Impact of Iron on the Fe-Co-Ni Ternary Nanocomposites Structural and Magnetic Features Obtained via Chemical Precipitation Followed by Reduction Process for Various Magnetically Coupled Devices Applications.

This paper presents the synthesis of Fe-Co-Ni nanocomposites by chemical precipitation, followed by a reduction process. It was found that the influence of the chemical composition and reduction temperature greatly alters the phase formation, its structures, particle size distribution, and magnetic properties of Fe-Co-Ni nanocomposites. The initial hydroxides of Fe-Co-Ni combinations were prepared by the co-precipitation method from nitrate precursors and precipitated using alkali. The reduction process was carried out by hydrogen in the temperature range of 300-500 °C under isothermal conditions. The nanocomposites had metallic and intermetallic phases with different lattice parameter values due to the increase in Fe content. In this paper, we showed that the values of the magnetic parameters of nanocomposites can be controlled in the ranges of MS = 7.6-192.5 Am2/kg, Mr = 0.4-39.7 Am2/kg, Mr/Ms = 0.02-0.32, and HcM = 4.72-60.68 kA/m by regulating the composition and reduction temperature of the Fe-Co-Ni composites. Due to the reduction process, drastic variations in the magnetic features result from the intermetallic and metallic face formation. The variation in magnetic characteristics is guided by the reduction degree, particle size growth, and crystallinity enhancement. Moreover, the reduction of the surface spins fraction of the nanocomposites under their growth induced an increase in the saturation magnetization. This is the first report where the influence of Fe content on the Fe-Co-Ni ternary system phase content and magnetic properties was evaluated. The Fe-Co-Ni ternary nanocomposites obtained by co-precipitation, followed by the hydrogen reduction led to the formation of better magnetic materials for various magnetically coupled device applications.

Novel Conjugated Quinazolinone-Based Hydroxamic Acids: Design, Synthesis and Biological Evaluation.

BACKGROUND: The target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development. Histone deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing conjugated quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating conjugated 6-hydroxy-2 methylquinazolin- 4(3H)-ones (15a-l) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1. Molecular simulations were finally performed to gain more insight into the structureactivity relationships. RESULTS: It was found that among novel conjugated quinazolinone-based hydroxamic acids synthesized, compounds 15a, 15c and 15f were the most potent, both in terms of HDAC inhibition and cytotoxicity. Especially, compound 15f displayed up to nearly 4-fold more potent than SAHA (vorinostat) in terms of cytotoxicity against MCF-7 cell line with IC50 value of 1.86 µM, and HDAC inhibition with IC50 value of 6.36 µM. Docking experiments on HDAC2 isozyme showed that these compounds bound to HDAC2 with binding affinities ranging from -10.08 to -14.93 kcal/mol compared to SAHA (-15.84 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward SKLu-1than MCF-7 and HepG-2. CONCLUSION: The resesrch results suggest that some hydroxamic acids could emerge for further evaluation and the results are well served as basics for further design of more potent HDAC inhibitors and antitumor agents.

Age-related changes in the cranial thickness of Japanese macaques ( Macaca fuscata ) / Cambios relacionados con la edad en el grosor craneal de los macacos japoneses ( Macaca fuscata )

Craniometry has revealed that continuous skull expansion occurs after dental maturity in macaques and other nonhuman primates. Endocranial volume has been shown to increase with age from mid-adulthood to older age in macaques. Thus, neurocranial thickness may decrease with age, especially from mid-adulthood to older age. Here, we investigated age-related changes in the cranial thickness of Japanese macaques (Macaca fuscata). Ten cranial thickness measurements (ten neurocranial landmarks) were made using computed tomographic scans of 140 crania from adult macaques (67 males and 73 females). The cranial thickness at many sites was shown to increase in the neurocranium from young adulthood (7-9 years) to early-mid adulthood (14-19 years) in males and latemid adulthood (19-24 years) in females, while it was decreased in the oldest age group (>24 years). The cranial thickness at various sites showed a significant decrease from mid-adulthood to very old age in both sexes, although females had more sites with decreasing thickness than did males. The difference between sexes in terms of age-related changes in cranial thickness at sites on the mid-sagittal plane may be associated with the differences in the size of the projecting face and canines between males and females. The greater number of sites with decreasing thickness in females than in males may be associated with postmenopausal estrogen depletion in female macaques.

