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.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
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.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
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.Apoptotic Activity of Curcumin and EF-24 in HTB-41 Human Salivary Gland Epidermoid Carcinoma Cells.
Ji Won KIM ; Seul Ah LEE ; Dae San GO ; Byung Sun PARK ; Su Gwan KIM ; Sun Kyoung YU ; Ji Su OH ; Chun Sung KIM ; Jeongsun KIM ; Jong Tae PARK ; Do Kyung KIM
International Journal of Oral Biology 2015;40(2):63-69
Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.
Apoptosis
;
Carcinoma, Squamous Cell*
;
Caspase 3
;
Cell Death
;
Cell Nucleus
;
Cell Proliferation
;
Curcuma
;
Curcumin*
;
Drug Therapy
;
Humans
;
Intestinal Absorption
;
Rhizome
;
Salivary Glands*
9.Accuracy of GenediaTM H. pylori ELISA for the Diagnosis of Helicobacter pylori Infection in Korean Population.
In Sik CHUNG ; Sang Woo KIM ; Jae Sung GO ; Na Young KIM ; Jae Gyu KIM ; Jin Ho KIM ; Hak Yang KIM ; Jae Jun KIM ; Jae Geon SIM ; Im Hwan ROE ; Hyeong Sik AHN ; Byung Chul YOON ; Sang Woo LEE ; Yong Chan LEE ; Hwoon Yong JUNG ; Won Seon HONG ; Kyoo Wan CHOI
Korean Journal of Medicine 2001;61(1):17-23
BACKGROUND: GenediaTM H. pylori ELISA is a newly developed diagnostic method which detects serum anti-H. pylori IgG antibody. The aim of this study was to assess the accuracy of GenediaTM H. pylori ELISA for the diagnosis of H. pylori infection in Korean population. METHODS: GenediaTM H. pylori ELISA and GAP-IgG were performed in 353 adult sera and Pyloriset-IgG EIA in 184 subjects. In children, 43 serum samples were tested with GenediaTM H. pylori ELISA. H. pylori infection was determined by rapid urease test, histology, culture or 13C-urea breath test in adults. In children, the subject was considered to be H. pylori positive if 13C-urea breath test was positive. RESULTS: In adults, the sensitivity and specificity of GenediaTM H. pylori ELISA were 93.2% and 83.5% with positive and negative predictive values of 85.1% and 92.5%. Those for GAP-IgG and Pyloriset-IgG EIA were 67.2%, 82.4%, 79.3%, 71.4% and 89.1%, 88.4%, 71.9%, 96.1%, respectively. In children, sensitivity, specificity, positive and negative predictive values of GenediaTM H. pylori ELISA were 80%, 84.8%, 61.5%, and 93.3%. Sensitivity and negative predictive value of GenediaTM H. pylori ELISA were significantly higher than those of GAP-IgG (93.2% vs. 67.2%; plt;0.005 and 92.5% vs 71.4%; p<0.005, respectively). CONCLUSION: GenediaTM H. pylori ELISA is a relatively accurate method for the serodiagnosis of H. pylori infection in Korean subjects compared to GAP-IgG. These results may suggest the clinical use of GenediaTM H. pylori ELISA for epidemiological studies of H. pylori infection in Korea.
Adult
;
Breath Tests
;
Child
;
Diagnosis*
;
Enzyme-Linked Immunosorbent Assay*
;
Helicobacter pylori*
;
Helicobacter*
;
Humans
;
Immunoglobulin G
;
Korea
;
Sensitivity and Specificity
;
Serologic Tests
;
Urease
10.Choledocho-duodenal Fistula Caused by Tuberculosis.
Sang Jeong YOON ; Byung Min JOHN ; Sung Hee JUNG ; Anna KIM ; Byeong Seong KO ; Hyeon Woong YANG ; Young Sook PARK ; Hoon GO ; Gi Young CHOI ; Jun Hyoung KIM ; Jae Min LEE ; Hyo Jung NAM ; Soon Hyun PARK
Korean Journal of Gastrointestinal Endoscopy 2005;30(5):286-289
Choledocho-duodenal fistula is a rare condition. It is usually developed as a complication of the gallstone disease, and rarely developed by penetrating peptic ulcer, trauma and neoplasm. Tuberculosis as a etiology of choledocho-duodenal fistula is very rare, and only a few cases were reported. We experienced a case of choledocho-duodenal fistula due to tuberculous lymphadenitis in a 26 year-old man presented with epigastric pain. After 6 months of anti-tuberculous medication, He was free of symptom and the fistula was closed spontaneously. We report the case with a review of literatures.
Adult
;
Fistula*
;
Gallstones
;
Humans
;
Peptic Ulcer
;
Tuberculosis*
;
Tuberculosis, Lymph Node