1.Up-Regulation of MiR-1915 Inhibits Proliferation, Invasion, and Migration of Helicobacter pylori-Infected Gastric Cancer Cells via Targeting RAGE.
Xin cai XU ; Wen bin ZHANG ; Chun xing LI ; Hua GAO ; Qi PEI ; Bo wei CAO ; Tie han HE
Yonsei Medical Journal 2019;60(1):38-47
PURPOSE: Helicobacter pylori (HP)-infected gastric cancer (GC) is known to be a fatal malignant tumor, but the molecular mechanisms underlying its proliferation, invasion, and migration remain far from being completely understood. Our aim in this study was to explore miR-1915 expression and its molecular mechanisms in regulating proliferation, invasion, and migration of HP-infected GC cells. MATERIALS AND METHODS: Quantitative real-time PCR and western blot analysis were performed to determine miR-1915 and receptor for advanced glycation end product (RAGE) expression in HP-infected GC tissues and gastritis tissues, as well as human gastric mucosal cell line GES-1 and human GC cell lines SGC-7901 and MKN45. CCK8 assay and transwell assay were performed to detect the proliferation, invasion, and migration capabilities. MiR-1915 mimics and miR-1915 inhibitor were transfected into GC cells to determine the target relationship between miR-1915 and RAGE. RESULTS: MiR-1915 was under-expressed, while RAGE was over-expressed in HP-infected GC tissues and GC cells. Over-expressed miR-1915 could attenuate cellular proliferation, invasion, and migration capacities. RAGE was confirmed to be the target gene of miR-1915 by bioinformatics analysis and luciferase reporter assay. Moreover, HP-infected GC cellular proliferation, invasion, and migration were inhibited after treatment with pcDNA-RAGE. CONCLUSION: MiR-1915 exerted tumor-suppressive effects on cellular proliferation, invasion, and migration of HP-infected GC cells via targeting RAGE, which provided an innovative target candidate for treatment of HP-infected GC.
Blotting, Western
;
Cell Line
;
Cell Proliferation
;
Computational Biology
;
Gastritis
;
Helicobacter pylori
;
Helicobacter*
;
Humans
;
Luciferases
;
Rage*
;
Real-Time Polymerase Chain Reaction
;
Stomach Neoplasms*
;
Up-Regulation*
2.Oncologic, Perioperative Outcomes of Female Radical Cystectomy: Results from a Multicenter Study in Korea
Ji Sung SHIM ; Ho Kyung SEO ; Ja Hyeon KU ; Byong Chang JEONG ; Bumsik HONG ; Seok Ho KANG ;
Cancer Research and Treatment 2019;51(3):1064-1072
PURPOSE: The lower incidence of bladder cancer among women has led to a lack of information on female radical cystectomy (RC). This study aimed to analyze the characteristics related with female RC in a cohort from multiple academic institutions. MATERIALS AND METHODS: This was a retrospective review of 384 female patients who underwent RC for bladder cancer. Epidemiologic, perioperative variables including urologic referral periodwith consequent pathologic stage distributions were assessed. The changes in surgical techniques over time were illustrated. Also, we evaluated recurrence-free survival (RFS) at 2 and 5 years and overall survival (OS) at 5 years with stage-specific analyses using the Kaplan-Meier method. RESULTS: The mean follow-up time was 35 months (interquartile rage [IQR], 9 to 55). The average time to urologic referral with initial symptoms was 5.5 (IQR, 1 to 6) months and over 20% of patients visited clinics after 6 months. In subsequent stage distributions according to referral period, T2 or higher stage distributions were abruptly increased after 1 year. Overall 2-year/5-year RFS rates were 0.72/0.57 and 5-year OS was 0.61. Notable surgical descriptions were as follows: 91% of patients underwent open RC; 80% of patients underwent an ileal conduit; and 83% of patients received anterior exenteration. However, the proportions of robotic surgery, orthotopic neobladder and organ sparing cystectomy have increased recently. CONCLUSION: We identified the general characteristics and changes in pattern of female RC. Our results also suggest that women are susceptible to delays in referral to an urologist and are at greater risk for worse prognosis.
