Expressions of JNK and p-JNK in advanced prostate cancer and their clinical implications / 中华男科学杂志

Objective@#To investigate the expressions of JNK and p-JNK in advanced prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their implications.@*METHODS@#Using immunohistochemistry, we detected the expressions of JNK and p-JNK proteins in 40 cases of paraffin wax-embedded PCa and 21 cases of BPH tissues and analyzed their relationships with advanced PCa and BPH as well as with the pathologic features of advanced PCa.@*RESULTS@#Statistically significant differences were not found in the positive expression rate of the JNK protein between BPH and PCa (42.86% vs 52.50%, P>0.05), non-metastatic and metastatic PCa (53.85% vs 51.85%, P >0.05), Gleason ≤7 and Gleason >7 (58.82% vs 47.82%, P >0.05), PSA ≤20 μg/L and PSA >20 μg/L (57.14% vs 51.52%, P >0.05), or survival >5 yr and survival ≤5 yr (60.00% vs 45.00%, P >0.05), nor in the expression level of p-JNK between BPH and PCa (33.33% vs 35.00%, P >0.05), non-metastatic and metastatic PCa (30.77% vs 37.03%, P >0.05), Gleason ≤7 and Gleason >7 (35.29% vs 34.78%, P >0.05), or PSA ≤20 μg/L and PSA >20 μg/L (43.75% vs 10.93%, P >0.05). However, the expression of p-JNK was significantly higher in the survival >5 yr than in the survival ≤5 yr group of the PCa patients (50.00% vs 20.00%, P <0.05).@*CONCLUSIONS@#PCa patients with highly expressed p-JNK have a longer survival time and the high positive rate of p-JNK is associated with the prognosis of PCa.

Expressions of ERK and p-ERK in advanced prostate cancer / 中华男科学杂志

Objective@#To investigate the expressions of extracellular signal-regulated kinase (ERK) and p-ERK in benign and malignant prostate tissues, and whether it can be used as a marker for the prognosis of advanced prostate cancer (PCa).@*METHODS@#Using immunohistochemical Envision, we detected the expressions of ERK1/2 and p-ERK1/2 in 20 cases of benign prostatic hyperplasia (BPH) and 40 cases of advanced PCa and analyzed their correlation with PCa metastasis, Gleason score, PSA level, and prognosis.@*RESULTS@#The expression of ERK1/2 was remarkably higher in the advanced PCa than in the BPH cases (82.5% vs 55%, P5 yr, and survival ≤ 5 yr groups were 61.9%, 89.5%, 57.9%, and 90.5%, respectively, with statistically significant differences among these groups (P<0.05).@*CONCLUSIONS@#ERK1/2 and p-ERK1/2 proteins are highly expressed in advanced PCa and p-ERK1/2 is associated with the metastasis and prognosis of advanced PCa.

Elevated peroxidative glutathione redox status in atherosclerotic patients with increased thickness of carotid intima media / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis.</p><p><b>METHODS</b>A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group (A), 42 in carotid artery intima-thickening group (B), and 34 in normal carotid artery intima-thickness group (C). All patients were subjected to the measurement of plasma glutathione (GSH) (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (NADP) (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (oxLDL), and malondialdehyde (MDA). The GSH/GSSG and NADPH/NADP(+) redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed.</p><p><b>RESULTS</b>With the thickening of artery intima (from group C to A), GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased (more positive) (P < 0.05). The NADPH and NADPH/NADP(+) redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima (P < 0.05). The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations (P < 0.05). The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming.</p><p><b>CONCLUSION</b>Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.</p>

Effects of peroxisome proliferators activated receptors on caveolin-1 expression in foam cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study the effect of peroxisome proliferators activated receptors (PPAR) alpha, gamma ligand on ATP-binding cassette transporter A1 (ABCA1) and caveolin-1 expressions and cholesterol, ox-LDL contents in human monocyte derived foam cells.</p><p><b>METHOD</b>Malondialdehyde (MDA) was measured by TBARS method, ox-LDL detected by ELISA method, cholesterol measured by fluorescence spectrophotometric method, ABCA1, caveolin-1 mRNA and protein expressions determined by RT-PCR and Western blot, in human monocytes, foam cells [human monocyte-derived macrophage induced by myristate acetate (PMA) further treated with 50 mg/L ox-LDL for 24 h], foam cells plus 10 micromol/L pioglitazone for 48 h, foam cells plus 5 micromol/L clofibrate for 48 h.</p><p><b>RESULT</b>The intracellular total cholesterol (TC), free cholesterol (FC), cholesteryl ester (CE), ox-LDL and lipid peroxide were significantly increased and the membrane expressions of ABCA1, caveolin-1 were down-regulated in foam cells compared to monocytes (all P < 0.05) and these changes were significantly attenuated by cotreatment with PPARalpha, gamma ligand.</p><p><b>CONCLUSION</b>The anti-atherosclerosis effects of PPARalpha, gamma ligand are related to reducing cholesterol contents and up-regulating ABCA1, caveolin-1 expressions in foam cells.</p>

