From core/shell to hollow Fe/γ-Fe2O3 nanoparticles: evolution of the magnetic behavior.

High quality Fe/γ-Fe2O3 core/shell, core/void/shell, and hollow nanoparticles with two different sizes of 8 and 12 nm were synthesized, and the effect of morphology, surface and finite-size effects on their magnetic properties including the exchange bias (EB) effect were systematically investigated. We find a general trend for both systems that as the morphology changes from core/shell to core/void/shell, the magnetization of the system decays and inter-particle interactions become weaker, while the effective anisotropy and the EB effect increase. The changes are more drastic when the nanoparticles become completely hollow. Noticeably, the morphological change from core/shell to hollow increases the mean blocking temperature for the 12 nm particles but decreases for the 8 nm particles. The low-temperature magnetic behavior of the 12 nm particles changes from a collective super-spin-glass system mediated by dipolar interactions for the core/shell nanoparticles to a frustrated cluster glass-like state for the shell nanograins in the hollow morphology. On the other hand for the 8 nm nanoparticles core/shell and hollow particles the magnetic behavior is more similar, and a conventional spin glass-like transition is obtained at low temperatures. In the case of the hollow nanoparticles, the coupling between the inner and outer spin layers in the shell gives rise to an enhanced EB effect, which increases with increasing shell thickness. This indicates that the morphology of the shell plays a crucial role in this kind of exchange-biased systems.

Pharmacokinetics, dose proportionality and permeability of S002-333 and its enantiomers, a potent antithrombotic agent, in rabbits.

1. S002-333 [(2-(4'-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-pyrido (3,4-b) indole-3-carboxylic acid amide)] is a novel and potent antithrombotic active agent. The present work investigates the pharmacokinetics, bioavailability, dose proportionality and permeability of the racemate, S002-333 in male New Zealand White (NZW) rabbits. 2. Rabbits were administered single intravenous (i.v.) (2 mg/kg) and three oral doses of 10, 20 and 40 mg/kg of S002-333, respectively, at different occasions to evaluate dose proportionality. Serial blood samples were collected and analyzed by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Since S002-333 is a racemate consisting of S004-1032 (R) and S007-1558 (S), same samples were analyzed using a chiralcel column so as to evaluate the respective enantiomers. 3. The peak plasma concentration, after oral administration, occurred at ∼10 h post-dose. The clearance (CL) and volume of distribution (Vd) after i.v. dose were found to be 3.05 ± 0.09 l/h/kg and 6.73 ± 1.16 l/kg, respectively. The absolute oral bioavailability of S002-333 was 16.32%, whereas it was 6.62 and 5.90% for R- and S-enantiomers, respectively. The absolute bioavailability of 10, 20 and 40 mg/kg doses were found to be 27.91, 14.39 and 16.91%, respectively. The PAMPA (parallel artificial membrane permeability assay) assay shows that S002-333 has a low-passive permeability at gastric and intestinal environment. 4. In conclusion, S002-333 has low-passive permeability, low CL and large Vd. The R-enantiomer has a "slightly" greater bioavailability than the S-enantiomer.

Synthesis of novel ß-carboline based chalcones with high cytotoxic activity against breast cancer cells.

A series of novel ß-carboline based chalcones was synthesized and evaluated for their cytotoxic activity against a panel of human cancer cell lines. Among them we found that two of the compounds 7c and 7d, showed marked anti-proliferative activity in a panel of solid tumor cell lines with highest effect in breast cancer. The compounds 7c and 7d showed an IC50 of 2.25 and 3.29 µM, respectively against human breast cancer MCF-7 cell line. Further, the compound 7c markedly induced DNA fragmentation and apoptosis in breast cancer cells.

Exchange bias effect in Au-Fe3O4 nanocomposites.

We report exchange bias (EB) effect in the Au-Fe3O4 composite nanoparticle system, where one or more Fe3O4 nanoparticles are attached to an Au seed particle forming 'dimer' and 'cluster' morphologies, with the clusters showing much stronger EB in comparison with the dimers. The EB effect develops due to the presence of stress at the Au-Fe3O4 interface which leads to the generation of highly disordered, anisotropic surface spins in the Fe3O4 particle. The EB effect is lost with the removal of the interfacial stress. Our atomistic Monte Carlo studies are in excellent agreement with the experimental results. These results show a new path towards tuning EB in nanostructures, namely controllably creating interfacial stress, and opens up the possibility of tuning the anisotropic properties of biocompatible nanoparticles via a controllable exchange coupling mechanism.

Polymer nanocomposites exhibiting magnetically tunable microwave properties.

Polymer nanocomposites (PNCs) have been synthesized using Rogers polymer and CoFe2O4 nanoparticles (CFO NPs). X-ray diffraction (XRD) confirms the inverse spinel crystal structure of CFO NPs and transmission electron microscopy (TEM) images show the uniform dispersion of nanoparticles (10 nm ± 1) into the polymer matrix. Magnetic measurements indicate superparamagnetic response near room temperature for all PNCs. A blocking temperature T(B)~298 K was observed and does not vary for different loading fractions of CFO NPs for the PNCs. The saturation magnetization (M(s)) was found to be 11 emu g⁻¹ for 30 wt% CFO, increasing to 32 emu g⁻¹ for the 80 wt% CFO loaded PNC. A large value of coercivity (H(c) = 19 kOe) is also observed at 10 K and is not affected by varying CFO loading. Microwave measurements show significant absorption in the 80 wt% CFO loading PNC and the quality factor shows a strong enhancement with applied magnetic field.

Evaluation of the genotoxic potential of standardized extract of Glycyrrhiza glabra (GutGard™).

Glycyrrhiza glabra Linn. (licorice) is widespread throughout the Mediterranean region and certain areas of Asia. Historically, the dried rhizome and root of the plant were used by the Chinese, Egyptian, Greek, Indian, and Roman civilizations as expectorant and carminative. In the modern medicinal system, licorice is used to treat liver ailments, dyspepsia, bronchitis, rheumatoid arthritis etc. Despite the extensive pharmacological applications, the genotoxic potential of G. glabra extract (GutGard™) has not been evaluated. Hence, this study was conducted to investigate the genotoxic potential of GutGard™ using battery of in vitro test systems: bacterial reverse mutation test (Ames II™), chromosome aberration (CA) and micronucleus (MN) tests. GutGard™ did not show significant increase in number of revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with/without S9 fraction. In CA and MN studies, GutGard™ did not show clastogenic effect at 4 and 18 h treatments with and without S9 fraction. Results indicated that GutGard™ is not mutagenic in a battery of genotoxicity tests.

Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha.

ETHNOPHARMACOLOGICAL RELEVANCE: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary. AIM OF THE STUDY: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. The developed method was successfully applied to the in-vitro ADME investigation of WN. MATERIAL AND METHODS: The passive permeability of WN was assayed using PAMPA plates and the plasma protein binding (PPB) was performed using the equilibrium dialysis method. Pooled liver microsomes of rat (RLM) and human (HLM) were used for the microsomal stability, CYP phenotyping, and inhibition studies. CYP phenotyping was evaluated using the specific inhibitors. CYP inhibition study was performed using specific probe substrates along with WN or specific inhibitors. RESULTS: WN was found to be stable in the simulated gastric and intestinal environment and has a high passive permeability at pH 4.0 and 7.0 in PAMPA assay. The PPB of WN at 5 and 20 µg/mL concentrations were found to be high i.e. 82.01 ± 1.44 and 88.02 ± 1.15%, respectively. The in vitro half-life of WN in RLM and HLM was found to be 59.63 ± 2.50 and 68.42 ± 2.19 min, respectively. CYP phenotyping results showed that WN was extensively metabolized by CYP 3A4 and1A2 enzymes in RLM and HLM. However, the results of CYP Inhibition studies showed that none of the CYP isoenzymes were potentially inhibited by WN in RLM and HLM. CONCLUSION: The in vitro results of pH-dependent stability, plasma stability, permeability, PPB, blood partitioning, microsomal stability, CYP phenotyping, and CYP inhibition studies demonstrated that WN could be a better phytochemical for neurological disorders.

Static and dynamic magnetic properties of Co nanoparticles.

Co nanoparticles have been synthesized using wet-chemical methods. As-synthesized particles show a sharp low temperature peak in zero-field cooled (ZFC) magnetization well below the blocking transition temperature and this feature is associated with surface spin disorder. We have investigated the dynamic magnetic properties of Co using ac susceptibility and resonant RF transverse susceptibility (TS). We also studied the memory and relaxation effects in these nanoparticle systems. From these measurements we show a typical blocking behavior of an assembly of superparamagnetic nanoparticles with a wide distribution of blocking temperatures. The transverse susceptibility measurements on these particles show the presence of anisotropy even above the blocking temperature. The role of surface anisotropy and the size distribution of the particles on the observed memory and magnetic relaxation effects are discussed.

White spongy nevus: a nonhereditary presentation.

White spongy nevus (WSN) is a rare hereditary dyskeratotic hyperplasia of the mucous membranes. It is an autosomal dominant disorder with variable penetrance. A few cases of WSN occur due to de novo mutations. We report a case of WSN in a 12-year-old female child, with none of her family members having similar lesions.

Sella Turcica Bridging As A Predictor Of Class II Malocclusion-An Investigative Study.

BACKGROUND: Sella turcica, the bony depression located in sphenoid bone houses and protects the pituitary gland. Formation and development of the sella turcica and teeth share, in common, the involvement of neural crest cells. The anterior part of the sella turcica is believed to develop mainly from neural crest cells, and dental epithelial progenitor cells differentiate through sequential and reciprocal interaction with neural crest-derived mesenchyme. Thus, any structural deviations in the sella, like bridging or roofing, are believed to be related to specific deviations in the facial skeleton and dental anomalies. Until now, there have been no studies concerning the prevalence of sella turcica bridging in skeletal Class II subjects. OBJECTIVE: The aim of this study was to analyse the prevalence of sella turcica bridging in subjects with class I and class II skeletal types and to check whether sella can be considered as diagnostic marker for skeletal class II malocclusion. MATERIALS AND METHODS: Lateral cephalometric images of 205 subjects in the age range of 13 to 25 years were retrospectively analysed and classified for the type of skeletal malocclusion and the radiographs were evaluated for the prevalence of bridging of the sella in these subjects. RESULTS: The results show significance in the prevalence of sella turcica bridging (partial/complete) among subjects with skeletal class II malocclusion.

Paratharmone related protein (peptide): A novel prognostic, diagnostic and therapeutic marker in Head & Neck cancer.

Parathyroid hormone-related protein (PTHrP) is a promising modality of assessment of different critical features of cancer. It is a protein member of parathyroid hormone family, secreted by certain physiologic cells and by malignant tumors in an increased amount. Recent studies have confirmed that PTHrP massively contributes to malignant behaviour of oral cancers-cell proliferation, migration and invasiveness. Strong correlation was found between PTHrP overexpression and local bone invasion and percentage of tumor cells in metastatic nodes. Normal range of PTHrP in serum is 0.7-2.6ρmol/litre. Its down-regulation blocks cell cycle of cancer cell lines and inhibits cell proliferation and colony formation. PTHrP can be used as a diagnostic aid, prognostic marker and excellent research arena for designing novel anti-neoplastic drugs.

Prevalence of temporal bone pneumatization in relation to temporomandibular joint - A computed tomographic study.

BACKGROUND: Pneumatic spaces represent sites of minimal resistance, facilitating the spread of various pathological processes into the joint such as tumors, infection or fractures or vice versa. Considering the clinical importance of temporomandibular joint, prevalence of pneumatic spaces of the temporal bone in relation to TMJ in the roof of the TMJ fossa; articular eminence; zygomatic process and peritubal area was determined using Computed tomography. Laterality and gender wise prevalence of pneumatic spaces around the TMJ was also assessed. MATERIALS AND METHODS: A total of 100 high-resolution CT images of adult patients subjected to CT scan for the base of skull/temporal bone were utilized. Axial, reformatted coronal and sagittal images were analyzed on a DICOM viewer for the presence and distribution of pneumatic spaces of the temporal bone around TMJ in the roof of TMJ fossa, articular eminence, zygomatic process and peritubal area. RESULTS: The extent of pneumatization of the temporal bone varied considerably. The prevalence of pneumatization of the roof of the TMJ fossa was 52%, articular eminence (12%), the root of the zygomatic process (5%) and peritubal area was 56%. Higher frequency of bilateral pneumatization was seen. No statistically significant correlation was seen in gender wise distribution of pneumatization. CONCLUSION: The present study revealed higher prevalence of pneumatization of temporal bone around TMJ. The knowledge of these air spaces is helpful for the interpretation of imaging studies and to understand the spread of pathological processes into the joint.

Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements.

Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are "natural." But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X™ (feed efficiency enhancer), KOLIN PLUS™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test.

Relating surface roughness and magnetic domain structure to giant magneto-impedance of Co-rich melt-extracted microwires.

Understanding the relationship between the surface conditions and giant magneto-impedance (GMI) in Co-rich melt-extracted microwires is key to optimizing their magnetic responses for magnetic sensor applications. The surface magnetic domain structure (SMDS) parameters of ~45 µm diameter Co69.25Fe4.25Si13B13.5-xZrx (x = 0, 1, 2, 3) microwires, including the magnetic domain period (d) and surface roughness (Rq) as extracted from the magnetic force microscopy (MFM) images, have been correlated with GMI in the range 1-1000 MHz. It was found that substitution of B with 1 at. % Zr increased d of the base alloy from 729 to 740 nm while retaining Rq from ~1 nm to ~3 nm. A tremendous impact on the GMI ratio was found, increasing the ratio from ~360% to ~490% at an operating frequency of 40 MHz. Further substitution with Zr decreased the high frequency GMI ratio, which can be understood by the significant increase in surface roughness evident by force microscopy. This study demonstrates the application of the domain period and surface roughness found by force microscopy to the interpretation of the GMI in Co-rich microwires.

Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A-ß-Catenin Signaling and Restricts Tumor Growth and Metastasis.

Molecular hybridization of different pharmacophores to tackle both tumor growth and metastasis by a single molecular entity can be very effective and unique if the hybrid product shows drug-like properties. Here, we report synthesis and discovery of a novel small-molecule inhibitor of PP2A-ß-catenin signaling that limits both in vivo tumor growth and metastasis. Our molecular hybridization approach resulted in cancer cell selectivity and improved drug-like properties of the molecule. Inhibiting PP2A and ß-catenin interaction by selectively engaging PR55α-binding site, our most potent small-molecule inhibitor diminished the expression of active ß-catenin and its target proteins c-Myc and Cyclin D1. Furthermore, it promotes robust E-cadherin upregulation on the cell surface and increases ß-catenin-E-Cadherin association, which may prevent dissemination of metastatic cells. Altogether, we report synthesis and mechanistic insight of a novel drug-like molecule to differentially target ß-catenin functionality via interacting with a particular subunit of PP2A. Mol Cancer Ther; 16(9); 1791-805. ©2017 AACR.

Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

Ferromagnetic glass-coated microwires with good heating properties for magnetic hyperthermia.

The heating properties of Fe71.7Si11B13.4Nb3Ni0.9 amorphous glass-coated microwires are explored for prospective applications in magnetic hyperthermia. We show that a single 5 mm long wire is able to produce a sufficient amount of heat, with the specific loss power (SLP) reaching a value as high as 521 W/g for an AC field of 700 Oe and a frequency of 310 kHz. The large SLP is attributed to the rectangular hysteresis loop resulting from a peculiar domain structure of the microwire. For an array of parallel microwires, we have observed an SLP improvement by one order of magnitude; 950 W/g for an AC field of 700 Oe. The magnetostatic interaction strength essential in the array of wires can be manipulated by varying the distance between the wires, showing a decreasing trend in SLP with increasing wire separation. The largest SLP is obtained when the wires are aligned along the direction of the AC field. The origin of the large SLP and relevant heating mechanisms are discussed.

Chemically fabricated magnetic quantum dots of InP:Mn.

Quantum dots of InP:Mn are chemically prepared by following hot colloidal nanochemistry with starting precursors that obviate the need for external surfactant. These quantum dots are uniform spheres with 3-nm diameters; they are crystalline, photoluminescent, and magnetic. The crystallographic and optical properties are similar to those of undoped InP nanocrystallites, while the magnetism is consistent with the ferromagnetic response observed in a class of diluted magnetic semiconductors. Because of the ultrafine sizes, the sample shows superparamagnetic behavior, whereas ferromagnetic hysteresis loops are clearly seen below the blocking temperature. Structural characterization and analysis confirm that the magnetism in these quantum dots is not due to segregated binary MnP or MnO phases and that they truly represent a homogeneous dilute magnetic semiconductor.

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis.

Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research.

Nanocomposite magneto-rheological fluids with uniformly dispersed Fe nanoparticles.

A systematic study of the magnetic and rheological properties of magneto-rheological (MR) fluids containing micron-size and nano-size iron particles is presented. The MR fluids were prepared with hydraulic oil as the carrier liquid and lecithin as an effective surfactant medium that promotes uniform particle dispersion. Magnetic measurements on micron-, hybrid-(nano + micron), and nano-MR fluids clearly indicate that the partial replacement of the micro-size particles by nanoparticles results in a better suspension and robust chain formation under applied external magnetic fields. For nano-MR fluids, the measured yield stress was found to be lower than micron-MR fluids. However, better flow properties and sharper magnetic switching make nanoparticle-based MR fluids appealing for microfluidics device applications where higher yield stress is not required.