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1.  A Candidate Single Nucleotide Polymorphism in the 3′ Untranslated Region of Stearoyl-CoA Desaturase Gene for Fatness Quality and the Gene Expression in Berkshire Pigs 
Fatness qualities in pigs measured by the amount of fat deposition and composition of fatty acids (FAs) in pork have considerable effect on current breeding goals. The stearoyl-CoA desaturase (SCD) gene plays a crucial role in the conversion of saturated FAs into monounsaturated FAs (MUFAs), and hence, is among the candidate genes responsible for pig fatness traits. Here, we identified a single nucleotide polymorphism (SNP, c.*2041T>C) in the 3′ untranslated region by direct sequencing focused on coding and regulatory regions of porcine SCD. According to the association analysis using a hundred of Berkshire pigs, the SNP was significantly associated with FA composition (MUFAs and polyunsaturated FAs [PUFAs]), polyunsaturated to saturated (P:S) FA ratio, n-6:n-3 FA ratio, and extent of fat deposition such as intramuscular fat and marbling (p<0.05). In addition, the SNP showed a significant effect on the SCD mRNA expression levels (p = 0.041). Based on our results, we suggest that the SCD c.*2041T>C SNP plays a role in the gene regulation and affects the fatness qualities in Berkshire pigs.
doi:10.5713/ajas.14.0529
PMCID: PMC4283158  PMID: 25557809
Stearoyl-CoA Desaturase [SCD]; Polymorphism; Gene Expression; Fatness Quality; Berkshire
2.  Red Ginseng (Panax ginseng) Decreases Isoproterenol-Induced Cardiac Injury via Antioxidant Properties in Porcine 
Journal of Medicinal Food  2014;17(1):111-118.
Abstract
Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The present study was designed to evaluate the cardioprotective potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI), by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for 9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as evidenced by improved ventricular hemodynamic functions and reduced ST segment and QRS complex intervals. Also, RG significantly ameliorated myocardial injury parameters such as antioxidants. Malonaldialdehyde formation was also inhibited by RG. Based on the results, it is concluded that RG possesses significant cardioprotective potential through the inhibition of oxidative stress and may serve as an adjunct in the treatment and prophylaxis of MI.
doi:10.1089/jmf.2013.2768
PMCID: PMC3901382  PMID: 24456361
antioxidant; hemodynamic function; myocardial infarction; myocardial protection; red ginseng
3.  A review of deoxycorticosterone acetate-salt hypertension and its relevance for cardiovascular physiotherapy research 
[Purpose] The purpose of this review was to elucidate the deoxycorticosterone acetate (DOCA)-salt-related hypertensive mechanism and to contribute to future studies of cardiovascular physiotherapy. [Methods] This paper focuses on the signal transductions that control hypertension and its mechanisms. We include results reported by our laboratory in a literature review. [Results] Our results and the literature show the various mechanisms of DOCA-salt hypertension. [Conclusion] In this review paper, we carefully discuss the signal transduction in hypertension based on our studies and with reference to cardiovascular physiotherapy research.
doi:10.1589/jpts.27.303
PMCID: PMC4305587  PMID: 25642096
Deoxycorticosterone acetate-salt hypertension; Signal transduction; Cardiovascular physiotherapy
4.  Phosphorylation of Heat Shock Protein 27 is Increased by Cast Immobilization and by Serum-free Starvation in Skeletal Muscles 
Journal of Physical Therapy Science  2014;26(12):1975-1977.
