bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel single‐chain variable fragment antibody against FGF‐1 inhibits the growth of breast carcinoma cells by blocking the intracrine pathway of FGF‐1
Authors: Shi Heng‐Liang , Yang Tao , Deffar Khalissa , Dong Chun‐Guang , Liu Jing‐Ying , Fu Chun‐Ling , Zheng Da‐Xue , Qin Bo , Wang Jun‐Jie , Wang Xing‐Zhi , Zhu Xiao‐Juan 
Published: February 2011

AbstractThe fibroblast growth factors (FGFs) are important for embryo development, wound healing, hematopoiesis, and angiogenesis. FGF‐1, a member of FGF family, is involved in both receptor‐dependent pathways and an intracrine pathway. Studies have recently shown that FGF‐1 is overexpressed in the early stages of several kinds of cancer. Thus, FGF‐1 is a candidate for cancer immunotargeting. To study the potential use of therapeutic antibodies against FGF‐1, a monoclonal hybridoma 1C9 secreting monoclonal antibody specific for FGF‐1 was developed. Then, a single‐chain variable fragment (scFv) antibody was genetically engineered from hybridama 1C9. The binding of the scFv1C9 to the antigen FGF‐1 was demonstrated by ELISA and immunoprecipitation assays. Functional analysis showed that the overexpressed scFv1C9 in MCF‐7 cells targeted endogenous FGF‐1 and prevented the translocation of FGF‐1 into the nucleus, resulting in the blockade of the intracrine pathway of FGF‐1, which caused the G1 arrest by p21 up‐regulation. These results suggest that the generated scFv1C9 is an effective inhibitor of the intracrine pathway of FGF‐1 and has a potential application as anti‐tumoral agent in breast cancer. © 2011 IUBMB IUBMB Life, 63(2): 129–137, 2011
Physiological role and potential clinical interest of mycobacterial pigments
Authors: Robledo Jaime A. , Murillo Ana M. , Rouzaud Francois 
Published: February 2011

AbstractThe production of pigments by bacterial colonies has sparked interest among bacteriologists since the 19th century, whether for taxonomy or, in the case of carotenoids for their association with antibiotics resistance. Mycobacteria have gained a very special place in the bacterial world due to their clinical importance. Alone, Mycobacterium tuberculosis is responsible for about two million deaths annually worldwide making tuberculosis one of the most influential diseases in the history of mankind. Almost half of the Nontuberculous Mycobacteria species identified are associated with opportunistic infections in animals and humans. Mycobacterial pigmentary characteristics started to be documented about 80 years ago; but to date, their main use has been only for limited taxonomic and identification purposes. While mycobacterial pigments, especially carotenoids have been clearly associated with cellular photoprotection and survival, the regulation of their production and their physiological role have been largely unstudied. Recent advances in deciphering mycobacterial genomes and characterization of carotenoid synthesis genes, combined with an urgent need for innovative approaches to understand Mycobacterium tuberculosis pathogenic properties open new avenues for exciting research opportunities that might lead to new therapeutic strategies against a devastating secular disease. © 2011 IUBMB IUBMB Life, 63(2): 71–78, 2011
miR‐210: More than a silent player in hypoxia
Authors: Devlin Cecilia , Greco Simona , Martelli Fabio , Ivan Mircea 
Published: February 2011

AbstractMultiple studies have consistently established that miR (microRNA)‐210 induction is a feature of the hypoxic response in both normal and transformed cells. Here, we discuss the emerging biochemical functions of this miRNA and anticipate potential clinical applications. miR‐210 is a robust target of hypoxia‐inducible factor, and its overexpression has been detected in a variety of cardiovascular diseases and solid tumors. High levels of miR‐210 have been linked to an in vivo hypoxic signature and associated with adverse prognosis in cancer patients. A wide spectrum of miR‐210 targets have been identified, with roles in mitochondrial metabolism, angiogenesis, DNA repair, and cell survival. Such targets may broadly affect the evolution of tumors and other pathological settings, such as ischemic disorders. Harnessing the knowledge of miR‐210's actions may lead to novel diagnostic and therapeutic approaches. © 2011 IUBMB IUBMB Life, 63(2): 94–100, 2011
Cytocompatibility study of a natural biomaterial crosslinker—Genipin with therapeutic model cells
Authors: Wang Chunming , Lau Ting Ting , Loh Wei Li , Su Kai , Wang Dong‐An 
Published: February 2011

