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1.  The Relationship between Height and Cognitive Function among Community-dwelling Elderly: Hallym Aging Study 
Epidemiology and Health  2013;35:e2013002.
OBJECTIVES
Height is known as an index that reflects the environment of the fetal, childhood, and adolescent periods, which affect adult health. This study was conducted to elucidate whether height is associated with cognitive impairment in community-dwelling elders in Korea.
METHODS
The study subjects were recruited among community dwelling elderly individuals aged 65 or over who participated in the 2004 Hallym Aging Study. They were invited to a general hospital and were evaluated for socioeconomic status, smoking history, and various clinical measures. Cognitive function measurement was performed using the Korean-Mini Mental State Examination. Logistic regression was used to evaluate the association between height and cognitive function.
RESULTS
After adjusting for potential covariates such as age and education, the smallest group was associated with higher risk of cognitive impairment compared with the tallest group among elderly men (odds ratio [OR], 4.20; 95% confidence interval [CI], 1.02-17.36), but not among elderly women (OR,1.65; 95% CI, 0.62-4.40).
CONCLUSIONS
The reason for this difference according to sex may be explained by the differential effects of education on cognitive function by sex. A larger population-based prospective cohort study is needed to examine the association between height and cognitive function according to sex.
doi:10.4178/epih/e2013002
PMCID: PMC3654091  PMID: 23682335
Body height; Cognition; Hallym Aging Study
2.  Noninvasive Measurement of Conductivity Anisotropy at Larmor Frequency Using MRI 
Anisotropic electrical properties can be found in biological tissues such as muscles and nerves. Conductivity tensor is a simplified model to express the effective electrical anisotropic information and depends on the imaging resolution. The determination of the conductivity tensor should be based on Ohm's law. In other words, the measurement of partial information of current density and the electric fields should be made. Since the direct measurements of the electric field and the current density are difficult, we use MRI to measure their partial information such as B1 map; it measures circulating current density and circulating electric field. In this work, the ratio of the two circulating fields, termed circulating admittivity, is proposed as measures of the conductivity anisotropy at Larmor frequency. Given eigenvectors of the conductivity tensor, quantitative measurement of the eigenvalues can be achieved from circulating admittivity for special tissue models. Without eigenvectors, qualitative information of anisotropy still can be acquired from circulating admittivity. The limitation of the circulating admittivity is that at least two components of the magnetic fields should be measured to capture anisotropic information.
doi:10.1155/2013/421619
PMCID: PMC3608348  PMID: 23554838
3.  The Relationship between Smoking, Socioeconomic Status and Grip Strength among Community-dwelling Elderly Men in Korea: Hallym Aging Study 
Epidemiology and Health  2013;35:e2013001.
OBJECTIVES
Low grip strength is associated with decline in bone mineral density (BMD) and increased risk of spine fracture among the elderly. Smoking, a major factor determining BMD, is also known to have an indirect effect on bone loss. This study investigated whether smoking is associated with grip strength in the community-dwelling elderly in Korea.
METHODS
This study was an outcome of the second of three waves of the Hallym Aging Study from January to May 2007, a population-based study of Koreans aged 45 years and upwards dwelling in Chuncheon. Its 218 subjects comprised men aged 65 years or over. They were evaluated at a general hospital for socioeconomic status, smoking history, and various clinical measures including grip strength.
RESULTS
Grip strength was higher in non-, ex-, and current smokers (33.7 kg, 30.6 kg, and 29.3 kg, respectively). Current smoking was found to increase the risk of decreased grip strength (adjusted odds ratio [aOR], 4.58; 95% confidence interval [CI],1.31 to 16.04) compared with non-smoking, after adjustment for potential covariates including socioeconomic status. After adjustment for smoking effect, education of fewer than six years and monthly income of fewer than 500,000 Korean won increased the risk of decreased grip strength compared with education of more than six years (aOR, 2.88; 95% CI, 1.08 to 7.66) and monthly income of more than 1,500,000 Korean won (aOR, 2.86; 95% CI, 1.08 to 7.54).