[Purpose] Cast immobilization- and cell starvation-induced loss of muscle mass are closely associated with a dramatic reduction in the structural muscle proteins. Heat shock proteins are molecular chaperones that are constitutively expressed in several eukaryotic cells and have been shown to protect against various stressors. However, the changes in the phosphorylation of atrophy-related heat shock protein 27 (HSP27) are still poorly understood in skeletal muscles. In this study, we examine whether or not phosphorylation of HSP27 is changed in the skeletal muscles after cast immobilization and serum-free starvation with low glucose in a time-dependent manner. [Methods] We undertook a HSP27 expression and high-resolution differential proteomic analysis in skeletal muscles. Furthermore, we used western blotting to examine protein expression and phosphorylation of HSP27 in atrophied gastrocnemius muscle strips and L6 myoblasts. [Results] Cast immobilization and starvation significantly upregulated the phosphorylation of HSP27 in a time-dependent manner, respectively. [Conclusion] Our results suggest that cast immobilization- and serum-free starvation-induced atrophy may be in part related to changes in the phosphorylation of HSP27 in rat skeletal muscles.
doi:10.1589/jpts.26.1975
PMCID: PMC4273071  PMID: 25540511
Heat shock protein 27; Cast immobilization and serum-free starvation; Muscle atrophy
5.  Epigenetic regulation of miR-122 by PPARγ and hepatitis B virus X protein in hepatocellular carcinoma cells 
Hepatology (Baltimore, Md.)  2013;58(5):1681-1692.
MiR-122, a pivotal liver specific miRNA, has been implicated in several liver diseases including hepatocellular carcinoma (HCC) and hepatitis C and B viral infection. This study aimed to explore epigenetic regulation of miR-122 in human hepatocellular carcinoma (HCC) cells and to examine the effect of hepatitis C virus (HCV) and hepatitis B virus (HBV). We performed microRNA microarray analysis and identified miR-122 as the most up-regulated miRNA (6-fold) in human hepatocellular cancer cells treated with 5′aza-2′deoxycytidine (5-Aza-CdR, DNA methylation inhibitor) and 4-phenylbutyric acid (PBA, histone deacetylation inhibitor). Real-time PCR analysis verified significant upregulation of miR-122 by 5′aza and PBA in HCC cells, and to a lesser extent in primary hepatocytes. Peroxisome proliferator activated receptor-gamma (PPARγ) and retinoid X receptor alpha (RXRα) complex was found to be associated with the DR1 and DR2 consensus site in the miR-122 gene promoter which enhanced miR-122 gene transcription. 5-Aza-CdR and PBA treatment increased the association of PPARγ/RXRα, but decreased the association of its co-repressors (N-CoR and SMRT), with the miR-122 DR1 and DR2 motifs. The aforementioned DNA-protein complex also contains SUV39H1, a H3K9 histone methyl transferase, which downregulates miR-122 expression. Our findings establish a novel role of the PPARγ binding complex for epigenetic regulation of miR-122 in human HCC cells. Moreover, we show that hepatitis B virus X protein (HBX) binds PPARγ and inhibits the transcription of miR-122, whereas hepatitis C viral particles exhibited no significant effect; these findings provide mechanistic insight into reduction of miR-122 in patients with HBV but not with HCV infection.
doi:10.1002/hep.26514
PMCID: PMC3773012  PMID: 23703729
miR-122; PPARγ; HCC; epigenetic regulation; Hepatitis B virus X protein; HCV; liver; hepatocytes
6.  Decrease of PKB/Akt Phosphorylation is Partially Mediated by SAPK/JNK Activation in Serum-free L6 Myoblasts Starved with Low Glucose 
Journal of Physical Therapy Science  2014;26(11):1757-1760.
[Purpose] Studies have been using cell cultures of muscle cells to mimic atrophy in in vivo and in vitro tests. However, changes in the activation of atrophy-related PKB/Akt is not fully understood in serum-free starved skeletal muscle cells. The purpose of the present study was to determine the change of PKB/Akt phosphorylation in L6 myoblasts under serum-free starvation conditions. [Methods] We used western blotting to examine PKB/Akt expression and phosphorylation in atrophied L6 myoblasts. [Results] The phosphorylation of PKB/Akt was significantly lower in L6 myoblasts under serum-free starvation than that of the control group. Serum-free starvation for 6, 12, 24, 36, 48, 72, 96, and 120 hours significantly decreased the phosphorylation of PKB/Akt. Furthermore, the decrease of PKB/Akt phosphorylation under serum-free starvation was partially restored by SP600125, an inhibitor of SAPK/JNK. [Conclusion] These results suggest that decrease of PKB/Akt phosphorylation due to serum-free starvation with low glucose is partially related to the activity of SAPK/JNK in L6 myoblasts.