AbstractGenipin has been widely used as a natural crosslinker to substitute chemical crosslinkers such as glutaraldehyde to crosslink various biomaterials like gelatin, collagen, and chitosan. However, there are contradicting views on the cytotoxicity and safety of genipin in tissue engineering. Therefore in this study, we aimed to evaluate the toxicity of genipin on skeletal tissues cells—osteoblasts and chondrocytes as they are also representatives of typical anchorage‐dependent cells (ADCs) and nontypical ADCs. Results suggest that genipin toxicity is dose dependent and acute but not time dependent on both osteoblasts and chondrocytes. In particular, chondrocytes exhibit substantial alterations in the gene expression when exposed to Maximum nontoxic concentration (MaxNC) of genipin but there were no significant changes in the genes tested in osteoblasts. Since osteoblasts are typical ADCs, cellular focal adhesion assessment was carried out with F‐actin being more contracted and unorganized when exposed to minimum toxic concentration (MinTC) of genipin. The mechanisms involved in cell deaths in both cell types are believed to be similar and hence using osteoblast as the model, cells were stained positive for Annexin‐V and Reactive oxygen species (ROS) level were elevated at MinTC of genipin. Collectively, genipin induced cell apoptosis via ROS production, and apparently, gene expressions could also be altered at MaxNC. For this reason, we recommend the dose of genipin to be controlled within 0.5 mM. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater , 2011.
The elimination of free radicals in irradiated UHMWPEs with and without vitamin E stabilization by annealing under pressure
Authors: Oral Ebru , Ghali Bassem W. , Muratoglu Orhun K. 
Published: February 2011

AbstractRadiation crosslinking of ultrahigh molecular weight polyethylene (UHMWPE) has been used to decrease the wear of joint implant bearing surfaces. While radiation crosslinking has been successful in decreasing femoral head penetration into UHMWPE acetabular liners in vivo, postirradiation thermal treatment of the polymer is required to ensure the oxidative stability of joint implants in the long term. Two types of thermal treatment have been used: (i) annealing below the melting point preserves the mechanical properties but the residual free radicals trapped in the crystalline regions are not completely eliminated, leading to oxidation in the long‐term and (ii) annealing above the melting point (melting) eliminates the free radicals but leads to a decrease in mechanical properties through loss of crystallinity during the melting process. In this study, we hypothesized that free radicals could be reduced by annealing below the melting point under pressure effectively without melting due to the elevation of the melting point. By avoiding the complete melting of UHMWPE, mechanical properties would be preserved. Our hypothesis tested positive in that we found the radiation‐induced free radicals to be markedly reduced (below the detection limit of state‐of‐the‐art electron spin resonance) by thermal annealing under pressure in radiation crosslinked virgin UHMWPE and UHMWPE/vitamin‐E blends without loss of mechanical properties. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
An evaluation of electrical stimulation for improving periprosthetic attachment
Authors: Isaacson Brad M. , Brunker Lucille B. , Brown Amalia A. , Beck James P. , Burns Gregory L. , Bloebaum Roy D. 
Published: February 2011

AbstractTranscutaneous osseointegrated implants (TOI) have been shown to improve functionality for patients with limb loss by allowing direct skeletal attachment between an exoprosthesis and host bone. However, a lengthy rehabilitation period has limited the expansion of TOI and may be accelerated with electrical stimulation. The purpose of this study was to determine the ability of direct current (DC) cathode stimulation to enhance osseointegration of intramedullary implants in skeletally matured rabbits. Bilateral implants were inserted in the hind limbs of 25 adult female rabbits. The left hind limb of each animal was continually stimulated with a potential difference of 0.55 volts based on finite element analysis predictions. After sacrifice, the limbs were divided into two groups: Group I for histology and Group II for biomechanical testing. The bone‐implant construct was evaluated in the Group I animals using appositional bone index (ABI), mineral apposition rates (MAR), histological staining, and scanning electron microscopy (SEM). Group II implants were sectioned and subjected to mechanical push‐out tests. Data indicated no statistical differences for ABI, MAR, and porosity between the electrically stimulated implants (ESI) and the unstimulated control implants (UCI) at three weeks and six weeks. Higher mechanical push‐out forces were observed in the UCI group at six weeks (p = 0.034). Data indicated that DC cathode stimulation may improve suboptimal implant “fit and fill” as an increase in trabecular bone was noted around the cathode in the ESI group. However, longer time duration animal studies and variations in electrical modalities may be required before electrically induced osseointegration becomes clinically feasible. © 2011 Wiley Periodicals, Inc.* J Biomed Mater Res Part B: Appl Biomater, 2011.
Novel methods to evaluate fracture risk models
Authors: Donaldson Meghan G , Cawthon Peggy M , Schousboe John T , Ensrud Kristine E , Lui Li-Yung , Cauley Jane A , Hillier Teresa A , Taylor Brent C , Hochberg Marc C , Bauer Douglas C , Cummings Steven R ,   for the Study of Osteoporotic Fractures (SOF)
Published: February 2011