Cohort Studies
;
Cystectomy
;
Female
;
Follow-Up Studies
;
Humans
;
Incidence
;
Korea
;
Methods
;
Prognosis
;
Rage
;
Referral and Consultation
;
Retrospective Studies
;
Urinary Bladder Neoplasms
;
Urinary Diversion
3.CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinson's Disease Model
Jaesuk LEE ; Delger BAYARSAIKHAN ; Roshini ARIVAZHAGAN ; Hyejung PARK ; Byungyoon LIM ; Peter GWAK ; Goo Bo JEONG ; Jaewon LEE ; Kyunghee BYUN ; Bonghee LEE
International Journal of Stem Cells 2019;12(1):114-124
BACKGROUND AND OBJECTIVES: Parkinson’s disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD. METHODS: The soluble RAGE (sRAGE) secreting Umbilical Cord Blood—derived Mesenchymal Stem Cell (UCB-MSC) was generated by gene editing method using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9). These cells were transplanted into Corpus Striatum of rotenone-induced PD animal models then behavioral test, morphological analysis, and immunohistochemical experiments were performed to determine the neuronal cell death and recovery of movement. RESULTS: The neuronal cell death in Corpus Striatum and Substantia Nigra was dramatically reduced and the movement was improved after sRAGE secreting UCB-MSC treatment in PD mice by inhibition of RAGE in neuronal cells. CONCLUSIONS: We suggest that sRAGE secreting UCB-MSC based therapeutic approach could be a potential treatment strategy for neurodegenerative disease including PD.
Animals
;
Behavior Rating Scale
;
Cell Death
;
Corpus Striatum
;
Mesenchymal Stromal Cells
;
Methods
;
Mice
;
Microglia
;
Models, Animal
;
Nervous System
;
Neurodegenerative Diseases
;
Neurons
;
Parkinson Disease
;
Rage
;
Substantia Nigra
;
Umbilical Cord
4.Association between cadmium and anti-Mullerian hormone in premenopausal women at particular ages
Yu min LEE ; Hye Won CHUNG ; Kyungah JEONG ; Yeon Ah SUNG ; Hyejin LEE ; Shinhee YE ; Eun Hee HA
Annals of Occupational and Environmental Medicine 2018;30(1):44-
BACKGROUND: Anti-Mullerian hormone (AMH) in women is secreted by granulosa cells of antral follicles. AMH appears to be a very stable marker for ovarian function. It may be used to diagnosis cases of premature ovarian failure, polycystic ovary syndrome (PCOS), and ovarian tumors. It has been suggested that cadmium exposure can reduce female fecundity. The purpose of this study was to investigate whether environmental exposure to cadmium was associated with alterations in AMH with regards to age. METHODS: In a cross-sectional study, the data of premenopausal women living in Seoul, ranging from 30 to 45 of age was collected. The study included a total of 283 women who completed serum AMH and whole blood cadmium assessments. Linear regression analyses were used in order to examine the association between cadmium and AMH. Given that age was the strongest confounder in both cadmium and AMH concentrations, we stratified subjects by 5 years old and analyzed their data. RESULTS: Geometric mean concentrations of blood cadmium and AMH were 0.97 μg/L and 3.02 ng/ml, respectively. Total association between cadmium and AMH was statistically significant (adjusted coefficient = − 0.34 (0.15), p = 0.02). After stratification, the only age group with a negative association between cadmium and AMH were the women raging between 30 and 35 years (adjusted coefficient = − 0.43 (0.18), p = 0.01). CONCLUSIONS: The results of this study suggest that environmental exposure to cadmium may alter the AMH level of premenopausal women, depending on their age group.
Anti-Mullerian Hormone
;
Cadmium
;
Cross-Sectional Studies
;
Diagnosis
;
Environmental Exposure
;
Female
;
Fertility
;
Granulosa Cells
;
Humans
;
Linear Models
;
Polycystic Ovary Syndrome
;
Primary Ovarian Insufficiency
;
Rage
;
Seoul
5.Ameliorative Effects of Nilotinib on CCl4 Induced Liver Fibrosis Via Attenuation of RAGE/HMGB1 Gene Expression and Oxidative Stress in Rat
Vahid KHANJARSIM ; Jamshid KARIMI ; Iraj KHODADADI ; Adel MOHAMMADALIPOUR ; Mohammad Taghi GOODARZI ; Ghasem SOLGI ; Mohammad HASHEMNIA
Chonnam Medical Journal 2017;53(2):118-126
Nilotinib as a tyrosine kinase inhibitor has been recently used to improve the liver fibrosis process, but the exact mechanisms still require further clarification. In this study, we investigated the anti-fibrotic effects of Nilotinib via RAGE/HMGB1axis and antioxidant mechanisms. This experimental study was performed in the Hamadan University of Medical Sciences, Iran, from May 2015 to December 2016. Liver fibrosis was induced in Wistar male rats by CCL₄. Rats were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-α and TGF-β mRNA expression were evaluated by quantitative RT-PCR. TNF-α protein levels were measured using the immunoassay method. Thiol groups, carbonyl groups, nitric oxide levels and glutathione peroxidase activity were measured by spectrophotometric methods.The results showed that Nilotinib decreased TNF-α, TGF-β, RAGE and HMGB1 mRNA expression (p<0.001) in the liver tissues of the fibrosis group. Nilotinib also decreased carbonyl groups and nitric oxide levels and increased thiol groups and glutathione peroxidase activity in the fibrosis groups. The histopathological changes were found to be attenuated by Nilotinib. In conclusion, Nilotinib can improve liver fibrosis and open new mechanisms of the anti-fibrotic properties of Nilotinib.
