Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

Characteristic response of striatal astrocytes to dopamine depletion.

Astrocytes and astrocyte-related proteins play important roles in maintaining normal brain function, and also regulate pathological processes in brain diseases and injury. However, the role of astrocytes in the dopamine-depleted striatum remains unclear. A rat model of Parkinson's disease was therefore established by injecting 10 µL 6-hydroxydopamine (2.5 µg/µL) into the right medial forebrain bundle. Immunohistochemical staining was used to detect the immunoreactivity of glial fibrillary acidic protein (GFAP), calcium-binding protein B (S100B), and signal transducer and activator of transcription 3 (STAT3) in the striatum, and to investigate the co-expression of GFAP with S100B and STAT3. Western blot assay was used to measure the protein expression of GFAP, S100B, and STAT3 in the striatum. Results demonstrated that striatal GFAP-immunoreactive cells had an astrocytic appearance under normal conditions, but that dopamine depletion induced a reactive phenotype with obvious morphological changes. The normal striatum also contained S100B and STAT3 expression. S100B-immunoreactive cells were uniform in the striatum, with round bodies and sparse, thin processes. STAT3-immunoreactive cells presented round cell bodies with sparse processes, or were darkly stained with a large cell body. Dopamine deprivation induced by 6-hydroxydopamine significantly enhanced the immunohistochemical positive reaction of S100B and STAT3. Normal striatal astrocytes expressed both S100B and STAT3. Striatal dopamine deprivation increased the number of GFAP/S100B and GFAP/STAT3 double-labeled cells, and increased the protein levels of GFAP, S100B, and STAT3. The present results suggest that morphological changes in astrocytes and changes in expression levels of astrocyte-related proteins are involved in the pathological process of striatal dopamine depletion. The study was approved by Animal Care and Use Committee of Sun Yat-sen University, China (Zhongshan Medical Ethics 2014 No. 23) on September 22, 2014.

Nuclear factor erythroid 2-related factor 2 antibody attenuates thermal hyperalgesia in the dorsal root ganglion: Neurochemical changes and behavioral studies after sciatic nerve-pinch injury.

Oxidative stress is generated in several peripheral nerve injury models.Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated to have a role in antioxidant effect. After nerve injury, the severely painful behavior is also performed. However, little has been explored regarding the function of Nrf2 in this painful process. Therefore, in this study, we compared the effects of Nrf2 antibody administration following sciatic nerve-pinch injury on painful behavior induced in young mice and neurochemical changes in dorsal root ganglion neurons. After pinch nerve injury, we found that the magnitude of the thermal allodynia was significantly decreased after application of Nrf2 antibody (5ul, 1mg/ml) in such injured animals and phosphorylated ERK(p-ERK) as well as the apoptotic protein (i.e., Bcl-6) in DRG neurons were also down-regulated in the anti-Nrf2-treated injured groups compared to the saline-treated groups. Taken collectively, these data suggested that the Nrf2 antibody reduced thermal hyperalgesia via ERK pathway and the down regulation of Bcl-6 protein from the apoptosis pathway might be protecting against the protein deletions caused by anti-Nrf2 effect and suggested the new therapeutic strategy with Nrf2 inhibitor following nerve injury.

Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway.

Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases including Alzheimer's disease (AD), in which dysregulation of double-stranded RNA-dependent protein kinase (PKR)-like ER-resident kinase (PERK) is considered to play a critical role. Allicin, a garlic extract, has been demonstrated a protective role in AD model. The present study was designed to investigate the possible protective effect of allicin on ER stress-induced cognitive deficits and underlying mechanisms in rats. In this study, 72h of lateral ventricular infusion of tunicamycin (TM), an ER stress stimulator, induced significant cognitive deficits. TM increased tau phosphorylation, Aß42 deposit, and oxidative stress, and reduced antioxidative enzymes activity in the hippocampus. TM moderately elevated the expression of PERK and its downstream substrate nuclear factor erythroid-derived 2-like 2 (Nrf2) in the hippocampus. All these impaired changes by TM were significantly improved by allicin pretreatment. Allicin markedly increased PERK and Nrf2 expression in the hippocampus. Thus, our data demonstrate the protective role of allicin in ER stress-related cognitive deficits, and suggest that PERK/Nrf2 antioxidative signaling pathway underlies the action mechanism.

One-dimensional carbon nanotube@barium titanate@polyaniline multiheterostructures for microwave absorbing application.

