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Objective: Little is known about telomere dynamics in keloids. As keloid formation is dependent on cell replication, in theory telomeres should be shorter in keloids than in normal skin. We examined this concept in the present study., Methods: We measured by Southern blot analysis telomere length in keloids and in adjacent normal skin of 16 individuals. When available, we also measured telomere length in blood (leukocytes) and subcutaneous fat., Results: Telomere length was highly variable among individuals but highly correlated among tissues (cells) within the individual. The mean telomere length in the keloids was longer than that in the adjacent normal skin and displayed a length gradient, with the mean length of telomeres shorter just below the epidermis and longer at the base of the keloids. No apparent telomerase activity was detected in the keloids., Conclusions: Our findings suggest a transient activation of telomerase, the reverse transcriptase that prevents telomere shortening, probably during the early phase of keloid formation. The activation of telomerase serves to maintain (or even elongate) telomere length in the keloid. However, telomerase activity is repressed in the fully developed keloid.

Objective: To investigate the feasibility of establishment of physiological micturition reflex arc by simultaneously reconstructing the sensory and the motorial nerve of atonic bladder after spinal cord injury., Methods: Eight 1-year-old Beegle male canine were selected, weighing 7-12 kg. The left side was the experimental side, while the right side was the control side. Epidural microanastomosis of vertebral canal of the left L7 ventral root to S2 ventral root and L7 dorsal root to S2 dorsal root was performed to reconstruct the sensory and the motorial function of atomic bladder. The right side was used as a control without treatment. The new motor-to-motor, and sensory-to-sensory physiological bladder reflex pathway were established after 12 months of axonal regeneration. Then S1-4 segmental spinal cord was destroyed for preparation of complete paraplegia. The electrophysiological examination and the bladder pressure were detected before and after paraplegia. The canine micturition was observed for 3 months after paraplegia. Neurohistological observation was performed after canine sacrifice., Results: Of 8 canine, 7 canine survived. After paraplegia, canines displayed urinary incontinence and frequent micturition at first, nocturnal continence was achieved gradually without frequent micturition after 1 month. Urinary infection at different degrees occurred in 3 canines and was controlled after Norfloxacin was administered orally. The bladder pressure increased to (1.00 +/- 0.13) kPa, (0.90 +/- 0.12) kPa after trains of stimulation (300 mV, 0.3 ms, 20 Hz, 5 seconds) of S2 dorsal root at the experimental side before and after paraplegia respectively, showing no significant difference (P > 0.05). It increased to (1.90 +/- 0.10) kPa after the same train of stimulation of S2 dorsal root at control side. There was significant difference between the experimental side and the control side (P < 0.01). Single stimulation (300 mV, 0.3 ms) of the S2 dorsal root at the experimental side resulted in evoked potentials recorded from the left S2 ventral root before and after paraplegia. Before and after paraplegia, the amplitudes of the evoked potentials were (0.68 +/- 0.11) mV and (0.60 +/- 0.08) mV respectively, showing no significant difference (P > 0.05). It was (1.21 +/- 0.13) mV while stimulating at the control side. There was significant difference between the experimental side and the control side (P < 0.01). Neurofibra of L7 dorsal and ventral root grew into S2 dorsal and ventral root on tissue slice under light microscope., Conclusion: Reconstruction of the bladder physiological micturition reflex arc is feasible by anastomosis of sacral dorsal and ventral root below injured spinal plane with the suprasacral survival dorsal and ventral root above the plane respectively for restoration of atonic bladder after spinal cord injury.

Telomeres are engaged in a host of cellular functions, and their length is regulated by multiple genes. Telomere shortening, in the course of somatic cell replication, ultimately leads to replicative senescence. In humans, rare mutations in genes that regulate telomere length have been identified in monogenic diseases such as dyskeratosis congenita and idiopathic pulmonary fibrosis, which are associated with shortened leukocyte telomere length (LTL) and increased risk for aplastic anemia. Shortened LTL is observed in a host of aging-related complex genetic diseases and is associated with diminished survival in the elderly. We report results of a genome-wide association study of LTL in a consortium of four observational studies (n = 3,417 participants with LTL and genome-wide genotyping). SNPs in the regions of the oligonucleotide/oligosaccharide-binding folds containing one gene (OBFC1; rs4387287; P = 3.9 x 10(-9)) and chemokine (C-X-C motif) receptor 4 gene (CXCR4; rs4452212; P = 2.9 x 10(-8)) were associated with LTL at a genome-wide significance level (P < 5 x 10(-8)). We attempted replication of the top SNPs at these loci through de novo genotyping of 1,893 additional individuals and in silico lookup in another observational study (n = 2,876), and we confirmed the association findings for OBFC1 but not CXCR4. In addition, we confirmed the telomerase RNA component (TERC) as a gene associated with LTL (P = 1.1 x 10(-5)). The identification of OBFC1 through genome-wide association as a locus for interindividual variation in LTL in the general population advances the understanding of telomere biology in humans and may provide insights into aging-related disorders linked to altered LTL dynamics.