Animals
;
Fibrosis
;
Gene Expression
;
Glutathione Peroxidase
;
HMGB1 Protein
;
Humans
;
Immunoassay
;
Iran
;
Liver Cirrhosis
;
Liver
;
Male
;
Methods
;
Nitric Oxide
;
Oxidative Stress
;
Protein-Tyrosine Kinases
;
Rage
;
Rats
;
RNA, Messenger
6.A Case of Hypersomnolence with Subclinical Hypothyroidism Treated with Levothyroxine.
Minkyeong KIM ; Song Hwa CHAE ; Eun Hye OH ; Baik Kyun KIM ; Dae Jin KIM ; Jae Wook CHO
Journal of Sleep Medicine 2015;12(1):23-25
We present a patient who complained of excessive daytime sleepiness (EDS), which started three years ago. She had no other medical, neurological, and psychiatric disorders. Nocturnal polysomnography did not indicate any sleep disorders, which might cause daytime EDS, such as obstructive sleep apnea. The following multiple sleep latency test was not compatible for narcolepsy. Her laboratory findings were remarkable for subclinical hypothyroidism, although free T4 and T3 were within reference rage, she had elevated thyroid stimulating hormone. After four weeks of levothyroxine treatment, her EDS resolved. The hypersomnolence, as a presenting symptom of subclinical hypothyroidism, was optimally treated after thyroid hormone replacement.
Disorders of Excessive Somnolence*
;
Humans
;
Hypothyroidism*
;
Narcolepsy
;
Polysomnography
;
Rage
;
Sleep Apnea, Obstructive
;
Sleep Wake Disorders
;
Thyroid Gland
;
Thyrotropin
;
Thyroxine*
7.Would medical students enter an exclusion zone in an infected district with a high mortality rate? An analysis of book reports on 28 (secondary publication).
Kun HWANG ; Hyung Sun HONG ; Won Young HEO
Journal of Educational Evaluation for Health Professions 2014;11(1):15-
This study aimed to ascertain whether medical students would enter a closed area where there was a raging epidemic of an infectious disease with a high fatality rate, and includes reasons for the students entering or refusing to enter. Participants included 50 second-year medical students. They were assigned to read a novel entitled 28, written by Youjeong Jeong, and discuss it in groups. Using their book reports, their decisions of whether or not to enter Hwayang, the city from the novel, and the reasons for their decisions were analyzed; we furthermore investigated the factors affecting their decisions. Among the 50 respondents, 18 students (36%) answered that they would enter, and the remaining 32 students (64%) answered that they would not enter the zone. The reasons given for entering were responsibility (44%), sense of ethics (33%), social duty (17%), and sense of guilt (6%). The reasons the students provided for not entering were inefficiency (44%), worry regarding family (28%), needlessness of sacrifice (19%), and safety not ensured (9%). Students who had four or fewer family members were more likely to enter Hwayang than were students who had five or more family members (odds ratio, 1.85). Students who had completed over 100 hours of volunteer work were more likely to enter Hwayang than were students who had volunteered less than 100 hours (odds ratio, 2.04). Owing to their "responsibility" as a doctor, 36% of medical students answered that they would enter an exclusion zone in an infected district with a high fatality rate. However, 64% answered they would not enter because of "inefficiency." For the medical students it is still a question 'To enter or not to enter?'
Communicable Diseases
;
Surveys and Questionnaires
;
Ethics
;
Guilt
;
Humans
;
Mortality*
;
Odds Ratio
;
Rage
;
Students, Medical*
;
Volunteers
;
Writing
8.Up-Regulation of the Receptor for Advanced Glycation End Products in the Skin Biopsy Specimens of Patients with Severe Diabetic Neuropathy.