Multiple-phase nanocomposites filled with carbon nanotubes (CNTs) have been developed for their significant potential in microwave attenuation. The introduction of other phases onto the CNTs to achieve CNT-based heterostructures has been proposed to obtain absorbing materials with enhanced microwave absorption properties and broadband frequency due to their different loss mechanisms. The existence of polyaniline (PANI) as a coating with controllable electrical conductivity can lead to well-matched impedance. In this work, a one-dimensional CNT@BaTiO3@PANI heterostructure composite was fabricated. The fabrication processes involved coating of an acid-modified CNT with BaTiO3 (CNT@BaTiO3) through a sol-gel technique followed by combustion and the formation of CNT@BaTiO3@PANI nanohybrids by in situ polymerization of an aniline monomer in the presence of CNT@BaTiO3, using ammonium persulfate as an oxidant and HCl as a dopant. The as-synthesized CNT@BaTiO3@PANI composites with heterostructures were confirmed by various morphological and structural characterization techniques, as well as conductivity and microwave absorption properties. The measured electromagnetic parameters showed that the CNT@BaTiO3@PANI composites exhibited excellent microwave absorption properties. The minimum reflection loss of the CNT@BaTiO3@PANI composites with 20 wt % loadings in paraffin wax reached -28.9 dB (approximately 99.87% absorption) at 10.7 GHz with a thickness of 3 mm, and a frequency bandwidth less than -20 dB was achieved from 10 to 15 GHz. This work demonstrated that the CNT@BaTiO3@PANI heterostructure composite can be potentially useful in electromagnetic stealth materials, sensors, and electronic devices.

Synthesis and microwave absorption properties of electromagnetic functionalized Fe3O4-polyaniline hollow sphere nanocomposites produced by electrostatic self-assembly.

Highly regulated Fe3O4-polyelectrolyte-modified polyaniline (Fe3O4-PE@PANI) hollow sphere nanocomposites were successfully synthesized using an electrostatic self-assembly approach. The morphology and structure of the Fe3O4-PE@PANI nanocomposites were characterized using field-emission scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The results showed that the as-prepared nanocomposites had well-defined sizes and shapes, and the average size is about 500 nm. The assembly process was investigated. Magnetization measurements showed that the saturation magnetization of the nanocomposites was 38.6 emu g-1. It was also found that the Fe3O4-PE@PANI nanocomposites exhibited excellent reflection loss abilities and wide response bandwidths compared with those of PANI hollow spheres in the range 0.5-15 GHz. The Fe3O4-PE@PANI nanocomposites are, therefore, promising for microwave absorption applications.

Facile synthesis of BaTiO3 nanotubes and their microwave absorption properties.

Uniform BaTiO(3) nanotubes were synthesized via a simple wet chemical route at low temperature (50 °C). The as-synthesized BaTiO(3) nanotubes were characterized using powder X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The results show that the BaTiO(3) nanotubes formed a cubic phase with an average diameter of ~10 nm and wall thickness of 3 nm at room temperature. The composition of the mixed solvent (ethanol and deionized water) was a key factor in the formation of these nanotubes; we discuss possible synthetic mechanisms. The microwave absorption properties of the BaTiO(3) nanotubes were studied at microwave frequencies between 0.5 and 15 GHz. The minimum reflection loss of the BaTiO(3) nanotubes/paraffin wax composite (BaTiO(3) nanotubes weight fraction = 70%) reached 21.8 dB (~99.99% absorption) at 15 GHz, and the frequency bandwidth less than -10 dB is from 13.3 to 15 GHz. The excellent absorption property of BaTiO(3) nanotubes at high frequency indicates that these nanotubes could be promising microwave-absorbing materials.

[Expression of hypoxia induced factor-1alpha and function of epididymis in varicocele: experiment with rats].

