Porphyrin Homeostasis Maintained by ABCG2 Regulates Self-Renewal of Embryonic Stem Cells

Under appropriate culture conditions, undifferentiated embryonic stem (ES) cells can undergo multiple self-renewal cycles without loss of pluripotency suggesting they must be equipped with specific defense mechanisms to ensure sufficient genetic stability during self-renewal expansion. The ATP binding cassette transporter ABCG2 is expressed in a wide variety of somatic and embryonic stem cells. However, whether it plays an important role in stem cell maintenance remains to be defined.Here we provide evidence to show that an increase in the level of ABCG2 was observed accompanied by ES colony expansion and then were followed by decreases in the level of protoporphyrin IX (PPIX) indicating that ABCG2 plays a role in maintaining porphyrin homoeostasis. RNA-interference mediated inhibition of ABCG2 as well as functional blockage of ABCG2 transporter with fumitremorgin C (FTC), a specific and potent inhibitor of ABCG2, not only elevated the cellular level of PPIX, but also arrest the cell cycle and reduced expression of the pluripotent gene Nanog. Overexpression of ABCG2 in ES cells was able to counteract the increase of endogenous PPIX induced by treatment with 5-Aminolevulinic acid suggesting ABCG2 played a direct role in removal of PPIX from ES cells. We also found that excess PPIX in ES cells led to elevated levels of reactive oxygen species which in turn triggered DNA damage signals as indicated by increased levels of gammaH2AX and phosphorylated p53. The increased level of p53 reduced Nanog expression because RNA- interference mediated inhibition of p53 was able to prevent the downregulation of Nanog induced by FTC treatment.The present work demonstrated that ABCG2 protects ES cells from PPIX accumulation during colony expansion, and that p53 and gammaH2AX acts as a downstream checkpoint of ABCG2-dependent defense machinery in order to maintain the self-renewal of ES cells

Soil Erosion And Non-Point Source Pollution Impacts Assessment With The Aid Of Multi-Temporal Remote Sensing Images

Soil erosion associated with non-point source pollution is viewed as a process of land degradation in many terrestrial environments. Careful monitoring and assessment of land use variations with different temporal and spatial scales would reveal a fluctuating interface, punctuated by changes in rainfall and runoff, movement of people, perturbation from environmental disasters, and shifts in agricultural activities and cropping patterns. The use of multi-temporal remote sensing images in support of environmental modeling analysis in a geographic information system (GIS) environment leading to identification of a variety of long-term interactions between land, resources, and the built environment has been a highly promising approach in recent years. This paper started with a series of supervised land use classifications, using SPOT satellite imagery as a means, in the Kao-Ping River Basin, South Taiwan. Then, it was designed to differentiate the variations of eight land use patterns in the past decade, including orchard, farmland, sugarcane field, forest, grassland, barren, community, and water body. Final accuracy was confirmed based on interpretation of available aerial photographs and global positioning system (GPS) measurements. Finally, a numerical simulation model (General Watershed Loading Function, GWLF) was used to relate soil erosion to non-point source pollution impacts in the coupled land and river water systems. Research findings indicate that while the decadal increase in orchards poses a significant threat to water quality, the continual decrease in forested land exhibits a potential impact on water quality management. Non-point source pollution, contributing to part of the downstream water quality deterioration of the Kao-Ping River system in the last decade, has resulted in an irreversible impact on land integrity from a long-term perspective. © 2005 Elsevier Ltd. All rights reserved

Structure and Mechanical Properties of As-Cast Ti–5Sn–xMo Alloys

Ti–5Sn–xMo (x = 0, 1, 3, 5, 7.5, 10, 12.5, 15, 17.5, and 20 wt %) alloys were designed and prepared for application as implant materials with superior mechanical properties. The results demonstrated that the crystal structure and mechanical properties of Ti–5Sn–xMo alloys are highly affected by their Mo content. The as-cast microstructures of Ti–5Sn–xMo alloys transformed in the sequence of phases α′ → α″ → β, and the morphologies of the alloys changed from a lath structure to an equiaxed structure as the Mo content increased. The α″-phase Ti–5Sn–7.5Mo (80 GPa) and β-phase Ti–5Sn–10Mo (85 GPa) exhibited relatively low elastic moduli and had excellent elastic recovery angles of 27.4° and 37.8°, respectively. Furthermore, they exhibited high ductility and moderate strength, as evaluated using the three-point bending test. Search for a more suitable implant material by this study, Ti–5Sn–xMo alloys with 7.5 and 10 wt % Mo appear to be promising candidates because they demonstrate the optimal combined properties of microhardness, ductility, elastic modulus, and elastic recovery capability

Opposite associations of osteoprotegerin and ZBTB40 polymorphisms with bone mineral density of the hip in postmenopausal Taiwanese women