CONCLUSIONS
These results showed that current smoking, low education and low income were independent risk factors for decreased grip strength among elderly men in Korea.
doi:10.4178/epih/e2013001
PMCID: PMC3575580  PMID: 23440903
Elderly men; Hand strength; Smoking; Socioeconomic
4.  Colorectal Cancer Epidemic in Korea 
Annals of Coloproctology  2013;29(1):1-4.
doi:10.3393/ac.2013.29.1.1
PMCID: PMC3624979  PMID: 23586006
5.  Balloon-Occluded Percutaneous Transhepatic Obliteration of Isolated Vesical Varices Causing Gross Hematuria 
Korean Journal of Radiology  2012;14(1):94-96.
Gross hematuria secondary to vesical varices is an unusual presentation. We report such a case recurrent gross hematuria in a male patient who had a history of bladder substitution with ileal segments that had been treated by balloon-occluded percutaneous transhepatic obliteration of vesical varices.
doi:10.3348/kjr.2013.14.1.94
PMCID: PMC3542309  PMID: 23323037
Hematuria; Vesical varix; Percutaneous transhepatic obliteration
6.  Umbilical cord blood mesenchymal stem cells protect amyloid-β42 neurotoxicity via paracrine 
World Journal of Stem Cells  2012;4(11):110-116.
AIM: To understand the neuroprotective mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) against amyloid-β42 (Aβ42) exposed rat primary neurons.
METHODS: To evaluate the neuroprotective effect of hUCB-MSCs, the cells were co-cultured with Aβ42-exposed rat primary neuronal cells in a Transwell apparatus. To assess the involvement of soluble factors released from hUCB-MSCs in neuroprotection, an antibody-based array using co-cultured media was conducted. The neuroprotective roles of the identified hUCB-MSC proteins was assessed by treating recombinant proteins or specific small interfering RNAs (siRNAs) for each candidate protein in a co-culture system.
RESULTS: The hUCB-MSCs secreted elevated levels of decorin and progranulin when co-cultured with rat primary neuronal cells exposed to Aβ42. Treatment with recombinant decorin and progranulin protected from Aβ42-neurotoxicity in vitro. In addition, siRNA-mediated knock-down of decorin and progranulin production in hUCB-MSCs reduced the anti-apoptotic effects of hUCB-MSC in the co-culture system.
CONCLUSION: Decorin and progranulin may be involved in anti-apoptotic activity of hUCB-MSCs exposed to Aβ42.
doi:10.4252/wjsc.v4.i11.110
PMCID: PMC3536832  PMID: 23293711
Human umbilical cord blood-derived mesenchymal stem cells; Decorin; Progranulin; Aβ42; Anti-apoptosis
7.  Two Replication Fork Maintenance Pathways Fuse Inverted Repeats to Rearrange Chromosomes 
Nature  2013;501(7468):569-572.
Replication fork (RF) maintenance pathways preserve chromosomes, but their faulty application at nonallelic repeats could generate rearrangements causing cancer, genomic disorders and speciation1-3. Potential causal mechanisms are homologous recombination (HR) and error-free postreplication repair (EF-PRR). HR repairs damage induced DNA double strand breaks (DSBs) and single-ended DSBs within replication. To facilitate HR, the recombinase RAD51 and mediator BRCA2 form a filament on the 3’ DNA strand at a break to enable annealing to the complementary sister chromatid4 while the RecQ helicase, BLM (Bloom syndrome mutated) suppresses crossing over to prevent recombination5. HR also stabilizes6,7 and restarts8,9 RFs without a DSB10,11. EF-PRR bypasses DNA incongruities that impede replication by ubiquitinating PCNA (proliferating cell nuclear antigen) using the RAD6/RAD18 and UBC13/MMS2/RAD5 ubiquitin ligase complexes12. Some components are common to both HR and EF-PRR like RAD51 and RAD1813,14. Here we delineate two pathways that spontaneously fuse inverted repeats to generate unstable chromosomal rearrangements in wild type mouse embryonic stem (ES) cells. Gamma-radiation induced a BLM-regulated pathway that selectively fused identical, but not mismatched repeats. By contrast, UV light induced a RAD18-dependent pathway that efficiently fused mismatched repeats. Furthermore, TREX2 (a 3’→5’ exonuclease) suppressed identical repeat fusion but enhanced mismatched repeat fusion, clearly separating these pathways. TREX2 associated with UBC13 and enhanced PCNA ubiquitination in response to UV light, consistent with it being a novel member of EF-PRR. RAD18 and TREX2 also suppressed RF stalling in response to nucleotide depletion. Interestingly, RF stalling induced fusion for identical and mismatched repeats implicating faulty replication as a causal mechanism for both pathways.