doi:10.1589/jpts.26.1757
PMCID: PMC4242949  PMID: 25435694
PKB/Akt; Serum-free starvation; L6 myoblasts
7.  Cofilin Phosphorylation Decreased by Serum-free Starvation with Low Glucose in the L6 Myoblasts 
Journal of Physical Therapy Science  2014;26(10):1543-1545.
[Purpose] Many studies have been using cell culture models of muscle cells with exogenous cytokines or glucocorticoids to mimic atrophy in in vivo and in vitro tests. However, the changes in the phosphorylation of atrophy-related cofilin are still poorly understood in starved skeletal muscle cells. In this study, we first examined whether or not phosphorylation of cofilin is altered in L6 myoblasts after 3, 6, 12, 24, 48, and 72 hours of serum-free starvation with low glucose. [Methods] We used Western blotting to exam protein expression and phosphorylation in atrophied L6 myoblasts. [Results] L6 cell sizes and numbers were diminished as a result of serum-free starvation in a time-dependent manner. Serum-free starvation for 3, 6, 12, 24, 48, and 72 hours significantly decreased the phosphorylation of cofilin, respectively. [Conclusion] These results suggest that starvation-induced atrophy may be in part related to changes in the phosphorylation of cofilin in L6 myoblasts.
doi:10.1589/jpts.26.1543
PMCID: PMC4210392  PMID: 25364107
Cofilin; Serum-free starvation; L6 myoblasts
8.  Somatotype Analysis of Elite Boxing Athletes Compared with Nonathletes for Sports Physiotherapy 
Journal of Physical Therapy Science  2014;26(8):1231-1235.
[Purpose] The purpose of this study was to show somatotype and physical characteristic differences between elite boxing athletes and non-athletes. [Methods] The somatotypes of 23 elite boxing athletes and 23 nonathletes were measured with the Heath-Carter method. The subjects were divided into four weight divisions as follows: lightweight, light middleweight, middleweight, and heavyweight class. [Results] The endomorphic component values of the boxing athletes were lower than those of the nonathletes. However, the mesomorphic component values of the boxing athletes were higher than those of the nonathletes. There was no significant difference in the ectomorphic component between the two groups. The higher weight divisions tended to have higher values of height, weight, and BMI than the lower weight divisions. The higher weight divisions also tended to have higher values for the endomorphic and mesomorphic components and a lower value for the ectomorphic component than the lower weight divisions. The group of nonathletes consisted of eight endomorphs, four mesomorphs, six ectomorphs, and five central types. Among the boxing athletes, there were 16 mesomorphic, four ectomorphic, and two central types and one endomorphic type. Subdividing the athletes into 13 somatotypes resulted in five balanced mesomorphs, five endomorphic mesomorphs, five mesomorph-ectomorphs, three mesomorph-endomorphs, two mesomorphic ectomorphs, two central types, and one ectomorphic mesomorph type. [Conclusion] The data from this study provides in part physical characteristics of elite boxing athletes that can be used to establish a reference for systemic study of sports physiotherapy.
