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1.  A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats 
International Journal of Nanomedicine  2014;9(Suppl 2):79-92.
Purpose
The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days.
Methods
The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs.
Results
No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated.
Conclusion
A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.
doi:10.2147/IJN.S57926
PMCID: PMC4279770  PMID: 25565828
negative charge; oral toxicity study; rat; ZnO
2.  Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats 
International Journal of Nanomedicine  2014;9(Suppl 2):109-126.
Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.
doi:10.2147/IJN.S57928
PMCID: PMC4279774  PMID: 25565830
zinc oxide nanoparticles; surface charge; 90-day oral dose toxicity; no observed adverse effect level
3.  Smoking among Individuals with Schizophrenia in Korea: Gender Differences 
Archives of psychiatric nursing  2013;27(5):241-245.
Objective
This study examined gender differences in smoking and quitting among individuals diagnosed with schizophrenia in Korea. In addition, the study investigated differences in caffeine use by gender and smoking status.
Method
An anonymous self-report survey was conducted with psychiatric inpatients.
Results
Compared to males, females were less likely to be current smokers (p < 0.001) and more likely to be former smokers (p < 0.01). Females were also less likely to be daily caffeine users (p < 0.001). Having more years of education (p < 0.05) and higher nicotine dependence scores (p < 0.05) were associated with decreased odds of intending to quit smoking, whereas having more previous quit attempts (p < 0.01) was associated with increased odds. These findings were significant even after adjusting for gender. Smokers were more likely to be daily caffeine users (p < 0.001) than their non-smoking counterparts.
Conclusion
Nurses in Korea should play an active role in tobacco control for patients with schizophrenia by providing cessation counseling and educating the effect of caffeine use on cigarette consumption, while tailoring the service to gender differences found in this study.
doi:10.1016/j.apnu.2013.06.002
PMCID: PMC3785671  PMID: 24070993
schizophrenia; smoking; gender; Korea; caffeine use
4.  Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells 
BMC Cancer  2014;14:481.
Background
The role of omega-3 polyunsaturated fatty acids (ω3-PUFAs) in cancer prevention has been demonstrated; however, the exact molecular mechanisms underlying the anticancer activity of ω3-PUFAs are not fully understood. Here, we investigated the relationship between the anticancer action of a specific ω3-PUFA docosahexaenoic acid (DHA), and the conventional mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38 whose dysregulation has been implicated in human cancers.
Methods
MTT assays were carried out to determine cell viability of cancer cell lines (PA-1, H1299, D54MG and SiHa) from different origins. Apoptosis was confirmed by TUNEL staining, DNA fragmentation analysis and caspase activity assays. Activities of the conventional MAPKs were monitored by their phosphorylation levels using immunoblotting and immunocytochemistry analysis. Reactive oxygen species (ROS) production was measured by flow cytometry and microscopy using fluorescent probes for general ROS and mitochondrial superoxide.
Results
DHA treatment decreased cell viability and induced apoptotic cell death in all four studied cell lines. DHA-induced apoptosis was coupled to the activation of the conventional MAPKs, and knockdown of ERK/JNK/p38 by small interfering RNAs reduced the apoptosis induced by DHA, indicating that the pro-apoptotic effect of DHA is mediated by MAPKs activation. Further study revealed that the DHA-induced MAPKs activation and apoptosis was associated with mitochondrial ROS overproduction and malfunction, and that ROS inhibition remarkably reversed these effects of DHA.
Conclusion
Together, these results indicate that DHA-induced MAPKs activation is dependent on its capacity to provoke mitochondrial ROS generation, and accounts for its cytotoxic effect in human cancer cells.
doi:10.1186/1471-2407-14-481
PMCID: PMC4094407  PMID: 24993937
Docosahexaenoic acid; Reactive oxygen species; Mitogen-activated protein kinases; Apoptosis; Cancer
5.  The Validities and Efficiencies of Korean ADHD Rating Scale and Korean Child Behavior Checklist for Screening Children with ADHD in the Community 
Psychiatry Investigation  2014;11(3):258-265.
Objective
The purpose of this study is to examine the validity of primary screening tools for attention deficit hyperactivity disorder (ADHD) in a community-based sample of children using the Korean version of the Child Behavior Checklist (K-CBCL) and the Korean version of the ADHD Rating Scale (K-ARS).
