Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach’s alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. Results: A Cronbach’s alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). Conclusion The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach’s alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. Results: A Cronbach’s alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). Conclusion The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach’s alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. Results: A Cronbach’s alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). Conclusion The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement.

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach’s alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. Results: A Cronbach’s alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). Conclusion The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.