1.The Senolytic Drug JQ1 Removes Senescent Cells via Ferroptosis
Seokhyeong GO ; Mikyung KANG ; Sung Pil KWON ; Mungyo JUNG ; Ok Hee JEON ; Byung-Soo KIM
Tissue Engineering and Regenerative Medicine 2021;18(5):841-850
BACKGROUND:
Ferroptosis is an iron-dependent, non-apoptotic programmed cell death. Cellular senescence contributes to aging and various age-related diseases through the expression of a senescence-associated secretory phenotype (SASP). Senescent cells are often resistant to ferroptosis via increased ferritin and impaired ferritinophagy. In this study, we investigated whether treatment with JQ1 could remove senescent cells by inducing ferroptosis.
METHODS:
Senescence of human dermal fibroblasts was induced in vitro by treating the cells with bleomycin. The senolytic effects of JQ1 were evaluated using a SA-β gal assay, annexin V analysis, cell counting kit-8 assay, and qRT-PCR. Ferroptosis following JQ1 treatment was evaluated with qRT-PCR and BODIPY staining.
RESULTS:
At a certain range of JQ1 concentrations, JQ1 treatment reduced the viability of bleomycin-treated cells (senescent cells) but did not reduce that of untreated cells (non-senescent cells), indicating that JQ1 treatment can selectively eliminate senescent cells. JQ1 treatment also decreased SASP expression only in senescent cells. Subsequently, JQ1 treatment reduced the expression of ferroptosis-resistance genes in senescent cells. JQ1 treatment induced lipid peroxidation in senescent cells but not in non-senescent cells.
CONCLUSION
The data indicate that JQ1 can eliminate senescent cells via ferroptosis. This study suggests ferroptosis as a new mechanism of senolytic therapy.
2.The Senolytic Drug JQ1 Removes Senescent Cells via Ferroptosis
Seokhyeong GO ; Mikyung KANG ; Sung Pil KWON ; Mungyo JUNG ; Ok Hee JEON ; Byung-Soo KIM
Tissue Engineering and Regenerative Medicine 2021;18(5):841-850
BACKGROUND:
Ferroptosis is an iron-dependent, non-apoptotic programmed cell death. Cellular senescence contributes to aging and various age-related diseases through the expression of a senescence-associated secretory phenotype (SASP). Senescent cells are often resistant to ferroptosis via increased ferritin and impaired ferritinophagy. In this study, we investigated whether treatment with JQ1 could remove senescent cells by inducing ferroptosis.
METHODS:
Senescence of human dermal fibroblasts was induced in vitro by treating the cells with bleomycin. The senolytic effects of JQ1 were evaluated using a SA-β gal assay, annexin V analysis, cell counting kit-8 assay, and qRT-PCR. Ferroptosis following JQ1 treatment was evaluated with qRT-PCR and BODIPY staining.
RESULTS:
At a certain range of JQ1 concentrations, JQ1 treatment reduced the viability of bleomycin-treated cells (senescent cells) but did not reduce that of untreated cells (non-senescent cells), indicating that JQ1 treatment can selectively eliminate senescent cells. JQ1 treatment also decreased SASP expression only in senescent cells. Subsequently, JQ1 treatment reduced the expression of ferroptosis-resistance genes in senescent cells. JQ1 treatment induced lipid peroxidation in senescent cells but not in non-senescent cells.
CONCLUSION
The data indicate that JQ1 can eliminate senescent cells via ferroptosis. This study suggests ferroptosis as a new mechanism of senolytic therapy.
3.Effect of β-carotene on Cell Growth Inhibition of KB Human Oral Cancer Cells.
Sung Su YANG ; Su Gwan KIM ; Byung Sun PARK ; Dae San GO ; Sun Kyoung YU ; Chun Sung KIM ; Jeongsun KIM ; Do Kyung KIM
International Journal of Oral Biology 2016;41(3):105-111
β-carotene is present in carrots, pumpkins, and sweet potatoes. It suppresses many types of cancers by regulating cellular proliferation and apoptosis through a variety of mechanisms. However, the effects of β -carotene on oral cancer cells have not been clearly established. The main goal of this study was to investigate the effects of β-carotene on cell growth and apoptosis in oral cancer cells. Our results demonstrate that treatment with β-carotene induced inhibition of cell growth, and that the effect was dependent on β-carotene treatment time and concentration in KB cells. Furthermore, treatment with β-carotene induced nuclear condensation and fragmentation in KB cells. β-carotene promoted proteolytic cleavage of procaspase-3, -7, -8 and -9 with associated increases in the concentration of cleaved caspase-3, -7, -8 and -9. In addition, the level of cleaved PARP was increased by β-carotene treatment in KB cells. These results suggest that β-carotene can suppress cell growth and induce apoptosis in KB human oral cancer cells, and that it may have potential usefulness in anti-cancer drug discovery efforts.
