• Title/Summary/Keyword: therapeutic relationship

Search Result 433, Processing Time 0.025 seconds

MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling

  • Zhang, Shiqing;Sun, Peng;Xiao, Xinru;Hu, Yujie;Qian, Yan;Zhang, Qian
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.26 no.4
    • /
    • pp.239-253
    • /
    • 2022
  • Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

Tat-Thioredoxin-like protein 1 attenuates ischemic brain injury by regulation of MAPKs and apoptosis signaling

  • Hyun Ju Cha;Won Sik Eum;Gi Soo Youn;Jung Hwan Park;Hyeon Ji Yeo;Eun Ji Yeo;Hyun Jung Kwon;Lee Re Lee;Na Yeon Kim;Su Yeon Kwon;Yong-Jun Cho;Sung-Woo Cho;Oh-Shin Kwon;Eun Jeong Sohn;Dae Won Kim;Duk-Soo Kim;Yu Ran Lee;Min Jea Shin;Soo Young Choi
    • BMB Reports
    • /
    • v.56 no.4
    • /
    • pp.234-239
    • /
    • 2023
  • Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H2O2-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury.

The Unique Relationship between Neuro-Critical Care and Critical Illness-Related Corticosteroid Insufficiency : Implications for Neurosurgeons in Neuro-Critical Care

  • Yoon Hee Choo;Moinay Kim;Jae Hyun Kim;Hanwool Jeon;Hee-Won Jung;Eun Jin Ha;Jiwoong Oh;Youngbo Shim;Seung Bin Kim;Han-Gil Jung;So Hee Park;Jung Ook Kim;Junhyung Kim;Hyeseon Kim;Seungjoo Lee
    • Journal of Korean Neurosurgical Society
    • /
    • v.66 no.6
    • /
    • pp.618-631
    • /
    • 2023
  • The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.

Monte Carlo Simulation of Absorbed Energy by Gold Nano-Particles for Proton (양성자에 대한 금 나노입자의 밀도에 따른 흡수 에너지의 몬테카를로 전산모사)

  • Kwon Su Chon
    • Journal of the Korean Society of Radiology
    • /
    • v.18 no.1
    • /
    • pp.1-9
    • /
    • 2024
  • Proton therapy is known for its superior treatment method due to Bragg peak. To enhance the therapeutic effects of protons, research has been conducted on distributing gold nanoparticles within tumors to increase the absorbed dose. While previous studies focused on handling gold nanoparticles at micrometer and nonometer scale, this study proposes a method to computationally estimate the effect of gold nanoparticles at the millimeter scale. The Geant4 toolkit was applied to computational modeling. Assuming a uniform distribution of water, similar to the human body, and gold nanoparticles, the concentration of gold nanoparticles was adjusted using density ratios. When the density ratio was 5%, the gain in absorbed energy due to gold nanoparticles was nearly twice that of the pure water phantom at the Bragg peak. As the density ratio increased, the gain in absorbed energy linearly increased. When gold nanoparticles were distributed in only one voxel at the Bragg peak, the energy of the protons affected only the neighboring voxels. However, in cases where gold nanoparticles were distributed over a wide area, the volume showing 95% of the maximum absorbed energy (9.46 keV) for the pure water phantom (9.95 keV) exhibited an improvement in absorbed energy over a region 16 times larger, and this region increased as the density ratio increased. Further research is needed to quantify the relationship between the density ratio of gold nanoparticles and the relative biological effect (RBE) in the millimeter scale.

