Search

A photoinduced flexible Li-CO2 battery with well-designed, hierarchical porous, and free-standing In2 S3 @CNT/SS (ICS) as a bifunctional photoelectrode to accelerate both the CO2 reduction and evolution reactions (CDRR and CDER) is presented. The photoinduced Li-CO2 battery achieved a record-high discharge voltage of 3.14 V, surpassing the thermodynamic limit of 2.80 V, and an ultra-low charge voltage of 3.20 V, achieving a round trip efficiency of 98.1 %, which is the highest value ever reported (

Photoassisted electrochemical reaction is regarded as an effective approach to reduce the overpotential of lithium-oxygen (Li-O

The photoassisted lithium-oxygen (Li-O

Directly converting and storing abundant solar energy in next-generation energy storage devices is of central importance to build a sustainable society. Herein, a new prototype of a light-promoted rechargeable and flexible Li-CO

The photo-assisted lithium-oxygen (Li-O2) system emerged as an important direction for future development by effectively reducing the large overpotential in Li-O2 batteries. However, the advancement is greatly hindered by the rapidly recombined photoexcited electrons and holes upon the discharging and charging processes. Herein, we make a breakthrough in overcoming these challenges by developing a new magnetic and optical field multi-assisted Li-O2 battery with 3D porous NiO nanosheets on the Ni foam (NiO/FNi) as a photoelectrode. Under illumination, the photogenerated electrons and holes of the NiO/FNi photoelectrode play a key role in reducing the overpotential during discharging and charging, respectively. By introducing the external magnetic field, the Lorentz force acts oppositely on the photogenerated electrons and holes, suppressing the recombination of charge carriers. The magnetic and optical field multi-assisted Li-O2 battery achieves an ultra-low charge potential of 2.73 V, a high energy efficiency of 96.7%, as well as a good cycling stability of 200 h. This external magnetic and optical field multi-assisted technology paves a new way of developing high-performance Li-O2 batteries and other energy storage systems.

A photoinduced flexible Li-CO

Photo-assisted charging is considered an effective approach to reducing the overpotential in lithium-oxygen (Li-O2 ) batteries. However, the utilization of photoenergy during the discharge process in a Li-O2 system has been rarely reported, and the functional mechanism of such a process remains unclear. Herein, a novel bifunctional photo-assisted Li-O2 system is established by employing a hierarchical TiO2 -Fe2 O3 heterojunction, in which the photo-generated electrons and holes play key roles in reducing the overpotential in the discharging and charging processes, respectively. Moreover, the morphology of the discharge product (Li2 O2 ) can be modified via the dense surface electrons of the cathode under illumination, resulting in promoted decomposition kinetics of Li2 O2 during the charging progress. Accordingly, the output and input energies of the battery can be tuned by illumination, giving an ultralow overpotential of 0.19 V between the charge and discharge plateaus with excellent cyclic stability (retaining a round-trip efficiency of ≈86% after 100 cycles). The investigation of the bifunctional photo-assisted process presented here provides significant insight into the mechanism of the photo-assisted Li-O2 battery and addresses the overpotential bottleneck in this system.

A new piperidine alkaloid and three known tetranortriterpenoids were isolated from the methanol extracts of the rhizomes of Arisaema decipiens Schott (Araceae) and their chemical structures were identified as (-)-(2R*,3S*,6S*)-N,2-dimethyl-3-hydroxy-6-(9-phenylnonyl) piperidine (1), 6-deacetylnimbin (2), 28-deoxonimbolide (3) and nimbin (4). The N-methylated derivative (1a) of 1 was synthesized. Compound 1 exhibited weak inhibitory activity against the MCF-7 cell line, while compound 1a showed potential inhibitory activity against the MCF-7 cell line with an IC₅₀ value of 4.6 μM and weak inhibitory activity against K562 and SK-OV-3 cells. This plant in genus Arisaema is firstly reported as the source of limonoids that are considered a natural antitumor herbal medicine.