Su Yeon PARK ; Young A KIM ; Yoon Ho HONG ; Min Kyong MOON ; Bo Kyeong KOO ; Tae Wan KIM
Journal of Clinical Neurology 2014;10(4):334-341
BACKGROUND AND PURPOSE: The receptor for advanced glycation end products (RAGE) may contribute to the development of diabetic neuropathy. To assess its relevance in humans, this study examined the expression of RAGE in the skin biopsy samples of patients with diabetes mellitus, and investigated its correlation with intraepidermal nerve-fiber density (IENFD) and clinical measures of neuropathy severity. METHODS: Forty-four patients who either had type 2 diabetes or were prediabetes underwent clinical evaluation and a 3-mm skin punch biopsy. The clinical severity of their neuropathy was assessed using the Michigan Diabetic Neuropathy Score. IENFD was measured along with immunohistochemical staining for RAGE in 29 skin biopsy samples. The expression of RAGE was also quantified by real-time reverse-transcription PCR in the remaining 15 patients. RESULTS: RAGE was localized mostly in the dermal and subcutaneous vascular endothelia. The staining was more intense in patients with a lower IENFD (p=0.004). The quantity of RAGE mRNA was significantly higher in patients with severe neuropathy than in those with no or mild neuropathy (p=0.003). The up-regulation of RAGE was related to dyslipidemia and diabetic nephropathy. There was a trend toward decreased sural nerve action-potential amplitude and slowed peroneal motor-nerve conduction with increasing RAGE expression. CONCLUSIONS: The findings of this study demonstrate up-regulation of RAGE in skin biopsy samples from patients with diabetic neuropathy, supporting a pathogenic role of RAGE in the development of diabetic neuropathy.
Biopsy*
;
Diabetes Mellitus
;
Diabetic Nephropathies
;
Diabetic Neuropathies*
;
Dyslipidemias
;
Glycosylation End Products, Advanced*
;
Humans
;
Michigan
;
Polymerase Chain Reaction
;
Prediabetic State
;
Rage
;
RNA, Messenger
;
Skin*
;
Sural Nerve
;
Up-Regulation*
;
Advanced Glycosylation End Product-Specific Receptor
9.The characteristics of medical students' personality types and interpersonal needs.
Korean Journal of Medical Education 2013;25(4):309-316
PURPOSE: Medical students' personality types and interpersonal needs must be considered. The purpose of this study was to examine the characteristics of personality types and interpersonal needs. METHODS: A total of 171 students in Konyang University College of Medicine were examined using the Myers-Briggs Type Indicator (MBTI) and Fundamental Interpersonal Relations Orientation-Behavior (FIRO-B). The data were analyzed by frequency analysis, t-test, and one-sample proportion test. RESULTS: The proportion of the 4 pairs of MBTI dimensions were Extroversion (E)-Introversion (I) (53.2% vs. 46.8%), Sensing (S)-Intuition (N) (63.2% vs. 36.8%), Thinking (T)-Feeling (F) (59.7% vs. 40.4%), and Judging (J)-Perceiving (P) (56.1% vs. 43.9%). The predominant personality types were ISTJ (16.4%), ESTJ (14.0%), and ESFJ (10.5%). The level of interpersonal needs were medium rage that was inclusion (mean=8.1), control (mean=8.8), affection (mean=8.1), expressed behavior (mean=12.1), wanted behavior (mean=12.9), and overall interpersonal needs (mean=25.0). Of the basic social needs, males and females differed significantly with regard to control needs (p=0.028). CONCLUSION: Educational programs that take into account personality types and characteristics of interpersonal needs are crucial in providing effective medical education. Our results suggest that the characteristics of personality types and interpersonal needs should be considered in developing an interpersonal relations improvement program for medical students.
Education, Medical
;
Extraversion (Psychology)
;
Female
;
Humans
;
Interpersonal Relations
;
Male
;
Personality Inventory
;
Rage
;
Students, Medical
;
Thinking
10.Receptor for Advanced Glycation Endproducts (RAGE), Its Ligands, and Soluble RAGE: Potential Biomarkers for Diagnosis and Therapeutic Targets for Human Renal Diseases.
Genomics & Informatics 2013;11(4):224-229
Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that is able to bind several different ligands, including advanced glycation endproducts, high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-beta-protein, Mac-1, and phosphatidylserine. Its interaction is engaged in critical cellular processes, such as inflammation, proliferation, apoptosis, autophagy, and migration, and dysregulation of RAGE and its ligands leads to the development of numerous human diseases. In this review, we summarize the signaling pathways regulated by RAGE and its ligands identified up to date and demonstrate the effects of hyper-activation of RAGE signals on human diseases, focused mainly on renal disorders. Finally, we propose that RAGE and its ligands are the potential targets for the diagnosis, monitoring, and treatment of numerous renal diseases.
Apoptosis
;
Autophagy
;
Biomarkers*
;
Diagnosis*
;
Humans*
;
Inflammation
;
Kidney Diseases
;
Ligands*
;
Rage*
;
Signal Transduction
;
Advanced Glycosylation End Product-Specific Receptor

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