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Biomedical subjects

Ling Qin

Publications and source records attributed to Ling Qin.

At least 37 records · Page 2Linked to original sources

Low-intensity pulsed ultrasound accelerates osteogenesis at bone-tendon healing junction.

This study was designed to evaluate low-intensity pulsed ultrasound (LIPUS) in acceleration of mineralization and remodeling of the new bone formed at the healing interface of bone-tendon junction. Thirty-two mature New Zealand white rabbits underwent partial patellectomy and direct repair of the patellar tendon and proximal patella. Animals were then divided into LIPUS treatment group (20 min/d, 5 times/wk) and placebo control group and were euthanized at week 8 and 16 postoperatively (n = 8, for each group and time point). The main outcome measures included new bone size and its bone mineral density (BMD). Results showed that the size of new bone was found to be 2.6 and 3.0 times significantly greater in the LIPUS group compared with that of the control group at weeks 8 and 16, respectively. In addition, the LIPUS group showed significantly higher BMD at week 8 than controls, but not at week 16. In conclusion, this was the first experimental study to show that LIPUS was able to enhance osteogenesis at the healing bone-tendon junction, especially before the postoperative week 8. Findings of this study formed a scientific basis for future clinical trials and establishment of indication of LIPUS for enhancing bone-tendon junction repair.

Animals↗

Age-associated decrease of type IIA/B human skeletal muscle fibers.

Elderly individuals often fall because of poor muscle strength and reduced balancing ability related to muscle aging. However, it is unclear whether changes in muscle fiber types contribute to poor strength or imbalance. We studied age- associated changes in human skeletal muscle fibers using muscle biopsy specimens taken from 65 male and female Chinese patients aged 17-96 years. The muscle specimens were cryosectioned with alkaline triphosphatase staining at pH 4.4, followed by image analysis. We analyzed morphologic observations and performed quantitative analyses of the number, size, and area percentage of different types of skeletal muscle fibers and connective tissues. Types IIA and IIB muscle fibers decreased with age in the area percentage, fiber number percentage, and mean fiber area, whereas Type I fibers increased in area and number but not in size. Morphologically, Type II fibers appeared smaller and flatter. Our findings suggest deterioration in muscle quality and balancing coordination in elderly patients. We provide data to help determine treatments for reversing muscle fiber changes and reducing the number of falls and related fractures in patients.

Accidental Falls↗

Understanding parathyroid hormone action.

In addition to regulating serum calcium and stimulating bone resorption, parathyroid hormone (PTH) is known to stimulate bone formation under certain conditions. The mechanisms behind this counterintuitive anabolic action are largely unknown. We have set out to identify PTH-regulated genes that might be responsible for each of these contrasting effects of the hormone. This article describes our work on a select number of those genes.

Amphiregulin↗

Linking cDNA-AFLP-based gene expression patterns and ESTs.

Massive amounts of DNA sequence data, generated from expressed sequence tag (EST) and genome sequencing projects, require efficient methods to link sequence databases with temporal and spatial expression profiles. To meet this need, we have developed a powerful computer program (GenEST), which links cDNA sequence data (including EST sequences) with transcript profiles revealed by cDNA-amplified fragment length polymorphism (AFLP). cDNA-AFLP is a highly reproducible differential display method based on restriction enzyme digests and selective amplification under high stringency conditions. GenEST predicts the sizes of virtual transcript derived fragments (TDFs) from cDNA sequences digested in silico. The resulting virtual TDFs could be traced back among the thousands of TDFs displayed on cDNA-AFLP gels. As a consequence, cDNA sequence databases can be screened very efficiently to identify genes with relevant expression profiles. Vice versa, using the restriction enzyme recognition sites, the primer extensions and the estimated TDF size as identifiers, the DNA sequence(s) corresponding to a TDF with an interesting expression pattern can be identified.

Automation↗

Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway.

Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an EGF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.

Amphiregulin↗

Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls.

