The Effect of Boron-Containing Nano-Hydroxyapatite on Bone Cells

Biological Trace Element Research - Metabolic diseases or injuries damage bone structure and self-renewal capacity. Trace elements and hydroxyapatite crystals are important in the development of...     

Transcriptome and proteome profiles of human umbilical cord vein CD146+ stem cells

Molecular Biology Reports - In this study we used two different techniques in order to isolate pericytes from the wall of human umbilical cord vein and get two different groups of cells were named...     

Higher Serum Concentrations of N-Terminal Pro-B-Type Natriuretic Peptide Associate with Prevalent Hypertension whereas Lower Associate with Incident Hypertension

BackgroundThe role of the natriuretic peptides (NPs) in hypertension is complex. Thus, a higher blood NP concentration is a robust marker of pressure-induced cardiac damage in patients with hypertension, whereas genetically elevated NP concentrations are associated with a reduced risk of hypertension and overweight individuals presumably at high risk of hypertension have lower NP concentrations.ObjectiveTo investigate the associations between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), used as a surrogate marker for active BNP, and prevalent as well as 5-year incident hypertension in a Danish general population sample.MethodsCross-sectional and prospective population-based study.ResultsAt baseline, among 5,307 participants (51.3% women, mean age 46.0±7.9 years) with a complete set of data, we recorded 1,979 cases with prevalent hypertension (PHT). Among 2,389 normotensive participants at baseline with a complete set of data, we recorded 324 cases with incident hypertension (IHT) on follow-up 5 years later. In models adjusted for age, sex, lifestyle, social, dietary, anthropometric, pulmonic, lipid, metabolic and renal risk factors, as well as heart rate and baseline blood pressure (only incident model), one standard deviation increase in baseline log-transformed NT-proBNP concentrations was on one side associated with a 21% higher risk of PHT (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.13-1.30], P<0.001), and on the other side with a 14% lower risk of IHT (OR: 0.86 [95%CI:0.76-0.98], P = 0.020).ConclusionsHigher serum concentrations of NT-proBNP associate with PHT whereas lower concentrations associate with IHT. This suggests that a lower amount of circulating BNP, resulting in diminished vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.     

Regulation of mTOR Complex 1 (mTORC1) by Raptor Ser863 and Multisite Phosphorylation

The rapamycin-sensitive mTOR complex 1 (mTORC1) promotes protein synthesis, cell growth, and cell proliferation in response to growth factors and nutritional cues. To elucidate the poorly defined mechanisms underlying mTORC1 regulation, we have studied the phosphorylation of raptor, an mTOR-interacting partner. We have identified six raptor phosphorylation sites that lie in two centrally localized clusters (cluster 1, Ser⁶⁹⁶/Thr⁷⁰⁶ and cluster 2, Ser⁸⁵⁵/Ser⁸⁵⁹/Ser⁸⁶³/Ser⁸⁷⁷) using tandem mass spectrometry and generated phosphospecific antibodies for each of these sites. Here we focus primarily although not exclusively on raptor Ser⁸⁶³ phosphorylation. We report that insulin promotes mTORC1-associated phosphorylation of raptor Ser⁸⁶³ via the canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner. mTORC1 activation by other stimuli (e.g. amino acids, epidermal growth factor/MAPK signaling, and cellular energy) also promote raptor Ser⁸⁶³ phosphorylation. Rheb overexpression increases phosphorylation on raptor Ser⁸⁶³ as well as on the five other identified sites (e.g. Ser⁸⁵⁹, Ser⁸⁵⁵, Ser⁸⁷⁷, Ser⁶⁹⁶, and Thr⁷⁰⁶). Strikingly, raptor Ser⁸⁶³ phosphorylation is absolutely required for raptor Ser⁸⁵⁹ and Ser⁸⁵⁵ phosphorylation. These data suggest that mTORC1 activation leads to raptor multisite phosphorylation and that raptor Ser⁸⁶³ phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation (e.g. on Ser⁸⁵⁹ and Ser⁸⁵⁵). Importantly, mTORC1 containing phosphorylation site-defective raptor exhibits reduced in vitro kinase activity toward the substrate 4EBP1, with a multisite raptor 6A mutant more strongly defective that single-site raptor S863A. Taken together, these data suggest that complex raptor phosphorylation functions as a biochemical rheostat that modulates mTORC1 signaling in accordance with environmental cues.     