Importance of an Integrated Assessment of Functional Disability and Work Ability in Workers Affected by Low Back Pain

  • Fabrizio Russo;Cristina Di Tecco;Simone Russo;Giorgia Petrucci;Gianluca Vadala;Vincenzo Denaro;Sergio Iavicoli
    • Safety and Health at Work
    • /
    • v.15 no.1
    • /
    • pp.66-72
    • /
    • 2024
  • Background: This study examines the relationship between functional disability and work ability in workers affected by low back pain (LBP) through an analysis of correlations between the Oswestry Disability Index (ODI) and Work Ability Index (WAI). The role of personal and work factors on functional disability/work ability levels has also been studied. LBP is the most common musculoskeletal problem and a major disabling health problem worldwide. Its etiology is multifactorial. Multidisciplinary approaches may help reduce the burden of pain and disability and improve job continuity and reintegration at work. Methods: A cohort of 264 patients affected by LBP from an Italian outpatient clinic were included in a clinical diagnostic/therapeutic trial aiming at rehabilitation and return to work through an integrated investigation protocol. Data were collected during the first medical examination using anamnestic and clinical tools. The final sample is composed of 252 patients, 57.1% man, 44.0 % blue collars, 46.4% with the high school degree, 45.6% married. Results: WAI and ODI reported a negative and fair correlation (r = -0.454; p = .000). Workers with acute LBP symptoms have a higher probability of severe disability than those with chronic LBP symptoms. White collars without depressive symptoms reported higher work ability - even in chronic disability conditions-than those with depressive symptoms. Conclusion: The study found that ODI and WAI have a convergent validity and this suggests that the two tools measure capture distinctive aspects of disability related to personal, environmental, and occupational characteristics. The most important and modifiable prognostic factors found for ODI and WAI were depressive symptoms, workday absence, and intensity of back pain. The study also found a mild association between age and ODI. The study's findings highlight the importance of using a multidisciplinary approach to manage and prevent disability due to LBP.

Effects of a supportive workplace environment on the success rate for smoking cessation camp

  • Woojin Kim;A Ram Kim;Minsu Ock;Young-Jee Jeon;Heun Lee;Daehwan Kim;Minjun Kim;Cheolin Yoo
    • Annals of Occupational and Environmental Medicine
    • /
    • v.35
    • /
    • pp.48.1-48.13
    • /
    • 2023
  • Background: This study was conducted to identify the success rate for smoking cessation over time after participation in a therapeutic smoking cessation camp, and to identify how participant characteristics, including a supportive workplace environment for smoking cessation (SWESC), affect the success rate for smoking cessation. Methods: In all, 296 participants at smoking cessation camps in Ulsan between 2015 and 2020 were investigated. The success rates of smoking cessation after weeks 4, 6, 12, and 24 at camp were investigated. The participants were grouped as workers with an SWESC, and workers without an SWESC, and variables (age, education, household income, marital status, drinking, exercise, body mass index, morbidity, job, number of counseling sessions, cigarettes smoked per day and smoking initiation age) were investigated. Multiple logistic regression analysis was conducted at each time point. In addition, Cox regression analysis was performed to evaluate the variables affecting the success rate for smoking cessation over time. Results: The smoking cessation success rate of workers with an SWESC at week 24 (90.7%) was higher than that for workers without an SWESC (60.5%). Multiple logistic regression was performed to determine the relationship between each variable and the success rates for smoking cessation at week 6, 12, and 24. SWESC was confirmed as significant (p < 0.05) variables for increased success rate for smoking cessation at all 3 time points. After adjusting for all variables, the Cox proportional hazards survival analysis showed a hazard ratio of 6.17 for SWESC (p < 0.001,; 95% confidence interval: 3.08-12.38). Conclusions: At a professional treatment smoking cessation camp, participants with an SWESC showed a significantly higher success rate for smoking cessation. Supportive workplace environment for workers' health is expected to be an important factor for smoking cessation projects as well as other health promotion projects at workplace.