Generalized osteopenia and spinal deformity occur concomitantly in adolescent idiopathic scoliosis (AIS) during the peripubertal period. No large-scale study has been performed to reveal the link between scoliotic deformity and bone-mineral status in AIS. In a cross-sectional study, the extent of scoliotic-curve severity in relation to bone-mineral status was examined for 619 AIS girls and compared with those of 300 healthy non-AIS counterparts aged 11-16 years. Curve severity was categorized into a moderate (10-39 degrees) and a severe group (> or = 40 degrees) based on Cobb angle. Anthropometric parameters, bone mineral-density (BMD) and bone mineral-content (BMC) of lumbar spine, proximal femur and distal tibia were determined by dual-energy X-ray absorptiometry and peripheral QCT. Differences in anthropometric parameters and bone mass among control and the AIS-moderate and AIS-severe groups were tested by one-way ANOVA. Association between Cobb angle and bone mass was determined by univariate and multivariate analyses. Mean Cobb angle of the moderate and severe groups were 25+/-6.3 degrees and 50.2+/-11.3 degrees, respectively. Arm span and leg length among the moderate and severe AIS subjects were almost all longer than for the controls from age 13 years. Age-adjusted arm span and leg length were significantly correlated with curve severity (p < 0.015). Starting from age 13 years, most axial and peripheral BMD and BMC of the moderate or severe AIS group was significantly lower than for the controls (p < 0.029). Age-adjusted Cobb angle was inversely correlated with BMD and BMC of the distal tibia and lumbar spine among AIS subjects (p < or = 0.042). The proportion of osteopenic AIS girls in the severe group was significantly higher than that in the moderate group (p < or = 0.033). Multivariate analysis indicated that Cobb angle was inversely and independently associated with axial and peripheral BMD and BMC (p < or = 0.042). To conclude, curve severity was an inverse and independent associated factor on bone mineral mass of AIS during peripuberty. The study implied that prevention of osteopenia could be as important as controlling spinal progression in the management of AIS.

Absorptiometry, Photon↗

Metagenomics-based drug discovery and marine microbial diversity.

As the global threat of drug-resistant pathogens continues to rise, new strategies and resources are required to accelerate and advance the drug discovery process. We believe that rapid progress in metagenomics has opened up a new era in the study of marine microbial diversity that enables direct access to the genomes of numerous uncultivable microorganisms. This review outlines recent developments and future trends in metagenomics-based drug discovery in marine microbial communities and their associated chemical prosperity.

Chromosome Mapping↗

Parathyroid hormone stimulation and PKA signaling of latent transforming growth factor-beta binding protein-1 (LTBP-1) mRNA expression in osteoblastic cells.

Parathyroid hormone (PTH) regulates bone remodeling and calcium homeostasis by acting on osteoblasts. Recently, the gene expression profile changes in the rat PTH (1-34, 10(-8)M)-treated rat osteoblastic osteosarcoma cell line, UMR 106-01, using DNA microarray analysis showed that mRNA for LTBP-1, a latent transforming growth factor (TGF-beta)-binding protein is stimulated by PTH. Latent TGF-beta binding proteins (LTBPs) are required for the proper folding and secretion of TGF-beta, thus modifying the activity of TGF-beta, which is a local factor necessary for bone remodeling. We show here by real time RT-PCR that PTH-stimulated LTBP-1 mRNA expression in rat and mouse preosteoblastic cells. PTH also stimulated LTBP-1 mRNA expression in all stages of rat primary osteoblastic cells but extended expression was found in differentiating osteoblasts. PTH also stimulated TGF-beta1 mRNA expression in rat primary osteoblastic cells, indicating a link between systemic and local factors for intracellular signaling in osteoblasts. An additive effect on LTBP-1 mRNA expression was found when UMR 106-01 cells were treated with PTH and TGF-beta1 together. We further examined the signaling pathways responsible for PTH-stimulated LTBP-1 and TGF-beta1 mRNA expression in UMR 106-01 cells. The PTH stimulation of LTBP-1 and TGF-beta1 mRNA expression was dependent on the PKA and the MAPK (MEK and p38 MAPK) pathways, respectively in these cells, suggesting that PTH mediates its effects on osteoblasts by several intracellular signaling pathways. Overall, we demonstrate here that PTH stimulates LTBP-1 mRNA expression in osteoblastic cells and this is PKA-dependent. This event may be important for PTH action via TGF-beta in bone remodeling.

Animals↗

[Trabecular bone micro-architecture in adolescent idiopathic scoliosis compared between concave and convex site of the facet joints].

