Potential redox-sensitive Akt activation by dopamine activates Bad and promotes cell death in melanocytes

Dopamine (DA) is a well known oxidative neurotoxin. In addition, Akt has been reported to deliver a survival signal that inhibits apoptosis. However, it has also been reported that chronic Akt activation leads to apoptosis in response to oxidative stress. The objective of the present study was to investigate the possible role of the Akt pathway in vitiligo and its possible relationship with DA-induced cell death using Mel-Ab cells. Cultured Mel-Ab cells were treated with DA with and without N-Acetyl-L-cysteine (NAC), which is known to have antioxidative properties. Cell viability was then assessed by a crystal violet assay and Annexin staining was performed. The changes in the expression of Akt were analyzed by western blot analysis. The cell viability was reduced by approximately 60% in response to treatment with 500 µM DA, and NAC effectively prevented this cytotoxic effect. Likewise, treatment with DA produced numerous Annexin positive cells, while treatment with NAC prevented this apoptotic cell death. Akt was slowly phosphorylated after treatment with DA, while NAC clearly inhibited the DA-induced Akt activation. Western blot analysis also showed that treatment with DA induced the activation of Bad. Finally, LY294002 exerted a protective effect against DA-induced apoptotic cell death. DA may induce redox-sensitive Akt activation and increase the level of Bad, which can promote cell death by heterodimerization with survival proteins. Moreover, NAC effectively protects against DA-induced melanocyte death via inhibition of DA-induced Akt activation

Effect of biochars pyrolyzed in N2 and CO2, and feedstock on microbial community in metal(loid)s contaminated soils

Little is known about the effects of applying amendments on soil for immobilizing metal(loid)s on the soil microbial community. Alterations in the microbial community were examined after incubation of treated contaminated soils. One soil was contaminated with Pb and As, a second soil with Cd and Zn. Red pepper stalk (RPS) and biochars produced from RPS in either N2 atmosphere (RPSN) or CO2 atmosphere (RPSC) were applied at a rate of 2.5% to the two soils and incubated for 30 days. Bacterial communities of control and treated soils were characterized by sequencing 16S rRNA genes using the Illumina MiSeq sequencing. In both soils, bacterial richness increased in the amended soils, though somewhat differently between the treatments. Evenness values decreased significantly, and the final overall diversities were reduced. The neutralization of pH, reduced available concentrations of Pb or Cd, and supplementation of available carbon and surface area could be possible factors affecting the community changes. Biochar amendments caused the soil bacterial communities to become more similar than those in the not amended soils. The bacterial community structures at the phylum and genus levels showed that amendment addition might restore the normal bacterial community of soils, and cause soil bacterial communities in contaminated soils to normalize and stabilize

The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation

AbstractTransmembrane 4 L six family member 5 (TM4SF5) enhances cell migration and invasion, although how TM4SF5 mechanistically mediates these effects remains unknown. In the study, during efforts to understand TM4SF5-mediated signal transduction, TM4SF5 was shown to bind c-Src and thus hepatoma cell lines expressing TM4SF5 were analyzed for the significance of the interaction in cell invasion. The C-terminus of TM4SF5 bound both inactive c-Src that might be sequestered to certain cellular areas and active c-Src that might form invasive protrusions. Wildtype (WT) TM4SF5 expression enhanced migration and invasive protrusion formation in a c-Src-dependent manner, compared with TM4SF5-null control hepatoma cell lines. However, tailless TM4SF5ΔC cells were more efficient than WT TM4SF5 cells, suggesting a negative regulatory role by the C-terminus. TM4SF5 WT- or TM4SF5ΔC-mediated formation of invasive protrusions was dependent or independent on serum or epidermal growth factor treatment, respectively, although they both were dependent on c-Src. The c-Src activity of TM4SF5 WT- or TM4SF5ΔC-expressing cells correlated with enhanced Tyr845 phosphorylation of epidermal growth factor receptor. Y845F EGFR mutation abolished the TM4SF5-mediated invasive protrusions, but not c-Src phosphorylation. Our findings demonstrate that TM4SF5 modulates c-Src activity during TM4SF5-mediated invasion through a TM4SF5/c-Src/EGFR signaling pathway, differentially along the leading protrusive edges of an invasive cancer cell

Acute perimyocarditis mimicking acute myocardial infarction in a 12-year-old boy with Duchenne muscular dystrophy

