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Cardiovascular disease， such as coronary heart disease and acute myocardial infarction， is a leading cause of death globally. Due to the limited proliferative and regenerative capacity of adult mammalian cardiomyocytes （CMs）， any of the current therapies cannot reverse the massive loss of CMs and subsequent fibrosis resulting from cardiac injury. Mammals mainly rely on glycolysis in the embryonic stage and fatty acid oxidation after birth for energy production. Recent reports have indicated that this metabolic pattern switch is closely related to the loss of CM proliferation. In this review， we summarize the biological characteristics of CMs and advances in heart regeneration， meanwhile shed light on the important role of CMs energy metabolism in cardiac regeneration.
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BACKGROUND: In recent years, resveratrol has been studied a lot on the inhibition of tissue fibrosis, but the effect of resveratrol on the rehabilitation of muscle injury has been rarely reported. OBJECTIVE: To observe the expression of basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF-1) protein in the repair of acute blunt trauma of the skeletal muscle, and to explore the mechanism by which resveratrol promotes the structural and functional recovery of damaged skeletal muscle. METHODS: Thirty-three New Zealand rabbits were randomly divided into three groups: Normal group (n=3), natural recovery group (n=15) and resveratrol group (n=15). The skeletal muscle contusion model was established by blunt violence except for the normal group. The natural recovery group was not treated and the resveratrol group was intragastrically given resveratrol after injury. The animals were euthanized at 1, 3, 7,14, and 21 days after injury. Infiltration of inflammatory cells and formation of collagen fibers were observed using hematoxylin-eosin staining and Masson staining. The expression of bFGF and IGF-1 protein in the skeletal muscle was detected by immunohistochemistry and immunoblotting. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results: In the normal group, the muscle fibers were presented with polygons, regular shape, tight arrangement, muscle nucleus evenly distributed under the sarcolemma, no hyperplasia and pyknosis, and sarcolemma intact. In the injury groups, blood cells were exuded at 1 day, and inflammatory cells infiltrated at 3 days, which reached the maximum at 7 days. The morphology of muscle fibers returned to normal at 21 days after injury. The resveratrol group was better than the natural recovery group in terms of inflammatory cell infiltration and repair time. (2) Masson staining results: There were few collagen fibers in normal muscle cells. After injury, the number of collagen fibers increased with the formation of scar tissue, and reached a peak at 14 days. The content of collagen fibers in the resveratrol group was lower than that in the natural recovery group. (3) Immunohistochemistry and immunoblotting results: The expression of bFGF and IGF-1 protein first increased and then decreased after injury. In both groups, the expression of bFGF and IGF-1 protein reached the peak at 7 days and was still at a high level at 21 days. The resveratrol group had significantly higher bFGF and IGF-1 levels than the natural recovery group (P<0.05). Overall, resveratrol can effectively accelerate the histological healing process and improve the healing quality of rabbit skeletal muscle after blunt trauma. Resveratrol significantly promotes the repair of damaged skeletal muscle by up-regulating bFGF and IGF-1 expression, but not altering the overall change of protein expression during skeletal muscle injury repair.
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The repair strategy after organs injuries has always been a hot topic in the field of regenerative medicine. Traditional injury repair measures mainly promote tissue repair through mesenchymal stem cells and various growth factors, but these strategies have been constrained in the aspects of security and economy. Hence, there is an urgent need to find new ways to promote tissue repair and regeneration. There have been a lot of evidences showing that the immune system plays an important role in tissue regeneration and repair. In recent years, more and more studies have been done on adaptive immunity in tissue repair, especially the regulatory T cells. Some evidences indicate that regulatory T cells participate in damage tissue repair and regeneration of multiple organs and tissue. This review briefly introduces the new advances in the repair effects and regulatory mechanism of regulatory T cells in different organ injuries, in order to provide new ideas for designing advanced repair materials with good immunoregulatory functions.
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DNA microarray generally refers to gene chips. Its basic principle is that a large number of oligonucleotide molecules were fixed on the support, and then hybridized with the labeled samples, and then the chip hybridization signal strength was scanned to determine the number of target in the samples. Gene chips can trace the nucleotide sequence in the samples for testing and analyzing. Its characteristics of high-throughput,rapid and parallel acquisition of biological information are better than that of other traditional gene detection technology. It has been widely used in various fields of medical research. This article reviews the application of DNA microarray technology in the study of orthopedics including biological characteristics, formation and development,injury and repair, degeneration and regeneration of articular cartilage.