Abstract
Fracture prediction models help to identify individuals at high risk who may benefit from treatment. Area under the curve (AUC) is used to compare prediction models. However, the AUC has limitations and may miss important differences between models. Novel reclassification methods quantify how accurately models classify patients who benefit from treatment and the proportion of patients above/below treatment thresholds. We applied two reclassification methods, using the National Osteoporosis Foundation (NOF) treatment thresholds, to compare two risk models: femoral neck bone mineral density (BMD) and age (simple model) and FRAX (FRAX model). The Pepe method classifies based on case/noncase status and examines the proportion of each above and below thresholds. The Cook method examines fracture rates above and below thresholds. We applied these to the Study of Osteoporotic Fractures (SOF). There were 6036 (1037 fractures) and 6232 (389 fractures) participants with complete data for major osteoporotic and hip fracture, respectively. Both models for major osteoporotic fracture (0.68 versus 0.69) and hip fracture (0.75 versus 0.76) had similar AUCs. In contrast, using reclassification methods, each model classified a substantial number of women differently. Using the Pepe method, the FRAX model (versus the simple model) missed treating 70 (7%) cases of major osteoporotic fracture but avoided treating 285 (6%) noncases. For hip fracture, the FRAX model missed treating 31 (8%) cases but avoided treating 1026 (18%) noncases. The Cook method (both models, both fracture outcomes) had similar fracture rates above/below the treatment thresholds. Compared with the AUC, new methods provide more detailed information about how models classify patients. © 2011 American Society for Bone and Mineral Research
WHO absolute fracture risk models (FRAX): Do clinical risk factors improve fracture prediction in older women without osteoporosis?
Authors: Hillier Teresa A , Cauley Jane A , Rizzo Joanne H , Pedula Kathryn L , Ensrud Kristine E , Bauer Douglas C , Lui Li-Yung , Vesco Kimberly K , Black Dennis M , Donaldson Meghan G , LeBlanc Erin S , Cummings Steven R 
Published: February 2011

Abstract
Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass. © 2011 American Society for Bone and Mineral Research
Chlorthalidone improves vertebral bone quality in genetic hypercalciuric stone-forming rats
Authors: Bushinsky David A , Willett Thomas , Asplin John R , Culbertson Christopher , Che Sara PY , Grynpas Marc 
Published: February 2011

Abstract
We have bred a strain of rats to maximize urine (u) calcium (Ca) excretion and model hypercalciuric nephrolithiasis. These genetic hypercalciuric stone-forming (GHS) rats excrete more uCa than control Sprague-Dawley rats, uniformly form kidney stones, and similar to patients, demonstrate lower bone mineral density. Clinically, thiazide diuretics reduce uCa and prevent stone formation; however, whether they benefit bone is not clear. We used GHS rats to test the hypothesis that the thiazide diuretic chlorthalidone (CTD) would have a favorable effect on bone density and quality. Twenty GHS rats received a fixed amount of a 1.2% Ca diet, and half also were fed CTD (4 to 5 mg/kg/d). Rats fed CTD had a marked reduction in uCa. The axial and appendicular skeletons were studied. An increase in trabecular mineralization was observed with CTD compared with controls. CTD also improved the architecture of trabecular bone. Using micro–computed tomography (µCT), trabecular bone volume (BV/TV), trabecular thickness, and trabecular number were increased with CTD. A significant increase in trabecular thickness with CTD was confirmed by static histomorphometry. CTD also improved the connectivity of trabecular bone. Significant improvements in vertebral strength and stiffness were measured by vertebral compression. Conversely, a slight loss of bending strength was detected in the femoral diaphysis with CTD. Thus results obtained in hypercalciuric rats suggest that CTD can favorably influence vertebral fracture risk. CTD did not alter formation parameters, suggesting that the improved vertebral bone strength was due to decreased bone resorption and retention of bone structure. © 2011 American Society for Bone and Mineral Research
Post–hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs is associated with lower mortality: A nationwide study in Finland
Authors: Nurmi-Lüthje Ilona , Sund Reijo , Juntunen Merja , Lüthje Peter 
Published: February 2011

