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Prevalence and Risk Factors of Self-Reported Sarcopenia and Its Association With Multimorbidity in Community-Dwelling Older Adults: A Cross-Sectional Study
Get PDFThis cross-sectional study aimed to identify the impact of multimorbidity on self-reported sarcopenia and compare the differences in the prevalence and associated factors of sarcopenia in community-dwelling older adults with and without multimorbidity. We enrolled 876 community-dwelling older adults in South Korea. Multimorbidity was defined as the coexistence of two or more chronic diseases, and sarcopenia was evaluated using the Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falling Questionnaire. Binomial logistic regression analyses were performed. Our study revealed that the prevalence of sarcopenia was significantly higher (43.5%) in older adults with multimorbidity than in those without multimorbidity (20.8%). This finding underscores the significant impact of multimorbidity on sarcopenia. We also found that poor perceived health status was the strongest predictor of sarcopenia in older adults with multimorbidity, while oldest-old age (≥ 85 years) was the strongest predictor of sarcopenia in those without multimorbidity. Large prospective cohort studies using objective sarcopenia screening tools are needed to demonstrate the synergistic effects of multimorbidity and sarcopenia on health outcomes among community-dwelling older adults
Activation of the mTOR pathway enhances PPARγ/SREBP-mediated lipid synthesis in human meibomian gland epithelial cells
Get PDFThe involvement of the mechanistic targets of rapamycin (mTOR) pathway in lipid metabolism has been recently elucidated. However, its specific role in the Meibomian gland, where lipid metabolism is significant, remains not fully understood. We investigated the role of mTOR signaling system in the lipogenesis and differentiation of human meibomian gland epithelial cells (HMGECs). Treatment of HMGECs with rapamycin resulted in a reduction in lipid synthesis and the expression of PPARγ and SREBP-1, the major regulators of lipid synthesis. The phosphorylation of p70S6kinase and AKT, which are downstream signals of mTOR complexes 1 and 2, respectively, decreased following rapamycin treatment. In addition, when both mTOR complex 1 and 2 were suppressed using siRNA, there was a significant reduction in the expression of PPARγ and SREBP-1, along with a decrease in lipid synthesis in HMGECs. Our findings suggest that inhibiting the mTOR pathway diminishes the differentiation and adipogenesis of meibomian gland epithelial cells, and both mTOR complexes 1 and 2 appear to play a role in this activity
Development of a small molecule-based twophoton photosensitizer for targeting cancer cells
No full textPhotodynamic therapy (PDT) employing two-photon (TP) excitation is increasingly recognized to induce cell damage selectively in targeted areas, underscoring the importance of developing TP photosensitizers (TP-PSs). In this study, we developed BSe-B, a novel PS that combines a selenium containing dye with biotin, a cancer-selective ligand, and is optimized for TP excitation. BSe-B demonstrated enhanced cancer selectivity, efficient generation of type-I based reactive oxygen species (ROS), low dark toxicity, and excellent cell-staining capability. Evaluation across diverse cell lines (HeLa, A549, OVCAR-3, WI-38, and L-929) demonstrated that BSe-B differentiated and targeted cancer cells while sparing normal cells. BSe-B displayed excellent in vivo biocompatibility. In cancer models such as three-dimensional spheroids and actual colon cancer tissues, BSe-B selectively induced ROS production and cell death under TP irradiation, demonstrating precise spatial control. These findings highlight the potential of BSe-B for imaging-guided PDT and its capability for micro treatment within tissues. Thus, BSe-B demonstrates robust TP-PDT capabilities, making it a promising dual-purpose tool for cancer diagnosis and treatment