doi:10.1038/nature12500
PMCID: PMC3805358  PMID: 24013173
8.  A Case of Serum Sickness-Like Reaction and Anaphylaxis - Induced Simultaneously by Rifampin 
Rifampin is commonly used as a first-line anti-tuberculosis drug, but it can induce a serum sickness-like reaction or anaphylaxis. However, it is possible for 1 drug antigen to induce 2 or more simultaneous immunologic reactions. Here, we report a case of a serum-sickness-like reaction and anaphylaxis induced concurrently by rifampin. A 25-year-old male presented with high fever and a maculopapular rash with vesicles on the hands, which developed 2 weeks following regular administration of anti-tuberculosis drugs for tuberculous meningitis, including rifampin. Elevated liver enzymes, peripheral neuropathy, and decreased serum C3 and C4 levels were found. Interestingly, these symptoms were accompanied by severe hypotension. A serum-sickness-like reaction was considered after excluding other potential causes for the fever. A drug provocation test showed that the fever developed after oral administration of rifampin, suggesting that rifampin was the cause of the allergic reaction. However, hypotension, epigastric discomfort, and diarrhea also accompanied these symptoms, indicating that IgE-mediated type I hypersensitivity could be part of the serum sickness-like reaction. An intradermal skin test clearly showed an immediate positive reaction to rifampin. This case was diagnosed as concurrent serum-sickness-like reaction and anaphylaxis induced by rifampin. One drug may therefore induce combined allergic reactions via 2 or more simultaneous hypersensitivity responses.
doi:10.4168/aair.2014.6.2.183
PMCID: PMC3936050  PMID: 24587958
Rifampin; serum sickness, anaphylaxis
9.  Gender differences in adiponectin levels and body composition in older adults: Hallym aging study 
BMC Geriatrics  2014;14:8.
Background
Body composition changes with ageing can influence the adiponectin concentration. However, the component of body composition that is associated with adiponectin concentrations in older adults remains unclear.
Methods
There were 152 males and 168 females aged 65 years or older that participated in the 2010 Hallym Aging Study (HAS). Body composition (assessed by dual energy X-ray absorptiometry; DXA), anthropometric parameters and adiponectin were obtained from all participants. Multivariate linear regression models assessed the association of body fat percentage, regional muscle and bone mineral contents of body composition and waist/height ratio with adiponectin concentration. Age, albumin, testosterone concentration and metabolic parameters were considered as confounding factors.
Results
In correlation analysis, age was positively associated with adiponectin in males (P < 0.01), but not in females. Fasting glucose, albumin, arm skeletal muscle mass and bone mineral content were negatively associated with adiponectin in males (P < 0.05). Testosterone and leg bone mineral content were negatively associated with adiponectin in females (P < 0.05). In multivariate linear regression models, body fat percentage and albumin (P < 0.05) were negatively associated with adiponectin, and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) and age (P < 0.01) were positively associated with adiponectin in older males. In older females, the only factors that correlated significantly with adiponectin concentration were the homeostasis model assessment of insulin resistance (P < 0.001) and HDL-C (P < 0.05). The waist/height ratio and bone mineral content were not associated with adiponectin in either gender.