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Objective:To evaluate the effects of glial cell line-derived neurotrophic factor(GDNF) gene-activated matrix(GAM) in protection of neurons after sciatic nerve injury.Methods:The peripheral nerve extracellular matrix was harvested by chemical extraction.GDNF GAM was comprised of the extracellular matrix and plasmids encoding GDNF.Sixty adult Wistar rats were randomly divided into three groups:group A(GDNF GAM conduits,n=20),group B(ECM conduits,n=20),group C(autografts,n=20).Lumbar enlargement was processed for Nissl staining,immunohistochemistry and RT-PCR for GDNF or iNOS and fluorescence observation.Fluorescence observation was used to confirm the expressing of GDNF in the spinal cord.Motoneurons(MN) of lesioned(L) and normal(N) sides were counted,and MN survival ratio(MSR=L/N) was calculated.Results:GDNF DNA can be retained in GAM,promoting transgene expressing in axotomized neurons in spinal cord for 12 weeks.In GAM group,the expression of GDNF mRNA was maintained for 12 weeks while the number of iNOS positive cells was decreased in comparison with ECM group.GAM grafts obviously increased the survival rate of motor neurons than that of ECM grafts(78.04%?3.50% vs 56.09%?1.89%) at 12 weeks postaxotomy.Conclusion:These results suggest that(1) GDNF GAM increases the GDNF mRNA and the amount of Nissl positive cells in the lumber enlargement;(2) GDNF GAM protects MN through a mechanism in relation to iNOS.
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Objective To investigate the effects of GDNF-modified Schwann cells on the repair of sciatic nerve defects in rats. Methods Forty adult Wistar rats were randomly divided into four groups: group A (nerve grafts, fabricated by extracellular gel and PLGA conduits, n=10), group B (Schwann cells and extracellular gel and PLGA conduits, n=10), group C (GDNF-modified Schwann cells and extracellular gel and PLGA conduits, n=10), and group D (autograft, n=10). Motoneuron conduction and morphology (including anatomical measures and ultrastructure) of the regenerated axons were investigated at 12 weeks postoperatively. Regeneration rate of the motoneuron in spinal cord was also evaluated by using HRP label technique. Results Higher rate of nerve regeneration or number of labeled motoneurons in spinal cord was observed using PLGA conduits seeded with GDNF enhanced expressing Schwann cells (group C) than that with PLGA conduits (group A) alone or PLGA conduits seeded with control Schwann cells (group B), but there was no significant difference as compared with that in the autograft group (group D). Conclusion These results suggest that using gene transfer techniques to increase neurotrophic factor expression in Schwann cells added to nerve grafts may be a promising method for improving nerve regeneration.
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Objective To evaluate the effects of glial cell line-derived neurotrophic factor(GDNF) gene-activated matrix(GAM) in bridging rat sciatic nerve defect.Methods The peripheral nerve extracellular matrix was harvested by chemical extraction.GDNF gene-activated matrix was comprised of the extracellular matrix and plasmids encoding GDNF.Ninety adult Wistar rats were randomly divided into three groups: group A(GDNF GAM conduits),group B(extracellular matrix conduits),group C (autografts).At the end of 12 weeks,rats from each group were subjected to walking tract analysis,electrophysiological and histomorphological studies.Results GDNF DNA could be retained in GAM,promoting transgene expression in the sciatic nerve,in GAM,and more importantly,in axotomized neurons in spinal cord for 12 weeks.The number of regenerated axons for the GAM grafts in the distal sciatic nerve was lower than that for autografts(2 117?294 vs 2 474?297) at 12 weeks.The sciatic nerve function index for the GAM grafts was lower than that for autografts [(30.92?2.98)% vs(26.27?2.71) %] at 12 weeks.Conclusion GDNF GAM may be a promising alternative to autografts for repair of rat sciatic nerve.
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Objective To observe the pathologic changes of the rabbit sciatic nerves after the exposure of high intensity ultrasound(HIU) (7.1 MHz,45.86 W/cm2)and to establish the experimental base for protection of the nerves near the organs and tissues treated with HIU. Methods The rabbit sciatic nerves were exposed to HIU of different doses as defined by the action time of the ultrsound(0, 15, 25 and 50 seconds, respectively); The Pathological changes of the nerves were observed at different times after exposed to HIU(1 week,2 weeks,1 month,3 months and 6 months). Results In 0 s (45.86 W/cm2?0 s)group, no significant pathological changes were observed. In 15 s(45.86 W/cm2?15 s) group, slight deformation of the myelin sheath were observed and recovery took place at 2 weeks. In 25 s (45.86 W /cm2?25 s) group, the nerves became broken partly and recovered at 3 months. In 50 s(45.86 W/cm2?50 s) group, great part of the nerves got coagulation necrosis and had not recovered at 6 months. Conclusion The larger the dosage of HIU, the higher degree the injury of the sciatic nerve, the more difficult the nerves to get repaired.