High glucose induces the aging of mesenchymal stem cells via Akt/mTOR signaling.

It has previously been demonstrated that glucose is important in the process of stem cell aging. However, the mechanisms of cell senescence induced by high glucose (HG) remain to be elucidated. The preliminary study indicated that D­galactose induced mesenchymal stem cell (MSCs) aging. The present study demonstrated, following treatment with 11.0 or 22.0 mM HG for 14 days, that HG significantly promoted MSCs aging and the expression levels of phosphorylated (p-)phosphatidylinositol 3-kinase/protein kinase B (Akt) and p­mammalian target of rapamycin signaling (mTOR) in the HG groups were increased compared with the control group. However, following Akt inhibition with 1.0 or 10.0 nM MK­2206, which is an Akt­specific small molecule inhibitor, the senescence­cell value in the HG group was significantly decreased compared with the control group. These results indicated that HG induced MSCs senescence and this effect was primarily mediated via the Akt/mTOR signaling pathway.

Coenzyme Q10 inhibits the aging of mesenchymal stem cells induced by D-galactose through Akt/mTOR signaling.

Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

[Effects of ginsenosides Rb1 on learning and memory and expression of somatostatin in sleep deprivation rats].

OBJECTIVE: To determine the effects of ginsenosides Rb1(GSRb1) on learning and memory and expression of somatostatin (SS) in the hippocampus and the frontal cortex in rat model of sleep deprivation (SD). METHODS: Rats were randomized into groups of SD 2 d, SD 4 d, SD 6 d, and SD 0 d, while each group was sub-divided into GSRb1 group and normal saline (NS) sub-groups. Rats were intraperitoneal administered with 30 mg/(kg*d) of GSRb1 or NS for 7 d, then the learning and memory abilities were examined by measuring average swimming speed and mean escape latency using Morris maze.Expression of somatostatin was detected with immunohistochemical method and image analysis in the hippocampus and the frontal cortex. RESULTS: Compared with SD 0 d rats, SD rats exhibited significant decrease in the average swimming speed and increase in the escape latency (P <0.01). The expression of somatostatin in the hippocampus was decreased significantly in SD 2 d, SD 4 d and SD 6 d rats (P<0.05). However, decrease was only observed in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05). Parallel comparison between NS control and GSRb1 treated rats demonstrated that rats treated with GSRb1 in each subgroup exhibited faster swimming speed and shorter escape latency (P <0.05). Meanwhile, the expression of somatostatin was increased in SD 2 d, SD 4 d and SD 6 d rats in the hippocampus and in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05), respectively. CONCLUSION: GSRb1 enhances the expression of somatostatin in sleep deprivation rats and subsequently may improve learning and memory abilities of rats.

Investigation of thrombospondin-1 and transforming growth factor-ß expression in the heart of aging mice.

Elderly patients face the problems of morbidity and mortality due to age-mediated disabilities. The purpose of the present study was to investigate the expression of thrombospondin-1 (TSP-1) and transforming growth factor-ß (TGF-ß) in aging mice, and its probable mechanism in the pathological changes of aging myocardium. The aging model group (AM) comprised 30-month-old mice, while the control group comprised 2-month-old mice. The pathological changes were explored by H&E staining, and the contents of superoxide dismulase (SOD) and malondialdehyde (MDA) in the hearts were determined by xanthine oxidation or TBA colorimetry. TSP-1 and TGF-ß expression in the left ventricular myocardium was also measured by immunohistochemistry. The results showed that the activities of SOD decreased and the MDA content increased markedly in the hearts of the AM group compared to the control group. H&E staining showed that the control group myocardial cells lined up in order with clear structure and stained equably, while the AM group myocardial cells lined up in disorder with an augmented cell body and the appearance of many granules and interstitial fibrosis. Compared to the control group, in the hearts of the AM group, TSP-1 and TGF-ß protein expression in myocardial cells showed a significant increase (P<0.01). TSP-1 and TGF-ß expression increased in the myocardium, which may be related to pathological changes of age-related heart diseases, such as hypertrophy, fibrosis of myocardial cells and microvessel dissepiment thickening.

[Marrow mesenchymal stem cell transplantation with sodium alginate gel for repair of spinal cord injury in mice].

OBJECTIVE: To investigate the effects of sodium alginate gels on marrow mesenchymal stem cell transplantation for repair of spinal cord injury (SCI) in mice. METHODS: In the present study, effects of different sterilization methods and concentrations of sodium alginate gels were examined. Marrow mesenchymal stem cells (mMSCs) were isolated from mice and cultured. Cells were cultured with sodium alginate gels and MTT assay was applied to determine the cell viability. Mice spinal cord injury was induced by spinal cord transection. mMSCs were transplanted into the cavity of injured spinal cord with sodium alginate gels. The effects of sodium alginate gel were assessed by BMS scales and immunofluorescence staining for NF-200. RESULTS: Compared with liquid form, solid form sodium alginate gel prepared with high pressure vapor sterilization had a better effect on cell viability. SCI mice treated with 10 % sodium alginate gel and mMSCs achieved higher score in BMS scale as well as higher expression of NF-200 compared with the untreated SCI group. CONCLUSION: Sodium alginate gel prepared with solid form sterilization induces mMSCs proliferation and thus can be used as the carrier of stem cell in treatment of SCI.

Anti-neuroinflammatory and neurotrophic effects of combined therapy with annexin II and Reg-2 on injured spinal cord.

The present study was designed to investigate the neuroprotective effects of Ca(2+)-dependent phospholipid-binding protein annexin II and a secreted protein Reg-2 (regeneration gene protein 2) in spinal cord injury (SCI) model produced by contusion SCI at T(9) using the weight drop method. The agents were delivered intrathecally with Alzet miniosmotic pumps. We found that annexin II and Reg-2 remarkably reduced neuronal death, attenuated tissue damage and alleviated detrimental inflammation in vivo; meanwhile, a significant increase in white matter sparing and myelination area was observed. The propriospinal axons and long-distance supraspinal pathways were protected by the treatments as revealed by retrograde tracing. Basso Beattie Bresnahan locomotor rating scores also revealed a measurable behavioral improvement. However, no evident behavioral improvements in locomotor performance were achieved by the combined treatment with annexin II and Reg-2, compared with the separate treatment with annexin II and Reg-2.

[Somatostatin mRNA expression in hippocampus of diabetic rats model].

OBJECTIVE: To investigate the relationship between diabetes and somatostatin (SOM). METHODS: We established a streptozocin-induced diabetic rats model and studied the changes of SOM mRNA in hippocampi of diabetic and normal rats by using in situ hybridication and computer image analysis. We studied the mechanism of chronic diabetes encephalopathy by observing the changes of somatostatin mRNA in the hippocampus of diabetic rats was studied. RESULT: The number, light density and average area of positive cells in dentate gyrus area of hippocampus in diabetes model were reduced significantly as compared with normal rats (P < 0.01). CONCLUSION: A decline in SOM mRNA expression may play a role in chronic diabetes encephalopathy because of SOM effect in brain.