The HO-1-expressing bone mesenchymal stem cells protects intestine from ischemia and reperfusion injury.

BACKGROUND: Bone mesenchymal stromal cells (BMSC) showed protective potential against intestinal ischemia. Oxygenase-1(HO-1) could alleviate oxidative stress. In the present study, we constructed HO-1-expressing BMSC and detected the effects of it on survival, intestinal injury and inflammation following intestinal ischemia and reperfusion injury (I/R). METHODS: In this experiment, eighty adult male mice were divided into Sham, I/R, I/R + BMSC, I/R + BMSC/HO-1 groups. Mice were anesthetized and intestinal I/R model were established by temporarily occluding the superior mesenteric artery for 60 min with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed for reperfusion. Prior to abdominal closure, BMSC/ HO-1 (2 × 106 cells) or BMSC (2 × 106 cells) were injected into the peritoneum of I/R mice respectively. Mice were allowed to recover for 24 h and then survival rate, intestinal injury and inflammation were determined. Reactive oxygen species (ROS) was assayed by fluorescent probe. TNFα and IL-6 were assayed by ELISA. RESULTS: BMSC/HO-1 increased seven day survival rate, improved intestinal injury and down-regulated inflammation after intestinal I/R when compared with sole BMSC (p < 0.05 respectively). Multiple pro-inflammatory media were also decreased following application of BMSC/HO-1, when compared with sole BMSC (p < 0.05) respectively, suggesting that BMSC /HO-1 had a better protection to intestinal I/R than BMSC therapy. CONCLUSION: Administration of BMSC/HO-1 following intestinal I/R, significantly improved intestinal I/R by limiting intestinal damage and inflammation.

SP1, MYC, CTNNB1, CREB1, JUN genes as potential therapy targets for neuropathic pain of brain.

Neuropathic pain (NP) may cause serious brain diseases, but the genes associated with the metabolic pathway and transcript factors of NP remain unclear. This study is aimed to identify the therapy target genes for NP and to investigate the metabolic pathways and transcript factors associated with NP. The differentially expressed genes of three brain tissues (nucleus accumbens, periaqueductal gray, and prefrontal cortex) dealt with NP stimulation were analyzed. Besides, The Database for Annotation, Visualization, and Integrated Discovery and Tfacts datasets were used in the analysis of the genes related to the metabolic pathway and transcript factors of the brain. Eight genes were found to coexpress in all three tissues. A functional enrichment analysis showed that the upregulated genes were mostly enriched in pathways as inflammatory response, calcium-mediated signaling, cytokine-cytokine receptor interaction, and extracellular matrix (ECM)-receptor interaction, whereas the downregulated genes were mostly enriched in pathways as phospholipid metabolic processes, positive regulation of protein kinase B signaling, and metabolism of xenobiotics by cytochrome P450. Finally, 135 and 98 transcript factors genes were upregulated and downregulated, among which SP1, MYC, CTNNB1, CREB1, JUN were identified as the most critical genes because the number of up- and downregulated gene ranked at the top. In conclusion, the pathways of immune response and cytokine-cytokine receptor interaction were determined as the main metabolic pathways of NP affecting the brain, and SP1, MYC, CTNNB1, CREB1, JUN genes were recognized as the most enriched genes in this process, which may provide evidence for the diagnosis and treatment research of neuropathic pain.

XIST accelerates neuropathic pain progression through regulation of miR-150 and ZEB1 in CCI rat models.

LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX-2, tumor necrosis factor (TNF)-α and IL-6 and in CCI rats. Previously, miR-150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR-150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR-150 and XIST. miR-150 was remarkably decreased in CCI rats and overexpression of miR-150 can significantly suppress neuroinflammation-related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR-150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR-150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR-150. It was revealed that XIST/miR-150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.

Inhibition of miR-200b/miR-429 contributes to neuropathic pain development through targeting zinc finger E box binding protein-1.

Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR-200b and miR-429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR-200b and miR-429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR-200b and miR-429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR-200b and miR-429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL-6, IL-1ß, and TNF-α in CCI rats. By carry out bioinformatics technology, Zinc finger E box binding protein-1 (ZEB1) was predicted as target of miR-200b, and miR-429 and dual-luciferase reporter assays confirmed the correlation between them. ZEB1 has been reported to regulate a lot of diseases. Here, we found that ZEB1 was greatly increased in CCI rats and miR-200b and miR-429 overexpression markedly suppressed ZEB1 mRNA expression in rat microglial cells. In addition, knockdown of ZEB1 can reduce neuropathic pain development and co-transfection of LV-anti-miR-200b/miR-429 reversed this phenomenon in vivo. Taken these together, our results suggested that miR-200b/miR-429 can serve as an important regulator of neuropathic pain development by targeting ZEB1.

[Expression characteristics of the Ccdc70 gene in the mouse testis during spermatogenesis].

OBJECTIVE: To investigate the expression characteristics of the gene of coiled-coil domain-containing protein 70 (Ccdc70) in the mouse testis and its potential role in spermatogenesis. METHODS: Using expression profile microarray, we screened the mouse testis-specific gene Ccdc70, studied its expression characteristics in the mouse testis by RT-PCR, real-time PCR, Western blot and immunohistochemistry, followed by bioinformatic analysis of the Ccdc70 protein. RESULTS: The Ccdc70 gene was expressed highly in the testis but lowly in the epididymis of the mice. The Ccdc70 protein was expressed mainly in the spermatocytes and round spermatids of the testis and in the epithelial cells of the epididymis. Bioinformatic analysis showed a structural domain in the Ccdc70 protein, which was highly conserved in mammalian evolution. CONCLUSION: The Ccdc70 gene is highly expressed in the mouse testis and mainly in the spermatocytes, round spermatids, and epididymal epithelial cells, which indicates that it is involved in the regulation of spermatogenesis and epididymal sperm maturation.

Long-Term Effectiveness of Total Hip Replacement with the Collum Femoris Preserving Prosthesis.

The objective of this study was to follow-up long term (5-12 years) patients with total hip arthroplasty with the collum femoris preserving prosthesis to evaluate clinical outcome and potential complications. Forty-six of 152 patients who underwent this procedure between September 2000 and September 2012 were followed up. The average follow-up time was 7.6 years, and assessed were radiographs, Harris score, limb length, hip function, and complications. Six patients had perioperative complications including five cases of femoral shaft fracture and one case of dislocation 1 week after the operation. No infections of the surgical site, no deep venous thrombosis or pulmonary embolism were observed. The last recorded Harris hip score improved from a preoperative average of 41.2 (range 17-60) to an average of 82.3 (74-96), with the score >80 in 38 patients, 70-80 in six patients, and <70 in two patients. Radiolucent lines were found on radiographs in two patients with acetabular prosthesis and one patient with femoral prosthesis. The remainder of patients had satisfactory positions of acetabular and femoral stem prostheses with no loosening or subsidence, and a good condition of femoral neck. Total hip arthroplasty with the collum femoris preserving prosthesis is a good option for younger patients who need prosthesis revision. This arthroplasty achieves satisfactory long-term effectiveness.