Direct effects of caffeine on osteoblastic cells metabolism: the possible causal effect of caffeine on the formation of osteoporosis

BACKGROUND: Caffeine consumption has been reported to decrease bone mineral density (BMD), increase the risk of hip fracture, and negatively influence calcium retention. In this study, we investigated the influence of caffeine on the osteoblasts behaviour. METHOD: Osteoblasts derived from newborn Wistar-rat calvaria was used in this study. The effects of various concentrations of caffeine on bone cell activities were evaluated by using MTT assay. Alkaline phosphatase (ALP) staining, von Kossa staining and biochemical parameters including ALP, lactate dehydrogenase (LDH), prostaglandin E(2 )(PGE(2)) and total protein were performed at day 1, 3, and 7. DNA degradation analysis under the caffeine influence was also performed. RESULTS AND DISCUSSION: The results showed that the viability of the osteoblasts, the formation of ALP positive staining colonies and mineralization nodules formation in the osteoblasts cultures decreased significantly in the presence of 10 mM caffeine. The intracellular LDH, ALP and PGE(2 )content decreased significantly, the LDH and PGE(2 )secreted into the medium increased significantly. The activation of an irreversible commitment to cell death by caffeine was clearly demonstrated by DNA ladder staining. CONCLUSION: In summary, our results suggest that caffeine has potential deleterious effect on the osteoblasts viability, which may enhance the rate of osteoblasts apoptosis

Comparison of extracorporeal shock wave lithotripsy running models between outsourcing cooperation and rental cooperation conducted in Taiwan

Background/PurposeWe conducted a retrospective study to compare the cost and effectiveness between two different running models for extracorporeal shock wave lithotripsy (SWL), including the outsourcing cooperation model (OC) and the rental cooperation model (RC).MethodsBetween January 1999 and December 2005, we implemented OC for the SWL, and from January 2006 to October 2011, RC was utilized. With OC, the cooperative company provided a machine and shared a variable payment with the hospital, according to treatment sessions. With RC, the cooperative company provided a machine and received a fixed rent from the hospital. We calculated the cost of each treatment session, and evaluated the break-even point to estimate the lowest number of treatment sessions to make the balance between revenue and cost every month. Effectiveness parameters, including the stone-free rate, the retreatment rate, the rate of additional procedures and complications, were evaluated.ResultsCompared with OC there were significantly less treatment sessions for RC every month (42.6±7.8 vs. 36.8±6.5, p=0.01). The cost of each treatment session was significantly higher for OC than for RC (751.6±20.0 USD vs. 684.7±16.7 USD, p=0.01). The break-even point for the hospital was 27.5 treatment sessions/month for OC, when the hospital obtained 40% of the payment, and it could be reduced if the hospital got a greater percentage. The break-even point for the hospital was 27.3 treatment sessions/month for RC. No significant differences were noticed for the stone-free rate, the retreatment rate, the rate of additional procedures and complications.ConclusionOur study revealed that RC had a lower cost for every treatment session, and fewer treatment sessions of SWL/month than OC. The study might provide a managerial implication for healthcare organization managers, when they face a situation of high price equipment investment

