Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.

Background Normal epithelial cells rapidly undergo apoptosis as soon as they lose contact with the extracellular matrix (ECM), which is termed as anoikis. However, cancer cells tend to develop a resistance mechanism to anoikis. This acquired ability is termed as anoikis resistance. Cancer cells, with anoikis resistance, can spread to distant tissues or organs via the peripheral circulatory system and cause cancer metastasis. Thus, inhibition of anoikis resistance blocks the metastatic ability of cancer cells. Methods Anoikis-resistant CAL27 (CAL27AR) cells were induced from CAL27 cells using the suspension culture approach. Transcriptome analysis was performed using RNA-Seq to study the differentially expressed genes (DEGs) between the CAL27ARcells and the parental CAL27 cells. Gene function annotation and Gene Ontology (GO) enrichment analysis were performed using DAVID database. Signaling pathways involved in DEGs were analyzed using Gene Set Enrichment Analysis (GSEA) software. Analysis results were confirmed by reverse transcription PCR (RT-PCR), western blotting, and gene correlation analysis based on the TCGA database. Results GO enrichment analysis indicated that the biological process (BP) of the DEGs was associated with epidermal development, DNA replication, and G1/S transition of the mitotic cell cycle. The analysis of cellular component (CC) showed that the most significant up-regulated genes were related to extracellular exosome. KEGG Pathway analysis revealed that 23 signaling pathways were activated (p-value ≤ 0.05, FDR q-value ≤ 0.05) and 22 signaling pathways were suppressed (p-value ≤ 0.05, FDR q-value ≤ 0.05). The results from the GSEA indicated that in contrast to the inhibition of EGFR signaling pathway, the VEGF signaling pathway was activated. The VEGF signaling pathway possibly activates STAT3 though induction of STAT3 phosphorylation. Gene correlation analysis revealed that the VEGFA- STAT3-KLF4-CDKN1A signal axis was not only present in head and neck squamous carcinoma (HNSCC) but also two other epithelial-derived carcinomas that highly express VEGFA, including kidney renal clear cell carcinoma (KIRC) and ovarian serous cystadenocarcinoma (OV).

Lung transplantation has become an established option in end-stage lung disease therapy. Some sequential double-lung transplantations require cardiopulmonary bypass (CPB) support during surgical procedure. However, conventional CPB increases the risks of bleeding and early allograft dysfunction. This report summarizes the perfusion techniques for replacing conventional CPB with extracorporeal membrane oxygenation (ECMO) during sequential double-lung transplantation procedure in our hospital. Between November 2002 and December 2006, nine cases of sequential double-lung transplantation were set up for ECMO during the surgical procedure. All patients suffered from end-stage lung disease. Eight patients were prepared for the procedure via transverse thoracostomy (clamshell) and cannulated through the ascending aorta and right atrium for ECMO before implantation of the second lung. The first patient who underwent bilateral thoracotomy for bilateral sequential lung transplantation required emergency ECMO via the femoral artery and vein during the second lung implantation. The Medtronic centrifugal pump and ECMO package were used for all of the cases. During ECMO, the blood flow was set at 1.8-2.0 L/m2/min; colloid oncotic pressure was maintained at more than 18 mm Hg, with albumin and hematocrit kept at 28% or more. There were two cases of early death in the group; the other cases were weaned from ECMO successfully. Extracorporeal membrane oxygenation duration was 1.83-67 hours, and postoperative intubation was 18-67 hours. As a successful technique of heart-lung support, ECMO can supply hemodynamic stabilization, reducing factors such as ischemia-reperfusion injury, anticoagulation requirement, and systemic inflammatory response for sequential double-lung transplantation.

Copper (Cu) ion is essential for the biological systems, however, high level of CuCl2 exposure causes detrimental effects, which leads to cell apoptosis. Nitric oxide (NO) is an efficient cell signal messenger, which plays an important role in cell apoptosis. However, the potential mechanism of an early phase Cu-induced acute cytotoxicity through the nitric oxide synthase (NOS) signaling pathway and its interaction has not been studied. In this report, we provide data showing that high level of CuCl2 could rapidly decrease the NO production with the release of Ca(2+) and Zn(2+), and then modulate the transcriptional and translational expression of NOSs in MCF-7 cells. The reactive oxygen species (ROS) level in cells was increased after high level of CuCl2 exposure, which led to the alpha subunit of eukaryotic initiation factor 2 phosphorylation. By using the free radical scavenger N-acetyl-L-cysteine or the NOS substrate L-arginine, it demonstrated that NOS played a critical role on the Cu-induced ROS generation, which further led to the oxidative stress and cell apoptosis. These results suggested that Cu-induced apoptosis was associated with the oxidative stress, and through the NOS-mediated signaling pathway.

Introduction: The superiority of pulsatile perfusion during cardiopulmonary bypass remains controversial. We analyzed the frequency-domain characteristics and organ protection of pulsatile and nonpulsatile flow in adult patients with valvular disease. Methods: EEP and SHE were used to calculate blood flow energy in 60 patients. The Fast Fourier Transform was employed to analyze the power spectral density and power density ratio (Rvpd) of flow energy. Changes in endothelin-1, nitric oxide, interleukin-6,10, tumor necrotic factor, S100β, NSE, blood and urinary β2-microglobulin levels were investigated to assess the endothelial function, inflammatory reaction, kidney and brain injury during CPB. Results: EEP and SHE in PP group at each time point were 1.52–1.62 times and 2.03–2.22 times higher respectively compared with NP group. Power spectral density analysis demonstrated that the blood flow energy frequencies in each group were all within 40 Hz and the low frequency energy (0–5 Hz) was dominant in physiological perfusion (>90%). The energy ratio of 0–5 Hz at radial artery was significantly decreased compared with that of post arterial filter in PP (81% vs 64%) and NP (63% vs 37%) group. The power density ratio (Rvpd) was higher than that of NP in all frequency ranges at the radial artery (9.51 vs 4.68 vs 3.59) and arterial filter (3.87 vs 2.69 vs 2.38). The S100β, NSE Urinary and plasma β2-microglobulin level were significantly increased at 6 and 24 hours after surgery in two group, and significantly higher in group NP. Conclusion: PP provided more energy than NP. The proportion of low frequency energy in the pulsatile or nonpulsatile flow is significantly reduced. The low-frequency energy is significantly attenuated during conduction to peripheral tissues in nonpulsatile flow. The surplus pulsatile energy influences the secretion of endothelial and inflammatory factors, and demonstrate better cerebral and kidney protective effect at the biological marker level.