OBJECTIVE: To evaluate the trabecular bone micro-structure from different sites of spine in adolescent idiopathic scoliosis patients. The target site consisted of the bilateral facet joints from apical vertebrae and from end vertebrae. METHODS: Nine AIS patients with mean age 14.9 years (range 12-17 years) and mean Cobb angle 56 degrees (ranged 48 degrees-84 degrees) were recruited into this study. Corrective surgery was indicated to these patients, and facet joint biopsies were collected during decortications for spinal fusion. Biopsy consents were obtained from patients. Bone specimens were fixed with routine histology procedures and scanned by micro computer tomography (muCT40, Scanco Medical, Switzerland). Ten pairs of facet joint were harvested from apical vertebrae and 12 pairs from end vertebrae. Three-dimensional reconstructed images with the resolution of 20 microm were achieved for histomorphometric analysis. RESULTS: The values of BV/TV (0.268 vs. 0.354, P < 0.05), TbTh (0.20 vs. 0.24, P < 0.05), TbSP (0.66 vs. 0.56, P < 0.05) and BS/BV (12.7 vs. 10.4, P < 0.05) between convex and concave side at the apex area were significantly different. No difference was found in any structural parameters between left and right side at end area, and upper thoracic (T5, 6) and thoracolumbar (T12, L1). CONCLUSION: Due to asymmetric compression and tension shared between convex and concave side, more bone and thicker and more profound trabecular bones are observed in the concave side than in the convex side, which seems to resist the progression of spinal curvature. This finding suggests that the provocative factors which cause the progression of the curve in certain patients may not lie in the bone component of spine.

Adolescent↗

Origin, distribution and 3D-modeling of Gr-EXPB1, an expansin from the potato cyst nematode Globodera rostochiensis.

Southern analysis showed that Gr-EXPB1, a functional expansin from the potato cyst nematode Globodera rostochiensis, is member of a multigene family, and EST data suggest expansins to be present in other plant parasitic nematodes as well. Homology modeling predicted that Gr-EXPB1 domain 1 (D1) has a flat beta-barrel structure with surface-exposed aromatic rings, whereas the 3D structure of Gr-EXPB1-D2 was remarkably similar to plant expansins. Gr-EXPB1 shows highest sequence similarity to two extracellular proteins from saprophytic soil-inhabiting Actinobacteria, and includes a bacterial type II carbohydrate-binding module. These results support the hypothesis that a number of pathogenicity factors of cyst nematodes is of procaryotic origin and were acquired by horizontal gene transfer.

Amino Acid Sequence↗

Generalized low bone mass of girls with adolescent idiopathic scoliosis is related to inadequate calcium intake and weight bearing physical activity in peripubertal period.

Generalized low bone mass has been well documented in patients with adolescent idiopathic scoliosis (AIS). However, studies linking calcium-intake (CA), weight-bearing physical-activity (PA) and bone mass of AIS are lacking. We aimed to study the relationship between CA, PA and bone mass in AIS girls and compared to those of healthy non-AIS controls during the peripubertal period. Newly diagnosed AIS girls (n=596) aged 11-16 years with Cobb angle >/=10 degrees were recruited to compare with age-matched healthy girls (n=302) in a cross-sectional study. Anthropometric parameters, pubertal status, CA and PA were assessed. Areal bone mass of lumbar spine and femoral neck, and volumetric bone mass of distal radius and tibia were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. The results showed that weight and body mass index (BMI) of AIS were lower than the controls (P<0.05). Corrected height and arm span of AIS were longer than those of controls from 13 years onwards (P<0.02). Median CA of AIS was <410 mg/day across the ages and did not differ from the controls (P=0.063). Median PA of AIS (1.6 h/day) was lower than the controls (1.8 h/day) (P=0.025). Bone mass of AIS was on average 6.5% lower than controls across the ages (P<0.05). CA and PA were significantly correlated with bone mass of AIS (P<0.04). Multivariate analysis showed that AIS in girls was associated with lower bone mass, and that both CA and PA were independent predictors of bone mass in AIS. In conclusion, AIS girls were found to have lower body weight and BMI, longer segmental lengths and generalized low bone mass. Inadequate calcium intake and weight-bearing physical activity were significantly associated with low bone mass in AIS girls during the peripubertal period. The importance of preventing generalized osteopenia in the control of AIS progression during the peripubertal period warrants further study.

Absorptiometry, Photon↗

Phytoestrogen-rich herb formula "XLGB" prevents OVX-induced deterioration of musculoskeletal tissues at the hip in old rats.

This study investigated a phytoestrogen-rich herb formula, Xianlinggubao (XLGB) (including genistein 510 microg/g and daidzein 2500 microg/g), concerning prevention of OVX-induced deterioration of musculoskeletal tissues in 11-month-old female Wistar rats, which were randomized into Sham, OVX, and XLGB groups. Daily oral administration of XLGB (250 mg/kg/day) started after OVX for 3 months. mRNA of MHC-I IIa IIb of abductor muscle was determined by RT-PCR. The proximal femoral BMD and geometry, microarchitecture, and mechanical strength were evaluated by pQCT, micro-CT, and compressive testing, respectively. The bone turnover biochemical markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) were evaluated. The results showed that (1) XLGB-treated OVX rats showed no difference compared to the Sham group, whereas OVX induced significant deterioration in variables related to bone density, microarchitecture, and mechanical strength (P < 0.05); (2) biochemical markers showed no difference between sham and XLGB groups as compared with higher bone turnover in OVX rats (P < 0.05); (3) mRNA expression of MHC-I IIa IIb was downregulated in OVX rats but upregulated after XLGB treatment (P < 0.05); and (4) as compared with the OVX group, no uterine hypertrophy was found in XLGB-treated rats. In conclusion, findings of this study suggested that the herbal preparation XLGB was able to prevent OVX-induced deterioration of musculoskeletal tissues at the hip without causing uterine stimulation.

