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RSF1 orchestrates p53 transcriptional activity by coordinating p300 acetyltransferase and FACT complex
Get PDFThe transcriptional regulation of p53-dependent genes in response to DNA damage is critical for effective DNA repair and cell survival. We previously established that RSF1 (remodeling and spacing factor 1) is necessary for p53-dependent gene transcription in response to DNA strand breaks. Here, we further elucidate that the role of RSF1 in p53 regulation by demonstrating that its depletion results in a reduction in the acetylated-Lys(K)382 level of p53, which governs its transcriptional activity. RSF1 was co-precipitated with p300 acetyltransferase upon etoposide treatment. Chromatin immunoprecipitation assays on the upstream region of CDKN1A gene revealed reduced p300 and TBP accumulation, which were accompanied with low H3H27ac and H3K4me1 levels in RSF1 knockout cells. Moreover, RSF1 depletion led to a reduced accumulation of SSRP1 and SPT16, subunits of FACT complex at the promoter of CDKN1A gene. These findings suggest that RSF1 promotes p53-dependent p21 gene transcription by facilitating the accumulation of p300 acetyltransferase at the enhancer and FACT at the promoter region of CDKN1A gene, respectively
A Review of Advanced Hydrogel Applications for Tissue Engineering and Drug Delivery Systems as Biomaterials
Get PDFHydrogels are known for their high water retention capacity and biocompatibility and have become essential materials in tissue engineering and drug delivery systems. This review explores recent advancements in hydrogel technology, focusing on innovative types such as self-healing, tough, smart, and hybrid hydrogels, each engineered to overcome the limitations of conventional hydrogels. Self-healing hydrogels can autonomously repair structural damage, making them well-suited for applications in dynamic biomedical environments. Tough hydrogels are designed with enhanced mechanical properties, enabling their use in load-bearing applications such as cartilage regeneration. Smart hydrogels respond to external stimuli, including changes in pH, temperature, and electromagnetic fields, making them ideal for controlled drug release tailored to specific medical needs. Hybrid hydrogels, made from both natural and synthetic polymers, combine bioactivity and mechanical resilience, which is particularly valuable in engineering complex tissues. Despite these innovations, challenges such as optimizing biocompatibility, adjusting degradation rates, and scaling up production remain. This review provides an in-depth analysis of these emerging hydrogel technologies, highlighting their transformative potential in both tissue engineering and drug delivery while outlining future directions for their development in biomedical applications
Risk Factors of Reoperation in Patients with Intestinal Behçet’s Disease Treated by Initial Bowel Resection
Get PDFBackground/Objectives: Intestinal Behçet’s disease (iBD) often requires surgical intervention, with a significant proportion of patients needing reoperation. This study aimed to investigate the risk factors associated with reoperation in patients with iBD who underwent initial bowel resection and to evaluate the perioperative and long-term outcomes in these patients. Methods: This was a retrospective case-control study analyzing patients who underwent their initial bowel resection due to iBD between 2005–2021 at a tertiary referral hospital. Reoperation was considered a surgery due to postoperative complications (within 30 days of the initial surgery) or disease progression. Results: A total of 81 patients were included. The median follow-up duration was 107.1 months, during which 26 patients (32%) underwent reoperation. Multivariable analysis showed that the presence of hematological disorders (hazards ratio [HR], 9.13; 95% confidence interval [CI], 3.79–22.02, p < 0.001), higher c-reactive protein (CRP) levels before the initial surgery (HR, 1.01; 95% CI, 1.01–1.02, p < 0.001), and a shorter specimen resection length (HR, 0.96; 95% CI, 0.93–0.99, p = 0.011) were risk factors for reoperation. Patients who underwent reoperation had higher rates of postoperative complications (69.2% vs. 43.6%, p = 0.031), required longer antibiotic use (12 vs. 7 days, p = 0.012), and had extended hospital stays (18 vs. 9 days, p = 0.011). They also had worse 5-year survival rates than those who did not undergo reoperation (83.5% vs. 98.4%, p = 0.012). Conclusions: Concurrent hematological disorders, high preoperative CRP levels, and short specimen resection were associated with an increased risk of reoperation in patients with iBD who underwent their initial bowel resections. They also had worse perioperative and long-term outcomes
Impact of the COVID-19 pandemic on telogen effluvium: a nationwide multicentre interrupted time series study
