1.The Pathological Role of Astrocytic MAOB in Parkinsonism Revealed by Genetic Ablation and Over-expression of MAOB
Heeyoung AN ; Jun Young HEO ; C. Justin LEE ; Min-Ho NAM
Experimental Neurobiology 2021;30(2):113-119
The cause of Parkinson’s disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc).This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson’s disease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson’s disease. However, whether genetic ablation and over-expression of MAOB can bidirectionally regulate parkinsonian motor symptoms has not been tested. Here we demonstrate that genetic ablation of MAOB blocks the MPTP-induced augmentation of astrocytic GABA-mediated tonic inhibition of neighboring dopaminergic neurons as well as parkinsonian motor symptoms, indicating the necessity of MAOB for parkinsonian motor symptoms. Furthermore, we demonstrate that GFAP-MAOB transgenic mice, in which MAOB is over-expressed under the GFAP promoter for astrocyte-specific over-expression, display exacerbated MPTP-induced tonic inhibition and parkinsonian motor symptoms compared to wild-type mice, indicating the importance of astrocytic MAOB for parkinsonian motor symptoms. Our study provides genetic pieces of evidence for the causal link between the pathological role of astrocytic MAOB-dependent tonic GABA synthesis and parkinsonian motor symptoms.
2.The Pathological Role of Astrocytic MAOB in Parkinsonism Revealed by Genetic Ablation and Over-expression of MAOB
Heeyoung AN ; Jun Young HEO ; C. Justin LEE ; Min-Ho NAM
Experimental Neurobiology 2021;30(2):113-119
The cause of Parkinson’s disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc).This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson’s disease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson’s disease. However, whether genetic ablation and over-expression of MAOB can bidirectionally regulate parkinsonian motor symptoms has not been tested. Here we demonstrate that genetic ablation of MAOB blocks the MPTP-induced augmentation of astrocytic GABA-mediated tonic inhibition of neighboring dopaminergic neurons as well as parkinsonian motor symptoms, indicating the necessity of MAOB for parkinsonian motor symptoms. Furthermore, we demonstrate that GFAP-MAOB transgenic mice, in which MAOB is over-expressed under the GFAP promoter for astrocyte-specific over-expression, display exacerbated MPTP-induced tonic inhibition and parkinsonian motor symptoms compared to wild-type mice, indicating the importance of astrocytic MAOB for parkinsonian motor symptoms. Our study provides genetic pieces of evidence for the causal link between the pathological role of astrocytic MAOB-dependent tonic GABA synthesis and parkinsonian motor symptoms.
3.Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019(COVID-19)
Joungha WON ; Solji LEE ; Myungsun PARK ; Tai Young KIM ; Mingu Gordon PARK ; Byung Yoon CHOI ; Dongwan KIM ; Hyeshik CHANG ; Won Do HEO ; V. Narry KIM ; C. Justin LEE
Experimental Neurobiology 2020;29(5):402-402
4.Antibacterial activity of essential oil from lavender (Lavandula angustifolia) against pet turtle-borne pathogenic bacteria.
Sabrina HOSSAIN ; Honghoi HEO ; B C J DE SILVA ; S H M P WIMALASENA ; H N K S PATHIRANA ; Gang Joon HEO
Laboratory Animal Research 2017;33(3):195-201
Pet turtles are well-known to harbor an array of bacterial pathogens which can cause zoonotic infections in humans as well as opportunistic infections in the turtles itself. Essential oils are the natural plant extracts which have been traditionally used for disease treatment. In the present study, the essential oil of lavender (EOL) was examined for its antibacterial activity against thirty-eight strains of turtle-borne pathogenic bacteria belonging to seven species; Aeromonas hydrophila, A. caviae, A. dhakensis, Citrobacter freundii, Proteus mirabilis, Salmonella enterica and Pseudomonas aeruginosa. Antibacterial activity of EOL was tested by means of disk diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) tests. In addition, the antimicrobial susceptibility pattern of 11 commonly used antimicrobials was examined and the multiple antibiotic resistance (MAR) index was calculated. The results revealed that EOL was active against all tested turtle-borne pathogenic bacteria except P. aeruginosa. The range of MIC and MBC values of EOL against isolates except P. aeruginosa were recorded as 0.5-1% (V/V) and 0.5-2% (V/V), respectively. The MBC/MIC ratio was detected as <4, revealing that the tested EOL was bactericidal. Besides, most of the isolates were resistant to different antimicrobials in antimicrobial disk diffusion test. MAR index values of the tested strains were ranging from 0.27 to 0.91. The outcomes indicate that EOL has a potential to be used as an antibacterial agent against pathogenic bacteria isolated from pet turtles.
