Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of <it>Emblica officinalis </it>fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.</p> <p>Methods</p> <p>The effects of extracts from <it>Emblica officinalis </it>on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of <it>Emblica officinalis </it>extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, <it>in vitro </it>effects of <it>Emblica officinalis </it>extracts on NF-kB transcription factor activity were determined by gel shift experiments.</p> <p>Results</p> <p>Extracts of <it>Emblica officinalis </it>were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. <it>Emblica officinalis </it>increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that <it>Emblica officinalis </it>extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that <it>Emblica officinalis </it>extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of <it>Emblica officinalis </it>on the expression levels of interleukin-6, a NF-kB specific target gene.</p> <p>Conclusion</p> <p>Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of <it>Emblica officinalis </it>extracts as an alternative tool for therapy applied to bone diseases.</p

Bone turnover markers in sheep and goat: a review of the scientific literature

Bone turnover markers (BTMs) are product of bone cell activity and are generally divided in bone formation and bone resorption markers. The purpose of this review was to structure the available information on the use of BTMs in studies on small ruminants, especially for monitoring their variations related to diet, exercise, gestation and metabolic lactation state, circadian and seasonal variations, and also during skeletal growth. Pre-clinical and translational studies using BTMs with sheep and goats as animal models in orthopaedic research studies to help in the evaluation of the fracture healing process and osteoporosis research are also described in this review. The available information from the reviewed studies was systematically organized in order to highlight the most promising BTMs in small ruminant research, as well as provide a wide view of the use of sheep and goat as animal models in orthopaedic research, type of markers and commercial assay kits with cross-reactivity in sheep and goat, method of sample and storage of serum and urine for bone turnover markers determination and the usefulness and limitations of bone turnover markers in the different studies, therefore an effective tool for researchers that seek answers to different questions while using BTMs in small ruminants.José Arthur de A. Camassa acknowledges to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, for his PhD scholarship 202248/2015-1.info:eu-repo/semantics/publishedVersio

Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies

Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

Resolving the strange behavior of extraterrestrial potassium in the upper atmosphere

It has been known since the 1960s that the layers of Na and K atoms, which occur between 80 and 105 km in the Earth's atmosphere as a result of meteoric ablation, exhibit completely different seasonal behavior. In the extratropics Na varies annually, with a pronounced wintertime maximum and summertime minimum. However, K varies semiannually with a small summertime maximum and minima at the equinoxes. This contrasting behavior has never been satisfactorily explained. Here we use a combination of electronic structure and chemical kinetic rate theory to determine two key differences in the chemistries of K and Na. First, the neutralization of K+ ions is only favored at low temperatures during summer. Second, cycling between K and its major neutral reservoir KHCO3 is essentially temperature independent. A whole atmosphere model incorporating this new chemistry, together with a meteor input function, now correctly predicts the seasonal behavior of the K layer

Particle identification in ALICE : a Bayesian approach

Peer reviewe

Flow Dominance and Factorization of Transverse Momentum Correlations in Pb-Pb Collisions at the LHC

We present the first measurement of the two-particle transverse momentum differential correlation function, P2≡ ΔpTΔpT/ pT2, in Pb-Pb collisions at sNN=2.76 TeV. Results for P2 are reported as a function of the relative pseudorapidity (Δη) and azimuthal angle (Δφ) between two particles for different collision centralities. The Δφ dependence is found to be largely independent of Δη for |Δη|≥0.9. In the 5% most central Pb-Pb collisions, the two-particle transverse momentum correlation function exhibits a clear double-hump structure around Δφ=π (i.e., on the away side), which is not observed in number correlations in the same centrality range, and thus provides an indication of the dominance of triangular flow in this collision centrality. Fourier decompositions of P2, studied as a function of the collision centrality, show that correlations at |Δη|≥0.9 can be well reproduced by a flow ansatz based on the notion that measured transverse momentum correlations are strictly determined by the collective motion of the system

K*(892)(0) and phi(1020)meson production at high transverse momentum in pp and Pb-Pb collisions at root sNN=2.76 TeV

The production of K∗(892)0 and φ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at √sNN = 2.76 TeV has been analyzed using a high luminosity data sample accumulated in 2011 with the ALICE detector at the Large Hadron Collider (LHC). Transverse momentum (pT) spectra have been measured for K∗(892)0 and φ(1020) mesons via their hadronic decay channels for pT up to 20 GeV/c. The measurements in pp collisions have been compared to model calculations and used to determine the nuclear modification factor and particle ratios. The K∗(892)0/K ratio exhibits significant reduction from pp to central Pb-Pb collisions, consistent with the suppression of the K∗(892)0 yield at low pT due to rescattering of its decay products in the hadronic phase. In central Pb-Pb collisions the pT dependent φ(1020)/π and K∗(892)0/π ratios show an enhancement over pp collisions for pT ≈ 3 GeV/c, consistent with previous observations of strong radial flow. At high pT, particle ratios in Pb-Pb collisions are similar to those measured in pp collisions. In central Pb-Pb collisions, the production of K∗(892)0 and φ(1020) mesons is suppressed for pT &gt; 8 GeV/c. This suppression is similar to that of charged pions, kaons, and protons, indicating that the suppression does not depend on particle mass or flavor in the light quark sector