Conclusion
Plasma adiponectin levels correlated negatively with body fat percentage in older males but not in older females. The differential results between older males and females suggest that certain gender-specific mechanisms may affect the association between adiponectin and age-related body composition changes.
doi:10.1186/1471-2318-14-8
PMCID: PMC3931323  PMID: 24460637
Adiponectin; Older adults; Body composition; Gender difference; Ageing
10.  Gradient Moment Compensated Magnetic Resonance Spectroscopic Imaging 
Spectroscopic imaging applications outside of the brain can suffer from artifacts due to inherent long scan times and susceptibility to motion. A fast spectroscopic imaging sequence has been devised with reduced sensitivity to motion. The sequence uses oscillating readout gradients and acquires k-space data in a spiral out–in fashion, which allows fast k-space coverage. We show that a spiral out–in readout acquisition is characterized by small gradient moments, reducing sensitivity to motion-induced artifacts. Data are acquired comparing the sequence to normal phase encoded spectroscopic imaging and conventional spiral spectroscopic imaging protocols. In addition, in vivo data are acquired from the liver, demonstrating potential usage as a multivoxel fat/water spectroscopic imaging tool. Results indicate that in the presence of motion, ghosting effects are reduced while metabolite signal increases of approximately 10% can be achieved.
doi:10.1002/mrm.21832
PMCID: PMC2835400  PMID: 19161164
MRSI motion; gradient nulling
11.  A Case of Immunoglobulin G4-Related Disease Presenting as a Pleural Mass 
Immunoglobulin G4 (IgG4)-related disease is a newly recognized condition characterized by fibroinflammatory lesions with dense lymphoplasmacytic infiltration, storiform-type fibrosis and obliterative phlebitis. The pathogenesis is not fully understood but multiple immune-mediated mechanisms are believed to contribute. This rare disease can involve various organs and pleural involvement is even rarer. We report a case of IgG4-related disease involving pleura. A 66-year-old man presented with cough and sputum production for a week. Chest radiography revealed consolidation and a pleural mass at right hemithorax. Treatment with antibiotics resolved the consolidation and respiratory symptoms disappeared, but the pleural mass was unchanged. Video-assisted thoracoscopic surgery was performed. Histopathology revealed dense lymphoplasmacytic infiltration and storiform fibrosis with numerous IgG4-bearing plasma cells. The serum IgG4 level was also elevated. Further examination ruled out the involvement of any other organ. The patient was discharged without further treatment and there is no evidence of recurrence to date.
doi:10.4046/trd.2014.76.1.38
PMCID: PMC3919964  PMID: 24523817
Immunoglobulin G; Autoimmune Diseases; Pleural Neoplasms
12.  Fast Multi-voxel Two-dimensional Spectroscopic Imaging at 3T 
Magnetic resonance imaging  2007;25(8):1155-1161.
The utility of multi-voxel two-dimensional chemical shift imaging in the clinical environment will ultimately be determined by the imaging time and the metabolite peaks that can be detected. Different k-space sampling schemes can be characterized by their minimum required imaging time. The use of spiral-based readout gradients effectively reduces this minimum scan time due to simultaneous data acquisition in three k-space dimensions (kx, ky, and kf2). A 3T spiral-based multi-voxel two-dimensional spectroscopic imaging sequence using the PRESS excitation scheme was implemented. Good performance was demonstrated by acquiring preliminary in vivo data for applications including brain glutamate imaging, metabolite T2 quantification, and high spatial resolution prostate spectroscopic imaging. All protocols were designed to acquire the data within a 17 minute scan time at a field strength of 3T.
doi:10.1016/j.mri.2007.01.118
PMCID: PMC2128753  PMID: 17418519
magnetic resonance spectroscopic imaging; spiral readout gradients; 2D J-resolved spectroscopy
13.  Acute stress causes rapid synaptic insertion of Ca2+-permeable AMPA receptors to facilitate long-term potentiation in the hippocampus 
Brain  2013;136(12):3753-3765.
The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+-permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.
doi:10.1093/brain/awt293
PMCID: PMC3859225  PMID: 24271563
long-term potentiation; metaplasticity; glucocorticoids; glutamate receptor; calcium
14.  AMP-activated protein kinase determines apoptotic sensitivity of cancer cells to ginsenoside-Rh2 
Journal of Ginseng Research  2013;38(1):16-21.