Aeromonas hydrophila
;
Animals
;
Bacteria*
;
Citrobacter freundii
;
Diffusion
;
Drug Resistance, Microbial
;
Guinea Pigs
;
Humans
;
Lavandula*
;
Microbial Sensitivity Tests
;
Oils, Volatile
;
Opportunistic Infections
;
Plant Extracts
;
Proteus mirabilis
;
Pseudomonas aeruginosa
;
Salmonella enterica
;
Turtles
;
Zoonoses
5.The First Report of Lasioderma Serricorne Infestation on Dried Fish Crackers in Malaysia (Liputan Pertama Infestasi Lasioderma Serricorne pada Keropok Ikan di Malaysia)
Azmiera, N. ; Singh, S. ; Heo, C. C.
Malaysian Journal of Health Sciences 2020;18(No.1):25-28
This paper is the first record of cigarette beetles collected from dried fish crackers (also known as “keropok ikan” in Malay) in Malaysia. The dead cigarette beetles were firstly isolated from a packet of dried fish crackers and were subsequently kept in 70% ethanol. The beetles were then identified as Lasioderma serricorne (Fabricius 1792) (Coleoptera: Anobiidae). They are common pests of stored products such as tobacco, flour, and cocoa beans but there is no record of this beetle infestation on dried fish crackers in Malaysia.
6.Effective Transport for Trauma Patients under Current Circumstances in Korea: A Single Institution Analysis of Treatment Outcomes for Trauma Patients Transported via the Domestic 119 Service.
Jiyoung KIM ; Yunjung HEO ; John C J LEE ; Sukja BAEK ; Younghwan KIM ; Jonghwan MOON ; Seok Hwa YOUN ; Heejung WANG ; Yo HUH ; Kyoungwon JUNG
Journal of Korean Medical Science 2015;30(3):336-342
In Korea, which still lacks a well-established trauma care system, the inability to transport patients to adequate treatment sites in a timely manner is a cause of low trauma patient survival. As such, this study was conducted to serve as a basis for the establishment of a future trauma transport system. We performed a comparative analysis of the transport time, and treatment outcomes between trauma victims transported by ground ambulance (GAMB) and those transported via the helicopter emergency medical service (HEMS) through the National Emergency Management Agency's 119 reporting system, which is similar to the 911 system of the United States, from March 2011 to May 2014. The HEMS-transported patients received treatment instructions, by remote communication, from our trauma specialists from the time of accident reporting; in certain instances, members of the trauma medical staff provided treatment at the scene. A total of 1,626 patients were included in the study; the GAMB and HEMS groups had 1,547 and 79 patients, respectively. The median transport time was different between 2 groups (HEMS, 60 min vs. GAMB, 47 min, P<0.001) but for all patients was 49 min (less than the golden hour). Outcomes were significantly better in the HEMS compared to the GAMB, using the trauma and injury severity score (survival rate, 94.9% vs. 90.5%; Z score, 2.83 vs. -1.96; W score, 6.7 vs. -0.8). A unified 119 service transport system, which includes helicopter transport, and the adoption of a trauma care system that allows active initial involvement of trauma medical personnel, could improve the treatment outcome of trauma patients.
Air Ambulances/*utilization
;
Emergency Service, Hospital/*statistics & numerical data
;
Female
;
Humans
;
Injury Severity Score
;
Male
;
Prognosis
;
Republic of Korea
;
Survival Rate
;
Time Factors
;
Trauma Centers
;
Treatment Outcome
;
Wounds, Nonpenetrating/*mortality/therapy
;
Wounds, Penetrating/*mortality/therapy
7.Effective Transport for Trauma Patients under Current Circumstances in Korea: A Single Institution Analysis of Treatment Outcomes for Trauma Patients Transported via the Domestic 119 Service.
Jiyoung KIM ; Yunjung HEO ; John C J LEE ; Sukja BAEK ; Younghwan KIM ; Jonghwan MOON ; Seok Hwa YOUN ; Heejung WANG ; Yo HUH ; Kyoungwon JUNG
Journal of Korean Medical Science 2015;30(3):336-342
In Korea, which still lacks a well-established trauma care system, the inability to transport patients to adequate treatment sites in a timely manner is a cause of low trauma patient survival. As such, this study was conducted to serve as a basis for the establishment of a future trauma transport system. We performed a comparative analysis of the transport time, and treatment outcomes between trauma victims transported by ground ambulance (GAMB) and those transported via the helicopter emergency medical service (HEMS) through the National Emergency Management Agency's 119 reporting system, which is similar to the 911 system of the United States, from March 2011 to May 2014. The HEMS-transported patients received treatment instructions, by remote communication, from our trauma specialists from the time of accident reporting; in certain instances, members of the trauma medical staff provided treatment at the scene. A total of 1,626 patients were included in the study; the GAMB and HEMS groups had 1,547 and 79 patients, respectively. The median transport time was different between 2 groups (HEMS, 60 min vs. GAMB, 47 min, P<0.001) but for all patients was 49 min (less than the golden hour). Outcomes were significantly better in the HEMS compared to the GAMB, using the trauma and injury severity score (survival rate, 94.9% vs. 90.5%; Z score, 2.83 vs. -1.96; W score, 6.7 vs. -0.8). A unified 119 service transport system, which includes helicopter transport, and the adoption of a trauma care system that allows active initial involvement of trauma medical personnel, could improve the treatment outcome of trauma patients.