Differential diagnosis of chest pain in the pediatric population is important but can be challenging. A 12-year-old boy with Duchenne muscular dystrophy presented with chest pain, cardiac enzyme elevation, and convex ST elevations in the inferior leads with reciprocal ST depression in the anterior leads on electrocardiogram. Echocardiography on admission revealed normal left ventricular function. Suspecting acute myocardial infarction, we performed invasive coronary angiography, which revealed normal coronary arteries. A follow-up electrocardiogram showed an acute pericarditis pattern with concave ST elevations in most leads and PR depression, and follow-up echocardiography revealed global left ventricular dysfunction, suggestive of acute perimyocarditis. Ibuprofen was administered for acute pericarditis, and a continuous milrinone infusion was commenced for myocardial dysfunction. The chest pain improved by the next day, and the ST segment elevations normalized on day 4. Echocardiography on day 9 revealed improved left ventricular function. The patient was discharged on day 11, and he is doing well without chest pain through 12 months of follow-up. The last electrocardiogram showed normal sinus rhythm without ST change. Differential diagnosis of acute myocardial infarction and acute perimyocarditis is important for proper treatment strategies and the different prognoses of these two conditions

Extraskeletal Ewing's Sarcoma of the Hard Palate

Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor morphologically indistinguishable from the more common Ewing's sarcoma of bone. We report a case of EES arising in the hard palate of 34-yr-old male patient. Microscopically, the monotonous small round cells without neuronal differentiation showed membranous positive immunoreactivity for MIC2/CD99 and vimentin. Ultrastructurally, the tumor cells showed a few intracytoplasmic organelles without evidence of neurosecretory granules or neurofilaments. The EWS-FLI1 chimeric gene was identified using the nested reverse transcriptase-polymerase chain reaction

Carbonic anhydrase XII expression is associated with histologic grade of cervical cancer and superior radiotherapy outcome

BACKGROUND: To investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer. METHODS: CA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome. RESULTS: Immunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade. CONCLUSIONS: Our study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors

Renal transplantation in a patient with Bartter syndrome and glomerulosclerosis

Bartter syndrome (BS) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism. There have been several case reports of BS complicated by focal segmental glomerulosclerosis (FSGS). Here, we have reported the case of a BS patient who developed FSGS and subsequent end-stage renal disease (ESRD) and provided a brief literature review. The patient presented with classic BS at 3 months of age and developed proteinuria at 7 years. Renal biopsy performed at 11 years of age revealed a FSGS perihilar variant. Hemodialysis was initiated at 11 years of age, and kidney transplantation was performed at 16 years of age. The post-transplantation course has been uneventful for more than 3 years with complete disappearance of BS without the recurrence of FSGS. Genetic study revealed a homozygous p.Trp(TGG)610Stop(TGA) mutation in the CLCNKB gene. In summary, BS may be complicated by secondary FSGS due to the adaptive response to chronic salt-losing nephropathy, and FSGS may progress to ESRD in some patients. Renal transplantation in patients with BS and ESRD results in complete remission of BS

Effects of Korean Red Ginseng on Cognitive and Motor Function: A Double-blind, Randomized, Placebo-controlled Trial

Ginseng has a long history of use for health enhancement, and there is some evidence from animal studies that it has a beneficial effect on cognitive performance. The purpose of this study was to investigate the effect of Korean red ginseng on cognitive performance in humans. A total of 15 healthy young males with no psychiatric or cognitive problems were selected based on an interview with a board-certified psychiatrist. The subjects were randomly assigned to receive a daily dose of 4,500 mg red ginseng or placebo for a 2-week trial. There were 8 subjects in the red ginseng group and 7 subjects in the placebo group. All of the subjects were analyzed with the Vienna test system and a P300 event-related potential (ERP) test. There were no significant differences in the Vienna test system scores between the red ginseng group and the placebo group. In the event-related potential test, the C3 latency of the red ginseng group tended to decrease during the study period (p=0.005). After 2 wk, significant decreases were observed in the P300 latencies at Cz (p=0.008), C3 (p=0.005), C4 (p=0.002), and C mean (p=0.003) in the red ginseng group. Our results suggest that the decreased latency in ERP is associated with improved cognitive function. Further studies with a higher dosage of ginseng, a larger sample size, and a longer follow-up period are necessary to confirm the clinical efficacy of Korean red ginseng.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/2014017262/7SEQ:7PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:2014017262ADJUST_YN:YEMP_ID:A079623DEPT_CD:801CITE_RATE:0DEPT_NM:의학과SCOPUS_YN:NCONFIRM: