An arabinogalactan isolated from the stems of Cistanche deserticola induces the proliferation of cultured lymphocytes

A purified polysaccharide ACDP-2 was isolated from water extract of the stems of Cistanche deserticola. Chemical and spectroscopic analyses indicated that ACDP-2 is a highly branched arabinogalactan polymer that composes of linked d-galactopyranose and d-glucopyranose, which contains predominantly a branching point at the 6-carbon. The branched side-chains compose of terminal-, 1,5-, and 1,3,5-linked arabinofuranosyl residues. ACDP-2 showed an effect in stimulating the immune response, which when applied onto the cultured mouse lymphocytes induced the cell proliferation in a dose-dependent manner.     

Neurotrophins,but not depolarization,regulate substance P expression in the developing optic tectum

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve‐dependent regulation of a substance P‐like immunoreactive (SP‐ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6‐cyano‐7‐nitroquinoxaline‐2,3 dione (CNQX) did not affect the percent of SP‐ir cells in the developing tectum. Treatment with d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (d‐AP‐5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) produced increases in SP‐ir cells in the treated lobes of normal animals, which were significant in the case of NT‐4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve‐transected tadpoles. These changes in the percent of SP‐ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT‐4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide‐expressing population of cells. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 131–149, 2001     

Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.

A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificity, that is, show a preference for the same P(1) residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both the S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability.     

The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy.     

Fine mapping of the recessive genic male-sterile gene (Bnms1) in Brassica napus L.

A recessive genic male sterility (RGMS) system, S45 AB, has been developed from spontaneous mutation in Brassica napus canola variety Oro, and is being used for hybrid cultivar development in China. The male sterility of S45 was controlled by two duplicated recessive genes, named as Bnms1 and Bnms2. In this study, a NIL (near-isogenic line) population from the sib-mating of S45 AB was developed and used for the fine mapping of the Bnms1 gene, in which the recessive allele was homozygous at the second locus. AFLP technology combined with BSA (bulked segregant analysis) was used. From a survey of 2,560 primer combinations (+3/+3 selective bases), seven AFLP markers linked closely to the target gene were identified, of which four were successfully converted to sequence characterized amplified region (SCAR) markers. For further analysis, a population of 1,974 individuals was used to map the Bnms1 gene. On the fine map, Bnms1 gene was flanked by two SCAR markers, SC1 and SC7, with genetic distance of 0.1 cM and 0.3 cM, respectively. SC1 was subsequently mapped on linkage group N7 using doubled-haploid mapping populations derived from the crosses Tapidor × Ningyou7 and DH 821 × DHBao 604, available at IMSORB, UK, and our laboratory, respectively. Linkage of an SSR marker, Na12A02, with the Bnms1 gene further confirmed its location on linkage group N7. Na12A02, 2.6 cM away from Bnms1, was a co-dominant marker. These molecular markers developed from this research will facilitate the marker-assisted selection of male sterile lines and the fine map lays a solid foundation for map-based cloning of the Bnms1 gene.     

Microbial Reduction of Cr (VI)-loaded Schwertmannite by Shewanella oneidensis MR-1

Microbial transformation of sulfate minerals plays an important role in controlling the behavior of heavy metals in mining areas. Here, the anaerobic reduction of Cr (VI)-loaded schwertmannite by Shewanella oneidensis MR-1 (S. oneidensis MR-1) was investigated. The release of ferrous iron (Fe(II)) to the solution demonstrated the microbial reduction of structural Fe(III) from the schwertmannite to Fe(II). The concentration of Cr in solution decreased in all treatments, indicating that no Cr was released to the solution during this bio-reduction process of schwertmannite. The incorporation of chromate into the mineral structure of schwertmannite increased the microbial stability of the mineral, retarding the formation of secondary phases during bio-reduction process. Analysis of the XRD, SEM and fourier transform infrared spectroscopy (FT-IR) results further showed that goethite formed after 3 or 7 days with a lower content (0.22% or 0.37%) of Cr in schwertmannite, while no secondary mineral was observed with a higher concentration of Cr (0.6 wt%) incorporated in schwertmannite until 22 days. These results imply that microbial reduction of Cr(VI)-loaded schwertmannite does not lead to the release of Cr to the solution, and the microbial stability of schwertmannite will be increased by the incorporation of chromate.     

The effect of mesenchymal stromal cells on doxorubicin-induced nephropathy in rats

Background aimsThe potential protective effects of mesenchymal stromal cells (MSCs) on some kidney diseases has been reported. However, the effect of MSCs on doxorubicin-induced nephropathy is still poorly understood.MethodsRats with doxorubicin-induced kidney injuries were treated with human cord-derived MSCs. Human MSCs were first labeled with 5-bromo-2′-deoxyuridine to track their homing in kidneys after infusion.ResultsAlleviation of proteinuria, decreased serum albumin, alleviation of lipid disorders and histologic alterations were found in rats 4 weeks after treatment with MSCs, particularly in rats that were given repeat doses. Decreases in serum levels of interleukin-6, tumor necrosis factor-α and prostaglandin E₂ and decreases in messenger RNA levels of kidney tissue cylooxygenase-2 and EP4 were found in MSC-treated rats. MSC-treated rats also displayed an increase in serum interleukin-10 levels.ConclusionsThese results indicate that MSCs ameliorate doxorubicin-induced kidney injuries and inflammation, suggesting a potential clinical treatment for inflammatory kidney diseases.