Ginseng saponins exert various important pharmacological effects with regard to the control of many diseases, including cancer. In this study, the anticancer effect of ginsenosides on human cancer cells was investigated and compared. Among the tested compounds, ginsenoside-Rh2 displays the highest inhibitory effect on cell viability in HepG2 cells. Ginsenoside-Rh2, a ginseng saponin isolated from the root of Panax ginseng, has been suggested to have potential as an anticancer agent, but the underlying mechanisms remain elusive. In the present study, we have shown that cancer cells have differential sensitivity to ginsenoside-Rh2-induced apoptosis, raising questions regarding the specific mechanisms responsible for the discrepant sensitivity to ginsenoside-Rh2. In this study, we demonstrate that AMP-activated protein kinase (AMPK) is a survival factor under ginsenoside-Rh2 treatment in cancer cells. Cancer cells with acute responsiveness of AMPK display a relative resistance to ginsenoside-Rh2, but cotreatment with AMPK inhibitor resulted in a marked increase of ginsenoside-Rh2-induced apoptosis. We also observed that p38 MAPK (mitogen-activated protein kinase) acts as another survival factor under ginsenoside-Rh2 treatment, but there was no signaling crosstalk between AMPK and p38 MAPK, suggesting that combination with inhibitor of AMPK or p38 MAPK can augment the anticancer potential of ginsenoside Rh2.
doi:10.1016/j.jgr.2013.11.010
PMCID: PMC3915337  PMID: 24558305
AMP-activated protein kinase; apoptosis; cancer; p38 MAPK; Panax ginseng
15.  Soyasaponin I Improved Neuroprotection and Regeneration in Memory Deficient Model Rats 
PLoS ONE  2013;8(12):e81556.
Soy (Glycine Max Merr, family Leguminosae) has been reported to possess anti-cancer, anti-lipidemic, estrogen-like, and memory-enhancing effects. We investigated the memory-enhancing effects and the underlying mechanisms of soyasaponin I (soya-I), a major constituent of soy. Impaired learning and memory were induced by injecting ibotenic acid into the entorhinal cortex of adult rat brains. The effects of soya-I were evaluated by measuring behavioral tasks and neuronal regeneration of memory-deficient rats. Oral administration of soya-I exhibited significant memory-enhancing effects in the passive avoidance, Y-maze, and Morris water maze tests. Soya-Ι also increased BrdU incorporation into the dentate gyrus and the number of cell types (GAD67, ChAT, and VGluT1) in the hippocampal region of memory-deficient rats, whereas the number of reactive microglia (OX42) decreased. The mechanism underlying memory improvement was assessed by detecting the differentiation and proliferation of neural precursor cells (NPCs) prepared from the embryonic hippocampus (E16) of timed-pregnant Sprague-Dawley rats using immunocytochemical staining and immunoblotting analysis. Addition of soya-Ι in the cultured NPCs significantly elevated the markers for cell proliferation (Ki-67) and neuronal differentiation (NeuN, TUJ1, and MAP2). Finally, soya-I increased neurite lengthening and the number of neurites during the differentiation of NPCs. Soya-Ι may improve hippocampal learning and memory impairment by promoting proliferation and differentiation of NPCs in the hippocampus through facilitation of neuronal regeneration and minimization of neuro-inflammation.
doi:10.1371/journal.pone.0081556
PMCID: PMC3852400  PMID: 24324703
16.  Epileptic Nystagmus and Vertigo Associated with Bilateral Temporal and Frontal Lobe Epilepsy 
Epileptic nystagmus is defined as a quick, repetitive jerky movement of the eyeball associated with seizure activity. In cases of epileptic nystagmus associated with ictal discharge from multiple brain areas, localization of the exact epileptogenic zone could be extremely difficult. In a nine-year-old patient with epileptic nystagmus and vertigo associated with bilateral temporal and frontal lobe epilepsy, we could infer the epileptic focus by interpreting the patient's clinical picture, characteristics of nystagmus, and findings of electroencephalography.
doi:10.3342/ceo.2013.6.4.259
PMCID: PMC3863677  PMID: 24353868
Epilepsy; Pathologic nystagmus; Vertigo; Electroencephalography
17.  Inverted-Takotsubo Cardiomyopathy in a Patient with Pulmonary Embolism 
Korean Circulation Journal  2013;43(12):834-838.
