1.Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study
Ying-Hsiang WANG ; Chi-Hsiang CHUNG ; Tien-Yu HUANG ; Chao-Feng CHANG ; Chi-Wei YANG ; Wu-Chien CHIEN ; Yi-Chiao CHENG
Intestinal Research 2025;23(1):76-84
		                        		
		                        			 Background/Aims:
		                        			Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.  
		                        		
		                        			Methods:
		                        			This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.  
		                        		
		                        			Results:
		                        			Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).  
		                        		
		                        			Conclusions
		                        			Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD. 
		                        		
		                        		
		                        		
		                        	
2.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
		                        		
		                        			
		                        			 6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research. 
		                        		
		                        		
		                        		
		                        	
3.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
		                        		
		                        			 Purpose:
		                        			Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. 
		                        		
		                        			Methods:
		                        			Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. 
		                        		
		                        			Results:
		                        			Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. 
		                        		
		                        			Conclusion
		                        			Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer. 
		                        		
		                        		
		                        		
		                        	
4.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
		                        		
		                        			
		                        			 6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research. 
		                        		
		                        		
		                        		
		                        	
5.Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study
Ying-Hsiang WANG ; Chi-Hsiang CHUNG ; Tien-Yu HUANG ; Chao-Feng CHANG ; Chi-Wei YANG ; Wu-Chien CHIEN ; Yi-Chiao CHENG
Intestinal Research 2025;23(1):76-84
		                        		
		                        			 Background/Aims:
		                        			Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.  
		                        		
		                        			Methods:
		                        			This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.  
		                        		
		                        			Results:
		                        			Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).  
		                        		
		                        			Conclusions
		                        			Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD. 
		                        		
		                        		
		                        		
		                        	
6.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
		                        		
		                        			 Purpose:
		                        			Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. 
		                        		
		                        			Methods:
		                        			Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. 
		                        		
		                        			Results:
		                        			Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. 
		                        		
		                        			Conclusion
		                        			Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer. 
		                        		
		                        		
		                        		
		                        	
7.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
		                        		
		                        			
		                        			 6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research. 
		                        		
		                        		
		                        		
		                        	
8.Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study
Ying-Hsiang WANG ; Chi-Hsiang CHUNG ; Tien-Yu HUANG ; Chao-Feng CHANG ; Chi-Wei YANG ; Wu-Chien CHIEN ; Yi-Chiao CHENG
Intestinal Research 2025;23(1):76-84
		                        		
		                        			 Background/Aims:
		                        			Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.  
		                        		
		                        			Methods:
		                        			This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.  
		                        		
		                        			Results:
		                        			Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).  
		                        		
		                        			Conclusions
		                        			Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD. 
		                        		
		                        		
		                        		
		                        	
9.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
		                        		
		                        			 Purpose:
		                        			Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. 
		                        		
		                        			Methods:
		                        			Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. 
		                        		
		                        			Results:
		                        			Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. 
		                        		
		                        			Conclusion
		                        			Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer. 
		                        		
		                        		
		                        		
		                        	
10.Innovative Nerve Root Protection in Full-Endoscopic Facet-Resecting Lumbar Interbody Fusion: Controlled Cage Glider Rotation Using the GUARD (Glider Used As a Rotary Device) Technique
Yu-Chia HSU ; Hao-Chun CHUANG ; Wei-Lun CHANG ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun-Sung KIM ; Cheng-Li LIN
Neurospine 2024;21(4):1141-1148
		                        		
		                        			
		                        			 This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes. 
		                        		
		                        		
		                        		
		                        	
            
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