Antiproliferative triterpenes from Melaleuca ericifolia

Three new 28-norlupane triterpenes, 28-norlup-20(29)-en-3beta-hydroxy-17beta-hydroperoxide (1), 28-norlup-20(29)-en-3beta-hydroxy-17alpha-hydroperoxide (2), and 20 S-17beta,29-epoxy-28-norlupan-3beta-ol (3), were isolated from the leaves of Melaleuca ericifolia along with eight known pentacyclic triterpenes. The structures of the new compounds were elucidated by spectroscopic methods including 1D and 2D NMR spectroscopy and mass spectrometry. The isolated triterpenes were evaluated for antiproliferative activity against the malignant +SA mammary epithelial cell line.     

Antiosteoporotic chemical constituents from Er-Xian Decoction, a traditional Chinese herbal formula

AIM OF THE STUDY: Er Xian Decoction (EXD), a traditional Chinese medicine formula, has long been used for the treatment of osteoporosis and menopausal syndrome in China. The present study was designed to investigate the antiosteoporotic constituents of EXD, and evaluate their antiosteoporotic effects in ovariectomized rats. MATERIALS AND METHODS: Osteoblasts in neonatal calvaria cultures and osteoclasts derived from rat marrow cells were used to bioactivity-guided screen the active constituents. The proliferation of osteoblast was assayed by MTT methods. The activity of ALP and TRAP was measured by p- nitrophenyl sodium phosphate assay. The antiosteoporotic effects of icariin (1), anemarsaponin B II (8) and berberine (6) were verified by using OVX rats model. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry using the small animal scan mode. The undecalcified longitudinal proximal tibial metaphysical (PTM) sections were cut and stained for the bone histomorphometric analysis. RESULTS: Bioactivity-guided fractionation has led to the successful isolation of antiosteoporotic constituents, i.e., icariin (1), icariside I (2), baohuoside I (3), mangiferin (4), neomangiferin (5), berberine (6), anemarsaponin B (7), anemarsaponin BII (8), anemarsaponin C (9), anemarrhenasaponin I (10), rubiadin-1-methyl ether (11) and obaculactone (12) from EXD. Further study showed that icariin (1), anemarsaponin BII (8) and berberine (6) increased the BMD in ovariectomized rats, and icariin (1) not only increased the bone formation, but also inhibited bone resorption; anemarsaponin BII (8) mainly increased bone formation and berberine (6) only inhibited the bone resorption in ovariectomized rats. CONCLUSION: Our findings demonstrate that multiple ingredients are responsible for antiosteoporotic activity in traditional Chinese medicine formula Er-Xian decoction.     

Hypocalcemia is common in the first 48 h of life in ELBW infants

BACKGROUND: The incidence of early hypocalcemia in extremely low birthweight (ELBW) infants is unknown because the distribution of serum calcium values in this population is not defined. OBJECTIVE: To determine the range of serum calcium values in ELBW infants during the first 48 h of life and the risks associated with low values. DESIGN/METHODS: Retrospective analysis of all ELBW infants admitted on day 1 of life from April 2004 to October 2006. Demographic variables, therapy, serum calcium (Ca), pH, albumin, and blood ionized Ca were recorded. RESULTS: There were 381 Ca levels obtained from 111 patients. Mean Ca was 6.90 mg/dL (1.73 mmol/L) (5(th)-95(th) percentile: 5.16-8.80). Ca levels rose after 24 h of life. Almost one quarter (23.1%) of the Ca levels were low by current standards. The majority of subjects (59.9%) had at least one hypocalcemic value. CONCLUSIONS: Serum Ca values are lower in ELBW infants and inconsequential. Thus, hypocalcemia should be re-defined for ELBW infants.     

Refractory hypertensive emergency associated with complete heart block resolved after permanent pacemaker implantation: A case report

Severe hypertension sometimes improves with treatment of bradycardia but this phenomenon is under‐reported. Here, an elderly gentleman with complete heart block and a hypertensive emergency was refractory to medical therapies and blood pressure only improved following pacemaker implantation. We discuss the possible mechanisms relating to heart rate and artificial pacing.     

The Effect of Dentifrice on Micro-Hardness,Surface Gloss,and Micro-Roughness of Nano Filled Conventional and Bulk-Fill Polymer Composite—A Micro Indentation and Profilometric Study

The aim of the present study was to evaluate the effect of brushing with two whitening dentifrices (Colgate Optic White (COW) and Colgate Optic White Charcoal (COC)) on surface gloss, micro-roughness, and micro-hardness of nanostructured hybrid conventional (Z350) and bulk-fill (Tetric N Ceram bulk-fill) polymer composite. In total, 96 disk samples using two nano-hybrid composite polymers (Z350 and Tetric N Ceram Bulk-fill) were prepared. All specimens were exposed to two different dentifrices (COW and COC), resulting in four main subgroups in the study. Specimens were assessed for surface gloss, micro-roughness (Ra), and micro-hardness using standardized methodology. Means and standard deviations of properties compared using paired t-test, one-way and two-way ANOVA, and post hoc test. The presence of dentifrices did not show any significant difference in micro-hardness values of Z350 (p > 0.05), whereas micro-hardness of bulk-fill composite significantly reduced on dentifrices exposure (p ≤ 0.05). Bulk-fill polymer composite showed significant reduction in gloss after dentifrice exposure (p < 0.05), however, Z350 showed no significant loss of gloss due to dentifrices (p > 0.05). A significant increase in Ra was observed for both resin materials after exposure to dentifrices (COC and COW). Conventional resin composite (Z350) showed comparable surface hardness and gloss before and after dentifrice exposure, however, micro-roughness increased significantly due to dentifrice exposure. Bulk-fill resin (Tetric N Ceram) showed significant loss of micro-hardness and gloss and increase in micro-roughness on dentifrice exposure. Conventional nano-hybrid composite polymer showed better durability in resisting loss of surface properties compared to bulk-fill resin polymer in the present experiment.     