No full textBackground There is ongoing debate regarding the association between telogen effluvium (TE) and COVID-19, as well as COVID-19 vaccines. Objectives To investigate the impact of the COVID-19 pandemic and vaccination on the development of TE among patients visiting dermatology clinics in South Korea. Methods Between 2017 and 2022, data regarding patients with TE and other types of hair loss were collected from 22 hospitals in South Korea. An interrupted time series analysis was conducted, dividing the time into periods before and after the COVID-19 pandemic, as well as before and after the COVID-19 vaccination. Results There was a significant slope change in the percentage of cases of TE during the postpandemic period (slope change 0.011, 95% confidence interval 0.005-0.017, P < 0.001), but no significant changes were observed after vaccination. The percentage of patients with other types of hair loss was not associated with COVID-19 or vaccination. The retrospective nature of the study may have limited the ability to establish causation. Conclusions This multicentre study provides insights into the epidemiology of TE, showing a significant increase in cases of TE following the COVID-19 pandemic. However, there was no association between the occurrence of TE and COVID-19 vaccines
Basilar artery occlusion management: An international survey of middle versus high-income countries
No full textBackground and Purpose: Two early basilar artery occlusion (BAO) randomized controlled trials (RCTs) did not establish the superiority of endovascular thrombectomy (EVT) over medical management. Yet many providers continued to recommend EVT. The goal of the present article is to compare physicians’ diagnostic and management strategies of BAO among middle-income and high-income countries (MICs and HICs, respectively). Methods: We conducted an international survey from January to March 2022 regarding management strategies in acute BAO, to examine clinical and imaging parameters influencing clinician management of patients with BAO. We compared responses between physicians from HIC and MIC. Results: Among the 1245 respondents from 73 countries, 799 (64.2%) were from HIC, with the remaining 393 (31.6%) from MIC. Most respondents perceived that EVT was superior to medical management for acute BAO, but more so in respondents from HIC (98.0% vs. 94.2%, p < 0.01). MIC respondents were more likely to believe further RCTs were warranted (91.6% vs. 74.0%, p < 0.01) and were more likely to find it acceptable to enroll any patient who met a trial’s criteria in the standard medical treatment arm (58.8% vs. 38.5%, p < 0.01). Conclusions: In an area where clinical equipoise was called into question despite the lack of RCT evidence, we found that respondents from MIC were more likely to express willingness to enroll patients with BAO in an RCT than their HIC counterparts
Structural brain changes and associated self-perceived cognitive deficits in chemotherapy-exposed patients with breast cancer: a longitudinal T1 and DTI study
Get PDFPrevious studies have prevalently reported self-perceived cognitive impairment in patients with breast cancer after chemotherapy. However, most brain structure studies in patients have revealed heterogeneous results, especially demonstrating a structural decrease immediately after chemotherapy and increases after 1 year of treatment. Therefore, precisely investigating the brain structure is important within a certain period after chemotherapy. We combined T1-weighted anatomical magnetic resonance imaging and diffusion tensor imaging (DTI) data to investigate longitudinal changes in the structural brain in patients with breast cancer before and after chemotherapy, especially within 6 months to 1 year after chemotherapy, using voxel-based morphometry (VBM) and tract-based spatial statistics approaches. T1 VBM analyses revealed an increased gray matter volume in several frontal areas, insula, and supramarginal gyrus after chemotherapy compared with that before chemotherapy. Additionally, increased white matter volume (WMV) was observed in the uncinate fasciculus (UF) and corpus callosum (CC), as well as WMV reduction in the cerebellum and occipital fusiform gyrus after chemotherapy. DTI analyses revealed increased axial diffusivity in widespread areas. Moreover, correlation analyses demonstrated a negative association between changes in WMV in the UF and CC and changes in scores on the Functional Assessment of Cancer Therapy-Cognitive Function scale. These results from combined T1 and DTI data provide insight into structural brain changes over time and their associated subjective cognitive impairment in chemotherapy-exposed patients with breast cancer
Association between gastroesophageal reflux disease and tinnitus in a nationwide population-based cohort study
