Ramipril and resveratrol co-treatment attenuates RhoA/ROCK pathway-regulated early-stage diabetic nephropathy-associated glomerulosclerosis in streptozotocin-induced diabetic rats.

Clinical studies have shown that hyperglycemia can induce early-stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial-mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)-induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF-ß signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co-treatment of STZ-induced DN rats showed that glomerulosclerosis in early-stage DN was reversible (P < .05 compared with that in STZ-induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.

Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles.

Ovulation induction therapy with clomiphene citrate can suppress endometrial receptivity. Raloxifene may be an alternative therapeutic for women with ovulatory disorders. This study aimed to compare the expression of endometrial receptivity markers, including homeobox gene 10 (HOXA10), integrin ß3, and leukemia inhibitory factor (LIF), as well as pinopode production during the implantation window in mice stimulated with raloxifene and clomiphene citrate and natural cycles. Thirty-six 8-week-old female Kunming mice were randomly divided into 3 groups (n = 12) and administered daily raloxifene (22 mg/kg), clomiphene citrate (18 mg/kg), and normal saline (1 mL), respectively, by gavage. Two days later, mice were injected with 5 IU human chorionic gonadotropin and mated. Successfully mated female animals were identified with vaginal plugs designated gestation day 1. At day 4.5, pregnant donor mice were euthanized, and uterus samples were collected for immunohistochemistry, quantitative polymerase chain reaction, Western blot, and scanning electron microscopy analyses. Homeobox gene 10, integrin ß3, and LIF messenger RNA (mRNA) and protein levels were significantly higher in the raloxifene-treated animals compared with the clomiphene citrate group (all P < .05) but not significantly different from saline group values, except for LIF and integrin ß3 mRNA levels (P < .05). Pinopodes were abundant and well developed in the raloxifene and saline groups; however, in the clomiphene citrate-treated mice, fewer and poorly developed pinopodes were obtained. In mice, raloxifene had no effect on HOXA10, integrin ß3, and LIF expression as well as pinopode production, suggesting it has no adverse effects on endometrial receptivity. Raloxifene may provide a viable alternative oral ovulation induction agent to clomiphene citrate.

Transgenic Spartina alterniflora for phytoremediation.

Perennial monoculture forming grasses are very important natural remediators of pollutants. Their genetic improvement is an important task because introduction of key transgenes can dramatically improve their remediation potential. Transfer of key genes for mercury phytoremediation into the salt marsh cordgrass (Spartina alterniflora) is reported here. S. alterniflora plays an important role in the salt marsh by cycling of elements, both nutrients and pollutants, protects the coastline from erosion, is a keystone species in the salt marsh supporting a large food web, which in turn supports a significant segment of economy, including tourism, has an impact on cloud formation and consequently on global weather, and is thus an ecologically important species relevant for our life-support systems. Embryogenic callus of S. alterniflora was co-inoculated with a pair of Agrobacterium strains LBA4404 carrying the organomercurial lyase (merB) and mercuric reductase (merA) genes, respectively, in order to co-introduce both the merA and the merB genes. Seven stable geneticin resistant lines were recovered. The presence of merA and merB genes was verified by PCR and Southern blotting. All but one transgenic lines contained both the merA and the merB sequences proving that co-introduction into Spartina of two genes from separate Agrobacterium strains is feasible and frequent, although the overall frequency of transformation is low. Northern blotting showed differences in relative expression of the two transgenes among individual transformants. The steady-state RNA levels appeared to correlate with the phenotype. Line #7 showed the highest resistance to HgCl(2) (up to 500 microM), whereas line #3 was the most resistant to phenylmercuric acetate (PMA). Wild-type (WT) callus is sensitive to PMA at 50 microM and to HgCl(2) at 225 microM.

Genetic modification of wetland grasses for phytoremediation.

Wetland grasses and grass-like monocots are very important natural remediators of pollutants. Their genetic improvement is an important task because introduction of key transgenes can dramatically improve their remediation potential. Tissue culture is prerequisite for genetic manipulation, and methods are reported here for in vitro culture and micropropagation of a number of wetland plants of various ecological requirements such as salt marsh, brackish water, riverbanks, and various zones of lakes and ponds, and bogs. The monocots represent numerous genera in various families such as Poaceae, Cyperaceae, Juncaceae, and Typhaceae. The reported species are in various stages of micropropagation and Arundo donax is scaled for mass propagation for selecting elite lines for pytoremediation. Transfer of key genes for mercury phytoremediation into the salt marsh cordgrass (Spartina alterniflora) is also reported here. All but one transgenic lines contained both the organomercurial lyase (merB) and mercuric reductase (merA) sequences showing that co-introduction into Spartina of two genes from separate Agrobacterium strains is possible.