Effects of Dietary Phosphate on Adynamic Bone Disease in Rats with Chronic Kidney Disease – Role of Sclerostin?

High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.     

The effects of culture media, solid substrates, and relative humidity on growth, sporulation and conidial discharge of Valdensinia heterodoxa

Valdensinia heterodoxa (Sclerotiniacae) is a potential fungal bioherbicide for control of salal (Gaultheria shallon). The effect of culture media, substrates and relative humidity (RH) on growth, sporulation and conidial discharge of V. heterodoxa was determined for two isolates PFC2761 and PFC3027 in vitro. Culture media significantly affected the growth, sporulation, and conidial discharge of V. heterodoxa. Of eight agar media used, colony radial growth was optimal on salal oatmeal agar and salal potato dextrose agar for isolates PFC2761 and PFC3027, respectively; whereas sporulation was at an optimum on salal oatmeal agar for both isolates. Of the eight liquid media tested, mycelial production was highest on wheat bran–salal–potato dextrose broth. Growth on solid substrates greatly stimulated sporulation and conidial discharge of V. heterodoxa. Of the 12 solid substrates used, the greatest numbers of discharged conidia were observed from wheat bran and wheat bran–salal within 14 d of sporulation. Sporulation on solid substrates continued for 42 d. RH significantly affected the sporulation and conidial discharge for both isolates across all solid substrates tested. No conidia were produced or discharged below 93 % RH on wheat bran–salal and millet. With an increase of the RH from 93 to 97 %, sporulation and the number of discharged conidia increased significantly for both isolates on wheat bran–salal, but not on millet.     

Recombinant hirudin treatment modulates aquaporin-4 and aquaporin-9 expression after intracerebral hemorrhage in vivo

Edema formation has been linked to thrombin toxicity induced by blood clot at the acute stage of intracerebral hemorrhage. Thrombin induces cell toxicity in neuron, microglia and astrocyte. Aquaporin (AQP) 4 and 9 are proteins expressed on astrocyte in rat brain and involved in the brain water accumulation in brain edema. Recombinant hirudin (r-Hirudin) is a direct inhibitor of thrombin that can block the toxicitic effect of thrombin. In this study, we demonstrated that autologous whole blood infusion in caudate nucleus up-regulates the expression of AQP4 and AQP9 mRNAs and proteins. AQP4 and AQP9 mRNAs expression peaked at about 6 h after blood infusion. The AQP4 protein peaked at about 48 h while AQP9 at about 24 h after blood infusion. Thrombin induced up-regulation of AQP4 and AQP9 were inhibited by r-Hirudin administration and significantly decreased the expression of both AQPs. We further investigated the relationship between edema formation and expression of AQP4 and AQP9. The data presented here may be helpful in optimizing r-Hirudin as an anti-thrombin drug in the treatment of edema at the acute stage of ICH. Zhe Sun and Zhenhuan Zhao contributed equally to this article.     

Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status

We have previously reported that As(2)O(3) affected cell cycle progression and cyclins D1 and B1 expression in two glioma cell lines differing in p53 status (U87MG-wt; T98G-mutated). In the present study, we further demonstrated that As(2)O(3) affected proliferation, viability and apoptosis of the two cell lines in a dose- and time-dependent manner, and T98G cells were more sensitive than U87MG cells to As(2)O(3) -induced apoptosis and inhibition of proliferation and viability. We further investigated the expression profiles of genes related with apoptosis and cell cycle in the two cell lines with a human cDNA-microarray (SuperArray) spotted with 267 genes of apoptosis and cell cycle. Thirty five genes were upregulated and 15 genes downregulated at least 2-fold by As(2)O(3) in U87-MG cells; whereas, 38 genes were upregulated and 21 genes downregulated at least 2-fold in T98G cells by As(2)O(3). After As(2)O(3) treatment, p53 expression was upregulated 56.5-fold in T98G cells, but only 6.0-fold in U87MG cells. The results indicate that As(2)O(3) suppresses the growth of U87MG cells mainly by regulating expression of genes of cell cycle arrest, stress and toxicity; whereas As(2)O(3) affects T98G cells mainly by regulating expression of genes belonging to Bcl-2, tumor necrotic factor receptor and ligand families. The data may be helpful for optimizing As(2)O(3) as an anti-cancer drug in the treatment of gliomas.     

TGF-beta promotes thyroid epithelial cell hyperplasia and fibrosis in IFN-gamma-deficient NOD.H-2h4 mice

IFN-gamma(-/-)NOD.H-2h4 mice given 0.05% NaI in their water develop severe thyroid epithelial cell (thyrocyte) hyperplasia and proliferation (TEC H/P) and fibrosis. Proliferating thyrocytes of IFN-gamma(-/-) mice with TEC H/P produce TGF-beta as demonstrated by immunohistochemical staining and in situ hybridization. Strong expression of activating phosphorylated Smad-2/3 and weak expression of inhibitory Smad-7 by proliferating thyrocytes correlate with the severity of TEC H/P. Splenocytes from IFN-gamma(-/-) mice with severe TEC H/P transfer severe TEC H/P to IFN-gamma(-/-)NOD.H-2h4.SCID mice. Mice given anti-TGF-beta had markedly reduced thyrocyte proliferation and decreased fibrosis compared with mouse Ig-treated controls, suggesting that TGF-beta plays an important role in development of TEC H/P induced by activated splenocytes. Moreover, transgenic IFN-gamma(-/-)NOD.H-2h4 mice expressing TGF-beta on thyrocytes all develop fibrosis and moderate to severe TEC H/P with accelerated kinetics, directly demonstrating a role for TGF-beta in severe TEC H/P and fibrosis.     