Modified total hepatic vascular exclusion for liver extracapsular resection of giant hepatic cavernous hemangioma / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the feasibility of intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature for extracapsular resection of giant hepatic hemangioma.</p><p><b>METHODS</b>The clinical data of 32 patients undergoing hepatic resection with total hepatic vascular exclusion requiring intraoperative autologous transfusion were analyzed retrospectively. The tumors in these cases involved the proximal hepatic veins and inferior vena cava, with hemangioma volume ranging from 12 cm x 15 cm to 18 cm x 40 cm.</p><p><b>RESULTS</b>The hemangioma were completely resected in all patients, who all recovered smoothly. In one case, hemangioma rupture occurred during dissociation of the liver, resulting in massive hemorrhage which required blood transfusion of 6000 ml. Four patients received blood transfusion of 400-800 ml, and the other 27 had no blood transfusion. Only 8 patients underwent pringle maneuver with resection, whereas the other 27 underwent total hepatic vascular exclusion during liver resection for 5-30 min (mean 16 min).</p><p><b>CONCLUSION</b>Intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature is feasible and safe for extracapsular resection of huge hepatic hemangioma adjacent to the major arteries.</p>

Dysfunction of endothelial NO system originated from homocysteine-induced aberrant methylation pattern in promoter region of DDAH2 gene / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperhomocysteinemia (HHcy)-mediated dysfunction of endothelial NO system is an important mechanism for atherosclerotic pathogenesis. Dimethylarginine dimethylaminohydrolase (DDAH) is the key enzyme for degrading asymmetric dimethylarginine (ADMA), which is an endogenous inhibitor of endothelial nitric oxide (NO) synthase (eNOS). This study was designed to investigate whether the dysfunction of endothelial NO system originates from HHcy-mediated aberrant methylation modification in promotor region of DDAH2 gene.</p><p><b>METHODS</b>Human umbilical vein endothelial cells (HUVECs) were cultured to the third generation and treated with homocysteine (Hcy) at different concentrations (0, 10, 30, 100, and 300 micromol/L) for 72 hours. The methylation pattern in promoter region CpG island of DDAH2 gene was analyzed by nested methylation-specific PCR (nMSP). The mRNA expression of eNOS gene and DDAH2 gene was detected by semi-quantitative RT-PCR. The activity of DDAH2 and eNOS in cells, and the concentrations of ADMA and NO in culture medium were assayed respectively.</p><p><b>RESULTS</b>Mild increased concentration of Hcy (10 and 30 micromol/L) induced hypomethylation, while high concentration of Hcy (100 and 300 micromol/L) induced hypermethylation in the promoter CpG island of DDAH2 gene. The mRNA expression of DDAH2 increased in mild enhanced concentration of Hcy, and decreased in high concentration of Hcy correspondingly. The inhibition of DDAH2 activity, the increase of ADMA concentration, the reduction of eNOS activity and the decrease of NO production were all consistently relevant to the alteration of Hcy concentration.</p><p><b>CONCLUSION</b>The increased concentration of Hcy induced aberrant methylation pattern in promotor region of DDAH2 gene and the successive alterations in DDAH/ADMA/NOS/NO pathway, which showed highly relevant and dose-effect relationship. The results suggested that the dysfunction of endothelial NO system induced by HHcy could be partially originated from Hcy-mediated aberrant methylation in DDAH2 gene.</p>