doi:10.1589/jpts.26.1231
PMCID: PMC4155226  PMID: 25202187
Somatotype analysis; Elite boxing athletes; Specialized sports physiotherapy
9.  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
10.  A Pilot Study on Pain and the Upregulation of Myoglobin through Low-frequency and High-amplitude Electrical Stimulation-induced Muscle Contraction 
[Purpose] It is well known that, in both in vivo and in vitro tests, muscle fatigue is produced by severe exercise, electrical stimulation, and so on. However, it is not clear whether or not low-frequency and high-amplitude modulation specifically affects serum myoglobin or urine myoglobin. The purpose of the present study was to determine the effect of low-frequency and high-amplitude modulation on serum myoglobin and urine myoglobin. [Methods] The study used whole blood samples and urine produced over 24 hours from the thirteen healthy subjects. [Results] There was a significant increase in serum myoglobin following electrical stimulation at a frequency of 10 Hz compared with the control group. Furthermore, within 24 hours, urine myoglobin also showed a significant increase for the test volunteers subjected to electrical stimulation at the 10 Hz frequency compared with the control group. However, there were no significant differences in the concentrations of hematologic results in subjects treated with electrical stimulation. [Conclusion] These results suggest that increased myoglobin related to muscle fatigue from electrical stimulation, particularly with a current of 10 Hz combined with a high-amplitude, may be partially related to increased muscle damage.
doi:10.1589/jpts.26.985
PMCID: PMC4135220  PMID: 25140079
Myoglobin; Pain; High-amplitude electrical stimulation
11.  Bleomycin-induced flagellate erythema: A case report and review of the literature 
Oncology Letters  2014;8(2):933-935.
Bleomycin has been used most commonly in the treatment of Hodgkin’s lymphoma, certain germ cell tumors (GCT) and for the sclerosis of recurrent pleural effusions. Bleomycin toxicity predominantly affects the skin and lungs. Skin toxicity includes Raynaud’s phenomenon, hyperkeratosis, nail-bed changes and palmoplantar desquamation. Flagellate erythema is an unusual rash occurring specifically during bleomycin use. In the present study, we report a case of bleomycin-induced flagellate erythema in a patient with GCT. A 42-year-old male was diagnosed with stage IIIB testicular cancer and treated with bleomycin, etoposide and cisplatin chemotherapy. After 10 days from the initiation of treatment, the patient subsequently developed a generalized pruritus and erythematous linear rash that was most prominent on the trunk, and upper and lower extremities. The patient was commenced on a short course of low-dose oral prednisolone, 20 mg daily, and antihistamine. Consequently, bleomycin was withheld from the patient’s treatment regimen. The present study describes the case, along with a review of the associated literature.
doi:10.3892/ol.2014.2179
PMCID: PMC4081419  PMID: 25009666
bleomycin; skin toxicity; flagellate erythema
12.  A Review of Signal Transduction of Endothelin-1 and Mitogen-activated Protein Kinase-related Pain for Nanophysiotherapy 
[Purpose] An understanding of pain is very important in the study of nanophysiotherapy. In this review, we summarize the mechanisms of endothelin-1 (ET-1)- and mitogen-activated protein kinase (MAPK)-related pain, and suggest their applications in pain physiotherapy. [Method] This review focuses on the signal transduction of pain and its mechanisms. [Results] Our reviews show that mechanisms of ET-1- and MAPK-related pain exist. [Conclusions] In this review article, we carefully discuss the signal transduction in ET-1- and MAPK-related pain with reference to pain nanophysiotherapy from the perspective of nanoparticle-associated signal transduction.
doi:10.1589/jpts.26.789
PMCID: PMC4047254  PMID: 24926154
Endothelin-1; Pain; Signal transduction
13.  Waveform Analysis of the Brachial-ankle Pulse Wave Velocity in Hemiplegic Stroke Patients and Healthy Volunteers: A Pilot Study 
[Purpose] Brachial-ankle pulse wave velocity (BaPWV), which has been reported as an index of arterial stiffness, is very closely related to cardiovascular risk factors. A high BaPWV indicates high cardiovascular risk. However, BaPWV and pressure waveforms after stroke are not fully understood. [Methods] BaPWV was measured in thirty-two subjects (twenty-two healthy volunteers and ten stroke patients) while they were in the supine position. It was measured in their bilateral upper and lower extremities. [Results] BaPWV was significantly increased in the stroke group compared with the healthy volunteers. It was also significantly increased on both the affected and non-affected sides of stroke patients in the stroke group. Furthermore, analysis of the pressure waveforms showed that the peak pressure was significantly increased in the stroke group compared with the control group. The peak pressure on both the affected and non-affected sides was also significantly greater than in the control group. However, the rise and decay times were significantly decreased in the stroke group compared with the control group. The rise and decay time on both the affected and non-affected sides were also significantly more decreased than in the control group. [Conclusion] The results demonstrated that increased BaPWV and changed pulse waves are closely associated with the pathologic states of hemiplegic stroke patients.
