• Title/Summary/Keyword: role-efficacy

Search Result 1,014, Processing Time 0.029 seconds

DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs): Beyond the DNA Double-Strand Break Repair

  • Ye-Rim Lee;Gi-Sue Kang;Taerim Oh;Hye-Ju Jo;Hye-Joon Park;G-One Ahn
    • Molecules and Cells
    • /
    • v.46 no.4
    • /
    • pp.200-205
    • /
    • 2023
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family is a well-known player in repairing DNA double-strand break through non-homologous end joining pathway. This mechanism has allowed us to understand its critical role in T and B cell development through V(D)J recombination and class switch recombination, respectively. We have also learned that the defects in these mechanisms lead to the severely combined immunodeficiency (SCID). Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in an attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level.

The Impact of Fatigue on Hazard Recognition: An Objective Pilot Study

  • Ibrahim, Abdullahi;Okpala, Ifeanyi;Nnaji, Chukwuma;Namian, Mostafa;Koh, Amanda
    • International conference on construction engineering and project management
    • /
    • 2022.06a
    • /
    • pp.450-457
    • /
    • 2022
  • The construction industry is demanding, dynamic, and complex making it difficult for workers to recognize hazards. The nature of construction tasks exposes workers to several critical risk factors, such as a high rate of exertion and fatigue. Recent studies suggest that fatigue may impact hazard recognition in the construction industry. However, most studies rely on subjective measures when assessing the relationship between physical fatigue and hazard recognition, limiting such studies' efficacy. Thus, this study examined the relationship between physical fatigue and hazard recognition using a controlled experiment. Worker fatigue levels were captured using physiological data and a subjective exertion scale. The findings confirmed that physical exertion plays a significant role in hazard recognition skills (p < 0.05). This research contributes to theory and practice by providing a process for objectively assessing the influence of physical fatigue on worker safety and providing construction professionals with some critical insight needed to improve workplace safety.

  • PDF

Ultrasonic Targeting of NK Cell in Vessel Bifurcation for Immunotherapy: Simulation and Experimental Validation

  • Saqib Sharif;Hyeong-Woo Song;Daewon Jung;Hiep Xuan Cao;Jong-Oh Park;Byungjeon Kang;Eunpyo Choi
    • Journal of Sensor Science and Technology
    • /
    • v.32 no.6
    • /
    • pp.418-424
    • /
    • 2023
  • Natural killer (NK) cells play a crucial role in combating infections and tumors. However, their therapeutic application in solid tumors is hindered by challenges, such as limited lifespan, tumor penetration, and delivery precision. Our research introduces a novel ultrasonic actuation technique to navigate NK cells more effectively in the vascular system, particularly at vessel bifurcations where targeted delivery is most problematic. We use a hemispherical ultrasonic transducer array that generates phase-modulated traveling waves, focusing on an ultrasound beam to steer NK cells using blood-flow dynamics and a focused acoustic field. This method enables the precise obstruction of non-target vessels and efficiently directs NK cells toward the tumor site. The simulation results offer insights into the behavior of NK cells under various conditions of cell size, radiation pressure, and fluid velocity, which inform the optimization of their trajectories and increase targeting efficiency. The experimental results demonstrate the feasibility of this ultrasonic approach for enhancing NK cell targeting, suggesting a potential leap forward in solid tumor immunotherapy. This study represents a significant step in NK cell therapeutic strategies, offering a viable solution to the existing limitations and promising enhancement of the efficacy of cancer treatments.