La craneometría ha revelado que la expansión continua del cráneo se produce después de la madurez dental en macacos y otros primates no humanos. Se ha demostrado que el volumen endocraneal aumenta con la edad desde mediados de la edad adulta hasta la edad más avanzada en macacos. Por lo tanto, el grosor neurocraneal puede disminuir con la edad, especialmente desde la edad adulta media hasta la edad avanzada. Aquí, investigamos los cambios relacionados con la edad en el grosor craneal de los macacos Japoneses (Macaca fuscata). Se realizaron diez mediciones del grosor craneal (considerando diez puntos de referencia neurocraneales) mediante tomografías computarizadas de 140 cráneos de macacos adultos (67 machos y 73 hembras). Se observó que el grosor craneal en muchos sitios aumentó en el neurocráneo desde la edad adulta joven (7-9 años) hasta la edad adulta media (14-19 años) en los hombres y en la edad adulta media tardía (19-24 años) en las mujeres, mientras que se redujo en el grupo de mayor edad (> 24 años). El grosor craneal en varios sitios mostró una disminución significativa desde la edad adulta media hasta la edad muy avanzada en ambos sexos, aunque las hembras tenían más sitios con grosor decreciente. La diferencia entre sexos, en términos de cambios relacionados con la edad, en el grosor craneal en los sitios en el plano mediano puede asociarse con las diferencias en el tamaño de la cara y en los caninos entre machos y hembras. El mayor número de sitios con grosor decreciente en las hembras respecto a los machos puede estar asociado con el agotamiento de los estrógenos posmenopáusicos en los macacos hembras.

Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23.

Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria Corallococcus coralloides M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the ß-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.

Daphnane and Phorbol Diterpenes, Anti-neuroinflammatory Compounds with Nurr1 Activation from the Roots and Stems of Daphne genkwa.

The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D. genkwa extract. Consistent with their higher Nurr1 activating activity, compounds 1, 4, 5, and 7 exhibited higher inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial BV-2 cells with an IC50 (µM) of 1-2, which was 15-30 times more potent than that of minocycline (29.9 µM), a well-known anti-neuroinflammatory agent. Additionally, these diterpenes reduced expression and transcription of LPS-induced pro-inflammatory cytokines in BV-2 cells. Thus, the daphnane-type and phorbol-type diterpenes had anti-neuroinflammatory activity with Nurr1 activation and could be responsible for the anti-PD effect of the roots and stems of D. genkwa.

Translocation of BBAP from the cytoplasm to the nucleus reduces the metastatic ability of vemurafenib-resistant SKMEL28 cells.

To the best of our knowledge, the present study is the first to demonstrate that treatment of vemurafenib-resistant SKMEL28 (SKMEL28-R) cells with paclitaxel leads to a shift in localization of the E3-ligase BBAP from the cytoplasm to the nucleus, consequently decreasing the metastatic ability of this cell line. The present study revealed that the movement of BBAP from the cytoplasm to nucleus initiated a change in cell morphology. In addition, the translocation of BBAP led to a decrease of metastatic characteristics in SKMEL28­R cells, including migration and invasion via downregulation of the phosphorylated form of focal adhesion kinase and N­cadherin, as well as an upregulation of p21 and E-cadherin. The results of the present study suggested that BBAP may not only be a novel biomarker for melanoma, but also a novel therapeutic target for treatment of metastatic melanoma.

Deoxyschisandrin inhibits H2O2-induced apoptotic cell death in intestinal epithelial cells through nuclear factor-kappaB.

Oxidative stress is a pathogenesis for a typical inflammatory intestinal disease known as ulcerative colitis (UC) characterized by erosion and mucosal ulceration. For the treatment of UC, many kinds of traditional Asian medical plants have been used. Schisandra chinensis fruits (SC) are known to possess anti-ulcer, anti-hepatotoxic and anti-neurotoxic activity. However, its mechanism is still unknown. In the present study, we investigated the cytoprotective effect of deoxyschisandrin, a lignan compound comprised of SC fruits, on H2O2-induced apoptotic cell death in human intestinal epithelial cells (HCT116). In flow cytometry assay using Annexin V and propidium iodide, deoxyschisandrin inhibited H2O2-induced apoptotic cell death. To further evaluate the apoptotic signaling by H2O2, we detected caspase-3 activation using cleavage of pro-caspase-3. Deoxyschisandrin inhibited H2O2-induced caspase-3 activation by blocking cleavage of pro-caspase-3. Furthermore, it has been reported that oxidative stress by H2O2 induces an activation of nuclear factor-kappaB (NF-kappaB). In our results, H2O2 stimulated the degradation of IkappaBalpha, inhibitor of NF-kappaB, in a concentration-dependent manner. On the contrary, deoxyschisandrin inhibited H2O2-stimulated degradation of IkappaBalpha and activation of NF-kappaB by blocking translocation of NF-kappaB to the nucleus. Therefore, we suggest that deoxyschisandrin inhibits H2O2-induced apoptotic cell death.