Animals↗

Regional variations in microstructural properties of vertebral trabeculae with aging.

The aim of this study was to identify regional variations in the three-dimensional microstructure of vertebral cancellous bones, and their relative differences with respect to aging. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadaver donors in two age groups, three aged 62 years and three aged 69 years; (n=45, each). In each vertebral body, five trabecular columns, each of 8x8x25 mm3, were cut from the anterior, posterior, central, right, and left regions. These columns were scanned, using high-resolution micro-computed tomography (microCT), three times, to obtain superior, middle, and inferior layers. Fifteen regions were obtained for each vertebral body. For all 90 trabecular specimens the bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as well as the three radii of the mean intercept length (MIL) ellipsoid (H1, H2, and H3) were determined. Regional variations in different transverse layers and vertical columns within and between the two age groups were then analyzed. The results showed significant differences in BV/TV, Tb.N, DA, and H2/H3 between the two age groups. The BV/TV and Tb.N were decreased, while the anisotropic parameters were increased significantly with age, increasing from age 62 to 69. Change in Tb.Th was not statistically significant, although the average was slightly smaller in the 69-year group. Each microstructural parameter followed its own pattern of regional variation within each group, suggesting both mechanical and age-related adaptation. This is the first study that has provided microstructural data of the vertebral body in a Chinese sample. These data may help us to gain more insight into the mechanism of the occurrence of lumbar osteoporosis and the related regional fracture risks, and may provide a reference for better enhancement of fracture repair.

Aged↗

Beneficial effects of regular Tai Chi exercise on musculoskeletal system.

This study was performed to evaluate the potential benefits of regular Tai Chi Chun (TCC) exercise on bone mineral density (BMD) and neuromuscular function in postmenopausal women. In this cross-sectional study, 99 healthy postmenopausal women, with a mean age of 55.9+/-3.1 years and within 10 years after the menopause, were recruited; including 48 subjects who had been regularly practicing TCC exercise for more than 3 h/week and 51 age- and sex-matched sedentary controls (CON). BMD was measured in the lumbar spine and proximal femur of the non-dominant leg (femoral neck, greater trochanter, and Ward's triangle), using dual-energy X-ray absorptiometry (DXA). Neuromuscular function was evaluated, including magnitude of trunk bend-and-reach, quadriceps muscle strength, and single-stance time on the nondominant leg. The TCC group showed overall higher BMD at all measurement sites, with a significant difference found at the spine (7.1%), greater trochanter (7.2%), and Ward's triangle (7.1%) of the proximal femur (all; P<0.05). Functional tests revealed an average 43.3% significantly greater quadriceps strength (P<0.01), and 67.8% significantly longer single-stance time in the TCC group as compared with the CON group (P<0.05), as well as a greater magnitude of trunk bend-and-reach in the TCC group (P=0.08). Bivariate linear correlation analysis showed that quadriceps muscle strength was significantly correlated with the single-stance time (r=0.41; P<0.01). This study revealed that regular TCC exercise may have an association with higher BMD and better neuromuscular function in early postmenopausal women.

Aged↗

Comparative study of osteoconduction on micromachined and alkali-treated titanium alloy surfaces in vitro and in vivo.

This study sought to evaluate osteoconduction of Ti-6Al-4V surfaces under various conditions, including micro-patterned, alkali-treated, micro-patterned plus alkali-treated, and surfaces without any treatment as the control. The through-mask electrochemical micromachining (EMM) was used to fabricate micro-hole arrays on the titanium alloy surface. In vitro calcium phosphate formation on titanium surfaces was in static and dynamic simulated body fluid (SBF). In vivo comparison was conducted in the medullary cavity of dog femur using the implant cages which could provide the same physiological environment for specimens with different surface conditions. In vitro experiments indicate good conduction of calcium phosphate on the alkali-treated surfaces, and also better calcium phosphate deposition on the micro-hole surface than on the flat surfaces in dynamic SBF. In vivo experiments confirm the beneficial effect of alkaline treatment on osteoconduction. The results of in vivo experiments also indicate a synergistic effect of the alkaline treatment and the topographic pattern on osteoconduction.