Identifying Personal Values Influencing the Lifestyle of Older Adults: Insights From Relative Importance Analysis Using Machine Learning (중고령 노인의 개인적 가치에 따른 라이프스타일 분류: 머신러닝을 활용한 상대적 중요도 분석 )

  • Lim, Seungju;Park, Ji-Hyuk
    • Therapeutic Science for Rehabilitation
    • /
    • v.13 no.2
    • /
    • pp.69-84
    • /
    • 2024
  • Objective : This study aimed to categorize the lifestyles of older adults into two types - healthy and unhealthy, and use machine learning to identify the personal values that influence these lifestyles. Methods : This cross-sectional study targeting middle-aged and older adults (55 years and above) living in local communities in South Korea. Data were collected from 300 participants through online surveys. Lifestyle types were dichotomized by the Yonsei Lifestyle Profile (YLP)-Active, Balanced, Connected, and Diverse (ABCD) responses using latent profile analysis. Personal value information was collected using YLP-Values (YLP-V) and analyzed using machine learning to identify the relative importance of personal values on lifestyle types. Results : The lifestyle of older adults was categorized into healthy (48.87%) and unhealthy (51.13%). These two types showed the most significant difference in social relationship characteristics. Among the machine learning models used in this study, the support vector machine showed the highest classification performance, achieving 96% accuracy and 95% area under the receiver operating characteristic (ROC) curve. The model indicated that individuals who prioritized a healthy diet, sought health information, and engaged in hobbies or cultural activities were more likely to have a healthy lifestyle. Conclusion : This study suggests the need to encourage the expansion of social networks among older adults. Furthermore, it highlights the necessity to comprehensively intervene in individuals' perceptions and values that primarily influence lifestyle adherence.

A Study for The Prognostic Indicators of Korean Alcoholics in Psychological, Social and Biological Aspects (한국인 알코올중독 환자의 예후인자에 관한 연구 : 심리적, 사회적, 생물학적 요인을 중심으로)

  • Sung, Sang-Kyung;Chang, Hwan-Il
    • Korean Journal of Biological Psychiatry
    • /
    • v.2 no.2
    • /
    • pp.218-236
    • /
    • 1995
  • The author studied prognostic indicators of sixty Korean male alcoholics in psychological, social and biological aspects who were divided into abstinent and drinking groups. Thirty patients were assigned to each group. They were controlled in age and sex. Both groups were compared in terms of the demographic characteristics, past drinking history, treatment history, famaily history, ego strength and personality factors differences and distribution of dopamine $D_2$ receptor gene Al allele. Also the author studied relation of clinical course, alcoholic family history and dopamine $D_2$ receptor gene Al allele in both groups. The results were as follows; 1) The abstinent group had higher rate of married state, higher economic status, longer education years and maintained more stable job than the drinking group. But made no differences in occupation and religion. 2) The abstinent group showed higher rate of living with family members than the drinking group, and wives and fellows of the alcoholics anonymous were important factors for maintenance of abstinence. Family loading and parent's characters were not different. 3) The abstinent group had longer maximal length of abstinence but mean amount of alcohol consumption per day were larger than the drinking group. But there were no differences in duration of past drinking, drinking pattern, main drinking time, first drinking age and preference of the kind of alcoholic beverage in the past drinking history. 4) The abstinent group showed stronger treatment motivation, absolute abstinence in treatment goal, more voluntary adimission and maintained longer therapeutic relationship otter discharge than the drinking group. But both groups showed negative attitude toward antabuse therapy. 5) The abstinent group had higher mean score in ego strength scale than the drinking group. 6) In the personality factor questionnaire, the abstinent group showed strong laugh poise and the trait of praxernia, conservatism personality but the drinking group showed tough poise, the trait of weak ego strength(unstableness) and tough mindedness personality. 7) In comparision of dopamine $D_2$ receptor gene A1 allele, the prevalence of A1 allele was seventy percent and the frequency was 0.38 in the abstinent group. The prevalence of A1 allele was sixty percent and the frequency was 0.42 in the drinking group. Both groups were not significantly different in A1 allele prevalence and frequency. 8) In comparision of dopamine $D_2$ receptor gene A1 allele according to alcoholic family history, the prevalence of A1 allele was seventy percent and the frequency was 0.43 in the family history positive group. The prevalence of A1 allele was sixty-one percent and the frequency was 0.38 in the family history negative group. Both groups were not significantly different in A1 allele prevalence and frequency. In comparision of past drinking history according to alcoholic family history, the family history positive group showed earlier first drinking and problem drinking, but the family history negative group hod longer duration of past drinking. The mean amount of alcohol consumption per day, the longest duration of abstinence and Alcoholism Screening Test of Seoul Natoinal Mental Hospital(NAST) results were not significant. In conclusion, the results suggest that successful prognostic indicators of Korean alcoholics are married state, higher economic status, longer education years, stable job, living with family members, longer abstinence during past drinking history, strong treatment motivation, absolute abstinence in treatment goal, voluntary adimission, maintained therapeufic relationship, strong ego strength and the trait of praxernia, conservatism personality. But occupation, religion, alcoholic family history, parent's characters, duration of past drinking, drinking pattern, main drinking time, first drinking age, preference of the kind of alcoholic beverage, attitude to antabuse therapy and distribution of dopamine $D_2$ receptor A1 allele were not significantly related to the prognostic indicators of Korean alcoholics.