Methods
A large-scale community-based study for ADHD screening was conducted in the Jeollabuk province in the Republic of Korea. In 2010-2011, we surveyed a total of 49,088 first- and fourth-grade elementary school students. All of the participants in this study were assessed by the K-ARS-Parent version (K-ARS-P) and the K-ARS-Teacher version (K-ARS-T) as the primary screening instruments. The Diagnostic Interview Schedule for Children Version IV (DISC-IV) was used for confirming the diagnosis of ADHD. DISC-IV was administered to subjects who received top 10% scores in the K-ARS-P or K-ARS-T tests.
Results
Of the 3,085 subjects who completed the DISC-IV, 1,215 were diagnosed as having ADHD. A reasonable level of sensitivity, specificity, and negative predictive value were obtained when the total K-ARS-P scores were ≥90th percentile. The positive predictive value and specificity increased significantly when the total K-ARS-P scores were ≥90th percentile, T scores were ≥60 in the attention problems of K-CBCL, and T scores were ≥63 in the total problems of K-CBCL.
Conclusion
These results suggested that the K-ARS-P could effectively serve as a primary screening tool to identify elementary school children with ADHD in the community. Also, there might be some increment in the effectiveness of K-ARS-P when combined with K-CBCL-A and K-CBCL-T as a secondary screening tool.
doi:10.4306/pi.2014.11.3.258
PMCID: PMC4124184  PMID: 25110498
Attention deficit hyperactivity disorder; Child Behavior Checklist; ADHD rating scale; Diagnostic Interview Schedule for Children Version IV; DISC-IV
6.  Cyberbullying, Problematic Internet Use, and Psychopathologic Symptoms among Korean Youth 
Yonsei Medical Journal  2014;55(3):826-830.
To evaluate the associations between cyberbullying behaviors and problematic internet use, and to compare psychopathologic symptoms in victims, perpetrators, and victims-perpetrators of cyberbullying to those in youths who were not involved in cyberbullying. A total of 4531 youths (11-14 years of age) were recruited from elementary and middle schools. Among 4531 youths, 9.7% were involved in cyberbullying; 3.3% were only victims; 3.4% were only perpetrators; and 3.0% were victims-perpetrators. Cyberbullying behaviors were associated with problematic internet use as well as various psychopathologic symptoms. Depressive symptoms were associated with cyberbullying victimization, and rule-breaking behaviors and aggressive behaviors have relevance to cyberbullying perpetration. Greater attention needs to be paid to identify youths earlier who are involved in cyberbullying and prevent serious adverse consequences in them.
doi:10.3349/ymj.2014.55.3.826
PMCID: PMC3990077  PMID: 24719154
Cyberbullying; problematic internet use; psychopathologic symptoms; Korean; youth
7.  PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting microtubule networks in HeLa cells 
BMC Cancer  2014;14:36.
Background
Combination therapy is key to improving cancer treatment efficacy. Phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator, increases the cytotoxicity of several anticancer drugs. Apicularen A induces cytotoxicity in tumor cells through disrupting microtubule networks by tubulin down-regulation. In this study, we examined whether PMA increases apicularen A-induced cytotoxicity in HeLa cells.
Methods
Cell viability was examined by thiazolyl blue tetrazolium (MTT) assays. To investigate apoptotic potential of apicularen A, DNA fragmentation assays were performed followed by extracting genomic DNA, and caspase-3 activity assays were performed by fluorescence assays using fluorogenic substrate. The cell cycle distribution induced by combination with PMA and apicularen A was examined by flow cytometry after staining with propidium iodide (PI). The expression levels of target proteins were measured by Western blotting analysis using specific antibodies, and α-tubulin mRNA levels were assessed by reverse transcription polymerase chain reaction (RT-PCR). To examine the effect of combination of PMA and apicularen A on the microtubule architecture, α-tubulin protein and nuclei were visualized by immunofluorescence staining using an anti-α-tubulin antibody and PI, respectively.
Results
We found that apicularen A induced caspase-dependent apoptosis in HeLa cells. PMA synergistically increased cytotoxicity and apoptotic sub-G1 population induced by apicularen A. These effects were completely blocked by the PKC inhibitors Ro31-8220 and Go6983, while caspase inhibition by Z-VAD-fmk did not prevent cytotoxicity. RNA interference using siRNA against PKCα, but not PKCβ and PKCγ, inhibited cytotoxicity induced by combination PMA and apicularen A. PMA increased the apicularen A-induced disruption of microtubule networks by further decreasing α- and β-tubulin protein levels in a PKC-dependent manner.