Systemic inflammation and remote organ injury following trauma require HMGB1

High-mobility group box 1 (HMGB1) is a 30-kDa DNA-binding protein that displays proinflammatory cytokine-like properties. HMGB1-dependent inflammatory processes have been demonstrated in models of sterile injury, including ischemia-reperfusion injury and hemorrhagic shock. Here, we tested the hypothesis that the systemic inflammatory response and associated remote organ injury that occur after peripheral tissue injury are highly dependent on HMGB1. Toll-like receptor 4 (TLR4) wild-type (WT) mice subjected to bilateral femur fracture after treatment with neutralizing antibodies to HMGB1 had lower serum IL-6 and IL-10 levels compared with mice treated with nonimmune control IgG. Similarly, compared with injured mice treated with control IgG, anti-HMGB1 antibody-treated mice had lower serum alanine aminotransferase levels and decreased hepatic and gut mucosal NF-kappaB DNA binding. TLR4 mutant (C3H/HeJ) mice subjected to bilateral femur fracture had less systemic inflammation and liver injury than WT controls. Residual trauma-induced systemic inflammation and hepatocellular injury were not ameliorated by treatment with a polyclonal anti-HMGB1 antibody, even though HMGB1 levels were transiently elevated just 1 h after injury in both WT and C3H/HeJ mice. Collectively, these data demonstrate a critical role for a TLR4-HMGB1 pathway in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury.     

鼎湖山季风常绿阔叶林木本植物个体死亡动态

采用永久样地生物多样性长期监测的方法,在对1hm^2永久样地DBH≥1cm的植物进行4次测定的基础上,研究了鼎湖山季风常绿阔叶林植物个体死亡的动态及其成因,并对不同物种和不同径级植物死亡率的格局差异进行了分析。结果表明,从1992年到2004年,12a内该样地DBH≥1cm的植物共死亡2411株,为该样地现有活立木的69．34％。共有92种木本植物发生了个体死亡,占样地108种木本植物的85．19％,其中乔木70种,灌木22种;年平均死亡株数呈直线上升;死亡涉及木本植物种数也呈上升趋势;样地内种群数量最多的云南银柴（Aporosa yunnanensis）和柏拉木（Blastus cochinchinensis）死亡株数也最多（分别为445株和440株）,分别占所有死亡株数的18．46％、18．25％;优势树种黄果厚壳桂由于受虫害的影响,种群死亡率达90．83％;小径级树木死亡较多,其中DBH≤5cm死亡株数占样地死亡总株数的79．22％。自疏作用、灾害性天气、虫害和人为干扰直接影响到样地内植物个体的死亡动态。     

亚热带不同纬度植物群落物种多样性分布规律

我国亚热带气候区植被资源丰富,对其典型植物群落的物种多样性分布随纬度和海拔变化规律的探索是一项非常有意义的研究工作。在亚热带区域按照纬度从高到低分别选取猫儿山、南岭和鼎湖山国家级自然保护区中的四个典型植物群落为研究对象。设立四个1hm²样地,采用国家标准方法调查和监测。通过对样地中胸径大于1cm的所有物种进行种-个体曲线分析,对优势种进行径级分布分析,以及对四个群落进行一系列α多样性和β多样性指数的比较和分析,发现四个植物群落的物种多样性随海拔和纬度变化趋势明显。研究结果显示:(1)海拔的差异对于种-个体的分布起到关键作用,个体数随海拔变化更加明显。纬度从南到北单个体种的出现频率逐渐下降,而单个体种对群落物种多样性的贡献也在低海拔地区更为显著。(2)海拔接近的南岭样地和鼎湖山样地α多样性差异显著:由于所处演替阶段不同,以及鼎湖山样地受到人为干扰大,物种多样性反而低于纬度较高的南岭样地。同一纬度不同海拔的猫儿山两块样地相比较,处于中纬度的红军亭样地α多样性高于海拔偏高的八角田样地。(3)四个群落之间由于生境的差异,物种组成明显不同。纬度和海拔对群落β多样性都有影响。...     

南亚热带常绿阔叶林地上碳储量空间分布特征及其影响因素

旨在探讨南亚热带常绿阔叶林地上碳储量空间分布特征及其影响因素,为了解该区域森林的碳汇功能提供理论依据。通过对鼎湖山南亚热带常绿阔叶林20 hm²固定森林样地调查数据,采用一元线性回归分析和主成分分析方法,划分优势种和非优势种,研究地上碳储量的空间分布和生物/非生物因素的影响,获取了以下结果:(1)优势种对鼎湖山南亚热带常绿阔叶林地上碳储量贡献更大(1533.85 Mg,74.72%),尤其是大径级物种(1389.68 Mg,67.69%)。优势种地上碳储量(CV=0.635)的空间分布较非优势种(CV=0.690)更加均匀。(2)物种多样性与优势种和总体地上碳储量负相关,而与非优势种正相关。(3)群落总体、优势种和非优势种的地上碳储量均与结构多样性显著正相关。然而,结构多样性对非优势种地上碳储量的影响程度高于优势种。(4)群落中的土壤营养度、凹凸度与地上碳储量正相关。综上所述,通过提升非优势种的物种多样性可以增加鼎湖山南亚热带常绿阔叶林地上碳储量。此外,改善土壤营养条件也有助于提升南亚热带森林的碳汇功能。