  • PDF

The Relationship between Intracellular Protein Kinase C Concentration and Invasiveness in U-87 Malignant Glioma Cells (교모세포종 세포주 U-87에서 세포내 PKC 농도와 종양침습성과의 상관 관계)

  • Ji, Cheol;Cho, Kyung-Keun;Lee, Kyung Jin;Park, Sung Chan;Cho, Jung Ki;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
    • /
    • v.30 no.3
    • /
    • pp.263-271
    • /
    • 2001
  • Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

  • PDF

Early and Midterm Results of Arterial Switch Operation for Double-Outlet Right Ventricle with Subpulmonary VSD (폐동맥하 심실증격결손을 동반한 양대혈관 우심실기시중에서 동맥전환술의 중단기 결과)

  • 양승인;이형두;김시호;조광조;우종수;이영석;성시찬
    • Journal of Chest Surgery
    • /
    • v.37 no.4
    • /
    • pp.313-321
    • /
    • 2004
  • Excellent clinical results of the arterial switch operation and the limited availablity of the intraventricular rerouting has recently made an arterial switch operation to become the therapeutic method of choice for the repair of double-outlet right ventricle (DORV) with subpulmonary ventricular septal defect (VSD). The early and midterm outcomes of arterial switch operation for this anomaly were evaluated. Material and Method: Between August 1994 and July 2002, 13 patients underwent an arterial switch operation for the correction of double-outlet right ventricle with subpulmonary VSD at Dong-A university hospital.. The 50% rule was used to define DORV. Median age and mean body weight were 27 days (range, 3-120 days) and 3.8$\pm$0.7kg (range, 2.92-5.3kg) respectively. Aortic arch anomalies were associated in 6 cases (46.2%), which were all repaired through one-stage operation. The relationship of the great arteries were side-by-side in 8 cases (61.5%) and anteroposterior in 5 (38.5%). Coronary artery patterns were 1 LCx-2R in 6 cases, retropulmonary left coronary artery (LCA) in 6, and intramural LCA in 1 respectively. The enlargement of VSD was required in 1 patient and the patch enlargement of right ventricular outflow tract was performed in another one patient. The Lecompte maneuver was used in all but 3 patients with a side by side relationship of the great arteries. Result: Overall postoperative hospital mortality was 23.1 % (3/13). All operative deaths were occurred in the patients with aortic arch anomalies. There was one late death related to the postoperative complication of the central nerve system during the mean follow-up of 41.3$\pm$30.7 months. Pulmonary valvar stenosis (>30mmHg of pressure gradient) developed in 1 patient (10%) and left pulmonary artery stenosis in 2 (20%), among them, one required reoperation 52 months after repair. There was an asymptomatic patient with moderate aortic regurgitation. 5-year survival rate including operative deaths was 68.3%. Conclusion: Although the operative mortality is high in the patients with aortic arch anomaly, the arterial switch operation for DORV with supbpulmonary VSD can be performed with low operative mortality and low reoperation rate in the patients Without arch anomaly. The arterial switch operation can be considered a good option for this complex anomaly.