Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration

Aneurismal subarachnoid hemorrhage in a Chilean population, with emphasis on risk factors

<p>Abstract</p> <p>Background</p> <p>Subarachnoid Hemorrhage (SAH) is caused principally by the rupture of intracranial aneurisms. Important risk factors have been described such as age, sex, hypertension (HT) and season of the year, among others. The objective is to investigate the demographic characteristics and possible risk factors in a population of Chilean patients.</p> <p>Methods</p> <p>This retrospective study was based on the analysis of 244 clinical records of patients diagnosed with aneurismal SAH who were discharged from the Instituto de Neurocirugía ASENJO in Santiago, Chile.</p> <p>Results</p> <p>The mean age of patients was 49.85 years and the male:female ratio was 1:2.7. The signs and symptoms were not different between sexes; cephalea (85.7%) was predominant, followed by loss of consciousness, vomiting/nausea and meningeal signs. Risk factors included sex, age and HT. Concordant with other reports, the incidence of SAH was greatest in spring.</p> <p>Conclusions</p> <p>The demographic characteristics and risk factors observed in patients with aneurismal SAH treated in ASENJO were comparable to those of other populations. We were not able to conclude that tobacco and alcohol consumption were risk factors for this population.</p

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Effect of obesity on intraoperative bleeding volume in open gastrectomy with D2 lymph-node dissection for gastric cancer

<p>Abstract</p> <p>Background</p> <p>To investigate the effect of obesity on open gastrectomy with D2 lymph-node dissection.</p> <p>Methods</p> <p>Between January 2005 and March 2007, 100 patients with preoperatively diagnosed gastric cancer who underwent open gastrectomy with D2 lymph-node dissection were enrolled in this study. Of these, 61 patients underwent open distal gastrectomy (ODG) and 39 patients underwent open total gastrectomy (OTG). Patients were classified as having a high body-mass index (BMI; ≥ 25.0 kg/m²; <it>n </it>= 21) or a normal BMI (<25.0 kg/m²; <it>n </it>= 79). The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed as identifiers of obesity using FatScan software. Patients were classified as having a high VFA (≥ 100 cm²; <it>n </it>= 34) or a normal VFA (<100 cm²; <it>n </it>= 66). The relationship between obesity and short-term patient outcomes after open gastrectomy was evaluated. Patients were classified as having high intraoperative blood loss (IBL; ≥ 300 ml; <it>n </it>= 42) or low IBL (<300 ml; <it>n </it>= 58). Univariate and multivariate analyses were used to identify predictive factors for high IBL.</p> <p>Results</p> <p>Significantly increased IBL was seen in the following: patients with high BMI versus normal BMI; patients with gastric cancer in the upper third of the stomach versus gastric cancer in the middle or lower third of the stomach; patients who underwent OTG versus ODG; patients who underwent splenectomy versus no splenectomy; and patients with high VFA versus low VFA. BMI and VFA were significantly greater in the high IBL group than in the low IBL group. There was no significant difference in morbidity between the high IBL group and the low IBL group. Multivariate analysis revealed that patient age, OTG and high BMI or high VFA independently predicted high IBL.</p> <p>Conclusion</p> <p>It is necessary to perform operative manipulations with particular care in patients with high BMI or high VFA in order to reduce the IBL during D2 gastrectomy.</p

Human Neural Stem Cells Over-Expressing VEGF Provide Neuroprotection, Angiogenesis and Functional Recovery in Mouse Stroke Model

BACKGROUND: Intracerebral hemorrhage (ICH) is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF) results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2–3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke

Evaluation of CD46 re-targeted adenoviral vectors for clinical ovarian cancer intraperitoneal therapy

Ovarian cancer accounts for >140 000 deaths globally each year. Typically, disease is asymptomatic until an advanced, incurable stage. Although response to cytotoxic chemotherapy is frequently observed, resistance to conventional platinum-based therapies develop rapidly. Improved treatments are therefore urgently required. Virotherapy offers great potential for ovarian cancer, where the application of local, intraperitoneal delivery circumvents some of the limitations of intravenous strategies. To develop effective, adenovirus (Ad)-based platforms for ovarian cancer, we profiled the fluid and cellular components of patient ascites for factors known to influence adenoviral transduction. Levels of factor X (FX) and neutralizing antibodies (nAbs) in ascitic fluid were quantified and tumor cells were assessed for the expression of coxsackie virus and adenovirus receptor (CAR) and CD46. We show that clinical ascites contains significant levels of FX but consistently high CD46 expression. We therefore evaluated in vitro the relative transduction of epithelial ovarian cancers (EOCs) by Ad5 (via CAR) and Ad5 pseudotyped with the fiber of Ad35 (Ad5T*F35++) via CD46. Ad5T*F35++ achieved significantly increased transduction in comparison to Ad5 (P<0.001), independent of FX and nAb levels. We therefore propose selective transduction of CD46 over-expressing EOCs using re-targeted, Ad35-pseudotyped Ad vectors may represent a promising virotherapy for ovarian cance