OBJECTIVE: To investigate the expression of hypoxia induced factor-la (HIF-1alpha) and the content of sialic acid and carnitine in the epididymis in varicocele (VC) and to investigate the mechanism of induction of epididymis dysfunction by VC. METHODS: Forty-five Wistar rats were randomly divided into 3 equal groups: experimental group undergoing decreasing of the diameter of the left renal vein so as to cause VC, control group, and sham operation group. 49 days after the operation the left epididymis samples were collected. Western blotting and immunohistochemistry were used to detect the HIF-1alpha expression. The contents of sialic acid and carnitine were detected. RESULTS: The HIF-1alpha expression level detected by Western blotting of the experimental group was 0.96 +/- 0.65, significantly higher than those of the control group (0.11 +/- 0.08) and sham operation group (0.07 +/- 0.05) (both P < 0.05); and the positive rate of HIF-1alpha detected with immunohistochemistry of the experimental group was 91.67%, significantly higher than those of the control group (16.67%) and sham operation group (21.43%) (both P < 0.01). The contents of sialic acid and carnitine in the epididymis of the experimental group were 6.3 +/- 2.3 and 1.1 +/- 0.3 respectively, both significantly lower than those of the control group (24.7 +/- 4.4 and 2.8 +/- 0.6) and sham operation group (26.1 +/- 4.4 and 3.2 +/- 0.6) (all P < 0.05). The contents of sialic acid and carnitine in the epididymis were significantly negatively correlated with the HIF-1alpha expression (r = -0.649, P = 0.017; r = -0.666, P = 0.013). CONCLUSION: VC causes epididymal hypoxia and epididymal dysfunction, and hypoxia plays an important role in VC induced epididymal dysfunction.

[Relationship of transforming growth factor beta1 and basic fibroblast growth factor to detrusor underactivity following bladder outlet obstruction: experiment with rats].

OBJECTIVE: To investigate the relationship of transforming growth factor beta1 (TGFbeta1) and basic fibroblast growth factor (bFGF) to detrusor underactivity following bladder outlet obstruction (BOO). METHODS: Female Wistar rats underwent ligation of the urethra to establish BOO models and were divided into BOO model 2-week group (11 rats) and BOO model 6-week group (10 rats). 8 rats underwent sham operation as control group. The detrusor urine was taken out and stimulated by carbachol to measure the detrusor contraction force (DCF). RT-PCR method was employed to measure the mRNA expression of TGFbeta1 and bFGF in the detrusor urine. Urine TGFbeta1 and bFGF were determined by ELISA. RESULTS: The maximum DCF levels of the BOO 2-week group under the 1 x 10(-4) mmol/L and 1 x 10(-3) mmol/L carbachol concentrations were 0.96 g +/- 0.11 g and 1.98 g +/- 0.21 g respectively, both significantly higher than those of the sham operation group (0.85 g +/- 0.18 g and 1.82 g +/- 0.19 g respectively, both P < 0.05). The maximum DCF levels of the BOO 6-week group under the 1 x 10(-5), 1 x 10(-4), 1 x 10(-3) and 1 x 10 (-2) mmol/L carbachol concentrations were 0.19 g +/- 0.02 g, 0.65 g +/- 0.06 g, 1.12 g +/- 0.08 g, and 1.40 g +/- 0.19 g respectively, all significantly lower than those of the BOO 2-week group (0.24 g +/- 0.03 g, 0.96 g +/- 0.11 g, 1.98 g +/- 0.21 g, and 2.16 g +/- 0.21 g respectively, all P < 0.05) and those of the sham operation group (0.23 g +/- 0.04 g, 0.85 g +/- 0.18 g, 1.82 g +/- 0.19 g, and 2.12 g +/- 0.26 g respectively, all P < 0.05). The mRNA expression of TGFbeta1 of the BOO 6-week group, BOO 2-week group, and sham operation group was 0.72 +/- 0.21, 0.34 +/- 0.10, and 0.32 +/- 0.01 respectively, there was a significant difference between the BOO 6-week group and the BOO 2-week group (P < 0.01). The mRNA expression level of bFGF of the BOO 6-week group was 0.38 +/- 0.13, significantly higher than those of the BOO 2-week group and sham operation group (0.21 +/- 0.07 and 0.10 +/- 0.05 respectively, both P <0.05). DCF was negatively correlated with the mNRA expression of TGFbeta1 and the mNRA expression bFGF in detrusor (both P < 0.05). The urine TGFbeta1 of the BOO 6-week group was (606 +/- 216) microg/mol Cr, significantly higher than that of the BOO 2-week group [(131 +/- 49) microg/mol Cr] and that of the sham operation group [(107 +/- 22) microg/mol Cr, both P <0.05]. CONCLUSION: With the progression of BOO, there is a sustained rise of bFGF mRNA expression in detrusor; however, the TGFbeta1 mRNA expression only increases during the decompensation stage. Urine TGFbeta1 level is very high 6 weeks after BOO, which may help predict the contraction function of bladder after BOO.