As the use of early coronary angiography and echocardiography become widely available in the setting of acute coronary syndrome, the gradual increase for variant forms of transient left ventricular (LV) apical ballooning syndrome have been recognized. This syndrome usually occurs in women and is frequently elicited by an intense emotional, psychological, and physical event. While the patients' characteristics between typical and non-typical LV ballooning syndrome seem to differ, the presentation, clinical features, and reversibility of LV wall motion abnormalities are similar. We present a middle-aged woman who experienced inverted takotsubo cardiomyopathy triggered by pulmonary embolism. To the best of our knowledge, this case is particularly unique and is rarely reported in the disease entity.
doi:10.4070/kcj.2013.43.12.834
PMCID: PMC3875701  PMID: 24385996
Stress cardiomyopathy; Takotsubo cardiomyopathy; Pulmonary embolism
18.  Short-course palliative radiotherapy for uterine cervical cancer 
Radiation Oncology Journal  2013;31(4):216-221.
Purpose
The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer.
Materials and Methods
Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions.
Results
The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity.
Conclusion
Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.
doi:10.3857/roj.2013.31.4.216
PMCID: PMC3912235  PMID: 24501709
Cervix uteri; Carcinoma; Palliation; Hypofractionation; Radiotherapy
19.  Danggui-Jakyak-San ameliorates memory impairment and increase neurogenesis induced by transient forebrain ischemia in mice 
Background
Danggui-Jakyak-San (DJS), a traditional herbal prescription, has been used to treat insufficient blood supplies. Recently, regenerative medication for the treatment of cerebral ischemia has drawn the attention of many researchers.
Methods
In this study, we examined whether DJS exerts a neuronal regenerative effect in the hippocampus of a transient forebrain ischemia mice model. Transient forebrain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). Animals were divided into three groups (sham, BCCAO + vehicle, and BCCAO + DJS). To test the effect of DJS on learning and memory, Morris water maze or passive avoidance test was conducted. To test neuroprotective and neurogenic effect, immunohistochemistry and Western blot analysis were used. Statistical significance was analyzed with Student t-test, one-way or two-way analysis of variance.
Results
We found that the administration of DJS ameliorated ischemia-induced spatial memory impairment in the Morris water maze task. Moreover, Akt/glycogen synthase kinase-3β (GSK3β)/β-catenin signaling was increased by DJS, which would be one possible mechanism of DJS for neurogenesis in the hippocampal dentate gyrus region.
Conclusions
These results suggest that DJS is a possible candidate for the treatment of ischemia-induced neuronal degeneration.
doi:10.1186/1472-6882-13-324
PMCID: PMC3840576  PMID: 24261472
Danggui-Jakyak-San; Transient forebrain ischemia; Neurogenesis; GSK-3β; β-catenin; Hippocampus
20.  Cloning, Characterization and Effect of TmPGRP-LE Gene Silencing on Survival of Tenebrio Molitor against Listeria monocytogenes Infection 
Peptidoglycan recognition proteins (PGRPs) are a family of innate immune molecules that recognize bacterial peptidoglycan. PGRP-LE, a member of the PGRP family, selectively binds to diaminopimelic acid (DAP)-type peptidoglycan to activate both the immune deficiency (Imd) and proPhenoloxidase (proPO) pathways in insects. A PGRP-LE-dependent induction of autophagy to control Listeria monocytogenes has also been reported. We identified and partially characterized a novel PGRP-LE homologue, from Tenebrio molitor and analyzed its functional role in the survival of the insect against infection by a DAP-type PGN containing intracellular pathogen, L. monocytogenes. The cDNA is comprised of an open reading frame (ORF) of 990 bp and encodes a polypeptide of 329 residues. TmPGRP-LE contains one PGRP domain, but lacks critical residues for amidase activity. Quantitative RT-PCR analysis showed a broad constitutive expression of the transcript at various stages of development spanning from larva to adult. RNAi mediated knockdown of the transcripts, followed by a challenge with L. monocytogenes, showed a significant reduction in survival rate of the larvae, suggesting a putative role of TmPGRP-LE in sensing and control of L. monocytogenes infection in T. molitor. These results implicate PGRP-LE as a defense protein necessary for survival of T. molitor against infection by L. monocytogenes.