Antagonistic effect of 3'-daidzein sulfonate sodium on prostatic hyperplasia in mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the antagonistic effect of 3'-daidzein sulfonate sodium (DSS) on benign prostatic hyperplasia (BPH) and its possible mechanism.</p><p><b>METHODS</b>Forty healthy mice were randomly divided into five groups: a normal control group without any treatment, a model group of BPH treated by subcutaneous injection of testosterone propionate, a positive control group with the BPH procedure treated by Qianliekang, a 20 mg/(kg x d) DSS group with the BPH procedure and a 40 mg/(kg x d) DSS group with the BPH procedure. After 12 days of the above treatments, the mice were sacrificed for measurement of the prostate glandular wet weight, the index of prostate gland (PI), the morphological changes of prostate gland by light microscopy and the contents of testosterone and estradiol in the serum.</p><p><b>RESULTS</b>The prostate wet weight and PI decreased dose-dependently after DSS treatment for 12 days compared with the BPH model group (P < 0.05 or P < 0.01). The hyperplastic epithelioglandular papilla waned and even disappeared in the DSS treated groups under the light microscope, the epithelial cells became cubical or flat. The effect of DSS at 40 mg/(kg x d) was similar to that of the positive anti-BPH drug Qianliekang. DSS reduced the serum testosterone, estradiol contents and the T/E2 ratio (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>DSS has significant antagonistic effect on BPH induced by testosterone propionate in mice, which may involve its regulatory action on the sex hormone balance.</p>

Establishment of rat model of psychical erectile dysfunction / 中华男科学杂志

<p><b>OBJECTIVE</b>To set up a method of establishing the animal model of psychical erectile dysfunction with emotional stress.</p><p><b>METHODS</b>All thirty-six male rats with normal sexual function were divided into three groups, i. e. normal group, model group and demasculinized group randomly according to their weights. The rats in the model group were suspended upside down in midair over the water and irritated repeatedly. Two weeks later, the sexual abilities of all rats, i. e. the times of mounting and intromitting the estrus female rats, the latent period of mounting, intromission and ejaculation, were recorded, and the number of rats that had sexual activities was also counted. And the hemorheology indices of the rats were measured.</p><p><b>RESULTS</b>Compared with the normal rats, the latency of mounting [(152.5 +/- 24.6) s vs (42.4 +/- 9.6) s] and intromission [(437.0 +/- 67.7) s vs (130.8 +/- 39.1) s] of the model rats were longer (P < 0.01), but the latency of ejaculation [(385.3 +/- 80.0) s vs (547.3 +/- 69.4) s] was shorter (P < 0.05) than that of the normal. There was no significant difference in the times of mounting between normal [(38.3 +/- 6.1) vices and model rats (38.5 +/- 5.4) vices], but the intromission times of model rats [(9.2 +/- 1.7) vices] was lower than that of the normal rats [(20.3 +/- 3.1) vices], P < 0.01. Compared with the normal rats, the sexual activity incidence of the model rats (mounting: 58.3%, intromission: 33.3%, ejaculation: 16.7%) was significant lower than that of the normal rats (100%) (P < 0.01). But there was no significant difference in the sexual ability between the model and the demasculinized rats (P > 0.05). The hemorheology indices, e. g. blood viscosity, hematocrit (Hct) and red cell aggregation (RCA), of the model rats was significant higher than that of the normal and demasculinized rats (P < 0.05), but there was no significant difference between the normal and demasculinized rats.</p><p><b>CONCLUSION</b>The rat model of psychical erectile dysfunction can be made ideally with psychical stress.</p>

Exploitation of a new noninvasive animal's blood pressure measuring apparatus and its function characterization / 中国应用生理学杂志

<p><b>AIM</b>To produce a new, noninvasive, animal's blood pressure measuring apparatus.</p><p><b>METHODS</b>By applying the principle similar with the measurement of human blood pressure, we developed a software which knowledge property owned by this research group and solved the problems of exactly demarcating the measuring spot of diastolic pressure. The blood pressure of rabbits was measured by the novel noninvasive animal's blood pressure measuring apparatus and the classic surgical catheterizing method simultaneously.</p><p><b>RESULTS</b>The novel noninvasive animal's blood pressure measuring apparatus was successfully set up. The measured blood pressures by this apparatus are very similar (r > 0.9) with the values obtained from the classic, surgical catheterizing method, no matter the blood pressures are normal, high or low.</p><p><b>CONCLUSION</b>Our new apparatus can be a reliable method for noninvasive measurement of the blood pressure of rabbits and rats.</p>