Apoptosis
;
Caspase 3
;
Cell Death
;
Cell Proliferation
;
Cucurbita
;
Daucus carota
;
Drug Discovery
;
Humans*
;
Ipomoea batatas
;
KB Cells
;
Mouth Neoplasms*
4.The Effects of the Preoperative Education about Analgesics and Patient-Controlled Analgesia (PCA) on the Consumption of Analgesics after Operation.
Jeong Heon PARK ; Min A KWON ; Myoung Shin KOO ; Yong Ik KIM ; Soon Im KIM ; Sun Chong KIM ; Jin Gu KANG ; Hyun Sung CHO ; Byung Dal LEE ; Gaab Soo KIM
Korean Journal of Anesthesiology 2006;51(6):715-719
BACKGROUND: The purpose of this study is to evaluate the patients' general perception about the analgesics and the effects of the preoperative education about analgesics and patient-controlled analgesia (PCA). METHODS: One hundred patients scheduled for elective gastrectomy were randomly allocated into two groups. In control group (n = 50), patients were given conventional preanesthetic visit with questionnaire survey on PCA one day before operation. In study group (n = 50), patients were sufficiently explained about postoperative analgesia and PCA by anesthesiologist and given precise explanation sheet about PCA. Total amounts of drug used in PCA as well as rescue analgesics, the pain scores, and side effects were compared. RESULTS: 62.2% of patients had much information from various sources that analgesics effects positively in the recovery phase, but actually 73.7% of patients considered that analgesics do not seem to have any influence on the recovery after operation. There was no difference between the amounts of total PCA used, rescue analgesics, and the pain scores. However, the educated patients complained less dizziness at postoperative days (POD) one. Also, the number of patients excluded from study due to the PCA discontinuation secondary to related side effects was less in educated patients (P = 0.025). CONCLUSIONS: Preoperative education about analgesics and PCA failed to demonstrate significant decrease in the amount of analgesics and of pain scores. However, it lowered the incidence of PCA discontinuation due to side effects.
Analgesia
;
Analgesia, Patient-Controlled*
;
Analgesics*
;
Dizziness
;
Education*
;
Gastrectomy
;
Humans
;
Incidence
;
Passive Cutaneous Anaphylaxis
;
Postoperative Care
5.Analysis of Scientific Papers Included in the Sciences Citation Index Expanded Written by South Korean Plastic Surgeons: 2001-2010.
Ju Young GO ; Goo Hyun MUN ; Byung Joon JEON ; So Young LIM ; Jai Kyong PYON ; Sa Ik BANG ; Kap Sung OH ; Myoung Soo SHIN
Archives of Plastic Surgery 2012;39(1):46-50
BACKGROUND: The purpose of our study was to analyze scientific papers published by South Korean plastic surgeons in journals included in the Science Citation Index Expanded (SCIE), and to evaluate the publication and research activities of Korean plastic surgeon. METHODS: We conducted a survey of SCIE papers in the field of plastic surgery published by South Korean authors between 2001 and 2010 using Web of Science software. We further analyzed these results according to the number of publications per year, journals, institution, and type of papers. We also compared the total number of citations to published scientific papers. We analyzed the rank of South Korea among other countries in representative journals. RESULTS: Overall, 667 papers were published by South Korean authors between 2001 and 2010. The number of publications increased dramatically from 2003 (n=31) to 2010 (n=139). Subsequently, the ten most productive Korean medical colleges were identified. All published papers received 2,311 citations and the citation to paper ratio was 3.49. The rank of Korea among other countries in terms of the number of published papers remained in the top 10 during the recent 10 years. CONCLUSIONS: Publication output of Korean plastic surgeon over the last 10 years showed a remarkable growth in terms of quantity and quality. Currently, Korea is among the top six countries in representative plastic surgery journals. Korean plastic surgeons have played a central role in this progress, and it is anticipated that they will continue to do so in the future.