doi:10.3390/ijms141122462
PMCID: PMC3856074  PMID: 24240808
peptidoglycan recognition protein; Tenebrio molitor; Listeria monocytogenes; PGRP domain; RNA interference
21.  Cardiovascular Health Metrics and All-cause and Cardiovascular Disease Mortality Among Middle-aged Men in Korea: The Seoul Male Cohort Study 
Objectives
This study estimated the association of cardiovascular health behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality in middle-aged men in Korea.
Methods
In total, 12 538 men aged 40 to 59 years were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics defined the following lifestyle behaviors proposed by the American Heart Association: smoking, physical activity, body mass index, diet habit score, total cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health metrics score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior. A Cox proportional hazards regression model was used to estimate the hazard ratio of cardiovascular health behavior. Population attributable risks (PARs) were calculated from the significant cardiovascular health metrics.
Results
There were 1054 total and 171 CVD deaths over 230 690 person-years of follow-up. The prevalence of meeting all 7 cardiovascular health metrics was 0.67%. Current smoking, elevated blood pressure, and high fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0 to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were 0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to 0.29) for CVD mortality.
Conclusions
Among cardiovascular health behaviors, not smoking, normal blood pressure, and recommended fasting blood glucose levels were associated with reduced risks of all-cause and CVD mortality. Meeting a greater number of cardiovascular health metrics was associated with a lower risk of all-cause and CVD mortality.
doi:10.3961/jpmph.2013.46.6.319
PMCID: PMC3859853  PMID: 24349653
Cardiovascular diseases; Cohort studies; Cox proportional hazards models; Life style; Mortality
22.  Total hip replacement arthroplasty with Mallory-Head system—minimum ten-year follow-up results 
International Orthopaedics  2012;36(10):2055-2059.
Purpose
The purpose of this study was to assess the clinical and radiographic results of a total hip arthroplasty with the double tapered Mallory-Head system.
Methods
The clinical and radiographic results of a consecutive series of 81 total hip replacements in 75 patients were reviewed 10–15 years (average 11.4 years) postoperatively. The patients’ underlying conditions were avascular necrosis in 46 hips (57 %), osteoarthritis in 12 hips (15 %), RA in nine hips (11 %), and others. Clinical results were evaluated based on the modified Harris hip score and modified Merle d’Aubigné-Postel score. A radiographic analysis was performed.
Results
The average modified Harris hip score improved from a preoperative score of 56 points to a postoperative 92 points. The average modified Merle d’Aubigné-Postel score was 15 points at the latest follow up, and 55 hips (68 %) were classified as the clinical grades of excellent or good results. One acetabular component was revised because of loosening, and one was revised for recurrent dislocation.
Conclusion
The clinical and radiological evaluations of the total hip replacements using the Mallory-Head system showed good results.
doi:10.1007/s00264-012-1627-1
PMCID: PMC3460082  PMID: 22864458
23.  Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-κB/AP-1 Pathways 
Biomolecules & Therapeutics  2013;21(5):332-337.
Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer’s disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.
doi:10.4062/biomolther.2013.069
PMCID: PMC3825195  PMID: 24244819
Microglia; Kalopanaxsaponin A; Anti-inflammation; JNK; NF-κB; AP-1
24.  Anticolitic Effect of the Rhizome Mixture of Anemarrhena asphodeloides and Coptidis chinensis (AC-mix) in Mice 
Biomolecules & Therapeutics  2013;21(5):398-404.