Get PDFGastroesophageal Reflux Disease (GERD) is characterized by the regurgitation of stomach contents. Recent research indicates that acid reflux may disrupt the homeostasis of the middle and inner ear through the Eustachian tube. Given this context, we hypothesized that an association between GERD and tinnitus may exist due to the imbalance of the middle and inner ear caused by acid reflux. To explore this connection, we conducted a retrospective cohort study involving 669,159 patients registered in the National Health Insurance Service-National Sample Cohort (2012–2019) in South Korea. Our data showed that GERD and tinnitus are highly associated. Nevertheless, the use of proton pump inhibitor medication in GERD patients did not show a significant decrease in the onset of tinnitus
Screen time among preschoolers: exploring individual, familial, and environmental factors
Get PDFScreen-based activity refers to the use of screened devices, which are changing from stationary devices such as tele-visions and desktop computers to newer portable devices such as smartphones and electronic tablets. The exposure of younger children to all types of screened devices has increased. This review aimed to provide an overview of previous studies and identify the correlations associated with screen-based activities in preschoolers. We conducted a systematic literature review of databases including PubMed, Embase, and PsycInfo targeting quantitative studies published between 2010 and 2019. We then analyzed the associations between screen time and various individual, familial, and environmental factors in healthy children aged 0–6 years. We specifically included studies that provided a subgroup analysis for this age category to systematically identify the factors influencing screen time patterns among preschoolers. The search yielded 36 articles that met the inclusion criteria. We investigated age, sex, and social, family, and personal factors as well as media parenting. The results suggested that media parenting for screen-based activities was an important protective factor. Limited research has been conducted on preschoolers' screen-based activities with both stationary and portable screened devices. Most factors have been studied using stationary devices and are too infrequent for solid conclusions to be reached. Parental screen time and the setting of appropriate media limits were crucial protective factors against exces-sive media exposure. However, information about family and personal factors remain scarce, and further research is needed
Analysis of various targeted therapies in head and neck cancer
No full textDoctorPART I. Epidermal growth factor receptor targeting immunotoxin shows potent anti-tumor activity in head and neck cancer 1
Ⅰ. Introduction 1
Ⅱ. Materials and Methods 6
A. Cell culture 6
B. Detection of EGFR expression by flow cytometry 6
C. Western blot analyses 7
D. Immunocytochemistry and Confocal Fluorescence Microscopy 7
E. Cell viability assay 7
F. Annexin-V and propidium iodide staining assay 8
G. Cell migration assay 8
H. Cell invasion assay 8
I. In vivo study with mouse xenograft tumor models 9
J. Immunohistochemical staining of tumor tissues 10
K. RNA isolation and quantitative real time-PCR 11
L. Statistical analysis 11
Ⅲ. Results 12
A. CTX-LR-LO10 binds to EGFR-positive HNC and inhibits EGFR signal transduction 12
B. CTX-LR-LO10 reduces the viability of HNC cells at very low doses 15
C. HNC cells exhibit different sensitivities to CTX treatment 17
D. CTX-LR-LO10 exhibits low IC50 values in HNC cells 18
E. CTX-LR-LO10 effectively induces apoptosis in HNC cells 20
F. CTX-LO-LP10 inhibits HNC migration and invasion 22
G. CTX-LR-LO10 exhibits strong tumor suppression in HNC xenograft models, independent of CTX sensitivity 24
H. CTX-LR-LO10 effectively increases apoptosis in HNC xenograft models 31
I. CTX-LR-LO10 alters gene expression in HNC cells 34
Ⅳ. Discussion 37
PART II. Immune checkpoint inhibitor monotherapy is sufficient to promote microenvironmental normalization in head and neck cancer 42
I. Introduction 42
II. Materials and Methods 44
A. Animals 44
B. HNSCC syngeneic model and treatment regimen 44
C. Statistical analyses 45
III. Results 46
A. Establishment of a syngeneic tumor model using murine HNSCC cells generated by a carcinogen-induced method 46
B. AOC cells exhibit intrinsic cellular properties of human HNSCC while also displaying distinct molecular characteristics among the different cells 48
C. Immunotherapy reduces tumor growth, combined with decreased blood vessel density and increased T-cell infiltration 51
D. Anti-PD-L1 immunotherapy normalizes the TME in HNSCC via the type I IFN pathway 55
E. Comparison of TME changes induced by Cisplatin, anti-VEGFR2 antibody, and anti-PD-L1 antibody therapies 58
IV. Discussion 62
References 64
국문 초록 7
초등 저학년 부모대상 자녀성교육 수행증진 프로그램 개발 및 효과
No full textDoctorI 서론 1
A 연구의 필요성 1
B 연구의 목적 5
C 연구 가설 6
D 용어 정의 7
Ⅱ 문헌고찰 10
A 자녀성교육을 위한 부모교육 프로그램 10
B 자녀성교육을 위한 부모교육 프로그램의 효과 16
C 보호이론과 자녀성교육 20
Ⅲ 이론적 기틀 25
Ⅳ 연구 방법 29
A 자녀성교육 수행증진 프로그램 개발 29
B 자녀성교육 수행증진 프로그램의 적용 및 효과검증 41
Ⅴ 연구 결과 54
A 실험군과 대조군의 동질성 검증 54
B 연구의 가설 검증 60
Ⅵ 논의 80
A 자녀성교육 수행증진 프로그램 개발 80
B 자녀성교육 수행증진 프로그램의 적용 및 효과검증 84
C 연구의 의의와 제한점 90
Ⅶ 결론 및 제언 92
A 결론 92
B 제언 94
참고문헌 95
부록 107
ABSTRACT 11