Air Ambulances/*utilization
;
Emergency Service, Hospital/*statistics & numerical data
;
Female
;
Humans
;
Injury Severity Score
;
Male
;
Prognosis
;
Republic of Korea
;
Survival Rate
;
Time Factors
;
Trauma Centers
;
Treatment Outcome
;
Wounds, Nonpenetrating/*mortality/therapy
;
Wounds, Penetrating/*mortality/therapy
8.Quinolone susceptibility and genetic characterization of Salmonella enterica subsp. enterica isolated from pet turtles.
B C J DE SILVA ; Sabrina HOSSAIN ; S H M P WIMALASENA ; H N K S PATHIRANA ; Mitchell WENDT ; Gang Joon HEO
Laboratory Animal Research 2017;33(2):49-56
Turtle-borne Salmonella enterica owns significance as a leading cause in human salmonellosis. The current study aimed to determine the quinolone susceptibility and the genetic characteristics of 21 strains of S. enterica subsp. enterica isolated from pet turtles. Susceptibility of four antimicrobials including nalidixic acid, ciprofloxacin, ofloxacin, and levofloxacin was examined in disk diffusion and MIC tests where the majority of the isolates were susceptible to all tested quinolones. In genetic characterization, none of the isolates were positive for qnr or aac(6')-Ib genes and no any target site mutations could be detected in gyrA, gyrB, and parC quinolone resistance determining regions (QRDR). In addition, neighbor-joining phylogenetic tree derived using gyrA gene sequences exhibited two distinct clads comprising; first, current study isolates, and second, quinolone-resistant isolates of human and animal origin. All results suggest that studied strains of S. enterica subsp. enterica isolated from pet turtles are susceptible to quinolones and genetically more conserved with regards to gyrA gene region.
Animals
;
Ciprofloxacin
;
Diffusion
;
Humans
;
Levofloxacin
;
Nalidixic Acid
;
Ofloxacin
;
Quinolones
;
Salmonella enterica*
;
Salmonella Infections
;
Salmonella*
;
Trees
;
Turtles*
9.Ultimate COVID-19 Detection Protocol Based on Saliva Sampling and qRT-PCR with Risk Probability Assessment
Joungha WON ; Hasan Hüseyin KAZAN ; Jea KWON ; Myungsun PARK ; Mehmet Ali ERGUN ; Sureyya OZCAN ; Byung Yoon CHOI ; Won Do HEO ; C. Justin LEE
Experimental Neurobiology 2021;30(1):13-31
In the era of COVID-19 outbreak, various efforts are undertaken to develop a quick, easy, inexpensive, and accurate way for diagnosis. Although many commercial diagnostic kits are available, detailed scientific evaluation is lacking, making the public vulnerable to fear of false-positive results.Moreover, current tissue sampling method from respiratory tract requires personal contact of medical staff with a potential asymptomatic SARSCOV-2 carrier and calls for safe and less invasive sampling method. Here, we have developed a convenient detection protocol for SARS-COV-2 based on a non-invasive saliva self-sampling method by extending our previous studies on development of a laboratory-safe and low-cost detection protocol based on qRT-PCR. We tested and compared various self-sampling methods of self-pharyngeal swab and self-saliva sampling from non-carrier volunteers. We found that the self-saliva sampling procedure gave expected negative results from all of the non-carrier volunteers within 2 hours, indicating cost-effectiveness, speed and reliability of the saliva-based method. For an automated assessment of the sampling quality and degree of positivity for COVID-19, we developed scalable formulae based on a logistic classification model using both cycle threshold and melting temperature from the qRT-PCR results. Our newly developed protocol will allow easy sampling and spatial-separation between patient and experimenter for guaranteed safety. Furthermore, our newly established risk assessment formula can be applied to a large-scale diagnosis in health institutions and agencies around the world.
10.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.