motor and sensory recovery after CC7 nerve transfer. METHODS: Chinese or English (i.e., "contralateral c-7", "contralateral c7", "c7 nerve root", and "seventh cervical nerve root") keywords were used for a literature search for articles related to CC7 nerve transfer in several databases (i.e., PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang Data). Clinical research articles were screened, and animal studies as well as duplicate publications were excluded. Muscle strength and sensory recovery were considered to be effective only when the scores on the United Kingdom Medical Research Council scale were equal to or higher than M3 and S3, respectively. RESULTS: The overall ipsilateral recipient nerve recovery rates were as follows: the efficiency rate for muscle strength recovery after CC7 nerve transfer was 0.57 (95% confidence interval [CI]: 0.48-0.66) and for sensory recovery was 0.52 (95% CI: 0.46-0.58). When the recipient nerve was the median nerve, the efficiency rate for muscle strength recovery was 0.50 (95% CI: 0.39-0.61) and for sensory was 0.56 (95% CI: 0.50-0.63). When the recipient nerve was the musculocutaneous nerve and the radial nerve, the efficiency rate for muscle strength recovery was 0.74 (95% CI: 0.65-0.82) and 0.50 (95% CI: 0.31-0.70), respectively. CONCLUSIONS: Transfer of CC7 nerves to musculocutaneous nerves leads to the best results. CC7 is a reliable donor nerve, which can be safely used for upper limb function reconstruction, especially for entirely BPAI. When modifying procedures, musculocutaneous nerves and median nerve can be combined as recipient nerves.

An Analysis of Paravertebral Ossification in Cervical Artificial Disc Replacement: A Novel Classification Based on Computed Tomography.

OBJECTIVE: Cervical artificial disc replacement (CADR) is a new technology in cervical spine surgery. However, CADR may result in paravertebral ossification (PO) after surgery and affect the mobility of the related spinal segments. The present widely used assessment method based on X-ray tomography cannot provide the position information of PO, and also PO detection rates by X-ray are low. The incidence of PO varies dramatically between studies. This study built a novel classification system based on cervical computer tomography (CT) scan to re-evaluate the incidence of PO and its influence on CADR, and also analyzed the predisposing factors of PO. METHODS: In this retrospective study, 71 patients (from January 2004 to December 2009) who received cervical artificial disc replacement in our hospital were enrolled, and 82 cervical segments were replaced by Bryan discs. The range of motion (ROM) of the related cervical segments and scores of neurological symptoms (neck disability index [NDI] and Japanese Orthopaedic Association [JOA] scores) for both pre-surgery and last follow-up were acquired, respectively. After the establishment of a novel grading system for PO based on CT scan, we analyzed the CT images acquired before surgery and at the last time follow-up. Occurrence and distribution of PO at both time points were calculated. ROM between pre-surgery and post-surgery was compared by paired t-test stratified by PO stages. One-way ANOVA was used to compare NDI and JOA scores between high-grade and low-grade PO groups after surgery. The χ2 -test was used to evaluate the risk (odds ratio) of predisposing factors in developing high-grade PO after surgery. RESULTS: The CT-based classification system has good inter-observer and intra-observer reliability. The detection rate of PO by CT scan is higher than for traditional X-ray examination. The incidence of low-grade PO in all 82 segments at last follow-up is 32.9%. The occurrences of high-grade PO at preoperational and last follow-up time are 15.9% and 67.1%, respectively. The high-grade PO is mainly distributed around the uncovertebral joint. The pre-surgery and post-surgery ROM are similar in patients with low-grade PO at last follow-up time (9.80° ± 3.65° vs 10.03° ± 3.73°, P = 0.801); however, in patients with high-grade PO the post-surgery ROM decreases significantly compared to the pre-surgery ROM (9.73° ± 4.03° vs 6.63° ± 4.21°, P < 0.001). There is no statistical difference for JOA and NDI scores after surgery between high-grade and low-grade PO patients at final follow-up (P = 0.264, P = 0.703). The χ2 -test indicates that patients with preoperational existence of PO have a high risk of high-grade PO after surgery (OR = 4, P = 0.012). CONCLUSIONS: The novel CT image-based PO classification system has good intra-observer reliability. The incidence of PO after Bryan cervical disk replacement is relative high, and the high-grade PO is mainly distributed at the uncovertebral joint. The high-grade PO will affect the ROM after surgery; however, it does not affect the neurologic symptoms.