Korea
;
Publications
;
Republic of Korea
;
Surgery, Plastic
6.Comprehensive Geriatric Assessment for Elderly Orthopedic Inpatients Consulted by Geriatric Medicine in a Hospital.
Go Eun KIM ; Sunyoung KIM ; Chang Won WON ; Hyun Rim CHOI ; Byung Sung KIM ; Yoon Je CHO
Journal of the Korean Geriatrics Society 2014;18(4):213-220
BACKGROUND: With a rapidly aging population, more elderly patients are being hospitalized than before. Thus, a comprehensive geriatric assessment medium is needed to carefully evaluate geriatric patients. The author's university hospital has a geriatric medicine team to where patients are referred for comprehensive evaluations. Their services will be introduced here. METHODS: From December 2010 to January 2012, the team performed comprehensive geriatric assessments comprising of a thorough review of systems, physical examination, and surveys, and reviewed past medical records of the elderly hospitalized patients aged 65 or over, referred from the Department of Orthopedics. RESULTS: Of total 58 patients, 4 patients (6.9%) had severe dysfunction in the activities of daily living with the score of 16 or higher. Twenty-two patients (73.3%) had cognitive impairment or dementia upon assessing cognitive function after excluding those previously diagnosed with dementia or those within 5 days after surgery, thus predisposed to delirium who had tested mini mental state examination for cognitive function level test. Fifteen patients (31.3%) had mild depression, while four (8.3%) had moderate depression; and 37 patients (67.3%) were at moderate risk and five (9.1%) were at high risk for developing delirium. CONCLUSION: A comprehensive evaluation of the functional status of elderly hospitalized patients was helpful in detecting medical problems other than the initial diagnosis. A significant proportion of the elderly patients we assessed were suspected to have cognitive impairment.
Activities of Daily Living
;
Aged*
;
Aging
;
Delirium
;
Dementia
;
Depression
;
Diagnosis
;
Geriatric Assessment*
;
Humans
;
Inpatients*
;
Medical Records
;
Orthopedics*
;
Physical Examination
7.Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells.
Yun Jung LEE ; Tae Joon WON ; Kyeong Eun HYUNG ; Mi Ji LEE ; Young hye MOON ; Ik Hee LEE ; Byung Sung GO ; Kwang Woo HWANG
The Korean Journal of Physiology and Pharmacology 2014;18(1):73-78
Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-kappaB) translocation.
Apoptosis
;
Autoimmune Diseases
;
Caspase 3
;
Cell Death*
;
Gene Expression
;
Humans
;
NF-kappa B
;
Peptide Hydrolases
;
Physiology
;
Receptors, Death Domain
;
RNA, Small Interfering
;
Signal Transduction
;
T-Lymphocytes*
;
TNF Receptor-Associated Factor 4
;
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
8.Identification and Diagnostic Utility of Serologic Reactive Antigens from Mycobacterium tuberculosis Sonic Extracts.
Yu Mi KWON ; Ki Hwan JUNG ; Go Eun CHOI ; A Rum SHIN ; Byung Su LEE ; Choul Jae WON ; Woo Sik KIM ; Sung Jae SHIN ; Jeong Kyu PARK ; Chulhun L CHANG ; Hwa Jung KIM
Journal of Bacteriology and Virology 2009;39(4):329-336
It is important to identify and to test serologically active antigens, so as to devise a cocktail of the best antigens or peptides. We searched for antigens that have serodiagnostic utility using two-dimensional fractionation of sonic extracts from Mycobacterium tuberculosis and probing with pools of sera from healthy subjects and patients with tuberculosis (TB). Reactive protein spots with patient sera were identified by tandem mass spectrometry. Three proteins, Rv0652, Rv2626c, and Rv3418c, which have not previously been described as serologic targets, were identified. Rv0652 protein among them was expressed in Escherichia coli and serum IgG antibodies against this antigen were measured in 150 patients with pulmonary TB and in 115 healthy subjects. The sensitivity and specificity were 39% and 92%, respectively. These results suggest that a newly identified protein, Rv0652 may be a valuable candidate to be included in a cocktail test kit for TB diagnosis.
Antibodies
;
Escherichia coli
;
Humans
;
Immunoglobulin G
;
Mycobacterium
;
Mycobacterium tuberculosis
;
Peptides
;
Proteins
;
Sensitivity and Specificity
;
Tandem Mass Spectrometry
;
Tuberculosis
9.Nontuberculous Mycobacterial Lung Disease Caused by Mycobacterium chelonae: A Case Report.
