CXCR4 heterogeneous expression in esophageal squamous cell cancer and stronger metastatic potential with CXCR4-positive cancer cells.

CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. In this study, we analyzed CXCR4 expression in tumor tissue and metastatic tumor tissues of lymph node by immunohistochemistry. CXCR4 was found to be an independent factor of patients' survival and heterogeneously expressed in tumor tissues. Compared with the primary tumor tissues, the scores of CXCR4 expression were significantly higher in corresponding metastatic tumor tissues of lymph nodes (P < 0.01). It was suggested CXCR4-positive cells were prone to migrate to lymph nodes. In the further experiments in vitro, we confirmed heterogeneous expression of CXCR4 in esophageal squamous cell cancer cell lines (KYSE70, Ec109, and CaES17) by flow cytometry analysis. Meanwhile, two subpopulations were isolated from Ec109 based on CXCR4 membrane expression by fluorescence-activated cell sorting. CXCR4-positive cells showed stronger migration ability in Boyden chamber assay than CXCR4 negative ones (P < 0.01). However, no significant difference of cell proliferation was found between the two subpopulations in colony formation assay (P > 0.05). We concluded that CXCR4 might be a key molecule in esophageal squamous cell cancer metastasis.

Incoherent c-axis interplane response of the iron chalcogenide FeTe(0.55)Se(0.45) superconductor from infrared spectroscopy.

We report on the interplane c-axis electronic response of FeTe(0.55)Se(0.45) investigated by infrared spectroscopy. We find that the normal-state c-axis electronic response of FeTe(0.55)Se(0.45) is incoherent and bears significant similarities to those of mildly underdoped cuprates. The c-axis optical conductivity σ(c)(ω) of FeTe(0.55)Se(0.45) does not display well-defined Drude response at all temperatures. As temperature decreases, σ(c)(ω) is continuously suppressed. The incoherent c-axis response is found to be related to the strong dissipation in the ab-plane transport: a pattern that holds true for various correlated materials as well as FeTe(0.55)Se(0.45).

Ligustilide, a major bioactive component of Angelica sinensis, promotes bone formation via the GPR30/EGFR pathway.

Angelica sinensis (Oliv.) Diels is a widely-used traditional Chinese herbal medicine in treating osteoporosis. Ligustilide (LIG) is the main component of A. sinensis and is considered to be the most effective biologically active ingredient in this plant. LIG has been found to have multiple pharmacological activities, such as anti-atherosclerosis, neuroprotection, anticancer, anti-inflammatory and analgesic. However, little is known regarding its anti-osteoporotic effects. The aims of this study were to investigate any protective effect of LIG on bone formation. The results showed that LIG significantly ameliorated inhibition of bone formation in zebrafish caused by prednisolone. LIG promoted osteoblast differentiation, including that of the pre-osteoblastic cell line MC3T3-E1 and bone marrow mesenchymal stem cells. LIG greatly improved the viability of MC3T3-E1 cells exposed to H2O2, attenuated H2O2-induced apoptosis and increased the expression of Bcl-2. Furthermore, LIG treatment lead to marked activation of phosphorylated EGFR and ERK1/2. These effects could be obviously inhibited by blocking GPR30 signaling with the specific inhibitor G15. Collectively, the results reveal that GPR30 is a positive switch for LIG to increase bone formation via regulation of EGFR, and these results provide evidence for the potential of LIG to treat osteoporosis.

Effects of nuclear cross sections at different energies on the radiation hazard from galactic cosmic rays.

The radiation hazard for astronauts from galactic cosmic rays (GCR) is a major obstacle to long-duration human space exploration. Space radiation transport codes have been developed to calculate the radiation environment on missions to the Moon, Mars, and beyond. We have studied how uncertainties in fragmentation cross sections at different energies affect the accuracy of predictions from such radiation transport calculations. We find that, in deep space, cross sections at energies between 0.3 and 0.85 GeV/nucleon have the largest effect in solar maximum GCR environments. At the International Space Station, cross sections at higher energies have the largest effect due to the geomagnetic cutoff.

High LET-induced H2AX phosphorylation around the Bragg curve.