Effects and Efficacy of Natural Product on Infectious Diseases of pseudomonas aeruginosa (천연물 유래 물질이 감염성 질환에 미치는 영향과 효능)

  • Ji-Won Park
    • Proceedings of the Plant Resources Society of Korea Conference
    • /
    • 2020.12a
    • /
    • pp.3-13
    • /
    • 2020
  • Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium causing serious infections. The P. aeruginosa T3SS is a syringe-like apparatus on the bacterial surface, with 4 effector toxins: ExoS, ExoT, ExoY, and ExoU. Here, we investigated the effect of ExoS and ExoT of the T3SS of P. aeruginosa K strain (PAK). The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. PAK clinical strains induce proinflammatory cytokine production through the T3SS, and this involves NF-κB activation in pneumonia mouse models. We tried to confirm the role of the NF-κB transcription factor in ExoS- and ExoT-induced pneumonia mouse models. pro-inflammatory cytokines induction in response to ExoS and ExoT infection relied on NF-κB activation. Our findings highlight the roles of natural poduct in inhibiting proinflammatory cytokine expression during ExoS and ExoT exposure in PAK infections, paving the way for a novel therapeutic approach for the treatment of pulmonary infections.

  • PDF

A Systems Engineering Approach to Ex-Vessel Cooling Strategy for APR1400 under Extended Station Blackout Conditions

  • Saja Rababah;Aya Diab
    • Journal of the Korean Society of Systems Engineering
    • /
    • v.19 no.2
    • /
    • pp.32-45
    • /
    • 2023
  • Implementing Severe Accident Management (SAM) strategies is crucial for enhancing a nuclear power plant's resilience and safety against severe accidents conditions represented in the analysis of Station Blackout (SBO) event. Among these critical approaches, the In-Vessel Retention (IVR) through External Reactor Vessel Cooling (IVR-ERVC) strategy plays a key role in preventing vessel failure. This work is designed to evaluate the efficacy of the IVR strategy for a high-power density reactor APR1400. The APR1400's plant is represented and simulated under steady-state and transient conditions for a station blackout (SBO) accident scenario using the computer code, ASYST. The APR1400's thermal-hydraulic response is analyzed to assess its performance as it progresses toward a severe accident scenario during an extended SBO. The effectiveness of emergency operating procedures (EOPs) and severe accident management guidelines (SAMGs) are systematically examined to assess their ability to mitigate the accident. A group of associated key phenomena selected based on Phenomenon Identification and Ranking Tables (PIRT) and uncertain parameters are identified accordingly and then propagated within DAKOTA Uncertainty Quantification (UQ) framework until a statistically representative sample is obtained and hence determine the uncertainty bands of key system parameters. The Systems Engineering methodology is applied to direct the progression of work, ensuring systematic and efficient execution.

BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway

  • Seobin Kim;Eun-Woo Lee;Doo-Byoung Oh;Jinho Seo
    • BMB Reports
    • /
    • v.57 no.5
    • /
    • pp.250-255
    • /
    • 2024
  • Due to their stem-like characteristics and immunosuppressive properties, Mesenchymal stem cells (MSCs) offer remarkable potential in regenerative medicine. Much effort has been devoted to enhancing the efficacy of MSC therapy by enhancing MSC migration. In this study, we identified deubiquitinase BRCA1-associated protein 1 (BAP1) as an inhibitor of MSC migration. Using deubiquitinase siRNA library screening based on an in vitro wound healing assay, we found that silencing BAP1 significantly augmented MSC migration. Conversely, BAP1 overexpression reduced the migration and invasion capabilities of MSCs. BAP1 depletion in MSCs upregulates ERK phosphorylation, thereby increasing the expression of the migration factor, osteopontin. Further examination revealed that BAP1 interacts with phosphorylated ERK1/2, deubiquitinating their ubiquitins, and thus attenuating the ERK signaling pathway. Overall, our study highlights the critical role of BAP1 in regulating MSC migration through its deubiquitinase activity, and suggests a novel approach to improve the therapeutic potential of MSCs in regenerative medicine.