Abstract
We previously found a positive association between calcium plus vitamin D and antiosteoporotic drugs and survival among hip fracture patients. Our aim was to verify this observation using a nationwide database. A retrospective cohort of home-discharged hip fracture patients aged 50 years or older (n = 23,615) was enrolled from the national database. Primary exposure was medical treatment for osteoporosis, and the outcome was all-cause mortality. Cumulative mortalities were calculated using the Kaplan-Meier estimator. The relationship between mortality and medication purchases was modeled using Cox's proportional hazards regression with time-dependent covariates for medication use. One in 4 women and 1 in 10 men with a hip fracture were treated for osteoporosis in Finland. Unadjusted 1-year mortality was lower among patients who purchased calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs than among those who did not purchase these medications [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.67–0.81]. The difference in unadjusted cumulative mortality remained in favor of the drug users for at least 5 years. Among men, the use of calcium plus vitamin D or vitamin D supplements was associated with lower 1-year mortality even after adjustments for observed confounders (HR = 0.74, 95% CI 0.56–0.97). Among women, the use of antiosteoporotic drugs was associated with lower mortality (HR = 0.79, 95% CI 0.67–0.93). There was a tendency to even better survival in both genders if calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs were used simultaneously, the HR being 0.72 (95% CI 0.50–1.03) in men and 0.62 (95% CI 0.50–0.76) in women. © 2011 American Society for Bone and Mineral Research
Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5
Authors: Frost Morten , Andersen Tom , Gossiel Fatma , Hansen Stinus , Bollerslev Jens , van Hul Wim , Eastell Richard , Kassem Moustapha , Brixen Kim 
Published: February 2011

Abstract
Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment-specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. To evaluate bone, serotonin, and bone turnover markers (BTM) in Lrp5-HBM patients, we studied 19 Lrp5-HBM patients (T253I) and 19 age- and sex-matched controls. DXA and HR-pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, dickkopf-related protein 1 (DKK1), and BTM were evaluated. Z-scores for the forearm, total hip, lumbar spine, forearm, and whole body were significantly increased (mean ± SD) between 4.94 ± 1.45 and 7.52 ± 1.99 in cases versus −0.19 ± 1.19 to 0.58 ± 0.84 in controls. Tibial and radial cortical areas, thicknesses, and BMD were significantly higher in cases. In cases, BMD at the lumbar spine and forearm and cortical thickness were positively associated and trabecular area negatively associated with age (r = 0.49, 0.57, 0.74, and −0.61, respectively, p &lt; .05). Serotonin was lowest in cases (69.5 [29.9–110.4] ng/mL versus 119.4 [62.3–231.0] ng/mL, p &lt; .001) and inversely associated with tibial cortical density (r = −0.49, p &lt; .05) and directly with osteocalcin (OC), bone-specific alkaline phosphatase (B-ALP), and procollagen type 1 amino-terminal propeptide (PINP) (r = 0.52–0.65, p &lt; .05) in controls only. OC and S-CTX were lower and sclerostin higher in cases, whereas B-ALP, PINP, tartrate-resistant acid phosphatase (TRAP), and dickkopf-related protein 1 (DKK1) were similar in cases and controls. In conclusion, increased bone mass in Lrp5-HBM patients seems to be caused primarily by changes in trabecular and cortical bone mass and structure. The phenotype appeared to progress with age, but BTM did not suggest increased bone formation. © 2011 American Society for Bone and Mineral Research
Better skeletal microstructure confers greater mechanical advantages in Chinese-American women versus white women
Authors: Liu X Sherry , Walker Marcella D , McMahon Donald J , Udesky Julia , Liu George , Bilezikian John P , Guo X Edward 
Published: February 2011

Abstract
Despite lower areal bone mineral density (aBMD), Chinese-American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese-American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image-analysis technique, and micro–finite-element analysis (µFEA) were applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese-American and white women. Chinese-American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p &lt; .001). With similar rodlike characteristics, the plate-to-rod ratio was twice as high in the Chinese-American than in white trabecular bone (p &lt; .001). Plate-rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese-American women (p &lt; .002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese-American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p &lt; .001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p &lt; .001) and 29% to 43% (distal tibia, p &lt; .01) greater trabecular bone strength, as assessed by Young's moduli, in the Chinese-American versus the white group. The observation that Chinese-American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD. © 2011 American Society for Bone and Mineral Research
Vibrational spectral signatures of peptide secondary structures: N‐methylation and side chain hydrogen bond in cyclosporin A
Authors: Qu Zheng‐Wang , Zhu Hui , May Volkhard 
Published: February 2011

AbstractMolecular dynamics simulations are performed to explore important conformations of cyclosporin A, an immunosuppressive cyclic undecapeptide drug, in different media including gas‐phase, chloroform, and acetonitrile. Density functional theory calculations are used to refine the low‐lying conformers and to predict their infrared and vibrational circular dichroism spectra. Vibrational spectral signatures in the important amide II, I, and A regions are identified for typical peptide secondary structures including β‐turn (type II′ or I), antiparallel β‐sheet (flat or twisted), inverse γ‐turn, N‐methylated peptide bond, and side chain H‐bond. New insights into the spectral signatures of secondary structures especially with N‐methylation and side chain hydrogen bond are provided, which can be very useful for further peptide conformation analysis in general. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011