Yousang KO ; Wooyoul KIM ; Beom Su SHIN ; Hongseok YOO ; Jung Seop EOM ; Ji Hyun LEE ; Byung Woo JHUN ; Su Young KIM ; Go Eun CHOI ; Sung Jae SHIN ; Won Jung KOH
Tuberculosis and Respiratory Diseases 2013;74(4):191-194
Mycobacterium chelonae lung disease is very rare. We report a case of lung disease caused by M. chelonae in a previously healthy woman. A 69-year-old woman was referred to our hospital because of hemoptysis. A computed tomography (CT) scan of the chest revealed bronchiolitis associated with bronchiectasis in the lingular division of the left upper lobe. Nontuberculous mycobacteria were isolated three times from sputum specimens. All isolates were identified as M. chelonae by various molecular methods that characterized rpoB and hsp65 gene sequences. Although some new lesions including bronchiolitis in the superior segment of the left lower lobe developed on the chest CT scan 35 months after diagnosis, she has been followed up without antibiotic therapy because of her mild symptoms. To the best of our knowledge, this is the first case of M. chelonae lung disease in Korea in which the etiologic organisms were confirmed using molecular techniques.
Bronchiectasis
;
Bronchiolitis
;
Female
;
Hemoptysis
;
Humans
;
Korea
;
Lung
;
Lung Diseases
;
Mycobacterium
;
Mycobacterium chelonae
;
Nontuberculous Mycobacteria
;
Sputum
;
Thorax
10.Hepatitis C Virus Infection in Pregnancy.
Yong Wook KIM ; Jong Min LEE ; Gwang Jun KIM ; Hayng Mi LEE ; Suk Young KIM ; Jee Sung LEE ; Sun LEE ; Young Jin KIM ; Young Soo SON ; Seung Hun CHOI ; Chan Yong PARK ; Soon Pyo LEE ; Byung Chul WHANG ; Yu Duk CHOI ; Ji Hong PARK ; Sang Ik NAM ; Bong Ho GO ; Sang Hee KIM ; Joo Hyun KIM
Korean Journal of Obstetrics and Gynecology 2000;43(4):597-603
OBJECTIVE: Our purpose was to estimate the prevalence of hepatitis C virus seropositivity and define the risk factors for HCV infection in a group of pregnant women and the effect of HCV infection to mother and baby at the time of delivery. METHODS: From March 1997 to February 1998, 5655 women who delivered over 20 gestational weeks at our hospital were screened for HCV-Antibody(RIA), and the samples of most of HCV-Ab positive cases were analyzed for HCV-RNA by polymerase chain reaction(PCR). We also studied the risk factors for HCV infection, the effect of HCV infection to mothers and neonates at delivery. RESULTS: Of 5655 mothers 25 (0.44%) were HCV-Ab positive, and 20 of HCV-Ab positive mothers were analyzed for HCV-RNA by PCR. Of 20 HCV-Ab positive mothers 12 cases (60%) were HCV-RNA positive. Risk factors significantly more prevalent among HCV-seropositive patients were : a history of habitual intraveneous drug use, a history of smoking, alcohol drinking during pregnancy, having liver cirrhorsis. The proportions who had received a blood transfusion, had a history or ongoing syphilis or were positive for hepatitis B virus surface antigen were not significantly different between seropositive and seronegative women. Liver function test at delivery was abnormal in 4 cases(16%) of HCV-Ab positive group. And the number of abnomal liver function test cases in HCV-Ab negative group were 47(0.83%). This had statistical difference. In neonates at delivery, all 20 neonates of 20 ones having HCV-Ab positive mother were HCV-Ab positive. But only 2 cases of 20 babies were HCV-RNA positive. CONCLUSION: Mothers who have risk factors such as injecting drug use, smoking, alchohol drinking and liver cirrhorsis, should undergo HCV-Ab testing and quantitative HCV-RNA testing by PCR. More advanced studies about vertical transmission of HCV infection are needed.
Alcohol Drinking
;
Antigens, Surface
;
Blood Transfusion
;
Drinking
;
Female
;
Hepacivirus*
;
Hepatitis B virus
;
Hepatitis C*
;
Hepatitis*
;
Humans
;
Infant, Newborn
;
Liver
;
Liver Function Tests
;
Mothers
;
Polymerase Chain Reaction
;
Pregnancy*
;
Pregnant Women
;
Prevalence
;
Risk Factors
;
Smoke
;
Smoking
;
Syphilis