The range of vertebrates that serve as intermediate hosts for parasites in the genus Sarcocystis remains incompletely defined. Here, we provide the first report of infections in treeshrews, describe the morphology of encysted parasites using light and transmission electron microscopy, and place this agent within a phylogenetic context by sequencing and comparing its 18S ribosomal DNA to that of related parasites. Muscle infections were diagnosed in four of 45 wild treeshrews captured in the vicinity of Kunming, Yunnan Province, Mainland China. Thread-like cysts (10.773+/-2.411mm in length, 0.106+/-0.009mm in width) had walls (0.538-0.746microm thick) that lacked perpendicular protrusions. The interior of the cyst was packed full with cyst merozoites, the shape of which was typical of Sarcocystis. The primary cyst wall consisted of a thin membrane supported by osmiophilic material, 31-60nm in thickness. The ground substance was about 105-526nm thickness. Cysts conformed to typical of 'type 1' sarcocysts. Freshly examined and frozen specimens did not differ in their cyst wall structure, however, the appearance of bradyzoites did differ: the conoid, rhoptries and micronemes were all visible in fresh bradyzoites; in stored bradyzoites, by contrast, the rhoptries appeared smaller, and although the conoid was visible, the micronemes were not. 18S rRNA gene was distinct from any previously reported sequence in GenBank. Their genetic and morphological uniformity suggest that these parasites, derived from treeshrews, represent a single biological species, Sarcocystis tupaia, sp. nov.

The phytochemical investigation of Dipteronia dyeriana (Aceraceae) resulted in the isolation and identification of three new cycloheximide derivatives: dipteronines A-C (1-3). Their structures were elucidated based on the 1D- and 2D-NMR spectra. Dipteronine A (1) is the first example of it 10,11-secocycloheximide. Cytotoxic and antifungal activities of these isolates were also evaluated.

The phytochemical investigation of Dipteronia dyeriana (Aceraceae) resulted in the isolation and identification of five new triterpenoid ester saponins, dipterosides A-E (1-5). Their structures were elucidated by spectroscopic methods and chemical evidence. The inhibitory activities of these compounds against human leukemia K562 and human hepatoma HepG2 cells were also evaluated.

To monitor human embryonic stem cell (hESC) self-renewal without differentiation, we used quantitative RT-PCR to study a selection of hESC genes, including markers for self-renewal, commitment/differentiation, and members of the TGF-beta superfamily and DAN gene family. Indeed, low commitment/differentiation gene expression, together with a significant self-renewal gene expres sion, provides a better pluripotency index than self-renewal genes alone. We demonstrate that matrices derived from human mesenchymal stem cells (hMSCs) can advantageously replace murine embryonic fibroblasts (MEF) or hMSC feeders. Moreover, a xenofree molecularly-defined SBX medium, containing a synthetic lipid carrier instead of albumin, can replace SR medium. The number of selected differentiation genes expressed by hESCs in these culture conditions was significantly lower than those expressed on MEF feeders in SR medium. In SBX, the positive effect of a non-physiological concentration of activin A (10-30 ng/mL) to reduce differentiation during self-renewal could also be obtained by physiological concentrations of TGF-beta(100-300 pg/mL). In contrast, these TGF-beta concentrations added to activin favored differentiation as previously observed with TGF-beta concentrations of 1 ng/mL or more. Compared to SR-containing medium, SBX medium promoted down-regulation of CER1 and LEFTIES and up-regulation of GREM1. Thus these genes better control self-renewal and pluripotency and prevent differentiation. A strategy is proposed to analyze, in more physiological, xenofree, molecularly-defined media and matrices, the numerous genes with still unknown functions controlling hESCs or human-induced pluripotent stem cells (iPS).

Isodon xerophilus has been used as a herbal cold tea for the prevention and treatment of sore throat and inflammation in southernwestern China. A phytochemical study on the ethyl acetate (EtOAc) soluble fraction of I. xerophilus leaves led to the isolation of two new ent-kauranoids, xerophinoids A (1) and B (2), together with 14 known diterpenoids. The structures of xerophinoids A (1) and B (2) were illustrated using spectroscopic methods including 1D and 2D NMR analyses. To study their biological activities, the effects of xerophinoids A (1) and B (2) on nitrite production, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were examined. In addition, xerophinoids A (1) and B (2) also exhibited potent cytotoxicity against several human tumor cell lines (IC50 < 11 microM), but they had no toxicity on human T-lymphocyte (C8166).

