Corrigendum to "Investigation of Hepatoprotective Activity of Induced Pluripotent Stem Cells in the Mouse Model of Liver Injury".

[This corrects the article DOI: 10.1155/2011/219060.].

microRNA-324 plays an oncogenic role in bladder cancer cell growth and motility.

BACKGROUND: Despite advances in the treatment of bladder cancer (BC), patients with late-stage BC have a high mortality rate. microRNA is a small, nonprotein coding RNA, and a dysfunction in its expression is frequently strongly correlated with the prognosis of patients with cancer. Aberrant expression of miR-324 has been reported to contribute to human carcinogenesis. However, the role of miR-324 in BC remains unclear. METHODS: The expression levels of miR-324-5p and miR-324-3p were analyzed by analyzing The Cancer Genome Atlas (TCGA) database and real-time polymerase chain reaction (PCR) approach. The biological role of miR-324-5p and miR-324-3p were assessed in BFTC950 cells with miR-324-5p or miR-324-3p mimics transfection, respectively. RESULTS: In this study, we demonstrated that high expression levels of miR-324-5p and miR-324-3p were significantly correlated with poor survival of patients with BC. Furthermore, miR-324-5p expression significantly accelerated BC cell proliferation, colony formation ability, and invasion ability, whereas miR-324-3p expression slightly increased BC cell growth and motility. CONCLUSION: Our data indicated that miR-324-5p and miR-324-3p play oncogenic roles in BC cells. This finding provides a new insight into potential therapeutic targets or putative biomarkers of BC.

Anti-epileptic drugs associated with fractures in the elderly: a preliminary population-based study.

OBJECTIVE: Although classic anti-epileptic drugs have been associated with increased fracture risk, data are lacking on the outcomes of newer anti-epileptic drugs, such as gabapentin (GBP), levetiracetam, pregabalin, oxcarbazepine (OXC), and topiramate. This study was designed to determine fracture risks in the elderly associated with newly-developed anti-epileptic drugs. METHODS: A total of 2,169 patients (median age = 71.01 years, SD = 11.25 years) who experienced fractures between 2006 and 2013 were selected. For each case, age-, sex-, and comorbidity-matched controls were selected. The assessed clinical outcome was any fracture, and the use of anti-epileptic drugs was used as an exposure variable. RESULTS: There were no differences in age, sex, or comorbidities between patients and controls, but patients with fractures often lived in urban areas (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.05-1.29) and had low income (OR = 1.14; 95% CI = 1.01-1.29) compared to controls. A significant increase in fractures was associated with OXC (OR = 3.31; 95% CI = 1.59-6.92), carbamazepine (CBZ; OR = 2.18; 95% CI = 1.31-3.61), and GBP (OR = 1.79; 95% CI = 1.01-3.18). Phenobarbital (OR = 1.97; 95%CI = 0.53-7.34), phenytoin (OR = 0.52; 95% CI = 0.23-1.16), levetiracetam (OR = 1.84; 95% CI = 0.55-6.16), valproic acid (OR = 1.01; 95% CI = 0.53-1.92), lamotrigine (OR = 1.44; 95% CI = 0.12-16.65), and topiramate (OR = 0.47; 95% CI = 0.10-2.31) were not associated with fracture risk. CONCLUSIONS: CBZ, GBP, and OXC users have a significantly higher risk of fracture. Most recently-developed anti-epileptic drugs are not associated with an increased risk of fracture in individuals aged ≥50 years.

Tight Junction Protein 1 Dysfunction Contributes to Cell Motility in Bladder Cancer.

BACKGROUND/AIM: Bladder cancer is the most common malignancy involving the urinary system. The mortality rate in late stages remains high, thus the development of effective biomarkers for diagnosis or prognosis is required in order to improve patient survival rates. Tight junction protein 1 (TJP1) is a membrane-associated protein that helps modulate cell-cell contact. However, the role of TJP1 in bladder cancer progression remains unclear. MATERIALS AND METHODS: The expression levels of TJP1 and miR-455-5p were examined by analyzing The Cancer Genome Atlas database. The biological role of TJP1 and miR-455-5p were assessed in T24 cells with siTJP1 or miR-455-5p mimics transfection, respectively. RESULTS: High levels of expression of TJP1 were significantly correlated with poor lymph node metastasis (pN stage; p=0.004). Knockdown of the TJP1 gene expression led to significant decrease of the growth and invasion of T24 cells. Using a bioinformatics approach, miR-455-5p was shown to suppress TJP1 expression by directly targeting its 3' prime untranslated region in bladder cancer cells. The ectopic expression of miR-455-5p revealed that bladder cancer cell migration, invasion, and proliferation were significantly suppressed. CONCLUSION: In summary, our results indicate that dysfunction of the miR-455-TJP1 axis is involved in bladder cancer cell growth and metastasis. These findings highlight potential therapeutic targets or putative biomarkers for bladder cancer.