Understanding the pathogenicity of Naegleria fowleri in association with N. fowleri antigen-1 (Nfa1)
Get PDFNaegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity
단순 포진 바이러스 1형에 의해 유도된 베체트병 마우스 모델에서 CCR1 발현의 역할
No full textDoctor1. INTRODUCTION 1
2. MATERIALS AND METHODS 3
2.1. Animal experiments 3
2.2. Symptoms of Behçet's disease in mice 3
2.3. Flow cytometry 4
2.4. Western blot analysis 4
2.5. Administration of cytokines, ligand, and antagonist 5
2.6. Drug treatments 6
2.7. Patients with Behçet's disease 6
2.8. CCL3 ELISA 7
2.9. Statistical analysis 8
3. RESULTS 9
3.1. Frequencies of CCR1+ cells in Behçet's disease mice 9
3.2. Interleukin-10 and GM-CSF affect frequencies of CCR1+ cells in normal mice 14
3.3. Interleukin-10 and GM-CSF up-regulate frequencies of CCR1+ cells in Behçet's disease mice 18
3.4. CCL3 down-regulates the expression of CCR1+ cells in normal mice 23
3.5. BX471, a CCR1 antagonist, does not down-regulate CCR1+ cells in normal mice 27
3.6. CCL3 and BX-471 regulates the expression of CCR1+ cells and deteriorates symptoms in Behçet's disease mice 30
3.7. Drug treatment regulates frequencies of CCR1+ cells in normal mice 34
3.8. Drug treatment regulates frequencies of CCR1+ cells in Behçet's disease mice 38
3.9. Anti-CCL3 antibody up-regulates the expression of CCR1+ cells normal mice 43
3.10. Anti-CCL3 antibody up-regulates the expression of CCR1+ cells and improves symptoms in Behçet's disease mice 47
3.11. Behcet's disease patient clinical and therapeutic history 53
3.12. Plasma levels of CCL3 in patients with Behçet's disease 56
4. DISCUSSION 58
5. CONCLUSION 6
유전체 안정성 조절기전에서 유전체 보호인자로서의 USP39 기능 규명
No full textDoctorI. INTRODUCTION 1
II. MATERIALS AND METHODS 6
1. Cell lines and culture 6
2. DUBs library cloning and plasmids 6
3. siRNA sequences, antibodies and chemicals 13
4. Live cell imaging with laser micro-irradiation 17
5. Immunoblotting 18
6. Immunofluorescene 18
7. Analysis of ionizing radiation-induced foci formation 19
8. Micronucleus assay 20
9. Purification of recombinant protein from Sf9 cells or E. coli 20
10. PAR overlay assay 21
11. HR and NHEJ repair analysis 22
12. Neutral comet assay 22
13. Clonogenic survival assay 22
14. Immunoprecipitation 23
15. Chromatin immunoprecipitation (ChIP) 23
16. Cell synchronization 25
17. Cell cycle analysis 25
18. In vitro aggregation assay and Transmission electron microscopy analysis 26
19. Quantitative real-time PCR 26
20. Protein microarray 27
21. Image quantification 28
22. Statistical analysis 28
III. RESULTS 29
PART 1. USP39 promotes non-homologous end-joining repair by poly(ADP-ribose)-induced liquid demixing 29
A. Screening for DUBs localized to DNA lesion(s) in a PAR-dependent manner 29
B. USP39 is an essential DUB for the regulation of DSB repair 39
C. The tripartite RG motif of USP39 is crucial for its recruitment to DNA lesions during NHEJ repair 51
D. The tripartite RG motif of USP39 is crucial for PAR chain-mediated liquid demixing at DNA lesions 61
E. USP39 directly drives XRCC4/LIG4 dependent NHEJ repair. 69
F. The USP39 ZF domain is important for XRCC4/LIG4 complex recruitment 81
G. USP39 regulates HR repair in a spliceosome complex-dependent manner 87
PART 2. USP39 regulates the chromatin dynamics and ATM activation through the SUV39H1-mediated H3K9me3 in DDR 91