Here we present a simple two-step in vitro model of vascularized trophoblastic tissue derived from human embryonic stem (hES) cells. The first step is the formation of cystic embryoid bodies (EBs) in suspension in a semisolid methyl cellulose medium, within which an endothelial platelet/endothelial cell adhesion molecule-1 (PECAM-1(+)) cell network develops. In a second step, deposition of these EBs on the bottom of nontreated, polystyrene tissue culture plates, leads by centrifugal outgrowth of the EB to the emergence of an adherent cell layer, with which a PECAM-1(+) network is associated. Cells of this adherent layer expressed VE-cadherin (CD144), PECAM-1 (CD31), and alpha-fetoprotein (alpha-FP). Trophoblastic differentiation was strongly suggested by the secretion of beta-human chorionic gonadotropin (beta-hCG) and by the presence of the cytotrophoblast and syncytiotrophoblast marker GB25. The INSL4 gene, a cyto and syncytio-trophoblast marker, was also highly expressed in the adherent layer, as well as other trophoblast genes such as CGA, CDX1, CDX2, and HAND1, compared to hES cell gene expression taken as reference. In contrast, expression of self-renewal genes, such as TERT, POU5F1, ZFP42, GDF3, and NODAL were decreased. No ectodermal or endodermal genes were expressed, but the mesodermal genes PECAM-1 and GATA2 were. The possibility of removing the EBs during the second step would permit analysis of their relative contribution to angiogenesis or possible hemangioblast formation, compared to that of the trophoblastic adherent layer. This primitive vascularized trophoblastic model could also provide a tool to study early steps of normal and pathological placental development.

Five new ent-kauranoids, xindongnins C - G ( 1 - 5), together with five known ones, xindongnins A and B ( 6 and 7), melissoidesin G ( 8), dawoensin A ( 9), and glabcensin V ( 10), were isolated from the leaves of Isodon rubescens var. rubescens, and structurally elucidated. Compounds 1, 4, and 6 - 10 showed inhibitory effects against human tumor K562 cells with IC (50) values ranging from 0.3 to 7.3 microg/mL. The structure of 6 was revised on the basis of its 2D-NMR spectral data.

Four new ent-kaurane diterpenoids lushanrubescensins F-I (1-4), together with 11 known ones, lasiodonin (5), oridonin (6), ponicidin (7), isodonoiol (8), isodonal (9), rabdosin B (10), rabdoternins A and B (11 and 12), enmenol (13), epinodosin (14), and inflexusin (15), were isolated from Isodon rubescens var. lushanensis, and the structures were elucidated by spectroscopic analysis. The inhibitory effect against the K562, Bcap37, BGC823, BIU87, CA, CNE, and Hela cell lines of compounds 3 and 5-10 were evaluated.

Four new ent-kaurane diterpenoids, sculponeatins F-I (1-4), together with six known compounds, sculponeatin E (5), epi-nodosin (6), epi-nodosinol (7), enmein (8), and macrocalyxoformins A and B (9 and 10), were isolated from the leaves of Isodon sculponeata. Also obtained were ursolic acid, 2alpha,3beta-dihydroxy-urs-12-en-28-oic acid, 2alpha,3beta,19alpha-trihydroxy-urs-12-en-28-oic acid, beta-sitosterol, daucosterol, quercetin, pedalitin, rosmarinic acid, caffeic acid and ethyl caffeic acid. Their structures were determined by spectral methods (1D-, 2D-NMR and MS). Some diterpenoids were tested for their cytotoxicity to inhibit three kinds of human tumor cells K562, A549 and T24. Compounds 3, 4, 6, 8, and 10 showed significant inhibitory effect toward K562 with IC(50) values ranging from 3.2 microg/ml to 8.2 microg/ml, while 3 and 6 exhibited potent antitumor activity against T24, but none exhibited cytotoxicity toward the cells of A549.