Alkalies↗

A comparative study between axial compression and lateral fall configuration tested in a rat proximal femur model.

BACKGROUND: Conventional testing method for evaluation of rat hip failure force is based on an axial compression approach. However, as the most osteoporotic hip fractures are a result of a lateral fall, it is necessary to establish mechanical testing methods more close to clinical conditions. This study was therefore designed to evaluate the differences in hip mechanical failure force to be tested between 'axial compression' and 'lateral fall configuration' in a rat proximal femur model. METHODS: Eighteen 10-month-old female Wistar rats were body-weight matched and divided into ovariectomized group (n = 9) and sham group (n = 9). All rats were euthanized 3 months after surgery. The bilateral proximal femora of each rat were excised. The left femur served for testing to failure in a fall configuration fashion while the right femur was tested using axial compression approach. After mechanical testing, the anterior-posterior radiographs were taken to identify the fracture mode and measure the Pauwel's angle between the fracture line and the line perpendicular to the femoral shaft long axis. FINDINGS: The failure force in fall configuration was significantly correlated with but lower than that tested in axial compression. A comparison between the ovariectomized and sham group showed that the failure force in both fall configuration and axial compression was found significantly higher in the sham group than that in the ovariectomized group. However, the logistic regression analysis revealed that the fall configuration approach had larger discrimination power. Radiographs showed that almost all samples fractured at the base of the femur neck. The Pauwel's angle in fall configuration group was significantly larger than that in axial compression group. INTERPRETATION: In comparison with the characteristics of axial compression test, the fall configuration approach generated higher shearing stress with larger bending moment to the bone and induced susceptibility to fracture at lower mechanical load. Although the failure force obtained from the two testing configurations revealed significant correlation, the mechanical testing in fall configuration demonstrated higher sensitivity in identifying the estrogen-deficiency induced deterioration of hip mechanical failure force as compared with that in axial compression. These findings suggested the potential application of lateral fall configuration in evaluation of improvement effects of intervention stratagems on hip mechanical failure force involving an ovariectomized rat model.

Accidental Falls↗

Delayed stimulatory effect of low-intensity shockwaves on human periosteal cells.

We investigated the effect of shockwaves on cells explanted from normal human periosteum to study the potential mechanisms of their responses and to determine suitable treatment settings. The cells were subjected to one shockwave treatment with systematic combinations of energy intensities (range, 0.05-0.5 mJ/mm) and number of shocks (range, 500-2000) whereas control cells received no treatment. The immediate effect on cell viability and the long-lasting effect on proliferation, viable cell number at Day 18, and mineralization at Day 35 were assessed. We observed an immediate dose-dependent destructive effect of shockwaves. Energy intensity and number of shocks contributed equally to viability. Total energy dose (intensity x number of shocks) was a better reference for determining the shockwave effect. We also found a long-term stimulatory effect on proliferation, viable cell number, and calcium deposition of human periosteal cells. At the same total energy dose, low-intensity shockwaves with more shocks (0.12 mJ/mm at 1250 shocks) were more favorable for enhancing cellular activities than high-intensity waves with fewer shocks (0.5 mJ/mm at 300 shocks). These findings document some of the biochemical changes of periosteal cells during shockwave treatments.

Cell Proliferation↗

Oxidative stress after muscle damage from immobilization and remobilization occurs locally and systemically.

Higher oxidative stress reportedly plays a key role in muscle damage caused by immobilization and subsequent remobilization. However, we have no clear understanding regarding oxidative stress during immobilization and remobilization. The purpose of this study was to clarify the characteristics of oxidative stress by measuring oxidative stress locally and systemically. Twenty-three New Zealand White rabbits were used in this study. Blood samples were collected on Days 1, 3, 7, 14, and 21 of immobilization, and Days 1, 2, 3, and 4 of remobilization. The soleus muscles in immobilized and nonimmobilized limbs were harvested on Day 21 of immobilization and Day 7 or Day 14 of remobilization. Muscle wet weight was determined as the indicator of muscle atrophy. The levels of lipid peroxidation and glutathione in plasma and soleus muscles were measured. Immobilization and remobilization induced an increase in the lipid peroxidation levels and a decrease in glutathione levels in muscle and blood. These findings suggest that oxidative stress occurs locally and systemically, lasts throughout the immobilization period, but peaks at the early phase of remobilization.

Animals↗