A. Identification of PAR-mediated USP39 binding protein using a human protein microarray 91
B. USP39 strongly interacts with SUV39H1 in a PAR-dependent manner and regulates the H3K9me3 levels 95
C. USP39 strongly binds to SUV39H1 and regulates chromatin dynamics upon DNA damage 100
D. USP39 leads to ATM activation by regulating SUV39H1-mediated H3K9me3 in the DDR 106
E. USP39 controls both H3K9me3 and H4K20me2 through interplay with SUV39H1 108
IV. DISCUSSION 114
REFERENCES 12
CABG 환자를 위한 간호사 주도 심장재활 프로그램 개발 및 효과
No full textDoctorⅠ. 서론 1
A. 연구의 필요성 1
B. 연구의 목적 5
C. 연구의 가설 5
D. 용어의 정의 7
Ⅱ. 문헌고찰 12
A. 관상동맥우회술 후 건강문제와 건강성과 12
B. 관상동맥우회술 후 심장재활 프로그램 15
C. IMB 모델과 심장재활 프로그램 20
Ⅲ. 이론적 기틀 24
Ⅳ. 연구 방법 27
A. IMB 모델 기반 심장재활 프로그램 개발 27
B. 프로그램 효과 검증 54
C. 연구대상 55
D. 연구도구 59
E. 자료수집 방법 및 연구진행절차 67
F. 자료분석 방법 76
G. 연구의 내⋅외적 타당도 77
H. 윤리적 고려 77
Ⅴ. 연구결과 79
A. 실험군과 대조군의 사전 동질성 검증 79
B. 연구의 가설검증 84
Ⅵ. 논의 101
A. IMB 모델기반 심장재활 프로그램 개발 101
B. IMB 모델기반 심장재활 프로그램의 효과검증 105
C. 연구의 기대효과 113
Ⅶ. 결론 및 제언 115
A. 결론 115
B. 제언 116
참고 문헌 118
부 록 145
ABSTRACT 17
Microbiome-derived Extracellular Vesicles Targeting Neutrophilic Asthma
No full textDoctorⅠ. Introduction 1
Ⅱ. Materials and Methods 3
A. Bacterial EV isolation 3
B. Metabolomic analysis 3
C. Patients recruitment 4
D. ELISA for EV-specific IgG antibodies 5
E. Dot blot analysis for EV-specific IgG antibodies 5
F. Mouse experiment 6
G. Flow cytometric analysis 7
H. EV fluorescence imaging 7
I. Metagenomic analysis 8
J. Airway epithelial cell stimulation 8
K. Isolation of mammalian EVs from airway epithelial cells 9
L. Microarray analysis 9
M. Monocyte isolation and activation 11
N. ILC isolation and activation 11
O. Neutrophil activation and migration 11
P. miRNA transfection 12
Q. Quantification of miRNA expression 12
R. Statistical analysis 13
Ⅲ. Results 14
A. Micrococcus luteus-derived extracellular vesicles: Therapeutic target for neutrophilic asthma by regulating miRNA in airway epithelial cells 14
1. Characterization of MlEV 14
2. Clinical characteristics of the study subjects 15
3. Lower prevalence of MlEV-specific IgG4 in asthmatic patients 17
4. Suppressive effect of MlEV on neutrophilic airway inflammation in mice 19
5. Effect of MlEV on pathophysiological conditions in AECs 22
6. Effect of miRNAs on IL-1β-producing monocytes 24
7. Clinical significance of hsa-miR-4517 in asthmatic patients 26
B. Lactobacillus paracasei-derived extracellular vesicles: Therapeutic strategy for neutrophilic asthma by inhibiting the JNK pathway in airway epithelial cells 28
1. Altered composition of gut microbial EVs in neutrophilic asthmatic mice 28
2. Characterization of LpEV 30
3. Low abundance of LpEV-specific IgG in mice with NA 31
4. Clinical characteristics of the study subjects 32
5. Lower prevalence of LpEV-specific IgG4 in asthmatic patients 34
6. Suppressive effect of LpEV on airway inflammation in mice with NA 36
7. Inhibition of the JNK pathway by LpEV metabolites in the airway 39
Ⅳ. Discussion 43
Ⅴ. Conclusion 45
Reference 46
국문요약 5
수술 중 C-arm fluoroscopy 를 이용한 후족부 정렬의 평가
No full textMasterI. Introduction 1
II. Materials and Methods 3
A. Participants 3
B. Saltzman View 4
C. Long Axial View 5
D. Modified Méary View 6
E. Intraoperative Modified Méary View 8
F. Statistics 10
III. Results 11
IV. Discussion 14
V. Conclusion 20
References 21
국문요약 2
원발성 간암의 중간 세포 암종에서의 전사체 프로파일링
No full textMasterⅠ. 서 론 1
Ⅱ. 재료 및 방법 3
1. 조직 표본의 선택 및 병리학적 분석 3
2. 면역조직화학의 구축 3
3. RNA 시퀀싱 프로파일링 및 전사체 데이터 분석 6
4. 공개 데이터 분석 6
5. 전장 유전체 시퀀싱 프로파일링 및 DNA 복제 수 분석 9
6. 스플라이싱 이벤트 추정 11
7. 통계적 분석 11
Ⅲ. 결과 12
1. INT-CA의 임상병리학적 특징 12
2. 간암 유형의 전사체 프로파일링 비교 16
3. 간암 유형 간의 DNA 복제 수 비교 29
4. INT-CA에서 인트론 보유의 스플라이싱 변이 35
Ⅳ. 고찰 40
Ⅴ. 결론 43
참고 문헌 44
영문요약 5