Three new ent-kaurane diterpenoids laxiflorin E (1), laxiflorin H (6) and laxiflorin I (8) were isolated from the leaves of Isodon eriocalyx var. laxiflora, along with nine known diterpenoids, eriocalyxin A (2), laxiflorin C (3), laxiflorin D (4), laxiflorin A (5), maoecrystal S (7), maoecrystal Q (9), eriocalyxin B (10), maoecrystal C (11) and enmelol (12). The structures of the new compounds were determined by spectroscopic methods. Compounds 1-5 are 6,7-seco-ent-kaurane-7,20-olide diterpenoids, and 6-12 belong to 7,20-epoxy-ent-kauranoids. The spectral data of enmelol (12) are reported here for the first time. Ten of these compounds were tested for their cytotoxicity toward K562 and T24 human tumor cells. Compounds 1, 3 and 10 showed significant inhibitory effects on K562 cells with IC50 values 0.077, 0.569 and 0.373 microg/mL, and compounds 1 and 10 also demonstrated significant inhibitory activities toward T24 cells with IC50 values 0.709 and 0.087 microg/mL. Compounds 8 and 11 also displayed inhibitory effect on both two kinds of cells with IC 50 value less than 6.5 microg/mL.

Bone marrow mesenchymal stem cells (BMSCs) are a kind of pluripotent stem cells derived from bone marrows, which can not only support hematopoiesis, but also have capabilities of multidifferentiation, high-proliferation and self-renewing. They have become one of hotspots in stem cell studies. Studies on in vitro intervention with BMSCs with TCMs have made remarkable progress in recent years. According to the findings, some traditional Chinese medicines can promote proliferation of BMSCs, some can inhibit the apoptosis of BMSCs, while others can induce BMSCs to differentiate into multiple cell types, such as osteoblast. Furthermore, some studies also involved relevant action mechanisms. The authors summarized the advance in relevant studies by reference to relevant literatures of this field.

A new sesquilignan, 70,80-didehydroherpetotriol (1), and a new lignan glycoside, (+)-isolariciresinol-9'-O-alpha-L-rhamnopyranosyl-(1 -> 6)-beta-D- glucopyranoside (2), were isolated from the branches of Dipteronia dyeriana. Their structures were elucidated by spectroscopic methods and chemical evidence. Compound 1 possessed inhibitory activity against human leukaemia K562 cells with an IC(50) value of 39 mu mol/L. (C) 2008 Chun Lin Long. Published by Elsevier B. V. on behalf of Chinese Chemical Society. All rights reserved.

The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose- dependent manner the number of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.

We have previously shown (Zhou et al: Blood, 72:1870, 1988) that IL3, added with low concentrations of CSF-1 (1 ng/ml) to normal human CD34+ enriched cells, promoted the development of various types of colonies including those containing immature monocytes. However, when high concentrations of CSF-1 (20 ng/ml) were added alone or together with IL3, smaller colonies with mature macrophages were found. Here we show by in situ hybridization that IL3 allows the development, from CD34+ cells, of a subpopulation of immature progenitors which express the CSF-1 receptor (c-fms) mRNA. The expression of c-FMS protein was also substantiated by immunocytochemical studies using anti-c-fms antibody. The percentage of c-fms positive cells peaked at day 7 and began to decrease thereafter. When anti-CSF-1 antibodies were included in the culture, the decrease in c-fms mRNA after day 7 was abrogated. This indicated that endogenous CSF-1 was produced as CD34+ cells developed into monocytes or progenitors of monocytes and that CSF-1 modulates c-fms expression. We further demonstrated that when a high dose of CSF-1 (20 ng/ml) was added at day 7 to IL3-stimulated CD34+ cells, a rapid down-regulation of c-fms mRNA and protein was seen. No down-regulation was observed with low concentration of CSF-1 (1 ng/ml). The possibility that different concentrations of CSF-1 could modulate the development of monocytic progenitors is discussed.

Human umbilical cord blood CD34+ cells were purified using a two-step procedure by elimination of the soybean agglutinin-binding cells and by a positive panning selection with a CD34 monoclonal antibody. The isolated fraction was 88-97% pure CD34+ cells. A yield of 48.5% was obtained when comparing the number of cells recovered in the CD34(+)-purified fraction and the number of CD34+ cells detected in the initial mononuclear cell fraction. By flow cytometry, we observed that the CD34+ cells that were not recovered were those that had the lower expression of CD34 antigen and were therefore the more mature cells. A high recovery of CFU-GEMM progenitors (73.9%) was also observed. These data suggest the possibility of purifying CD34+ umbilical cord blood cells for clinical applications, in particular for umbilical cord blood banking.