Flow characterization of a wavy-walled bioreactor for cartilage tissue engineering

Cartilage tissue engineering requires the use of bioreactors in order to enhance nutrient transport and to provide sufficient mechanical stimuli to promote extracellular matrix (ECM) synthesis by chondrocytes. The amount and quality of ECM components is a large determinant of the biochemical and mechanical properties of engineered cartilage constructs. Mechanical forces created by the hydrodynamic environment within the bioreactors are known to influence ECM synthesis. The present study characterizes the hydrodynamic environment within a novel wavy-walled bioreactor (WWB) used for the development of tissue-engineered cartilage. The geometry of this bioreactor provides a unique hydrodynamic environment for mammalian cell and tissue culture, and investigation of hydrodynamic effects on tissue growth and function. The flow field within the WWB was characterized using two-dimensional particle-image velocimetry (PIV). The flow in the WWB differed significantly from that in the traditional spinner flask both qualitatively and quantitatively, and was influenced by the positioning of constructs within the bioreactor. Measurements of velocity fields were used to estimate the mean-shear stress, Reynolds stress, and turbulent kinetic energy components in the vicinity of the constructs within the WWB. The mean-shear stress experienced by the tissue-engineered constructs in the WWB calculated using PIV measurements was in the range of 0-0.6 dynes/cm2. Quantification of the shear stress experienced by cartilage constructs, in this case through PIV, is essential for the development of tissue-growth models relating hydrodynamic parameters to tissue properties.     

Analysis of the Influences of Short-Term Levosimendan Exposure on Oxidant/Antioxidant Status and Trace-Element Levels in the Physiological Status of the Thoracic Aorta of Rats

The objective of this study was to evaluate the effect of levosimendan (chemical formula C₁₄H₁₂N₆O) exposure on oxidant/antioxidant status and trace-element levels in the thoracic aorta of rats. Eighteen male Wistar albino rats were randomly divided into two groups of eight animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12???g/kg) diluted in 10 ml 0.5?% dextrose was administered intraperitoneally to group 2. Animals of both groups were killed after 3?days, and their thoracic aortae were harvested for determination of changes in tissue oxidant/antioxidant status and trace-element levels. The animals in both groups were killed 72?h after levosimendan exposure, and thoracic aortae were harvested for determination of the lipid peroxidation product MDA and antioxidant GSH levels and the activities of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration. SOD and CA enzyme activities and the level of antioxidant GSH decreased in thoracic aortae of rats after levosimendan treatment. Pb, Cd and Fe levels of thoracic aortae were significantly higher (P?<?0.001) and Mg, Mn, Zn and Cu were significantly lower (P?<?0.001) in the levosimendan group compared to the control group. These results suggest that short-term levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in thoracic aortae of levosimendan-treated rats. It also causes a decrease or increase in many mineral levels of the thoracic aorta, which is an undesirable condition for normal pharmacological function.     

Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis

Background

Effective fixation of fracture requires careful selection of a suitable implant to provide stability and durability. Implant with a feature of locking plate (LP) has been used widely for treating distal fractures in femur because of its favourable clinical outcome, but its potential in fixing proximal fractures in the subtrochancteric region has yet to be explored. Therefore, this comparative study was undertaken to demonstrate the merits of the LP implant in treating the subtrochancteric fracture by comparing its performance limits against those obtained with the more traditional implants; angle blade plate (ABP) and dynamic condylar screw plate (DCSP).

Materials and Methods

Nine standard composite femurs were acquired, divided into three groups and fixed with LP (n?=?3), ABP (n?=?3) and DCSP (n?=?3). The fracture was modeled by a 20?mm gap created at the subtrochanteric region to experimentally study the biomechanical response of each implant under both static and dynamic axial loading paradigms. To confirm the experimental findings and to understand the critical interactions at the boundaries, the synthetic femur/implant systems were numerically analyzed by constructing hierarchical finite element models with nonlinear hyperelastic properties. The predictions from the analyses were then compared against the experimental measurements to demonstrate the validity of each numeric model, and to characterize the internal load distribution in the femur and load bearing properties of each implant.

Results

The average measurements indicated that the constructs with ABP, DCPS and LP respectively had overall stiffness values of 70.9, 110.2 and 131.4?N/mm, and exhibited reversible deformations of 12.4, 4.9 and 4.1?mm when the applied dynamic load was 400?N and plastic deformations of 11.3, 2.4 and 1.4?mm when the load was 1000?N. The corresponding peak cyclic loads to failure were 1100, 1167 and 1600?N. The errors between the displacements measured experimentally or predicted by the nonlinear hierarchical hyperelastic model were less than 18?%. In the implanted femur heads, the principal stresses were spatially heterogeneous for ABP and DCSP but more homogenous for LP, meaning LP had lower stress concentrations.

Conclusion

When fixed with the LP implant, the synthetic femur model of the subtrochancteric fracture consistently exceeds in the key biomechanical measures of stability and durability. These capabilities suggest increased resistance to fatigue and failure, which are highly desirable features expected of functional implants and hence make the LP implant potentially a viable alternative to the conventional ABP or DCSP in the treatment of subtrochancteric femur fractures for the betterment of clinical outcome.     

Behavioural analyses of quinine processing in choice, feeding and learning of larval Drosophila

Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.