The relationship between oxidized form glutathione, coenzyme II and carotid artery atherosclerosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between plasma redox status and atherosclerosis.</p><p><b>METHODS</b>IVUS was performed in common carotid in the neck of 167 patients with heart diseases. Patients were divided into three groups: plaque-forming group (A, n = 79), intima-thickening group (B, n = 52) and control group (C, n = 36). Plasma glutathione (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (ox-LDL) and malondialdehyde (MDA) were measured in all patients. The GSH/GSSG and NADPH/NADP(+) redox potential were calculated according to Nernst equation, and correlation analysis performed.</p><p><b>RESULTS</b>GSH and GSH/GSSG gradually reduced and GSH/GSSG redox potential gradually increased in proportion to the thickening of artery intima (from Group C to Group A, P < 0.05). Similar but milder results were shown for NADPH and NADPH/NADP(+) redox status. The products of oxidative stress ox-LDL and MDA also increased significantly (P < 0.05) in proportion to the thickening of artery intima. GSH/GSSG redox potential is positively correlated to ox-LDL (P < 0.05). The redox status shifted to oxidizing direction in proportion to the intima thickness.</p><p><b>CONCLUSION</b>The imbalance of plasma redox status deviating to oxidation might be implicated in oxidized injury of lipid, intima thickening and atherosclerosis progress.</p>

Increased atria expression of receptor activity-modifying proteins in heart failure patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a calcitonin gene related peptide (CGRP) receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an adrenomedullin(ADM) receptor. As CGRP and ADM may play a beneficial role in heart failure, this study aimed at the question whether RAMPs mRNAs are changed in heart failure.</p><p><b>METHODS</b>Semi-quantitative reverse transcription-PCR (RT-PCR) was used to detect and quantify the mRNAs of RAMP1 and RAMP3 in the atria of heart failing patients.</p><p><b>RESULTS</b>It was found that the expressions of RAMP1, RAMP2 and RAMP3 mRNAs increased with the worsening of heart function, but the expressions of RAMP1 and RAMP2 mRNA decreased at level IV of heart failure.</p><p><b>CONCLUSION</b>The above results demonstrated in the atria of heart failure patients an up-regulation of CGRP receptor by an increase of RAMP1 in association with CRLR and an up-regulation of ADM receptor by an increase of RAMP2 expression in association with CRLR, thus suggesting that CGRP and ADM receptors be playing a functional role in compensating the chronic heart failure in human.</p>

Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rg1 on the spectrum of gene expression in the endothelial cells stimulated by TNF-alpha and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rg1.</p><p><b>METHODS</b>Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells (HUVECs) was measured by using an NO assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rg1 in HUVECs which were activated by TNF-alpha were detected by oligonucleotide microarray analysis.</p><p><b>RESULTS</b>NO production in HUVECs was decreased significantly after TNF-alpha treatment, while pretreatment with ginsenoside Rg1 enhanced NO production in TNF-alphastimulated HUVECs. Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-alphastimulated HUVECs.</p><p><b>CONCLUSIONS</b>Ginsenoside Rg1 could enhance NO production and the expression of eNOS mRNA in TNF-alpha stimulated HUVECs. Ginsenoside Rg1 regulated sets of genes in endothelial cells and protected endothelial cells from TNF-alpha activation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.</p>

Proteomic analysis of the effects of tumor necrosis factor-? on endothelial cells / 中国病理生理杂志

AIM: To investigate the affected proteins by tumor necrosis factor (TNF)-? in endothelial cells, and further explore the potential molecular mechanism of TNF-? on endothelial cells. METHODS: Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells (HUVECs) was measured by a NO assay kit. Proteomic alterations were analyzed using two-dimensional electrophoresis, and peptide mass fingerprinting with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. RESULTS: NO production in HUVECs decreased significantly after TNF-? treatement. Proteomics analysis showed 21 protein spots were changed including 9 spots that were increased and 11 spots that were decreased after TNF-? stimulation, and 1 spot was only detected in TNF-? activated cell gels. CONCLUSIONS: The decreased expression of ecNOS by TNF-? might result in decrease in NO production. Up-regulated MAP/ERK kinase 3 expression might imply that TNF-? activates the expression of adhesion molecules. Cytoskeletal protein actin is also involved in TNF-? injuried HUVECs. Proteomic analysis can find some clues for identifying new potential target of TNF-?. [