Conclusions
These results suggest that the synergy between PMA and apicularen A is involved by PKCα activation and microtubule disruption, and that may inform the development of novel approaches to treat cancer.
doi:10.1186/1471-2407-14-36
PMCID: PMC3901760  PMID: 24447339
PMA; Apicularen A; PKCα; Cell death; Microtubule disruption
8.  A Case with Neutropenia Related with the Use of Various Atypical Antipsychotics 
Psychiatry Investigation  2013;10(4):428-431.
Herein, we report here a case of a 21-year-old patient with a conduct disorder, who had neutropenia associated with treatment with 4 different antipsychotics (olanzapine, quetiapine, risperidone, and aripiprazole) on a sequential basis. This case supports the hypothesis that patients who developed antipsychotic-induced neutropenia on one medication are more likely to develop neutropenia when taking other antipsychotics. Based on this finding, we may suggest that the number of white blood cell and neutrophil counts in patients with a history of antipsychotic-induced neutropenia needs to be carefully monitored during antipsychotic treatment.
doi:10.4306/pi.2013.10.4.428
PMCID: PMC3902164  PMID: 24474995
Multiple atypical antipsychotics; Neutropenia
9.  Inhibitory effect of Korean Red Ginseng on melanocyte proliferation and its possible implication in GM-CSF mediated signaling 
Journal of Ginseng Research  2013;37(4):389-400.
Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation (30 mJ/cm2), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.
doi:10.5142/jgr.2013.37.389
PMCID: PMC3825854  PMID: 24235857
Panax ginseng; Korean Red Ginseng; Ultraviolet radiation; Skin pigmentation; Granulocyte-macrophage colonystimulating factor
10.  The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53 
BioMed Research International  2013;2013:568671.
Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA.
doi:10.1155/2013/568671
PMCID: PMC3691929  PMID: 23841076
11.  Effects of Antidepressant Treatment on Sexual Arousal in Depressed Women: A Preliminary fMRI Study 
Psychiatry Investigation  2012;9(4):379-383.
Objective
There was a recent study to explore the cerebral regions associated with sexual arousal in depressed women using functional magnetic resonance imaging (fMRI). The purpose of this neuroimaging study was to investigate the effects of antidepressant treatment on sexual arousal in depressed women.
Methods
Seven depressed women with sexual arousal dysfunction (mean age: 41.7±13.8, mean scores of the Beck Depression Inventory (BDI) and the 17-item Hamilton Rating Scale for Depression (HAMD-17): 35.6±7.1 and 34.9±3.1, respectively) and nine healthy women (mean age: 40.3±11.6) underwent fMRI before and after antidepressant treatment. The fMRI paradigm contrasted a 1 minute rest period viewing non-erotic film with 4 minutes of sexual stimulation viewing an erotic video film. Data were analyzed by SPM 2. The relative number of pixels activated in each period was used as an index of activation. All depressed women were treated with mirtazapine (mean dosage: 37.5 mg/day) for 8 to 10 weeks.
Results
Levels of brain activity during sexual arousal in depressed women significantly increased with antidepressant treatment (p<0.05) in the regions of the hypothalamus (3.0% to 11.2%), septal area (8.6% to 27.8%) and parahippocampal gyrus (5.8% to 14.6%). Self-reported sexual arousal during visual sexual stimulation also significantly increased post-treatment, and severity of depressive symptoms improved, as measured by the BDI and HAMD-17 (p<0.05).
Conclusion
These results show that sexual arousal dysfunction of depressed women may improve after treatment of depression, and that this improvement is associated with increased activation of the hypothalamus, septal area, and parahippocampal gyrus during sexual arousal.
doi:10.4306/pi.2012.9.4.379
PMCID: PMC3521115  PMID: 23251203
Sexual arousal; Depression; Women; Treatment; Functional magnetic resonance imaging (fMRI); Cerebral region
12.  Dexamethasone Induces FcγRIIb Expression in RBL-2H3 Cells 
Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress FcεRI-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE (FcεR) I and increased the mRNA levels of the inhibitory Fc receptor for IgG FcγRIIb. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG (FcγR) I and FcγRIII. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced FcγRI and FcγRIII mRNA levels potently, while FcεRI and FcγRIIb were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only FcγRIIb protein expression was significantly enhanced by Dex treatment, while FcγRI, FcγRIII and FcεRI expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor FcγRIIb.
doi:10.4196/kjpp.2012.16.6.393
PMCID: PMC3526743  PMID: 23269901
Degranulation; Fc receptor; Glucocorticoid; Mast cells; Transcription
13.  Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53 
Autophagy  2011;7(11):1348-1358.
Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis. However, little is known about the effects of DHA on autophagy, another complex well-programmed process characterized by the sequestration of cytoplasmic material within autophagosomes. Here we show that DHA increased both the level of microtubule-associated protein 1 light chain 3 and the number of autophagic vacuoles without impairing autophagic vesicle turnover, indicating that DHA induces not only apoptosis but also autophagy. We also observed that DHA-induced autophagy was accompanied by p53 loss. Inhibition of p53 increased DHA-induced autophagy and prevention of p53 degradation significantly led to the attenuation of DHA-induced autophagy, suggesting that DHA-induced autophagy is mediated by p53. Further experiments showed that the mechanism of DHA-induced autophagy associated with p53 attenuation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of rapamycin. In addition, compelling evidence for the interplay between autophagy and apoptosis induced by DHA is supported by the findings that autophagy inhibition suppressed apoptosis and further autophagy induction enhanced apoptosis in response to DHA treatment. Overall, our results demonstrate that autophagy contributes to the cytotoxicity of DHA in cancer cells harboring wild-type p53.
doi:10.4161/auto.7.11.16658
PMCID: PMC3242799  PMID: 21811093
DHA; autophagy; apoptosis; p53; cancer; mTOR; AMPK; p27
14.  The Effects of Sociodemographic Factors on Psychiatric Diagnosis 
Psychiatry Investigation  2012;9(3):199-208.
Objective
Several studies have reported that ethnic differences influence psychiatric diagnoses. Some previous studies reported that African Americans and Hispanics are diagnosed with schizophrenia spectrum disorders more frequently than Caucasians, and that Caucasians are more likely to be diagnosed with affective disorders than other ethnic groups. We sought to identify associations between sociodemographic factors and psychiatric diagnosis.
Methods
We retrospectively examined the medical records of all psychiatric inpatients (ages over 18 years) treated at Kern county mental hospital (n=2,051) between July 2003 and March 2007 for demographic, clinical information, and discharge diagnoses.
Results
African American and Hispanic males were more frequently diagnosed with schizophrenia spectrum disorders than Caucasians, whereas Caucasian females were more frequently diagnosed with affective disorders than females in the other ethnic groups, suggesting that patient ethnicity and gender may influence clinical diagnoses. Demographic variables, that is, a lower education, failure of marriage, homelessness, and low quality insurance, were found to be significantly associated with a diagnosis of schizophrenia spectrum disorders after adjusting for clinical variables. And, the presence of a family psychiatric history, failure of marriage, not-homelessness, and quality insurance were found to be associated with a diagnosis of affective disorders.
Conclusion
Our results show that these demographic factors, including ethnicity, have effects on diagnoses in psychiatric inpatients. Furthermore, these variables may help prediction of psychiatric diagnoses.
doi:10.4306/pi.2012.9.3.199
PMCID: PMC3440467  PMID: 22993517
Ethnicity; Demographic variables; Clinical variables; Psychiatric diagnoses; Schizophrenia; Affective disorders
15.  Long-Acting Injectable Antipsychotics for First-Episode Schizophrenia: The Pros and Cons 
Clinical and psychosocial deterioration associated with schizophrenia occurs within the first few years following the onset of the illness. Therefore, to improve the long-term prognosis, it is important to provide schizophrenia patients with intensive treatment following their first episode. Relapse is highly associated with partial medication adherence or nonadherence in patients with first-episode schizophrenia. Recent studies suggest that long-acting injectable (LAI) antipsychotics compared with oral antipsychotics are more effective for medication adherence and relapse prevention. Moreover, some clinical guidelines for the treatment of schizophrenia suggested that LAI antipsychotics should be considered when patients are nonadherent “at any stage.” Decreased compliance is a common cause of relapse during the initial stages of the disease. Therefore, LAI antipsychotics should be highly considered when treating patients with first-episode schizophrenia. In the present paper, clinical trial data and current guidelines on the use of LAI antipsychotics for first-episode schizophrenia are discussed as well as the pros and cons of this treatment option.
doi:10.1155/2012/560836
PMCID: PMC3425805  PMID: 22966439
16.  DJ-1 Null Dopaminergic Neuronal Cells Exhibit Defects in Mitochondrial Function and Structure: Involvement of Mitochondrial Complex I Assembly 
PLoS ONE  2012;7(3):e32629.
DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O2 consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease.
doi:10.1371/journal.pone.0032629
PMCID: PMC3293835  PMID: 22403686
17.  Repair of the Complete Radial Tear of the Anterior Horn of the Medial Meniscus in Rabbits: A Comparison between Simple Pullout Repair and Pullout Repair with Human Bone Marrow Stem Cell Implantation 
Knee Surgery & Related Research  2011;23(3):164-170.
Purpose
To evaluate the degree of biological healing response that occurs between the anterior horn of the medial meniscus (MM) and the tibial plateau and investigate the biological healing response after injection of human bone marrow stem cells (hBMSCs) in a rabbit model.
Materials and Methods
Twenty-five rabbits with a mean body weight of 2.5 kg were chosen for this study. On the left knee, a complete radial tear was made at the anterior tibial attachment site of MM and after removal of tibial cartilage, pullout repair of the torn MM was performed on the tibial plateau. On the right knee, the same procedure was performed, and a scaff old (matrix gel) that contained human bone marrow stem cell was implanted between MM and the tibial plateau. A biopsy was performed at 2 (group 1), 4 (group 2), and 8 (group 3) weeks postoperatively. The authors compared the differences in the degree of biological healing of each group and investigated the degree of biologic healing after hBMSC implantation by comparing the left knee with the right knee.
Results
On the biopsy of 40 knees of 20 rabbits that survived after operation, all groups did not show the healing response between the undersurface of MM and the tibial plateau. There was no significant difference in terms of the pathological criteria such as fibroblasts and fibrochondrocytes etc., with and without hBMSC implantation.
Conclusions
There was no attachment between the repaired MM and the tibial plateau after complete radial tear on MM and the authors could not identify the effect of hBMSC.
doi:10.5792/ksrr.2011.23.3.164
PMCID: PMC3341836  PMID: 22570829
Medial meniscus; Meniscal root ligament tear; Pullout repair; Human bone marrow stem cell; Biologic response
18.  Effects of Aripiprazole and Haloperidol on Fos-like Immunoreactivity in the Prefrontal Cortex and Amygdala 
Objective
Aripiprazole, a dopamine system stabilizer, shows efficacy against both negative symptoms and positive symptoms in patients with schizophrenia. The aim of this study was to investigate the effects of aripiprazole and haloperidol on c-FOS expression in rat brain.
Methods
Aripiprazole (1, 10 and 30 mg/kg, i.p.) and haloperidol (0.1 and 1 mg/kg, i.p.) were administered to adult Male Sprague-Dawley rats. After 2 h of drug or vehicle administration, the rats were killed and their brains were removed and perfused with fixative, then cut into 40 µm slices on a freezing microtome. Brain regions of interest were the medial prefrontal cortex (mPFC), the nucleus accumbens core and shell (NAC-C and NAC-S), the hippocampus (CA1, CA3 and DG), the central amygdala (Ce), the basolateral amygdala (BL) and the temporal cortex (Tc). Immunohistochemistry was performed to label cell bodies containing c-FOS.
Results
The administration of aripiprazole at all doses (1, 10 or 30 mg/kg) resulted in greater Fos-like immunoreactivity (FLI) in the investigated brain areas, as compared to the vehicle. Comparable increases in FLI were demonstrated in the NAC-C and NAC-S in response to both aripiprazole and haloperidol treatment. The administration of haloperidol (0.1 or 1 mg/kg) also resulted in greater FLI in the investigated brain areas, except the mPFC, where no changes were observed. In the Ce and BL, a significant increase in Fos-positive neurons was observed only with 0.1 mg/kg of haloperidol.
Conclusion
Both aripiprazole and haloperidol increased FLI in limbic areas, which are considered important targets of antipsychotic drugs. The differential action of aripiprazole on FLI in the amygdala and mPFC as compared to haloperidol may be a good way to differentiate atypical from typical antipsychotics.
doi:10.9758/cpn.2011.9.1.36
PMCID: PMC3568653  PMID: 23431025
Aripiprazole; c-FOS; Haloperidol

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