Improvement of carbon tetrachloride-induced acute hepatic failure by transplantation of induced pluripotent stem cells without reprogramming factor c-Myc.

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl(4))-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl(4)-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl(4)-treated mice. CCl(4)-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases.

Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells.

INTRODUCTION: CD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved. MATERIALS AND METHODS: In the present study, we isolated CD133(+) cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133(-) cells. Bioinformatics analysis suggested that the STAT3 pathway might be important in MB and CD133(+) cells. To evaluate the effects of inhibiting the STAT3 pathway, MB-derived CD133(+/-) cells were treated with the potent STAT3 inhibitor, cucurbitacin I. Treatment with cucurbitacin I significantly suppressed the CSC-like properties and stemness gene signature of MB-derived CD133(+) cells. Furthermore, cucurbitacin I treatment increased the apoptotic sensitivity of MB-derived CD133(+) cells to radiation and chemotherapeutic drugs. Notably, cucurbitacin I demonstrated synergistic effects with ionizing radiation to inhibit tumorigenicity in MB-CD133(+)-inoculated mice. RESULTS: These results indicate that the STAT3 pathway plays a key role in mediating CSC properties in MB-derived CD133(+) cells. Targeting STAT3 with cucurbitacin I may therefore represent a novel therapeutic approach for treating malignant brain tumors.

The effects of researcher-composed music at mealtime on agitation in nursing home residents with dementia.

This study examined the effects of music at mealtimes on agitation in 22 nursing home residents with dementia. We used a pretest-posttest research design. We played researcher-composed music to residents at each of two mealtimes daily over a consecutive 4-week period. We observed and recorded agitation 24 hours daily for the 4-week period and the following 2-week period. Results revealed a significant decline in mean agitation scores. A cumulative dose effect and a short-term linger effect were observed. Findings suggest that soothing music may be beneficial in managing agitation in nursing home residents with dementia.

Investigation of hepatoprotective activity of induced pluripotent stem cells in the mouse model of liver injury.

To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3ß, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy.

Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells.

Induced pluripotent stem cells (iPSCs) with four reprogramming factors (Oct-4/Sox2/Klf-4/c-Myc) have been shown to differentiate into hepatic lineages. However, it was unclear whether obviation of the c-Myc oncogene in iPSCs affected hepatic differentiation or inhibited in vivo tumor formation. In this study, we demonstrated that iPSCs without c-Myc had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) with biological functions. As detected using planar-radionuclide imaging and Hoechst labeling assays, these iPSCs and iPSC-Heps tended to mobilize to the injured liver area in thioacetamide (TAA)-treated mice. Intravenous transplantation of both iPSCs and iPSC-Heps but not mouse embryonic fibroblasts (MEFs) reduced the hepatic necrotic area, improved liver functions, and rescued TAA-treated mice from lethal acute hepatic failure (AHF). In addition, microarray-based bioinformatics and quantitative RT-PCR showed high expression of antioxidant genes in iPSCs and iPSC-Heps compared to MEFs. In vivo and in vitro studies of NAC pretreatment confirmed that iPSCs and iPSC-Heps potentially suppressed ROS production and activated antioxidant enzymes in TAA-injured livers. Six months after transplantation in TAA-treated mice, tumor formation was not seen in non-c-Myc iPSC grafts. Therefore, reprogramming adult somatic cells without c-Myc may prevent oxidative stress-induced damage and provide a safer alternative for hepatic regeneration in AHF.

Dysregulated apoptosis through the intrinsic pathway in the internal spermatic vein of patients with varicocele.

BACKGROUND/PURPOSE: Apoptosis plays a critical role in various physiological processes. Varicocele is the most common cause of male infertility in adults. The dilated and thickened wall of the internal spermatic vein (ISV) in varicocele is considered similar to that in varicose veins. We investigated apoptotic protein expression in the ISV of varicocele, including Bcl-2, Fas, caspase-8 and caspase-9, to determine the intrinsic or extrinsic pathway. METHODS: The study group consisted of 10 patients with grade 3 left varicocele. The control group consisted of 10 patients with left indirect inguinal hernia. A 1-cm section of ISV was resected, using left inguinal incision, from each patient in both groups. The ISV sections were used to detect the mediators that regulate the intrinsic (Bcl-2 and caspase-9) and extrinsic (Fas and caspase-8) apoptotic pathways, by immunoblotting and immunohistochemical staining. Results were analyzed using Student's t tests. RESULTS: Bcl-2, Fas, caspase-8 and caspase-9 immunoblots from both groups revealed a single band. The relative intensities of the Bcl-2 and caspase-9 protein bands differed significantly between the varicocele and control groups. Thickening of the smooth muscle layer of the ISV was found in patients with varicocele compared with the control group. Bcl-2 overexpression and downregulation of caspase-9 expression were noted in the varicocele group. There was no significant difference in Fas or caspase-8 expression in either group. CONCLUSION: We showed overexpression of Bcl-2 and downregulation of caspase-9 expression in the ISV under hypoxic stress. This indicated dysregulated apoptosis through the intrinsic pathway in the ISV of patients with varicocele. To the best of our knowledge, this is the first study of the apoptotic pathway in the human ISV. Additional studies are needed to establish whether adjunctive hyperbaric oxygen therapy reduces the recurrence rate after varicocelectomy.

Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans.

BACKGROUND/PURPOSE: Cadmium (Cd) causes various genitourinary disorders and is a carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies heavy metals. We evaluated changes in Cd concentration and MT expression in human prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to clarify the relationship between Cd concentration and MT expression in prostatic diseases. METHODS: The experimental group consisted of 18 patients who underwent radical prostatectomy for CaP. The control group consisted of 35 patients who underwent transurethral resection of the prostate for BPH. Tissue samples were acquired from the gross tumor site and from resected chips. We determined Cd concentration by atomic absorption, MT expression by immunoblotting, and immunohistochemical staining. The significance of between-group differences for these outcomes was analyzed using Student's t tests. RESULTS: There was no statistically significant difference in Cd concentration between the CaP and BPH groups. Immunoblots from both groups revealed a single band. The relative intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in the CaP group. MT expression in patients with BPH was 3.4-fold higher than in those with CaP. CONCLUSION: MT may bind heavy metals and protect patients from CaP. Additional studies are needed to reveal the factors that influence the expression of MT in prostate epithelial cells, and to analyze the free and compound forms of Cd at the same time.

Cadmium accumulation and metallothionein overexpression in internal spermatic vein of patients with varicocele.

OBJECTIVES: To determine the possible molecular mechanism for the thickened wall in the internal spermatic vein (ISV) of patients with varicocele, we examined the cadmium (Cd) content and metallothionein (MT) expression in these diseased vessels. Previous studies have shown that Cd might play a role in the etiology of varicocele-associated infertility. MT, a metal-binding protein, protects against cell apoptosis during hypoxia. METHODS: The study group consisted of 20 patients with grade 3 left varicocele. The control group consisted of 15 volunteers with left-sided indirect inguinal hernia. Through a left inguinal incision, a 1-cm section of the ISV was resected from each patient to measure the Cd and MT levels. The results were analyzed using Student's t test. RESULTS: The Cd content in the ISV was 59.84 +/- 5.7 ng/g in the control group and 192.1 +/- 24.2 ng/g in the varicocele group. The relative intensity of the MT band was 40.52 +/- 3.74 in the control group and 78.26 +/- 5.61 in the varicocele group. MT expression was greater in the varicocele group than in the control group, and its deposition in the vascular endothelial layer was predominant using immunohistochemistry staining and confocal laser scanning. CONCLUSIONS: The results of the present study have demonstrated a greater accumulation of Cd in the ISV of the varicocele group than in the control group. The high Cd content and hypoxic conditions would induce overexpression of MT in the diseased vessels to protect the vascular cells from apoptosis. This might be a mechanism for the thickened wall of the ISV in patients with varicocele.

Involved intrinsic apoptotic pathway of testicular tissues in varicocele-induced rats.

INTRODUCTION: Increased testicular germ cell apoptosis has been reported in varicocele-induced rats. We studied intrinsic or extrinsic pathway of apoptosis by detecting Bcl-2, caspase-9, caspase-8, and activated caspase-3 expressions in the bilateral testes of experimental varicocele-induced rats. MATERIALS AND METHODS: Experimental left varicocele (ELV) was created by partial ligation of left renal vein in a study group of 24 adult male Sprague-Dawley rats. The other 24 rats were as control group. Eight rats from each group were killed at 4, 8, and 12 weeks following varicocele creation. Testicular tissues of both groups were sampled for TUNEL assay and immunoblotting. RESULTS: Increased apoptotic germ cell was found in the ipsilateral testis of varicocele group at 8 and 12 weeks after operation (P < 0.05). Increased activated caspase-3 expression in the contralateral (right) testis was noted at 12 weeks following varicocele creation (P < 0.05). CONCLUSIONS: Our study demonstrates down-regulation of Bcl-2 expression and increased expressions of caspase-9 and activated caspase-3 in the ipsilateral testis of ELV rats at 8 and 12 weeks, indicating gradually increased testicular tissues apoptosis through the intrinsic pathway in varicocele-induced rats. Simultaneously, increased apoptosis in the contralateral testis was observed at 12 weeks (P < 0.05) following varicocele creation also.

Bcl-2 overexpression in the internal spermatic vein of patients with varicocele.

BACKGROUND/PURPOSE: Varicocele is characterized by dilatation and tortuosity of the internal spermatic vein (ISV). Cross sections of ISV showed marked thickening of smooth muscle layer under microscopy. This study examined Bcl-2 (anti-apoptotic protein) expression in the ISV of patients with varicocele. METHODS: The study group consisted of eight patients with left varicocele, grade 3. The control group consisted of six volunteers with left indirect inguinal hernia. Using a left inguinal surgical incision, a 1-cm section of ISV was resected from each patient in both groups as specimens for immunoblotting and immunohistochemical staining of Bcl-2. Results were analyzed using Student's t test. RESULTS: Bcl-2 immunoblots from both groups revealed one single band. alpha-tubulin was used as loading control. The average relative intensity of the Bcl-2 was 25.82 +/- 10.53 in the control group and 113.49 +/- 27.49 in the varicocele group. Hematoxylin staining revealed a thickening ISV in the patients with varicocele, predominantly in the muscle layer, which was not found in the control group. Moreover, the intensity of Bcl-2 immunostaining was markedly higher in the study group than in the control group. CONCLUSION: This study showed Bcl-2 overexpression in the ISV of patients with varicocele. Additional studies are necessary to clarify the molecular mechanisms of varicocele formation and recurrence.

A Web-based short messaging service system to enhance family-centered surgical patient care.

The purpose of this study was to develop a web-based short messaging service (SMS) system in the operating room (OR). At the same time, we integrated and analyzed the limits of SMS in the OR. A cross-sectional study with quantitative methods and convenience sampling was used to gather data in this study. In the SMS project, we approached the content of SMS with operation diagnosis, patient sources and time series (pre-, intra-, and post-operation). We also default the contents of SMS by patient individual conditions. In this study, 177 participants received 346 text messages and 139 participants answered satisfaction questionnaires (78.53 %). The findings show the usability of SMS as applied to clinical care, especially for reducing family anxiety, for real time information, physician-patient communication, medical care processes and patient safety. Therefore, it is suggested to exploit the effectiveness of a personal medical care information database under global goal in the future and to develop comprehensive management of the surgical patient relationship.

Increased expression of hypoxia-inducible factor-1alpha in the internal spermatic vein of patients with varicocele.

PURPOSE: Varicocele is recognized as a cause of male infertility. Testis hypoxia may be one of the possible mechanisms of varicocele. We examined whether tissue hypoxia occurred in the ISV of patients with varicocele by detecting the expression of HIF-1alpha. MATERIALS AND METHODS: The study group consisted of 8 patients with grade 3 left varicocele. The control group consisted of 6 volunteers with left indirect inguinal hernia. Using a left inguinal surgical incision, a 1 cm section of ISV was resected from each patient in both groups as specimens for immunoblotting and immunohistochemical staining of HIF-1alpha. Results were analyzed using Student's t test. RESULTS: HIF-1alpha immunoblots from both groups revealed a single band. The relative intensity of the HIF-1alpha protein band was 10.92 +/- 2.70 in the control group and 73.15 +/- 8.93 in patients with varicocele (ie 7-fold higher). CONCLUSIONS: HIF-1alpha expression in the ISV of patients with varicocele was significantly higher than in the control group. This directly shows that hypoxia related pathophysiological changes have occurred in the ISV of patients with varicocele and that hypoxia may have also occurred in the testicular tissue. Thus, it would be of interest to investigate whether decreasing HIF-1alpha activation and testis hypoxia could reduce the recurrence of varicocele. To our knowledge, this is the first report on HIF-1alpha expression in human ISV. Additional studies will be necessary to clarify the relationship between testis hypoxia and male infertility in patients with varicocele.

Reducing the anxiety of surgical patient's families access short message service.

This study was to build a web-based short messaging service (SMS) system in operating room. We approached the efficiency of SMS for patient's families during the time series (pre-, intra-, and post-operation). In this study, 322 participants received 685 text messages. The findings show the usability of SMS that applied to the clinical care, especially for reducing family anxiety, improved their satisfaction. Therefore, it is suggested to exploit the effectiveness of personal medical care.