Objective: To investigate effects of the basic fibroblast growth factor (bFGF) and fibronection (FN) on the osteoblast adhesion on the bio-derived bone., Methods: The third generation of the osteoblast was treated with bFGF 0. 1, 1, 10, and 100 ng/ml, respectively, and then was seeded in the bio-derived bone, which had been modified with FN 0.1, 1, 10, and 100 microg/ml, or Polylysine, respectively. The cell adhesion was measured by the MTT assay. The cell density and the cell appearance were observed by the scanning electron microscope. The above-mentioned procedures were repeated by an application of the GRGDS peptide., Results: Both FN and bFGF could enhance the osteoblast adhesion efficiency on the bio-derived bone (P < 0.05). However, the osteoblast adhesion efficiency could be significantly strengthened by a combined use of FN and bFGF. FN and bFGF had a significant synergistic effect in statistics (P < 0.01), but Polylysine and bFGF had no such synergistic effect (P > 0.05). The combined use of FN and bFGF had a better effect on the cell density and the cell appearance than either of them when observed with the scanning electron microscope. Adhesion efficiency generated by the combined use of FN and bFGF was significantly blocked by the application of the GRGDS peptide., Conclusion: The combined use of FN and bFGF has a significant synergistic effect on the osteoblast adhesion efficiency on the bio-derived bone. This effect is probably mediated by the RGD-integrin alpha5beta1 pathway.

Objective: To explore the effects of the nerve growth factor (NGF) on N-methyl-D-asparate receptor 1 (NMDAR 1) after spinal cord injury., Methods: Spinal cord injury of Wistar rats was performed with Allen's method by a 10 gx2.5 cm impact on the posterior T8 spinal cord. NGF was given to the rats of the treatment group via subarachnoid space tube at once, 2, 4, 8, 12 and 24 hours after spinal cord injury, respectively. The expression of NMDAR1 mRNA in spinal cord was detected by in situ hybridization., Results: Rare expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal group. A strong expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal saline group. The expression of NMDAR1 mRNA in the NGF group was significantly decreased as compared with that in the normal saline group (P=0.01)., Conclusions: NGF can relieve damage of injured spinal cord by prohibiting the expression of NMDAR1 mRNA.

Objective: To explore the molecular mechanism of the protective effect of nerve growth factor (NGF) on injured spinal cord., Methods: The posterior T(8) (the 8th thoracic segment) spinal cords of 60 Wistar rats were injured by impacts caused by objects (weighing 10 g) falling from a height of 2.5 cm with Allen's way. Solution with nerve growth factors (NGF) was given to 30 rats (the NGF group) through a microtubule inserted into the subarachnoid cavity immediately, and at 2, 4, 8, 12 and 24 hours after spinal cord injury (SCI) respectively. Normal saline (NS) with same volume was given to the other 30 rats (the NS group) with the same method. And 5 normal rats were taken as the normal controls. The expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining., Results: The positive expression of bcl-2 protein was strong in the normal controls, but decreased in the NS group, and increased significantly in the NGF group as compared with that of the NS group (P<0.01). The positive expression of bax protein was also strong in the normal controls, but increased in the NS group, and decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Apoptotic neurons were found in the NS group, and they decreased significantly in the NGF group as compared with that of the NS group (P<0.01)., Conclusions: NGF can protect the injured nerve tissues through stimulating the expression of bcl-2 protein, inhibiting the expression of bax protein and inhibiting the neuronal apoptosis after SCI.

Objective: To explore the protective effects of nerve growth factor (NGF) on injured spinal cord., Methods: The spinal cord injury (SCI) model of Wistar rats was established by a 10 gx2.5 cm impact force on the T(8) spinal cord. NGF (60 microg/20 microl) was given to the rats of the treatment group immediately and at 2, 4, 8, 12, 24 hours after SCI. The level of neuronal constitutive nitric oxide synthase (ncNOS) and the expression of ncNOS mRNA in the spinal cord were detected by the immunohistochemistry assay and in situ hybridization method., Results: Abnormal expression of ncNOS was detected in the spinal ventral horn motorneuron in injured rats. The levels of ncNOS protein in the NGF group were significantly lower than those in the normal saline group (P<0.05 ). The ncNOS mRNA expression was found in the spinal ventral horn motorneuron in injured rats and the expression in the NGF group was significantly decreased compared with that in the normal saline group (P<<0.01)., Conclusions: NGF can protect the injured tissue of the spinal cord by prohibiting abnormal expression of nitric oxide synthase and the neurotoxicity of nitric oxide.