doi:10.1589/jpts.26.501
PMCID: PMC3996408  PMID: 24764620
Brachial-ankle pulse wave velocity; Pressure waveform; Stroke
14.  Decrease of Both Cofilin and LIM Kinase Phosphorylation in the Skeletal Muscles of Immobilization-induced Atrophy Rats 
[Purpose] Immobilization-induced atrophy is a general phenomenon caused by prolonged muscle disuse associated with orthopaedic conditions. However, changes in the phosphorylation of atrophy-related cofilin and LIM kinases are still poorly understood. In this study, we examined whether or not phosphorylation of cofilin and LIM kinases is altered in the skeletal muscles of rats after 3, 7, 14, and 21 days of cast immobilization. [Methods] We used two-dimensional gel electrophoresis, mass spectrometry, and western blotting to examine protein expression and phosphorylation in atrophied rat gastrocnemius muscles. [Results] The expression of the cofilin was detected in gastrocnemius muscle strips using proteomic analysis. Cast immobilization after 3, 7, 14, and 21 days significantly diminished the phosphorylation of cofilin and LIM kinases. [Conclusion] The present results suggest that cast immobilization-induced atrophy may be in part related to changes in the phosphorylation of cofilin and LIM kinases in rat skeletal muscles.
doi:10.1589/jpts.26.355
PMCID: PMC3977028  PMID: 24711688
Cofilin; LIM kinases; Skeletal muscle atrophy
15.  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
16.  Increase of Myoglobin in Rat Gastrocnemius Muscles with Immobilization-induced Atrophy 
Journal of Physical Therapy Science  2014;25(12):1617-1620.
[Purpose] Atrophy is a common phenomenon caused by prolonged muscle disuse associated with bed-rest, aging, and immobilization. However, changes in the expression of atrophy-related myoglobin are still poorly understood. In the present study, we examined whether or not myoglobin expression is altered in the gastrocnemius muscles of rats after seven days of cast immobilization. [Methods] We conducted a protein expression and high-resolution differential proteomic analysis using, two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry, and western blotting. [Results] The density and expression of myoglobin increased significantly more in atrophic gastrocnemius muscle strips than they did in the control group. [Conclusion] The results suggest that cast immobilization-induced atrophy may be related to changes in the expression of myoglobin in rat gastrocnemius muscles.
doi:10.1589/jpts.25.1617
PMCID: PMC3885852  PMID: 24409033
Myoglobin; Gastrocnemius muscle; Atrophy
17.  A Pilot Study on the Effect of Functional Electrical Stimulation of Stroke Patients in a Sitting Position on Balance and Activities of Daily Living 
Journal of Physical Therapy Science  2013;25(9):1097-1101.
[Purpose] This study investigated the effect of functional electrical stimulation (FES) of stroke patients in a sitting position on balance and activities of daily living. [Methods] FES was applied to stroke patients (six male, three female) while in a sitting and supine position. FES was applied six times for 30 minutes each for a total of six weeks. [Results] The timed up and go (TUG) values at weeks 2, 4, and 6 after FES treatment in a sitting position were noticeably decreased in a time-dependent manner, compared with controls. In the sitting, the functional reach test (FRT) values were significantly increased in a time-dependent manner. The same values in the supine position weakly showed a similar pattern to those in the sitting position. Furthermore, the functional independent measurement (FIM) values in the sitting position were markedly increased in a time-dependent manner. In the sitting position, the intensity of FES was markedly decreased in a time-dependent manner. The same values in the supine position weakly showed a similar pattern to those in the sitting position. [Conclusion] These results suggest that the conditions of stroke patients in both the sitting and supine positions after FES treatment were improved and that FES had a greater effect in the sitting position.