Background: An elevated annual incidence rate of hip fracture has been reported among elderly Taiwanese. Moreover, bone mineral density (BMD) is the single most reliable predictor of fragility fractures. We aimed to identify the association between gene sequence variants and hip BMD in postmenopausal Taiwanese women. Methods: We prospectively analyzed data from 163 postmenopausal Taiwanese women to test an association between rs7524102, rs6696981, or rs6993813 single-nucleotide polymorphisms (SNPs) and hip BMD. Results: Our study showed that rs6993813 (osteoprotegerin gene) and rs6696981 (ZBTB40 gene) SNPs have an opposite association with hip BMD. For rs6993813 genotypic frequencies, the adjusted odds ratio for hip osteoporosis was 9.53 for individuals with T/T minor allele homozygotes, compared with that of participants with C/C wild-type homozygotes. Hip BMD also had an association with rs6993813 SNPs, especially in T/T minor allele homozygotes. For rs6696981 SNPs, hip BMD in G/T heterozygotes and at least one mutated T allele was higher than that in wild-type G/G homozygotes. Conclusion: The gene sequence variant rs6993813 reduced hip BMD and increased the risk of hip osteoporosis, whereas rs6696981 increased hip BMD in postmenopausal Taiwanese women. This indicated that the two SNPs may provide some explanation for the high risk of hip fracture in this population

Association of interleukin-1 beta (-511C/T) polymorphisms with osteoporosis in postmenopausal women

Background and Objectives: Osteoporosis is a common disease of the elderly, in which genetic and clinical factors contribute to the disease phenotype. Since the production of interleukin-1 (IL-1) has been implicated in the bone mass and skeletal disorders, we investigated whether IL-1 system gene polymorphisms are associated with the pathogenesis of osteoporosis in postmenopausal Taiwanese women. Methods: Osteoporosis is diagnosed by dual-energy x-ray absorptiometry, which measures bone mineral density (BMD) at multiple skeletal sites. We studied the IL-1α (-889C/T), IL-1β (-511C/T) and the 86 base pair variable number tandem repeat (VNTR) in intron 2 of the IL-1 receptor antagonist (IL-1ra) gene in 117 postmenopausal women with osteoporosis and 135 control subjects without a history of symptomatic osteoporosis. These gene polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymerase. Blood sugar and other risk factors were also determined. Results: The frequencies of IL-1β (-511C/T) genotypes (P=.022, odds ratio=1.972) and alleles (P=.02, odds ratio=2.909) showed a statistically significant difference between the two groups. However, we did not find any statistically significant difference in IL-1β and IL-1ra polymorphisms (P>.05). We also observed a positive relationship between osteoporosis and cholesterol and a weak inverse relationship between blood sugar and osteoporosis in postmenopausal women. Conclusions: These experimental results suggest that the pathogenesis of osteoporosis is associated with IL-1β (-511C/T) polymorphism in postmenopausal women. This polymorphism is an independent risk factor for osteoporosis

Characterization of Nano-Scale Hydroxyapatite Coating Synthesized from Eggshells Through Hydrothermal Reaction on Commercially Pure Titanium

Commercially pure titanium (c.p. Ti) is often used in biomedical implants, but its surface cannot usually combine with the living bone. A coating of hydroxyapatite (HA) on the surface of titanium implants provides excellent mechanical properties and has good biological activity and biocompatibility. For optimal osteocompatibility, the structure, size, and composition of HA crystals should be closer to those of biological apatite. Our results show that the surface of c.p. Ti was entirely covered by rod-like HA nanoparticles after alkali treatment and subsequent hydrothermal treatment at 150 °C for 48 h. Nano-sized apatite aggregates began to nucleate on HA-coated c.p. Ti surfaces after immersion in simulated body fluid (SBF) for 6 h, while no obvious precipitation was found on the uncoated sample. Higher apatite-forming ability (bioactivity) could be acquired by the samples after HA coating. The HA coating featured bone-like nanostructure, high crystallinity, and carbonate substitution. It can be expected that HA coatings synthesized from eggshells on c.p. Ti through a hydrothermal reaction could be used in dental implant applications in the future

A Comparison of the Risk of Fracture in Rheumatoid Arthritis Patients with and without Receiving Chinese Herbal Medicine

Objective: Patients with rheumatoid arthritis (RA) often suffer from bone complications due to persistent joint inflammation, especially incident fracture. Nowadays, Chinese herbal medicines (CHMs) have provided safe and effective therapy for treating skeletal conditions, but it is unclear whether CHMs can prevent fracture onset among RA individuals. This study aimed to determine the association between the use of CHMs and the risk of fracture among them. Methods: This retrospective, population-based study retrieved administrative health data from the Taiwan National Health Insurance (NHI) database to identify patients with newly diagnosed RA between 2000 and 2009. Of the 6178 incident RA patients, 2495 matched pairs of CHMs users and non-CHMs users were identified by propensity score matching. Enrollees with hip fractures prior to RA onset were excluded. Included subjects were followed until the end of 2013. Incidence and adjusted hazard ratios (HR) of new-onset bone fracture in the multivariable Cox proportional hazard model were measured with 95% confidence interval (CI). Results: Fracture incidence was lower in CHMs users than in the comparison cohort (26.91 vs 32.94 per 1000 person-years, respectively), with an adjusted HR of 0.82 (95% CI: 0.73– 0.92). Subjects receiving CHMs for more than 2 years had a much lower risk of fracture onset by more than 50%. Some CHMs prescriptions (Yan Hu Suo, Bei Mu, Da Huang, Dang Shen, Fu-Zi, Shu-Jing-Huo-Xue-Tang, Dang-Gui-Nian-Tong-Tang, Jia-Wei-Xiao-Yao-San, Gan-Lu-Yin, and Gui-Zhi-Shao-Yao-Zhi-Mu-Tang) were associated with reduced fracture risk. Conclusion: Adding CHMs to routine treatment was found to be related to lower fracture risk in RA patients