The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats.
Rats were given a single injection of STZ to induce diabetic rat model. ...Rats' 24 hr urine was collected to test, urinary and the kidney tissues were harvested at the 8
and 20
weeks, respectively. Podocyte morphological changes were examined by electron microscopy and the ZO-1, podocin expressions in kidneys were detected by immunohistochemistry; the protein levels of Raptor and pS6 were measured by Western blot assay.
In the early stage of diabetic nephropathy (DN), sirolimus reduced the proteinuria significantly (
<0.05); but in the advanced stage of DN, sirolimus worsened proteinuria (
<0.05). Electron microscopy test suggested that sirolimus could reduce the injury of podocyte at the early DN, but increased the injury at the late DN podocyte. Immunohistochemistry results indicated that sirolimus increased the expressions of podocin and ZO-1 at the early DN (
<0.05), but reduced the expressions of ZO-1 and podocin (
<0.05) at the advanced DN. In the different periods of DN, the expression levels of Raptor and pS6 in sirolimus-treated groups were significantly lower than in the DN control groups (
<0.05).
Sirolimus can reduce proteinuria and alleviate the early DN podocyte injury in diabetic rat model by inhibiting the activity of mTORC1; but in the advanced stage of DN, sirolimus can increase podocyte injury and urine protein level.
Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized ...that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions.
In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions.
Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes.
NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.
Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and ...chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2+ elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2, cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.
•NMDA upregulates NR2D subtype expression in HFL-1 and MRC-5.•NMDAR activation increases HFL-1 proliferation and collagen production.•NR2D is the dominant NR2 subtype in the regulation of HFL-1 function.•NR2D mediated pERK stimulates HFL-1 activation.
In this work, TiO2 nanofibers (TiO2-NF) with multilevel structure and nanoparticles (TiO2-NP) were respectively prepared via template-assisted and single solvothermal methods. The degradation of ...methylene blue (MB) was used as the model reaction to evaluate the photocatalytic properties of these prepared materials. It was important that TiO2-NF, prepared via template-assisted solvothermal method, possessed multilevel structure. The photocatalytic results indicated that their activity order was TiO2-NF > TiO2-NP. It demonstrated that the multilevel structure of TiO2-NF played an important role for enhancing its photocatalytic activity and the enhanced property could be mainly ascribed to fast adsorption/desorption of MB molecules on its surface and high efficiency of absorbing irradiating light and the efficient electrons transfer by interparticles and interparticles to the wall of the fiber.
To investigate the expression of CP in Down syndrome (DS) mouse model, we especially observed the changes in neuronal CP. We systematically analyzed the level of CP in Ts65Dn mouse, including serum ...CP concentration and enzymatic activity, CP mRNA in brain, the expression of CP protein in brain. The applied technologies were ELISA, chemical colorimetry, RT-PCR, immunohistochemistry. Compared with the control group, there were no differences of significance in the concentration, enzymatic activity and unit activity of serum ceruloplasmin. By RT-PCR, we also found there were no significant differences in the level of CP mRNA. The expression of CP was positive in the endochylema of neuronal cells of both the groups, and there were no significant difference between the two groups. Meanwhile, there were no differences in four regions of the brain (cerebral cortex, hippocampus, thalamus and cerebella). Although the neurotoxic effects of CP related to some neurodegenerative diseases, but whether it does so in DS remains to be determined.
In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous age-related chronic diseases, including ...cardiovascular atherosclerosis, cancer, hypertension, and diabetes, but the biological processes and molecular pathways by which resveratrol induces these beneficial effects, as well as its safety and toxicology remain largely undefined. To explore the molecular mechanisms of resveratrol involved in the amelioration of endothelial dysfunction and vascular disease, in the present study the protein profile changes of human umbilical vein endothelial cells in response to resveratrol treatment were investigated using proteomics approaches (2-DE combined with MS/MS). As a result, four down-regulated protein species named elongation factor 2 (EEF2), carboxymethyl-cofilin-1 (cofilin-1), acetyl-eukaryotic translation initiation factor 5A-1 (acetyl-EIF5A) and barrier-to-autointegration factor, and five up-regulated protein species named heat shock protein beta-1 (HSP27), phospho-HSP27, phospho-stathmin, Nicotinate-nucleotide pyrophosphorylase and 1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase were identified. Among them, two translation-related protein species (EEF2 and acetyl-EIF5A) were the most significantly changed (over tenfold). Phospho-EEF2 was further verified to be dramatically up-regulated by immunoblot assays. It is notable that in the present study several protein species with post-transcriptional modification (carboxymethyl-, acetyl-, and phospho-) were found to be altered following exposure to resveratrol. These findings may improve our understanding of the molecular mechanisms underlying the pleiotropic effects of resveratrol on endothelial cells.
In this work, TiO sub(2) nanofibers (TiO sub(2)-NF) with multilevel structure and nanoparticles (TiO sub(2)-NP) were respectively prepared via template-assisted and single solvothermal methods. The ...degradation of methylene blue (MB) was used as the model reaction to evaluate the photocatalytic properties of these prepared materials. It was important that TiO sub(2)-NF, prepared via template-assisted solvothermal method, possessed multilevel structure. The photocatalytic results indicated that their activity order was TiO sub(2)-NF > TiO sub(2)-NP. It demonstrated that the multilevel structure of TiO sub(2)-NF played an important role for enhancing its photocatalytic activity and the enhanced property could be mainly ascribed to fast adsorption/desorption of MB molecules on its surface and high efficiency of absorbing irradiating light and the efficient electrons transfer by interparticles and interparticles to the wall of the fiber.
Hydroxyapatite Ca
10(PO
4)
6(OH)
2 (HAP) is known as a bioactive and biocompatible material, HAP coatings were used to improve the biocompatible of substrate by many researcher, In this work, HAP ...thin films on porous silicon (PS) substrates have been prepared by aqueous precipitation method with rapid thermal annealing (RTA) processes. The HAP films had been prepared under the annealing temperature ranging from 300 to 1000
°C. By the measurement of X-ray diffraction (XRD), it was found that for the crystallinity optimization, the heat-treatment at 850–950
°C for 1
h would be favorable. Atomic force microscopy (AFM) and scanning electron microscope (SEM) measurements reveal a dense and smooth surface of the HAP film, and tightly adherence of the coating on porous silicon substrate after sintered. Thus, by this method, porous silicon could be increased its bioactivity and so that could be used in the biomedical area.
PDF