During a screening program to search the anticolitic herbal medicines, 80% ethanol extract of the rhizome of Anemarrhena asphodeloides (AA) was found to potently inhibit the expression of proinflammatory cytokines TNF-α and IL-1β, as well as the activation of NF-κB in LPS-stimulated colonic macrophages, followed by that of the rhizome of C. chinensis (CC). AA also potently inhibited TNBS-induced colitic markers, shortening of the colon and increase of macroscopic score, myeloperoxidase activity, TNF-α, IL-1β, and IL-6, in mice. The synergistic effect of CC against the anticolitic effect of AA was investigated. CC synergistically inhibited the anticolitic effect of AA. AC-mix (AA+CC, 1:1) potently inhibited them. AC-mix also inhibited the activation of NF-κB, as well as the expression of TNF-α, IL-1β, IL-6, iNOS and COX-2. The effects of AC-mix against oxazolone-induced colitis were investigated in mice. AC-mix also potently inhibited oxazolone-induced inflammatory markers, colon shortening, macroscopic score, myeloperoxidase activity, NF-κB activation and proinflammatory cytokines. Overall, the anti-colitic effect of AC-mix was superior to that of mesalazine. Based on these findings, AC-mix may improve colitis by inhibiting NF-κB activation.
doi:10.4062/biomolther.2013.048
PMCID: PMC3825204  PMID: 24244828
Anemarrhena asphodeloides; Coptidis chinensis; AC-mix; Colitis
25.  Photothermal ablation of pancreatic cancer cells with hybrid iron-oxide core gold-shell nanoparticles 
Purpose
Photothermal ablation is a minimally invasive approach, which typically involves delivery of photothermal sensitizers to targeted tissues. The purpose of our study was to demonstrate that gold nanoparticles are phagocytosed by pancreatic cancer cells, thus permitting magnetic resonance imaging (MRI) of sensitizer delivery and photothermal ablation.
Patients and methods
Iron-oxide core/gold-shell nanoparticles (GoldMag®, 30 nm diameter; Xi’an GoldMag Biotechnology Co, Xi’an, People’s Republic of China) were used. In a 96-well plate, 3 × 104 PANC-1 (human pancreatic cancer cell line) cells were placed. GoldMag (0, 25, or 50 μg/mL) was added to each well and 24 hours allowed for cellular uptake. Samples were then divided into two groups: one treated with photothermal ablation (7.9 W/cm2) for 5 minutes, the other not treated. Photothermal ablation was performed using laser system (BWF5; B&W Tek, Inc, Newark, DE, USA). Intraprocedural temperature changes were measured using a fiber optic temperature probe (FTP-LN2; Photon Control Inc, Burnaby, BC, Canada). After 24 hours, the remaining number of viable cells was counted using trypan blue staining; cell proliferation percentage was calculated based on the total number of viable cells after treatment compared with control. MRI of GoldMag uptake was performed using a 7.0T ClinScan system (Bruker BioSpin, Ettlingen, Germany).
Results
Temperature curves demonstrated that with increased GoldMag uptake, laser irradiation produced higher temperature elevations in the corresponding samples; temperature elevations of 12.89°C, 35.16°C, and 79.51°C were achieved for 0, 25, and 50 μg/mL GoldMag. Without photothermal ablation, the cell proliferation percentage changed from 100% to 71.3% and 47.0% for cells treated with 25 and 50 μg/mL GoldMag. Photothermal ablation of PANC-1 cells demonstrated an effective treatment response, specifically a reduction to only 61%, 21.9%, and 2.3% cell proliferation for cells treated with 0, 25, and 50 μg/mL GoldMag. MRI was able to visualize GoldMag uptake within PANC-1 cells.
Conclusion
Our findings suggest that photothermal ablation may be effective in the treatment of pancreatic cancer. GoldMag nanoparticles could serve as photothermal sensitizers, and MRI is feasible to quantify delivery.
doi:10.2147/IJN.S47585
PMCID: PMC3771851  PMID: 24039426
photothermal ablation therapy; hybrid nanoparticles; magnetic resonance imaging

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