The Importance of Strengthening the Role of the Institutional Review Board and the Human Research Protections Program following the Revision of the Act on the Safety and Support of Advanced Regenerative Medicine and Advanced Biopharmaceuticals ('첨단재생의료 및 첨단바이오의약품 안전 및 지원에 관한 법률' 개정에 따른 '기관생명윤리위원회(Institutional Review Board)' 역할 및 '임상시험 및 대상자보호프로그램(Human Research Protections Program)' 강화의 중요성)

  • Byung Soo Kim
    • The Journal of KAIRB
    • /
    • v.6 no.1
    • /
    • pp.1-4
    • /
    • 2024
  • The strengthening of Institutional Review Board (IRB) and Human Research Protection Program (HRPP) for clinical research on advanced regenerative medicine reflecting the 3 Principles of the Belmont Report (Respect, Beneficence, Justice) is very important. The research institution IRB should naturally be in charge of managing the clinical research process. And it is crucial to reinforce HRPP for the protection of research subjects in institutions conducting advanced regeneration clinical research. So, it is needed to establish a Protection System for Advanced Regenerative Medical Research Subjects composed of clinical research management communication system for advanced regenerative medicine between KAIRB (Korean Association of IRB) of research institutes and National Management Agency for Advanced Regenerative Medical Research. In advanced regenerative medicine clinical research to verify safety and efficacy of the investigational drugs to the subjects with rare and incurable diseases rather than to treat the patients, it is hoped that a management system that guarantees the scientific characteristics of research and the rights of research subjects would be well organized and operated.

  • PDF

Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells

  • Ji-Sun Lee;Ho-Young Lee
    • Journal of Ginseng Research
    • /
    • v.48 no.3
    • /
    • pp.266-275
    • /
    • 2024
  • Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

Application of Negative Pressure Wound Therapy in the Foot and Ankle Field (족부족관절 영역에서 음압창상처치의 적용)

  • Jungtae Ahn;Dae-Cheol Nam
    • Journal of Korean Foot and Ankle Society
    • /
    • v.28 no.2
    • /
    • pp.41-47
    • /
    • 2024
  • Negative pressure wound therapy (NPWT) has emerged as a valuable tool for managing complex wounds within the foot and ankle field. This review article discusses the expanding applications of NPWT in this specialized field. Specifically, it discusses the efficacy of NPWT for various wound types, including diabetic foot wounds, traumatic wounds, surgical wounds, and wounds involving exposed bone or soft tissue defects. NPWT demonstrates versatile utility for foot and ankle wound management by promoting healing, potentially reducing the need for secondary surgery, improving diabetic and neuropathic ulcer healing times and outcomes, and optimizing the healing of high-risk incisions. In addition, this review explores the underlying mechanisms through which NPWT might enhance wound healing. By synthesizing current evidence, this review provides a comprehensive overview of the role of NPWT in foot and ankle surgery and offers valuable insights to clinicians navigating the complexities of wound care in this challenging anatomical area.

Modulation of Pro-inflammatory and Anti-inflammatory Cytokines in the Fat by an Aloe Gel-based Formula, QDMC, Is Correlated with Altered Gut Microbiota

  • Jinho An;Heetae Lee;Sungwon Lee;Youngcheon Song;Jiyeon Kim;Il Ho Park;Hyunseok Kong;Kyungjae Kim
    • IMMUNE NETWORK
    • /
    • v.21 no.2
    • /
    • pp.15.1-15.10
    • /
    • 2021
  • Abnormal inflammatory responses are closely associated with intestinal microbial dysbiosis. Oral administration of Qmatrix-diabetes-mellitus complex (QDMC), an Aloe gel-based formula, has been reported to improve inflammation in type 2 diabetic mice; however, the role of the gut microbiota in ameliorating efficacy of QDMC remains unclear. We investigated the effect of QDMC on the gut microbiota in a type 2 diabetic aged mouse model that was administered a high-fat diet. Proinflammatory (TNF-α and IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine levels in the fat were normalized via oral administration of QDMC, and relative abundances of Bacteroides, Butyricimonas, Ruminococcus, and Mucispirillum were simultaneously significantly increased. The abundance of these bacteria was correlated to the expression levels of cytokines. Our findings suggest that the immunomodulatory activity of QDMC is partly mediated by the altered gut microbiota composition.