Corrigendum to "Dual Inhibiting Senescence and Epithelial-to-Mesenchymal Transition by Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction".

[This corrects the article DOI: 10.1155/2013/308130.].

Neuroprotective Effect of Perilla Extracts on PC12 Cells.

Background: Perilla frutescens (L) Britton contains some active principles which had neuroprotective actions. Objective: The present study was aimed to investigate the effect of Perilla extracts on neuroprotection, antioxidation and neurite outgrowth in PC12 cells. Material and Method: The neuroprotective effect of freeze-dried ethanolic extract from Perilla leaves and cold-pressed seed oil were tested on PC12 induced with beta-amyloid protein. The inhibition of tau-protein hyperphosphorylation and the antioxidant enzyme activity were analyzed. The neurite outgrowth bearing cells were investigated and MEK-1 protein production was analyzed by enzyme immunometric assay. Results: In PC12 culture induced toxicity by beta-amyloid protein: (1) the decrease in cell viability was attenuated in cells pretreated with leaf extract 200 mg/ml and oil 50 mg/ml; (2) SOD activity seemed to decrease when pretreated cells with the extracts; (3) tau phosphorylation was decreased by pretreated cells with50 mg/ml of oil. Moreover, given Perilla leaf extract or seed oil to PC12 culture, the amount of neurite outgrowth bearing cells increased harmoniously with MEK-1 protein expression. Conclusion: Perilla leaf extract and seed oil reversed the effect of beta-amyloid induced toxicity by decreasing oxidative stress and inhibition of tau-protein hyperphosphorylation. The enhancement of neurite outgrowth by Perilla extracts was also revealed.

Erythropoietin Administration Promotes Expression of VEGF in Renal Ischemic­Reperfusion Injury in Rat Model.

Background: Acute ischemia-reperfusion (I/R) injury is the most common causes of acute renal failure in daily clinical practice. It has been recognized that endothelial cell dysfunction and microvascular injury as the pathophysiological changes during I/R injury. Protective effects of erythropoietin (EPO) have been demonstrated in various experimental models of I/R induced injury. Therefore, the aim of the present study was to investigate whether EPO administration has renoprotective effect against acute renal failure I/R injury in rats by promotion of endothelial progenitor cells (EPCs) mobilization and neovascularization. Material and Method: Male Sprague-Dawley rats were pretreated with EPO (1,000 IU/kg/day, ip); or the placebo for 3 days before the induction of I/R procedure. On day 4, the bilateral renal occlusion for 30 min operations to produce renal I/R injury or treatment with EPO 30 min before the initiation of I/R were done. At the end of the reperfusion period at day 1 day 2 and day 4, blood and renal tissues were collected to investigate renal function and pathohistological examination. The expression levels of CAV-1 and CD34 were determined for circulating of EPCs in blood, while CD34, CAV-1 and VEGFR-2 were investigated for mobilized EPCs in kidney, using real time PCR. The expression level of VEGF was also examined to indicate the angiogenesis in kidney using real time PCR and western blotting. Results: In the I/R group, the significantly increased values of serum urea and creatinine were found on Day 1 after ischemia, as compared to sham group. The development of tubular epithelial cell necrosis, peritubular capillary congestion and mild interstitial infiltration has been observed in this group. Administration of EPO in I/R rat was significantly improved renal function and significantly less the tubular damage. The treatment with EPO significantly increased in expression levels of CD34 and CAV-1 in blood, and also CAV-1, VEGFR-2 and VEGF in kidney tissue in this group, as compared to the I/R group. Conclusion: These results suggest that treatment with EPO protects the kidney from ischemic acute renal injury via increasing the mobilization and recruitment of EPCs, resulting in the induction of expression of VEGF that might play an important role in the repair response.

Scenemulator: an innovative tutor note to facilitate non-specialist tutor in PBL tutorial session.

BACKGROUND: The tutor notes are the principal learning material to assist the non-specialist tutors in facilitating the students in tutorial groups effectively. Objective: This research aimed to study which tutor notes (scenemulators = scene + simulator + tutor notes anda typical one) is best to ensure effectiveness amongst Thammasat University preclinical tutors to facilitate in tutorial sessions. MATERIAL AND METHOD: Three of the scenemulators and one of typical tutor notes were formed based on the endocrinologist and endocrine block committees. After completion of each scenario over 3 consecutive years, twenty-two items with a five- rating scale questionnaire were co-operated to be completed by preclinical tutors at the Faculty ofMedicine, Thammasat University (n = 21-22/year). Thirteen and six were the topics efficiency and the comparative satisfaction, respectively. The last three were the tutor notes most needed by the tutors. Data were analyzed using descriptive statistics (mean + SD) andANOVA. RESULTS: From the 85%-response data, mean scores (M) on the topics efficiency on scenemulators and the regular tutor notes were above 4.5 and 3, respectively. Noticeably, the more preferable tutor notes were scenemulator (p-value <0.001). CONCLUSION: The present study demonstrated the potential ofscenemulators in filling up uncertain significant matters and its effective use as a tool to assist non-specialist PBL tutors.

Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) occurs after the administration of intravenous iodinated contrast agents. Oxidative stress has been proposed as one of the most important mechanisms in the pathogenesis of CI-AKI. The objective of this study was to investigate the antioxidant effect of the extract from Phyllanthus emblica (PE) in preventing CI-AKI. METHODS: Male Sprague Dawley rats were subjected into eight groups, were given water (control) or PE extract (125 or 250 or 500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal function and oxidative stress markers; malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity were determined in plasma and renal tissue. Kidney sections were performed for histopathological examination. RESULTS: In the contrast media (CM) group, increases in blood urea nitrogen and serum creatinine were demonstrated which correlated with severity of tubular necrosis, peritubular capillary congestion and interstitial edema. Moreover, an increase in MDA and a decrease in TAC SOD and CAT activity in CM group were significantly changed when compared with the control (P<0.05). In contrast, CI-AKI-induced rats administrated with PE extract 250 and 500 mg/kg/day significantly preserved renal function and attenuated the severity of pathological damage (P<0.05) as well as significantly lower MDA and higher TAC, SOD and CAT than the CM group (P<0.05). CONCLUSIONS: This study demonstrated the protective role of PE extract against CI-AKI.

Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction.

This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-ß1, BMP-7, Smad2/3, Smad1/5/8, and p16(INK4a) was determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-ß1, Smad2/3, S100A4, and p16(INK4a) expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. p16(INK4a) was positively correlated with TGF-ß1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-ß, Smad2/3, S100A4, and p16(INK4a) and preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease.

Protective effect of alpha tocopherol on contrast-induced nephropathy in rats.

BACKGROUND: Contrast-induced nephropathy (CIN) is a prominent cause of in-hospital acute kidney injury occurring after the administration of intravenous radiocontrast medium. Oxidative stress has been proposed as one of the more important mechanisms in the pathogenesis of CIN. The aim of the present study has been to determine the effect of alpha tocopherol on the reduction of renal damage in a rat model of CIN. METHODS: Male Sprague Dawley rats were subjected into six groups pretreated with alpha-tocopherol (250 or 500 mg/kg/day) or the vehicle tweeen80 for 5 days before the induction of CIN. Renal function and oxidative stress markers; level of malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) activity were determined. Kidney tissues were sectioned for pathohistological examination. RESULTS: In the contrast media (CM) group, an increase in serum urea and creatinine was found. Tubular necrosis and peritubular capillary congestion were demonstrated in this group. Also, an imbalance of oxidative stress markers; an increase in MDA and a decreased SOD activity in kidney were shown. On the contrary, in CIN-induced rats administrated with alpha-tocopherol group, a significant reduction of renal function and renal MDA, together with a significant increase of renal SOD, were observed. Interestingly, a reduction in MDA and an increase of TAC in serum, along with prevention of tubular injury, were demonstrated in this group, as compared to the CM group. CONCLUSION: This present study demonstrated that alpha tocopherol showed protective effect on the rat renal damage induced CIN. Therefore, this vitamin could be used as an antioxidant to attenuate the radiocontrast oxidative damage.

Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a process which tubular epithelial cells (TEC) undergo a phenotypic conversion to the matrix-producing fibroblasts and myofibroblasts. Phenotypic alteration of TEC was induced by the important cytokine transforming growth factor-beta (TGF-beta) to development of renal fibrosis. However bone morphogenetic protein-7 (BMP-7) generally counteracts with TGF-beta to maintenance of epithelial phenotype. In the present study, the authors investigated the anti-fibrotic property of vitamin E on unilateral ureteral obstruction (UUO) model mice. MATERIAL AND METHOD: UUO or sham-operated mice were randomly assigned to receive vitamin E (alpha tocopherol) or placebo and were sacrificed on days 3, 7 and 14 after operation. Kidney specimens were fixed for pathological study and immunohistochemistry for BMP-7. Protein expression of BMP-7 was determined by western blot analysis. The mRNA expression of BMP-7 and TGF-beta1 were measured by real-time RT-PCR. RESULTS: Vitamin E treated UUO mice showed the less severity of renal fibrosis. Tubular atrophy and interstitial fibrosis were significantly attenuated in vitamin E treatment. Immunohistochemistry revealed decreasing of BMP-7 protein expression in cytoplasm of TEC in obstructed kidneys. Moreover decreasing of BMP-7 protein and downregulation of BMP-7 mRNA in UUO mice were confirmed by western blot and real time RT-PCR. In contrast, vitamin E treatment significantly maintained the expression of BMP-7 protein and mRNA in UUO mice compared with placebo treatment. On the other hand, TGF-beta1 mRNA expression showed progressive upregulation in UUO mice on day 3, 7 and 14 compared with sham controls. The expression of TGF-beta1 mRNA was significantly lower in all vitamin E treated UUO mice compared with placebo treatment. CONCLUSION: Vitamin E treatment attenuated the progression of renal fibrosis in obstructed kidney by inhibited the TGF-beta1 but maintained the BMP-7 during EMT. Thus, the renoprotective effects of vitamin E could have some therapeutic value to inhibit the progression of renal fibrosis in human.

Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice.

BACKGROUND: One striking feature of chronic kidney disease (CKD) is tubular atrophy and interstitial fibrosis (TA/IF). During chronic renal injury, transforming growth factor-beta (TGF-beta) is involved in this process causing progression of renal fibrosis. Smad2/3 proteins have been identified to have an important function in the expression of extracellular matrix (ECM) regulation through TGF-beta signaling pathway. In the present study, the authors investigated the effect of vitamin E on renal fibrosis in mice model of unilateral ureteral obstruction (UUO). MATERIAL AND METHOD: UUO or sham-operated mice were randomly assigned to receive vitamin E (alpha tocopherol) or placebo and were sacrificed on days 3, 7 and 14 after UUO or sham operation. Kidney specimens were fixed for pathological study and immunohistochemistry for TGF-beta1. Protein expression of TGF-beta1 and Smad2/3 was determined by western blot analysis. The mRNA expression of TGF-beta1 was measured by real-time RT-PCR. RESULTS: Vitamin E treated UUO mice had less severity of renal fibrosis than placebo treatment. TA/IF was significantly attenuated by vitamin E treatment. Immunohistochemistry revealed increasing of TGF-beta1 protein expression in the interstitium area of obstructed kidneys. Moreover increasing of TGF-beta1 protein and upregulation of TGF-beta1 mRNA in UUO mice were confirmed by western blot and real time RT-PCR. In contrast, vitamin E treatment significantly inhibited the expression of TGF-beta1 protein and mRNA in UUO mice compared with placebo treatment. Interestingly, Smad2/3 protein expression became progressive increasing in UUO mice on day 3, 7 and 14 compared with sham controls. The expression of Smad2/3 protein was significantly lower in vitamin E treated UUO mice than placebo treatment in any time points. CONCLUSION: Vitamin E treatment attenuated the progression of renal fibrosis in obstructed kidneys. The renoprotective effect of vitamin E could be mediated by inhibition of TGF-beta/Smad2/3 signaling pathway.

The oncoprotein gankyrin interacts with RelA and suppresses NF-kappaB activity.

Gankyrin is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It interacts with multiple proteins and accelerates degradation of tumor suppressors Rb and p53. Since gankyrin consists of 7 ankyrin repeats and is structurally similar to IkappaBs, we investigated its interaction with NF-kappaB. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFalpha-induced transcriptional activity of NF-kappaB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-kappaB DNA-binding activity or nuclear translocation of RelA induced by TNFalpha in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-kappaB activity, which was further suppressed by gankyrin. The inhibitory effect of gankyrin was abrogated by nicotinamide as well as down-regulation of SIRT1, a class III histone deacetylase. Thus, gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation via SIRT1.

Clinical significance of serum total sialic acid in cholangiocarcinoma.

BACKGROUND: High levels of serum total sialic acid (TSA) have been reported in cholangiocarcinoma (CCA) patients. In this study, the clinical value and possible cause of increased total sialic acid in the serum in cholangiocarcinoma patients were examined. METHODS: Total sialic acid was determined in 172 serum and 25 tumor tissue samples taken from cholangiocarcinoma patients using the periodate thiobarbituric acid method. RESULTS: The total sialic acid content of the tumor tissue was significantly greater than that of the serum and not related to the concentration found in the serum. The serum total sialic acid was not correlated with age, sex, body mass index, blood group, tumor location, tumor stage, metastatic condition, histological types and survival of the patients. The increased total sialic acid in the serum had a significant correlation with serum MUC5AC mucin, alkaline phosphatase and the CA19-9, and the numbers of white blood cell and neutrophils. CONCLUSIONS: The concentration of serum sialic acid was not associated with clinicopathologic features or the tumor burden. The glycoproteins secreted from the tumor and inflammatory cells might be responsible for the increased total sialic acid in the serum in these patients.