Assessment of Bioceramic Sealer Retreatability and Its Influence on Force and Torque Generation

This study assesses the retreatability of TotalFill bioceramic (TFBC) and AH Plus (AHP) sealers and their impact on retreatment force and torque. Twenty-six premolar teeth with single oval canals were instrumented, obturated using the matched gutta-percha cone technique with one of the tested sealers, and then temporized. After a 6-month incubation at 37 °C and 100% humidity, the canals were retreated with the XP Shaper system. During retreatment, the generated force and torque were measured. Micro-CT scanning was run before and after the retreatment procedure to analyze the remaining obturating materials in the canals. The apically directed maximum force in AHP was higher than that in TFBC. The coronally directed maximum force and the maximum torque were comparable between the groups. A higher amount of remaining obturating materials was found in the AHP compared to that in the TFBC. Based on these findings, endodontic sealer had an influence on retreatability, and the TFBC showed less remaining obturating materials and lower retreatment forces in the apical direction compared to the AHP in extracted teeth with oval canals.     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Evaluation of the Radiation Shielding Properties of a Tellurite Glass System Modified with Sodium Oxide

In this study, the X-ray and gamma attenuation characteristics and optical properties of a synthesized tellurite–phosphate–sodium oxide glass system with a composition of (85 − x)TeO₂–10P₂O₅–xNa₂O mol% (where x = 15, 20, and 25) were evaluated. The glass systems we re fabricated by our research group using quenching melt fabrication. The shielding parameters of as-synthesized systems, such as the mass attenuation coefficient (MAC), linear attenuation coefficient (LAC), effective atomic number (Z_eff), half-value layer (HVL), tenth value layer (TVL), mean free path (MFP), and effective electron density (N_eff) in a wide energy range between 15 keV and 15 MeV, were estimated using well-known PHY-X/PSD software and recently developed MIKE software. Herein, the optical parameters of prepared glasses, such as molar volume (V_M), oxygen molar volume (V_O), oxygen packing density (OPD), molar polarizability (αm), molar refractivity (R_m), reflection loss (R_L), and metallization (M), were estimated using MIKE software. Furthermore, the shielding performance of the prepared glasses was compared with that of commonly used standard glass shielding materials. The results show that the incorporation of sodium oxide into the matrix TeO₂/P₂O₅ with an optimum concentration can yield a glass system with good shielding performance as well as good optical and physical properties, especially at low photon energy.     

Hyperactive Transforming Growth Factor‐β1 Signaling Potentiates Skeletal Defects in a Neurofibromatosis Type 1 Mouse Model

Dysregulated transforming growth factor beta (TGF‐β) signaling is associated with a spectrum of osseous defects as seen in Loeys‐Dietz syndrome, Marfan syndrome, and Camurati‐Engelmann disease. Intriguingly, neurofibromatosis type 1 (NF1) patients exhibit many of these characteristic skeletal features, including kyphoscoliosis, osteoporosis, tibial dysplasia, and pseudarthrosis; however, the molecular mechanisms mediating these phenotypes remain unclear. Here, we provide genetic and pharmacologic evidence that hyperactive TGF‐β1 signaling pivotally underpins osseous defects in Nf1^flox/?;Col2.3Cre mice, a model which closely recapitulates the skeletal abnormalities found in the human disease. Compared to controls, we show that serum TGF‐β1 levels are fivefold to sixfold increased both in Nf1^flox/?;Col2.3Cre mice and in a cohort of NF1 patients. Nf1‐deficient osteoblasts, the principal source of TGF‐β1 in bone, overexpress TGF‐β1 in a gene dosage–dependent fashion. Moreover, Nf1‐deficient osteoblasts and osteoclasts are hyperresponsive to TGF‐β1 stimulation, potentiating osteoclast bone resorptive activity while inhibiting osteoblast differentiation. These cellular phenotypes are further accompanied by p21‐Ras–dependent hyperactivation of the canonical TGF‐β1–Smad pathway. Reexpression of the human, full‐length neurofibromin guanosine triphosphatase (GTPase)‐activating protein (GAP)‐related domain (NF1 GRD) in primary Nf1‐deficient osteoblast progenitors, attenuated TGF‐β1 expression levels and reduced Smad phosphorylation in response to TGF‐β1 stimulation. As an in vivo proof of principle, we demonstrate that administration of the TGF‐β receptor 1 (TβRI) kinase inhibitor, SD‐208, can rescue bone mass deficits and prevent tibial fracture nonunion in Nf1^flox/?;Col2.3Cre mice. In sum, these data demonstrate a pivotal role for hyperactive TGF‐β1 signaling in the pathogenesis of NF1‐associated osteoporosis and pseudarthrosis, thus implicating the TGF‐β signaling pathway as a potential therapeutic target in the treatment of NF1 osseous defects that are refractory to current therapies. © 2013 American Society for Bone and Mineral Research.