doi:10.1589/jpts.25.1097
PMCID: PMC3818750  PMID: 24259923
Functional electrical stimulation; Sitting position; Stroke patients
18.  Korean Red Ginseng Induced Cardioprotection against Myocardial Ischemia in Guinea Pig 
This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/dtmax) and maximal rate of relaxation (-dP/dtmax). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.
doi:10.4196/kjpp.2013.17.4.283
PMCID: PMC3741484  PMID: 23946687
Antioxidant; Cardioprotection; Hemodynamics; Ischemia and reperfusion injury; Korean red ginseng
19.  Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats 
Journal of Ginseng Research  2013;37(3):273-282.
The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure (+dP/dtmax) and minimal rate of developed left ventricular pressure (−dP/dtmax), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.
doi:10.5142/jgr.2013.37.273
PMCID: PMC3818953  PMID: 24198652
Panax ginseng; Isoproterenol; Cardiac ischemia; Hemodynamics; Myocardial preservation
20.  Ginsenoside-Re ameliorates ischemia and reperfusion injury in the heart: a hemodynamics approach 
Journal of Ginseng Research  2013;37(3):283-292.
Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (±dp/dtmax). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-α (TNF-α) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-α level. Treatment of G-Re at 30 and 100 μM doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-α level. In this study, G-Re at 100 μM dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than 30 μM. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.
doi:10.5142/jgr.2013.37.283
PMCID: PMC3818954  PMID: 24198653
Panax ginseng; Ginsenoside-Re; Cardiac injury; Hemodynamics; Myocardial preservation
21.  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
22.  Differences in Rheobase and Chronaxie between the Paretic and Non-Paretic Sides of Hemiplegic Stroke Patients: a Pilot Study 
[Purpose] Rheobase and chronaxie are used to confirm muscle degeneration. For stroke patients, however, the uses of rheobase and chronaxie in determining paretic side muscle degeneration is not yet fully understood. Thus, in this study, we examined the electrical properties of the quadriceps muscles of stroke patients’ paretic side and compared them with their respective values on the non-paretic side. [Method] The subjects were six stroke patients (three females, three males). The pad of an electrical stimulator was applied to the vastus lateralis and vastus medialis regions to measure rheobase and chronaxie until the contractive muscle response to electrical stimulation became visible. [Result] Rheobase was significantly increased on the paretic side compared to that of the non-paretic side of hemiplegic stroke patients. Furthermore, chronaxie was significantly increased on the paretic side compared to the non-paretic side of hemiplegic stroke patients. [Conclusion] These results suggest that stroke affects the sensitivity of skeletal muscle contraction. Therefore, this data may contribute to our understanding of the muscle status of stroke patients.
doi:10.1589/jpts.25.717
PMCID: PMC3805009  PMID: 24259837
Rheobase; Chronaxie; Hemiplegic stroke patients
23.  Protective effects of red ginseng extract against vaginal herpes simplex virus infection 
Journal of Ginseng Research  2013;37(2):210-218.
Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-γ secretion. Moreover, increased mRNA expression of IFN-γ, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.
doi:10.5142/jgr.2013.37.210
PMCID: PMC3659631  PMID: 23717174
Panax ginseng; Korean red ginseng; Herpes simplex virus; Mice; Natural killer cells
24.  Interstitial Pneumonitis after Treatment with Pemetrexed for Non-small Cell Lung Cancer 
Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. Pemetrexed has a modest toxicity profile and has not traditionally been regarded as a cause of interstitial pneumonitis. Here, we report on a rare case of pemetrexed-induced pneumonitis in a patient with NSCLC.
doi:10.4143/crt.2013.45.1.74
PMCID: PMC3629367  PMID: 23613674
Interstitial lung diseases; Pemetrexed; Non-small-cell lung carcinoma; Adenocarcinoma; Drug therapy
25.  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

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