We investigated the spatial distribution of the induction of the phosphorylated form of the histone protein H2AX (gamma-H2AX), known to be activated by DSBs. Following irradiation of human fibroblast cells with 600 MeV/nucleon silicon and 600 MeV/nucleon iron ions we observed the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in an x/y plane. Polyethylene shielding was used to achieve a Bragg curve distribution with beam geometry parallel to the monolayer of cells. We present data that highlights the formation of immunofluorescent gamma-H2AX tracks showing the ion trajectories across the Bragg peak of irradiated human fibroblast cells. Qualitative analyses of these distributions indicated potentially increased clustering of DNA damage before the Bragg peak, enhanced gamma-H2AX distribution at the peak, and provided visual evidence of high-linear energy transfer particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. Spatial assessment of gamma-H2AX fluorescence may provide direct insights into DNA damage across the Bragg curve for high charge and energy ions including the biological consequences of shielding and possible contributors to bystander effects.

Sterols from the fungus Lactarium volemus.

Seven ergostane-type sterols and two mono-glucosides were isolated from the ethyl acetate soluble fraction of Lactarium rolemus. Three are previously unknown, i.e. 3-O-beta-D-glucopyranosyl-22E,24R-5alpha,8alpha-epidioxyergosta-6,22-diene, 3-O-beta-D-glucopyranosyl-22E,24R-5beta,8beta-epidioxyergosta-6,22-diene and 22E,24R-ergosta-7,22-diene-3beta,5alpha,6beta,9alpha-tetraol. The structural elucidation of these compounds was mainly achieved by spectroscopic methods.

Cytotoxic ent-kaurene diterpenoids from Isodon gesneroides.

From Isodon gesneroides, three new cytotoxic diterpenoids, gesneroidins A, B and C, together with one known diterpenoid, dawoensin A, were isolated, and the structure determination and unambiguous assignment of their stereochemistry and NMR spectral data were made by a combination of one-and two-dimensional NMR techniques, computer modelling calculations and X-ray analysis.

Diterpenoids from Isodon eriocalyx var. laxiflora.

Three new, seco-ent-kaurane diterpenoids, laxiflorins A, B and C, together with four known diterpenoids eriocalyxin B, oriodonin, and maeocrystals A and B, were isolated from the leaves of Isodon eriocalyx var. laxiflora. Their structures were assigned by a combination of one- and two-dimensional NMR techniques and computer modeling calculations. Laxiflorin C displayed weak cytotoxic activity.

Cytotoxic ent-kaurene diterpenoids from three Isodon species.

From Isodon loxothyrsa, one new diterpenoid, loxothyrin A, together with one known diterpenoid, adenolin B, from I.pleiophyllus, three known diterpenoids, coetsoidins A, B and G, and from I. adenoloma, one known diterpenoid, longikaurin F, were isolated. The structure determination of loxothyrin A, and the unambiguous NMR spectral assignments of the known compounds were made by a combination of 1D and 2D NMR techniques and computer modelling calculations. The isolates showed potent cytotoxic activities.

Cytotoxic 7,20-epoxy ent-kauranoids from Isodon xerophilus.

Four 7,20-epoxy ent-kaurane diterpenoids, xerophilusins G (1) and I-K (2-4), were isolated from the leaves of Isodon xerophilus, along with four known ones, enanderianin C (5), rosthorin A (6), longikaurin B (7), and rabdoternin D (8). Their structures were determined primarily using NMR spectroscopic techniques. The structure and stereochemistry of 3 were confirmed by X-ray crystallography. Compounds 4 and 7 exhibited broad cytotoxicity against four kinds of human tumor cells (K562, HL-60, HCT, and MKN-28 cells) in the range of 2.23-15.35 and 0.30-8.61 microg/ml, respectively.

A new ent-kaurane diterpenoid from Isodon phyllostachys.

A new ent-kaurane diterpenoid, phyllostachysin C (1), together with five known compounds, sculponeatins B and C, nodosin, ursolic acid and 2 alpha-hydroxyursolic acid, were isolated from the leaves of Isodon phyllostachys. The structure of 1 was elucidated on the basis of its spectral properties.

Constituents of Craspedolobium schochii.

Nine phenolic compounds, including a new one, were isolated from 70% acetone extract of Craspedolobium schochii. The new compound was identified as 3-(3,4-dimethoxy-2-hydroxyphenyl)-7-hydroxy-coumarin (1) on the basis of spectroscopic evidence.

New steroids from Clerodendrum colebrookianum.

Five new steroids, colebrin A-E (1-5) were isolated from the aerial parts of Clerodendrum colebrookianum. The structures of the new compounds were elucidated on the basis of spectral evidence.

Constituents from Lethariella cladonioides.

The isolation from the acetone extract of Lethariella cladonioides of the new compound cladonioidesin (1) and 10 other constituents is reported.

[Responses mediated by GABAA and GABAB receptors on the somatic membrane of toad dorsal root ganglion neurones].

Intracellular recordings were made from neurons in toad dorsal root ganglion in vitro. Bath application of GABA (10(-4)-10(-3) mol/L) elicited either depolarization or depolarization followed by hyperpolarization respectively in 79% and 10% of the neurons. The remaining 11% did not show any response. The GABA-induced depolarization, which was accompanied by an increase of membrane conductance and usually a shortening of action potential duration (ApD), could be blocked by bicuculline. The GABA-depolarization was enhanced by low Cl- Ringer or reduced by high Cl- Ringer The membrane potential was not affected by 10(-4) mol/L baclofen. On the other hand, shortening of ApD could be produced by baclofen, but not blocked by bicuculline. Our results suggested that GABAA and GABAB receptors coexist on the somatic membrane of toad dorsal root ganglion neurons and mediate the changes respectively in membrane potential and shortening of ApD. The mechanism underlying presynaptic inhibition in the terminals of the primary afferents was discussed.

[Studies on the chemical constitutents of the traditional Chinese medicine "yun qian-hu" (Peucedanum rubricaule Shan et Shch.)].

A new coumarin-glycoside and twelve known coumarins together with seven other known compounds have been isolated from the roots of Peucedanum rubricaule Shan et Shch. (Umbelliferae). The new coumarin-glycoside named rubricauloside, has been elucidated as 5,7-dimethoxy-8-[2'-hydroxy-3'-methyl, 3'-O-beta-d- apiofuranosyl(1----6)-beta-D-glucopyranosyl-butyl]-courmarin by means of spectral and chemical analysis.

Cancer risk from low dose radiation depends directly on the organ mass in a general model of radiation-induced cancer risk.

Current methods of evaluating radiation-induced cancer risk depend on the organ dose but not explicitly on extensive quantities such as the organ mass. However, at the same organ dose, one may expect the larger number of cells in a larger organ to lead to a higher cancer risk. Here the author introduces organ- and radiation type-specific cell cancer risk coefficients and obtains analytical relations between cancer risk and the radiation environment, which contains the dependence of cancer risk on organ masses. The excess cancer risk induced by low dose radiation for an organ is shown to be directly proportional to the organ mass. Therefore the total excess risk for all solid cancers depends directly on organ masses and consequently on body weight or size. This method is also being compared with three existing methods of evaluating the radiation-induced cancer risk, and special cases where this formulation matches each method are demonstrated. The results suggest that the direct dependence of cancer risk on organ masses needs to be checked against existing epidemiological data and, if verified, should be included in the methodology for the evaluation of radiation-induced cancer risk, in particular the individual risk. This dependence is also expected to affect the cancer risk transport from one population group to another that is different in organ mass, body weight or height.

The radiation environment on the Moon from galactic cosmic rays in a lunar habitat.

We calculated how the radiation environment in a habitat on the surface of the Moon would have depended on the thickness of the habitat in the 1977 galactic cosmic-ray environment. The Geant4 Monte Carlo transport code was used, and a hemispherical dome made of lunar regolith was used to simulate the lunar habitat. We investigated the effective dose from primary and secondary particles including nuclei from protons up to nickel, neutrons, charged pions, photons, electrons and positrons. The total effective dose showed a strong decrease with the thickness of the habitat dome. However, the effective dose values from secondary neutrons, charged pions, photons, electrons and positrons all showed a strong increase followed by a gradual decrease with the habitat thickness. The fraction of the summed effective dose from these secondary particles in the total effective dose increased with the habitat thickness, from approximately 5% for the no-habitat case to about 47% for the habitat with an areal thickness of 100 g/cm(2).