Immunotoxicity and Anti-Inflammatory Characterizations of Prenylated Flavonoids-The Lipophilic 7-O-Terpenylated Wogonin.

Wogonin, one of the exceptional bioactive flavonoids found abundant in the roots of Huang-Qin (Scutellaria baicalensis Georgi), is a popular health-preserving Chinese medicine. The therapeutic applications can be expanded by improving its bioavailability. The 7-O-terpenylated wogonin consisting one to three prenyl units are chemically synthesized for increasing lipophilic nature for efficient uptake, and also an attempt in mimicry of naturally scarce terpenylated flavonoids found in limited plant families and bee propolis. Wogonin (W) and its lipophilic nature prenyl wogonin (W5), geranyl wogonin (W10), and farnesyl wogonin (W15) were comparatively studied with structure-relationship in immunotoxicity of cell livability on lymphoid, myeloid, and somatic origins cell lines. Anti-inflammatory functions characterized with nitric oxide inhibition and intracellular ROS level of LPS-activated murine macrophage RAW264.7 were assessed. Wogonin and its terpenylated derivatives have selectively influenced livability of lymphoid origin cells but not myeloid and somatic origin cells. The mitotic protein survivin gene expressions analysis further supported the selective suppressions on lymphoid origin YAC-1 cells by wogonin and geranyl wogonin, while oppositely boosted survivin expressions in LPS-activated macrophages. Moreover, wogonin exhibits dose-dependent inhibition on the nitric oxide (NO) production and iNOS gene expressions of LPS-activated RAW264.7 cells. Terpenylated wogonin exhibits profoundly superior control in intracellular ROS level and a sustained action with sound cell integrity than the wogonin. The enhanced cellular uptake with higher lipophilicity to membrane of 7-O-terpenylated wogonin may pose an important biological nature in facilitating better bioavailability and specific immunomodulatory actions of the category of terpenylated flavonoids. The 7-O-terpenylated wogonin having biological merit of fast membrane lipid bilayer integration, lower effective concentration, and better preserving immune cells functions and livability deserved further in-depth investigations and their broadly therapeutic applications.

Discovery of slow magnetic fluctuations and critical slowing down in the pseudogap phase of YBa2Cu3O y.

The origin of the pseudogap region below a temperature T* is at the heart of the mysteries of cuprate high-temperature superconductors. Unusual properties of the pseudogap phase, such as broken time-reversal and inversion symmetry are observed in several symmetry-sensitive experiments: polarized neutron diffraction, optical birefringence, dichroic angle-resolved photoemission spectroscopy, second harmonic generation, and polar Kerr effect. These properties suggest that the pseudogap region is a genuine thermodynamic phase and are predicted by theories invoking ordered loop currents or other forms of intra-unit-cell (IUC) magnetic order. However, muon spin rotation (µSR) and nuclear magnetic resonance (NMR) experiments do not see the static local fields expected for magnetic order, leaving room for skepticism. The magnetic resonance probes have much longer time scales, however, over which local fields could be averaged by fluctuations. The observable effect of the fluctuations in magnetic resonance is then dynamic relaxation. We have measured dynamic muon spin relaxation rates in single crystals of YBa2Cu3O y (6.72 < y < 6.95) and have discovered "slow" fluctuating magnetic fields with magnitudes and fluctuation rates of the expected orders of magnitude that set in consistently at temperatures Tmag ≈ T*. The absence of any static field (to which µSR would be linearly sensitive) is consistent with the finite correlation length from neutron diffraction. Equally important, these fluctuations exhibit the critical slowing down at Tmag expected near a time-reversal symmetry breaking transition. Our results explain the absence of static magnetism and provide support for the existence of IUC magnetic order in the pseudogap phase.

Clinical impact of in vitro cellular drug resistance on childhood acute lymphoblastic leukemia in Taiwan.

Despite the successful treatment of childhood acute lymphoblastic leukemia (ALL), the resistance to chemotherapy in ALL cells continues to play an important role in treatment failure. In vitro drug resistance determined using an MTT [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was carried out in 16 children with newly diagnosed ALL between November 2009 and December 2010. The in vitro therapeutic effects of asparaginase, vincristine, prednisolone, dexamethasone, epirubicin and cytarabine were examined. Although there was no significant association between in vitro drug resistance of leukemic cells and ALL subtypes, ETV6-RUNX1 ALL tended to be more sensitive to asparaginase, vincristine and prednisolone. Leukemic cells from girls were significantly more sensitive to epirubicin compared with boys (p = 0.008). Higher leukocyte count at diagnosis was correlated with in vitro resistance to asparaginase and prednisolone (p = 0.03 and 0.05, respectively). Relapse or death occurred in five patients. The leukemic cells from these five patients demonstrated increased in vitro resistance to asparaginase compared to those from the other 11 patients (p = 0.009). From the present case series, the demonstrated in vitro resistance to chemotherapeutic agents may have a prognostic value in children with ALL before comprehensive minimal residual disease measurement is available.

Ferromagnetic ordering and simultaneous fast magnetization tunneling in a Ni4 single-molecule magnet.

Low-temperature heat capacity and oriented single-crystal field-cooled and zero-field-cooled magnetization data for the single-molecule magnet [Ni(hmp)(dmb)Cl](4) are presented that indicate the presence of ferromagnetic ordering at approximately 300 mK, which has little effect on the magnetization relaxation rates.

Weak coupling magnetism in Ce4Pt12Sn25: a small exchange limit in the Doniach phase diagram.

Magnetic susceptibility, magnetization, specific heat, and electrical resistivity studies on single crystals of Ce4Pt12Sn25 reveal an antiferromagnetic transition at T(N) = 0.19 K, which develops from a paramagnetic state with a very large specific heat coefficient (C/T) of 14 J mol(-1) K(-2)-Ce just above T(N). On the basis of its crystal structure and these measurements, we argue that a weak magnetic exchange interaction in Ce4Pt12Sn25 is responsible for its low ordering temperature and a negligible Kondo-derived contribution to physical properties above T(N). The anomalous enhancement of specific heat above T(N) is suggested to be related, in part, to weak geometric frustration of f-moments in this compound.

Nephronectin expression in nephrotoxic acute tubular necrosis.

BACKGROUND: Acute tubular necrosis (ATN) is characterized by an initiation phase, followed by an extension phase, and a maintenance and recovery phase, the latter of which involves increased regeneration of tubular cells. Nephronectin (NPNT), a ligand for alpha8beta1 integrin, is expressed in the ureteric bud epithelium during kidney morphogenesis. However, little is known about the potential involvement of NPNT in the regeneration phase of ATN. METHODS: cDNA microarray, real-time polymerase chain reaction, in situ hybridization, immunohistochemistry, immuno-electron microscopy and immunoassay (for urine) were used to identify the time-course NPNT expression in a murine model of ATN. RESULTS: The gene transcript of NPNT was examined during a 14-day course of ATN by a cursory cDNA microarray analysis. Although NPNT was observed focally in normal renal tubular epithelium, it was greatly expressed in regenerating tubular cells during the maintenance and recovery phases of ATN. As early as day 1 following onset of ATN, NPNT was already present in the urine. Importantly, NPNT expression preceded proliferating cell nuclear antigen protein expression in regenerating renal tubular epithelial cells, as demonstrated by double immunohistochemistry. CONCLUSION: The present study was the first to identify an enhanced expression of NPNT in regenerating tubular epithelium in an experimental model of ATN. NPNT may play a crucial role in the regenerating process of nephrotoxic ATN. Our data also suggest that NPNT may provide a useful tissue and urine biomarker for both the development and evolution of nephrotoxic acute renal injury.