Three new humulane-type sesquiterpenes, 8-O-(p-coumaroyl)-5beta-hydroperoxy-1(10)E,4(15)-humuladien-8alpha-ol (1), 8-O-(3-nitro-p-coumaroyl)-1(10)E,4(15)-humuladien-5beta,8alpha-diol (2) and 8-O-(p-coumaroyl)-1(10)E,4(5)E-humuladien-8-ol (3), and a new copaborneol derivative, 1-O-p-coumaroyl-copaborneol (4), have been isolated from the methanol extract of Pileacavaleriei Levl. subsp. crenata C. J. Chen. Their structures were elucidated using spectroscopic methods. Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.

The phytochemical investigation of Dipteronia dyeriana (Aceraceae) resulted in the isolation and identification of three new cycloheximide derivatives: dipteronines A-C (1-3). Their structures were elucidated based on the 1D- and 2D-NMR spectra. Dipteronine A (1) is the first example of it 10,11-secocycloheximide. Cytotoxic and antifungal activities of these isolates were also evaluated.

Three new 7,20:14,20-diepoxy-ent-kaurane diterpenoids, xerophilusins A-C (1-3), together with a known one, macrocalin B (4), were isolated from the leaves of Isodon. xerophilus. Their structures were elucidated on the basis of their spectral properties and X-ray crystallographic analysis. Compounds 1, 2, and 4 showed significant cytotoxic activity against K562, HL-60, and MKN-28 cells.

We describe in this chapter the development of a xenofree molecularly defined medium, SBX, associated with xenofree matrices, to maintain human embryonic stem cell (hESC) pluripotency as determined by phenotypic, functional and TLDA studies. This simple, inexpensive, and more physiological culture condition has been chosen because (1) it is xenofree and molecularly defined; it is devoid of albumin, which is a carrier of undefined molecules; (2) it maintains pluripotency, but very significantly reduces differentiation gene expression during hESC self-renewal, as compared to the widely used culture conditions tested so far; and (3) it can be further improved by replacing high concentrations of expensive additives by physiological concentrations of new factors. Xenofree molecularly defined media and matrices represent valuable tools for elucidating still unknown functions of numerous embryonic genes using more physiological culture conditions. These genes encode potential new factors controlling hESC self-renewal and pluripotency.

Promoting human embryonic stem cell (hESC)-derived-neural progenitor survival in the pro-apoptotic niche is pivotal for stem cell replacement therapy. The present study was designed to investigate the protective effect of hepatocyte growth factor (HGF) on hESC-derived neural progenitor injured by hydrogen peroxide (H(2)O(2)) exposure. Treatment of hESC-derived neural progenitor cells with HGF prior to H(2)O(2) exposure conferred protective effect against oxidative stress-induced apoptosis. HGF treatment increased both phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. However, selective inhibition of each pathway supported that the activation of PI3K/AKT, but not ERK1/2, provides survival advantage to the neural progenitor cells. Further investigation indicated that HGF pretreatment could attenuate the decrease of the expression of Bcl-2 protein induced by H(2)O(2), whereas the level of Bax was not affected. Additionally, we observed that H(2)O(2)-induced decrease of mitochondrial transmembrane potential, release of cytochrome c and increase of caspase-3 activation were alleviated by HGF pretreatment. These effects of HGF could be reversed by inhibition of the PI3K/Akt and ERKs pathways, indicating PI3K/Akt and ERKs signaling might be involved in HGF-mediated regulation of mitochondrial apoptotic pathway mediated by H(2)O(2). The neuroprotective effect of HGF might potentially be useful in stem cell-based therapies for neurodegenerative disorders.

4 ng/ml bFGF is indispensable for hESC cultured on mouse embryonic fibroblasts (MEF), withdrawal of bFGF drives the hESC to differentiate. In order to exploit effect of bFGF on MEF, we collected a series of MEF conditioned medium (bFGF-MCM) by co-culturing MEF with increasing bFGF concentrations: 0.03, 0.1, 0.3, 1 and 4 ng/ml. The primitivity of hESC cultured in bFGF-MCM was estimated by morphology and alkaline phosphatase staining. Compared with the control medium (medium conditioned without bFGF: MCM), percentage of undifferentiated colony was increased from 23% to 29%, 44%, 74%, 77% and 78%, respectively. However, percentage of undifferentiated colony in the blank medium (medium conditioned with bFGF but without MEF: bFGF-SR) was from 13% to 31%. This indicated that low concentration of bFGF acted on MEF and stimulated MEF producing effective conditioned medium for maintaining hESC. To identify active elements in the effective conditioned medium can help to understand mechanisms of hESC self-renewal.