Stra13 regulates satellite cell activation by antagonizing Notch signaling

Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation

Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo

<p>Abstract</p> <p>Background</p> <p>Glycogen synthase kinase 3 (GSK3) encodes a serine/threonine protein kinase, is known to play roles in many biological processes. Two closely related GSK3 isoforms encoded by distinct genes: GSK3α (51 kDa) and GSK3β (47 kDa). In previously studies, most GSK3 inhibitors are not only inhibiting GSK3, but are also affecting many other kinases. In addition, because of highly similarity in amino acid sequence between GSK3α and GSK3β, making it difficult to identify an inhibitor that can be selective against GSK3α or GSK3β. Thus, it is relatively difficult to address the functions of GSK3 isoforms during embryogenesis. At this study, we attempt to specifically inhibit either GSK3α or GSK3β and uncover the isoform-specific roles that GSK3 plays during cardiogenesis.</p> <p>Results</p> <p>We blocked <it>gsk3α </it>and <it>gsk3β </it>translations by injection of morpholino antisense oligonucleotides (MO). Both <it>gsk3α</it>- and <it>gsk3β</it>-MO-injected embryos displayed similar morphological defects, with a thin, string-like shaped heart and pericardial edema at 72 hours post-fertilization. However, when detailed analysis of the <it>gsk3α</it>- and <it>gsk3β</it>-MO-induced heart defects, we found that the reduced number of cardiomyocytes in <it>gsk3α </it>morphants during the heart-ring stage was due to apoptosis. On the contrary, <it>gsk3β </it>morphants did not exhibit significant apoptosis in the cardiomyocytes, and the heart developed normally during the heart-ring stage. Later, however, the heart positioning was severely disrupted in <it>gsk3β </it>morphants. <it>bmp4 </it>expression in <it>gsk3β </it>morphants was up-regulated and disrupted the asymmetry pattern in the heart. The cardiac valve defects in <it>gsk3β </it>morphants were similar to those observed in <it>axin1 </it>and <it>apc</it>^{<it>mcr </it>}mutants, suggesting that GSK3β might play a role in cardiac valve development through the Wnt/β-catenin pathway. Finally, the phenotypes of <it>gsk3α </it>mutant embryos cannot be rescued by <it>gsk3β </it>mRNA, and vice versa, demonstrating that GSK3α and GSK3β are not functionally redundant.</p> <p>Conclusion</p> <p>We conclude that (1) GSK3α, but not GSK3β, is necessary in cardiomyocyte survival; (2) the GSK3β plays important roles in modulating the left-right asymmetry and affecting heart positioning; and (3) GSK3α and GSK3β play distinct roles during zebrafish cardiogenesis.</p

Lubricin Surface Modification Improves Tendon Gliding After Tendon Repair in a Canine Model In Vitro

Introduction: The role of friction as a source of adhesions has been recently investigated, with data suggesting that many strong repairs also have higher friction [1], and that this higher friction is associated with poorer results, at least in animal models [2]. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage [3,4]. Recent studies have identified lubricin on the surface of FDP tendon [5,6] suggesting that it may play a role in tendon lubrication. Tendon surface modification with gelatin and hyaluronic acid reduces the gliding resistance of both tendon graft and repaired tendon [7][8][9]. The purpose of this study was to investigate the effects of lubricin with or without hyaluronic acid (HA) on the gliding of repaired FDP tendon in a canine model in vitro. Materials and Methods: 32 flexor digitorum profundus (FDP) tendons from the 2nd -5th digits of forepaws from 4 adult mongrel dogs were used. The dogs were sacrificed for other IACUC approved projects. In each digit the proximal and middle phalanges, FDP tendon, flexor digitorum superficialis (FDS) tendon and FDS insertion, and proximal pulley were then harvested as a unit. The proximal interphalangeal joint was fixed in full extension. A complete laceration to the FDP tendon was made 6mm distal to the proximal pulley (analogous to the A2 pulley in humans) and repaired with a modified Pennington technique. After the gliding resistance of the repaired tendon was measured in vitro, the tendons were treated with one of four solutions (n=8 per group): Saline; 10% gelatin/1% HA/1% EDC (1-ethyl-3-(3-dimethylaminopropyl) carbdiimide hydrochloride) /1% NHS (Nhydroxysuccinimde) (cd-HA-gelatin); 10% gelatin/1% EDC/1% NHS + lubricin (cd-gelatin + lubricin); 10% gelatin/1% HA/1% EDC/1% NHS+ lubricin (cd-HA-gelatin + lubricin). Lubricin was purified from bovine synovial fluid [10]. After treatment, tendon gliding resistance was measured for 1000 cycles of simulated flexion/extension tendon motion. The average and peak gliding resistance over the flexion/extension cycle were calculated and compared to baseline. Treatment groups were compared using ANOVA. Following testing, the surface of the repaired tendon and its proximal pulley was also assessed qualitatively for surface smoothness by scanning electron microscopy. Results: The increase in average and peak gliding resistance in cd-HA-gelatin, cd-gelatin+lubricin, and cd-HA-gelatin+ lubricin tendons was significantly less than that of the saline control tendons after 1000 cycles (p&lt;0.05) Discussion: In this study, the cd-HA-gelatin, cd-gelatin+lubricin and cd-HAgelatin+lubricin all improved the gliding resistance of the repaired flexor tendon compared to the saline controls. The two lubricin treated groups had the lowest gliding resistance throughout testing. The cd-HA-gelatin+lubricin tendons were significantly lower than the tendons treated with cd-HA-gelatin alone. While not significant, there was clearly a trend for improved results with cd-gelatin+lubricin, as well. The addition of lubricin to a tendon surface pre-treated with cd-gelatin and HA significantly reduces gliding resistance and maintains a qualitatively smooth tendon and pulley surface after 1000 cycles of simulated flexion/extension tendon motion compared to the carbodiimide derivatized hyaluronic acid (cd-HA-gelatin) preparation alone. These findings may have important implications for the development of tissue engineered tendon surfaces to improve the results after tendon repair

Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass

Objective: To investigate the role of the cumulus cells and the cumulus matrix in affecting the penetrability, morphology, acrosome reaction, and motility of human spermatozoa penetrating the cumulus oophorus. Design: Controlled experimental laboratory study. Setting: University gynecology unit. Patient(s): Women undergoing assisted reproduction treatment and men visiting the subfertility clinics. Intervention(s): Human spermatozoa were allowed to penetrate through the cumulus oophorus and cell-depleted cumulus matrix in a capillary, and were treated with cumulus cell extract or hyaluronic acid. Main Outcome Measure(s): The morphology, acrosomal status, and motility of human spermatozoa were determined. Result(s): Fewer spermatozoa could penetrate the fresh cell-depleted matrix compared with intact cumulus oophorus. Spermatozoa that penetrated through the cumulus oophorus had higher percentages of normal morphology and acrosome reaction and had specific motility pattern. These effects were lost or reduced in the cell-depleted matrix that had been stored overnight. Hyaluronic acid, a main component of the cumulus matrix at concentration found in the cumulus oophorus, modulated sperm motility but did not affect spontaneous acrosome reaction. Cumulus cell extract did not affect sperm motility, but induced acrosome reaction. Conclusion(s): Both the cumulus matrix and the cumulus cells contribute to the effect of cumulus oophorus on spermatozoa penetrating through it. © 2009 American Society for Reproductive Medicine.postprin

A super Asian dust storm over the East and South China Seas: disproportionate dust deposition

A super Asian dust (SAD) storm that originated from North China has affected East Asia since 20 March 2010. The tempo-spatial and size distributions of aerosol Al, a tracer of wind-blown dust, were measured on a regional aerosol network in March 2010. Two dust events were recorded: the SAD and a relatively moderate AD event. The SAD clouds raised Al concentrations to ~50 µg/m3 on 21 and 22 March over the East China Sea (ECS) and occupied there for ~5 days. The SAD plume also stretched toward the South China Sea (SCS) on 21 March however, it caused a maximum Al concentration of ~8.5 µg/m3 only, much lower than that observed in the ECS. In comparison, a weaker dust plume on 16 March caused Al maximum of ~4 µg/m3 over the ECS, and comparably, ~3 µg/m3 in the SCS. Dry dust deposition was measured during the peak phase of the SAD at 178 mg/m2/d, which corresponded to dry deposition velocities of 0.2–0.6 cm/s only, much lower than the commonly adopted one (1–2 cm/s). The corresponding increase in dust deposition by the SAD was up to a factor of ~12, which was, however, considerably disproportionate to the increase in dust concentration (i.e., the factor of over 100). In certain cases, synoptic atmospheric conditions appear to be more important in regulating dust contribution to the SCS than the strength of AD storms

Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected