Apaf1 inhibition promotes cell recovery From apoptosis

The protein apoptoUc protease activating factor I （Apafl） is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apafl, cells recover from doxorubicinor hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apafl not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.

Near-Dead Cells to Special Tetraploidy to First Cells to Cancer Diagnostic Morphology: Unlikely Therapy-Gain from For-Profit Industrial Goliath

The objective in this experimental article is to gain evidential proof of near-dead cells, (sick-cells in relapse tumor) responding with recovery growth from special 4n, multi-chromatid chromosomes. Note, near-dead normal human cells with such converted chromosome structure gave rise to proliferative, fitness-gained, diploid first cells, which further gave rise to three different cell shape changed, recovery growth patterns. Previously, two cell shape changes had been recovered from same type normal human cells, transiently exposed to amino acid glutamine deficient growth medium with recovery growths also associated with presence of the special 4n cells. The 4n cell-division had been concluded to be a meiotic-like two-step division system to the fitness-gained diploid cells in numerous experiments. The main characteristics of this division system, was firstly whole genomes without polar oriented bent centromeres moving apart followed by much rarer simple fission division to two or three diploid cells, selectable for first cell proliferation. In general these 4n cells showed metaphase type rosette figures moving apart not in the normal spindle associated mitotic shape with centromeres polar-pointing with sloping arms. This sequence of events induced by glutamine-deficiency, was earlier shown to cause DNA breakage in metabolic studies however, the near-death condition was only assumed from normal fibro-blastic cell-sheet shrinkage. This was rectified by an RNA virus (Coxakie-B3), which virology known is a highly cell killing virus (4+ CPE on their scale). This virus replicates only in replicating cells, which led to recovery growths with progressive phenotypic cell-shape changes (spindle, polygonal and roundness cells), each intervened by “total” cell destruction. These three different growth patterns had morphologies, indistinguishably from today’s cancer diagnostic morphologies. “Mitotic” analyses of beginning growths for the three phenotypes revealed the special rosette figure separations from special 4n and higher ploidy level cells, and also total absence of spindle type mitoses. Tumorigenesis-relevant was centromere-puffing with premature chromatid separation, and chromatin compaction, a mechanism, that was suggested to protect the genome from damage (text). We suggest that the multi-chromatid polyploid cells with their genome reductive division system, can be a tractable in vitro model system for therapy information, when repeated from a cell-killing agent, producing virus-free recovery growths. Will it be enacted upon? Not likely with profit-greedy industrial Goliath in the helm of cancer research. But, a not for profit cancer organization, could change this appalling situation.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

The promise of stem cell-based therapeutics in ophthalmology

The promising role of cellular therapies in the preservation and restoration of visual function has prompted intensive efforts to characterize embryonic, adult, and induced pluripotent stem cells for regenerative purposes. Three main approaches to the use of stem cells have been described： sustained drug delivery, immunomodulation, and differentiation into various ocular structures. Studies of the differentiation capacity of all three types of stem cells into epithelial, neural, glial and vascular phenotypes have reached proof-of-concept in culture, but the correction of vision is still in the early developmental stages, and the requirements for effective in vivo implementation are still unclear. We present an overview of some of the preclinical findings on stem-cell rescue and regeneration of the cornea and retina in acute injury and degenerative disorders.

Influence of patients' age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury

Objective To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells (OECs). Methods One hundred and seventy-one SCI patients were included in this study. Of them,139 were male and 32 were female,with age ranging from 2 to 64 years (mean,34.9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages,the patients were divided into 5 groups: ≤20 years group (n=9),21-30 years group (n=54),31-40 years group (n=60),41-50 years group (n=34) and>51 years group (n=14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2-8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis,and the data were expressed as mean±SD. Results After surgery,the motor scores increased by 5.2±4.8,8.6±8.0,8.3±8.8,5.7±7.3 and 8.2±7.6 in 5 age groups respectively ( F =1.009,P =0.404); light touch scores increased by 13.9±8.1,15.5±14.3,12.0±14.4,14.1±18.5 and 24.8±25.3 respectively ( F =1.837,P =0.124); and pin prick scores increased by 11.1±7.9,17.2±14.3,13.2±11.8,13.6±13.9 and 25.4±24.3 respectively ( F =2.651,P =0.035). Restoration of pin prick in >51 years group was better than other age groups except 21-30 years group. Conclusion OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.

The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent development in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.