Xerophilusin B (XB), macrocalin B (MB) and eriocalyxin B (EB) belong to ent-kaurene diterpenoids. The inhibition effects of three ent-kaurane compounds on the proliferation of six tumour lines (K562, HL-60, A549, MKN, HCT and CA) were estimated by methyl-thiazol-tetrazolium, and the telomerase activity in K562 cells was measured by the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay. We found that XB, MB and EB could significantly inhibit the proliferation of tumour cells. Within the concentration range of 10(-4)-10(-8) mol L(-1), three ent-kaurane compounds could markedly inhibit the telomerase activity in K562 cells, and their effects on telomerase were exhibited in a dose-dependent manner. Our results demonstrate that XB, MB and EB can inhibit the proliferation of tumour cells and the telomerase activity, which provides data for developing ent-compounds as antitumour drugs.

Three new humulane-type sesquiterpenes, 8-O-(p-coumaroyl)-5beta-hydroperoxy-1(10)E,4(15)-humuladien-8alpha-ol (1), 8-O-(3-nitro-p-coumaroyl)-1(10)E,4(15)-humuladien-5beta,8alpha-diol (2) and 8-O-(p-coumaroyl)-1(10)E,4(5)E-humuladien-8-ol (3), and a new copaborneol derivative, 1-O-p-coumaroyl-copaborneol (4), have been isolated from the methanol extract of Pileacavaleriei Levl. subsp. crenata C. J. Chen. Their structures were elucidated using spectroscopic methods. Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.

We describe in this chapter the development of a xenofree molecularly defined medium, SBX, associated with xenofree matrices, to maintain human embryonic stem cell (hESC) pluripotency as determined by phenotypic, functional and TLDA studies. This simple, inexpensive, and more physiological culture condition has been chosen because (1) it is xenofree and molecularly defined; it is devoid of albumin, which is a carrier of undefined molecules; (2) it maintains pluripotency, but very significantly reduces differentiation gene expression during hESC self-renewal, as compared to the widely used culture conditions tested so far; and (3) it can be further improved by replacing high concentrations of expensive additives by physiological concentrations of new factors. Xenofree molecularly defined media and matrices represent valuable tools for elucidating still unknown functions of numerous embryonic genes using more physiological culture conditions. These genes encode potential new factors controlling hESC self-renewal and pluripotency.

In a previous paper [8] we have shown that, with human CD 34+ cells grown in culture with serum, antisense TGF-β oligonucleotides significantly enhanced the frequency of colony formation by multilineage, early erythroid and granulomonocytic progenitors, but did not affect colony formation by late progenitors. Single cell culture and limiting dilution analysis indicated that autocrine TGF-β is produced by a subpopulation of early progenitors. We now show that this effect is observed as well in serum-free culture which supports the development of mixed colonies. Therefore, the G0 phase control of some early progenitors, by an autocrine production of TGF-β, can be observed in vitro independently of serum or accessory cells.

We have used antisense oligonucleotides to study the roles of transforming growth factor beta (TGF-beta) and the two antioncogenes, retinoblastoma susceptibility (Rb) and p53, in the negative regulation of proliferation of early hematopoietic cells in culture. The antisense TGF-beta sequence significantly enhanced the frequency of colony formation by multi-lineage, early erythroid, and granulomonocytic progenitors, but did not affect colony formation by late progenitors. Single cell culture and limiting dilution analysis indicated that autocrine TGF-beta is produced by a subpopulation of early progenitors. Antisense Rb but not antisense p53 yielded similar results in releasing multipotential progenitors (colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte) from quiescence. Rb antisense could partially reverse the inhibitory effect of exogenous TGF-beta. Anti-TGF-beta blocking antibodies, antisense TGF-beta, or Rb oligonucleotides all had similar effects. No additive effects were observed when these reagents were combined, suggesting a common pathway of action. Our results are consistent with the model that autocrine production of TGF-beta negatively regulates the cycling status of early hematopoietic progenitors through interaction with the Rb gene product.

Bioassay-directed fractionation of the leaves of the medicinal plant Isodon xerophilus led to the isolation of a series of potential antitumor molecules. Thirteen new (1-13) and 23 (14-36) known diterpenoids were isolated and identified, representing ent-kauranoids of several structural types. The structures of 1-13 were determined by means of spectroscopic studies. The absolute configurations of the new compounds were clarified by CD spectroscopic studies or were postulated on biogenetic grounds. All compounds obtained were evaluated for their cytotoxic activity against the K562, MKN45, and HepG2 cell lines. Compounds 1, 2, 11, 16-19, 23, 26-28, 30, and 32 demonstrated significant cytotoxic activity for one or more cell lines.

Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24 h pre-treatment of Stro1+/GlycoA- or CD45-/GlycoA- subpopulations with a monoclonal antibody (mAb) against the IFNAR1 chain of the human type I IFN receptor (64G12), or with a polyclonal anti-IFNalpha antibody, resulted in a marked increase in the number of very large colonies (CFU-F >3000 cells) obtained in the presence of low, but necessary, concentrations of bFGF. Over a 2-month culture period, this short activation promoted a faster and greater amplification of mesenchymal progenitors for adipocytes and osteoblasts. Activation correlated with inhibition of STAT1 and STAT2 phosphorylation and of STAT1 nuclear translocation. A non-neutralizing anti-IFNAR1 mAb was ineffective. We demonstrate that control and activated MSCs express ST3GAL3, a sialyltransferase necessary to produce the embryonic antigens SSEA-3 and -4. Interestingly, activated MSC progeny expressed SSEA-3 and -4 at a higher level than control cultures, but this was not correlated with a significant expression of other embryonic markers. As MSCs represent an essential tool in tissue regeneration, the use of 64G12, which rapidly recruits a higher number of primitive cells, might increase amplification safety for cell therapy.

To study the biochemistry of lanthanides, the cooperative action of inorganic and organic anti-tumor drugs.A series of rare earth complexes were synthesized with Ln(NO3) 6H2O, Phen and 5-Fu. Their anti-tumor activity was measured by the improved MTT, SRB methods.The formula of complex Ln[(Phen)2(5-Fu)3(NO3)](NO3)2(Ln = Y, La, Ce, Sm, Gd, Dy, Er; Phen = 1, 10-phenanthroline; 5-Fu = fluorouracil) was characterized by elemental analyses, molar conductivity, IR, TGA, and 13C NMR spectra. The preliminary biological activity studies indicated that Lanthanide complex has strong anti-tumor activity in vitro.The complex might have anti-tumor cooperation action.

Maoecrystal V (1), a novel C(19) diterpenoid possessing a unique 6,7-seco-6-nor-15(8--9)-abeo-5,8-epoxy-ent-kaurane skeleton, was isolated from the leaves of a Chinese medicinal herb, Isodon eriocalyx. Its structure was determined by comprehensive NMR and MS spectroscopic analysis and confirmed by single-crystal X-ray diffraction study. Compound 1 showed remarkable inhibitory activity toward HeLa cells with IC(50) = 0.02 microg/mL (cis-platin: IC(50) = 0.99 microg/mL).

It had been reported that nuclear factor kappa b (NF kappa B) was associated with in vitro angiogenesis, but its role in angiogenesis of human ovarian carcinoma (HOC) had not been reported yet. The objective of this paper was to investigate the role and the mechanism of NF kappa B in HOC angiogenesis in chick chorioallantcic membrane (CAM).The HOC TYK cells were implanted into 10-day CAM by 1 x 10(9)/per egg to establish the HOC CAM model. (1) With 20 eggs, the levels of NF kappa B, integrin alpha V beta 3, basic fibroblast growth factor (bFGF) at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h time point after cells implanted were determined with ELISA. (2) The relationship among NF kappa B, bFGF,alpha V beta 3 and the effect of them on HOC angiogenesis in CAM were determined. Another 80 eggs were divided into 6 groups, normal saline (NS) (control group, 16 eggs), anti- NF kappa B (A group, 16 eggs), anti-bFGF (B group, 16 eggs), anti-NF kappa B + anti-bFGF(D group, 8 eggs) were added respectively into CAM at 6h time point after the cells implanted, and then anti-integrin alpha V beta 3 (C group, 16 eggs), anti-NF kappa B +anti-alpha V beta 3 (E group, 8 eggs) antibodies were added at 12h time point. Eight eggs from NS, A, B, C groups were taken out to determine the levels of NF kappa B, alpha V beta 3, bFGF at 48 h after the antibodies were added. The other eggs were incubated up to 5 days, and the vessel area/area were determined with image analysis.(1)The levels of NF kappa B and bFGF increased significantly at 6h, and that of V beta 3 increase significantly at 12 h time point after implantation (P0.01) (0.185+/-0.01, 0.771+/-0.16, 0.231+/-0.02), the peaks of the three levels were reached at 48 h (P0.01) (0.337+/-0.01, 1.639+/-0.01, 0.349+/-0.01). The levels of bFGF was significantly higher than those of NF kappa B and alpha V beta 3 at each time point (P0.01), but there were no significant difference between NF kappa B and alpha V beta 3 (P0.05). (2)The levels of NF kappa B,bFGF, and alpha V beta 3 in A and B groups were significantly lower than those of NS group (P0.01) (0.098+/-0.02, 0.156+/-0.02, 0.329+/-0.01; 1.106+/-0.33, 0.412+/-0.01, 1.591+/-0.13; 0.138+/-0.03, 0.114+/-0.02, 0.322+/-0.01). And the level of alpha V beta 3 in C group were significantly reduced compared with those of NS group (P0.01) (0.119+/-0.02, 0.322+/-0.01), while the levels of NF kappa B and bFGF had no change between the two groups (P0.05). The VA/A of the five groups of A, B, C, D, and E were significantly lower than that of NS group (P0.05) (26.10+/-13.71, 34.12+/-4.85, 25.50+/-11.41,14.32+/-3.11, 24.36+/-4.95, 66.62+/-17.64), and that of D group were significantly reduced compared with A group (P0.05) (14.32+/-3.11, 26.10+/-13.71), but there were no significant difference among the four groups of A, B, C, and E (P0.05).NF kappa B can stimulate the angiogenesis of ovarian carcinoma with bFGF by upregulating the expression of alpha V beta 3, bFGF, which can be used as a marker of angiogenesis and a therapy target molecule of ovarian carcinoma.

Five new ent-kaurane diterpenoids, enanderianins K-O (1-5), and one new ent-abietane diterpenoid, enanderianin P (6), together with five known ent-kaurane diterpenoids, rabdocoetsin A (7), rabdocoetsin B (8), rabdocoetsin D (9), megathyrin A (10), megathyrin B (11) were isolated from the aerial parts of Isodon enanderianus. Their structures were determined by spectral means. Some diterpenoids were tested for their cytotoxicity against the human tumor K562 cells. Compounds 1, 2, 6, 8, 9 showed significant inhibitory activities against K562 cells with IC50 values ranging from 0.13 to 0.87 microg/mL.

Four new ent-kaurane diterpenoids lushanrubescensins F-I (1-4), together with 11 known ones, lasiodonin (5), oridonin (6), ponicidin (7), isodonoiol (8), isodonal (9), rabdosin B (10), rabdoternins A and B (11 and 12), enmenol (13), epinodosin (14), and inflexusin (15), were isolated from Isodon rubescens var. lushanensis, and the structures were elucidated by spectroscopic analysis. The inhibitory effect against the K562, Bcap37, BGC823, BIU87, CA, CNE, and Hela cell lines of compounds 3 and 5-10 were evaluated.

Eight new abietane diterpenoids, coleon U 11-acetate (1), 16-acetoxycoleon U 11-acetate (2), and xanthanthusins F-K (3-8), together with five known analogues, coleon-U (9), 16-O-acetyleoleon C (10), coleon U-quinone (11), 8alpha,9alpha-epoxycoleon U-quinone (12), and xanthanthusin E (13), were isolated from the aerial parts of Coleus xanthanthus. The structures of 1-8 were elucidated on the basis of spectral methods. Compounds 1, 5, and 11-13 were evaluated for their cytotoxicity against K562 human leukemia cells.

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 mug/ml, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved.