BACKGROUND: Direct reprogramming of fibroblasts into chemically induced cardiomyocyte-like cells (CiCMs) through small molecules presents a promising cell source for cardiac regeneration and therapeutic development. However, the contaminating non-cardiomyocytes, primarily unconverted fibroblasts, reduce the effectiveness of CiCMs in various applications. This study investigated a metabolic selection approach using lactate to enrich CiCMs by exploiting the unique metabolic capability of cardiomyocytes to utilize lactate as an alternative energy source. METHODS: Primary mouse embryonic fibroblasts (pMEFs) were reprogrammed into CiCMs and subjected to a glucosedepleted, lactate-supplemented medium for 4 days. Afterward, cell viability was analyzed, and cardiomyocyte efficiency was assessed through the expression of cardiac-specific markers. Additionally, electrophysiological function was evaluated by examining drug-induced responses. RESULTS: The lactate treatment led to a significant decrease in the viability of non-cardiomyocytes (pMEF-LAC), while CiCMs (CiCM-LAC) showed minimal cell death. Specifically, the expression of all cardiac-related markers was increased in CiCM-LAC. Metabolically purified CiCMs exhibited enhanced contractile force and increased contraction frequency compared to non-purified CiCMs, as well as an elevated responsiveness to drugs. CONCLUSION This study demonstrates that lactate-based metabolic selection is an effective and practical approach for enriching CiCMs, offering a cost-effective alternative to other purification methods. The application of this strategy could potentially broaden the accessibility and utility of reprogrammed cardiomyocytes in cardiac regeneration and therapeutic development.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

BACKGROUND: Direct reprogramming of fibroblasts into chemically induced cardiomyocyte-like cells (CiCMs) through small molecules presents a promising cell source for cardiac regeneration and therapeutic development. However, the contaminating non-cardiomyocytes, primarily unconverted fibroblasts, reduce the effectiveness of CiCMs in various applications. This study investigated a metabolic selection approach using lactate to enrich CiCMs by exploiting the unique metabolic capability of cardiomyocytes to utilize lactate as an alternative energy source. METHODS: Primary mouse embryonic fibroblasts (pMEFs) were reprogrammed into CiCMs and subjected to a glucosedepleted, lactate-supplemented medium for 4 days. Afterward, cell viability was analyzed, and cardiomyocyte efficiency was assessed through the expression of cardiac-specific markers. Additionally, electrophysiological function was evaluated by examining drug-induced responses. RESULTS: The lactate treatment led to a significant decrease in the viability of non-cardiomyocytes (pMEF-LAC), while CiCMs (CiCM-LAC) showed minimal cell death. Specifically, the expression of all cardiac-related markers was increased in CiCM-LAC. Metabolically purified CiCMs exhibited enhanced contractile force and increased contraction frequency compared to non-purified CiCMs, as well as an elevated responsiveness to drugs. CONCLUSION This study demonstrates that lactate-based metabolic selection is an effective and practical approach for enriching CiCMs, offering a cost-effective alternative to other purification methods. The application of this strategy could potentially broaden the accessibility and utility of reprogrammed cardiomyocytes in cardiac regeneration and therapeutic development.

BACKGROUND: Direct reprogramming of fibroblasts into chemically induced cardiomyocyte-like cells (CiCMs) through small molecules presents a promising cell source for cardiac regeneration and therapeutic development. However, the contaminating non-cardiomyocytes, primarily unconverted fibroblasts, reduce the effectiveness of CiCMs in various applications. This study investigated a metabolic selection approach using lactate to enrich CiCMs by exploiting the unique metabolic capability of cardiomyocytes to utilize lactate as an alternative energy source. METHODS: Primary mouse embryonic fibroblasts (pMEFs) were reprogrammed into CiCMs and subjected to a glucosedepleted, lactate-supplemented medium for 4 days. Afterward, cell viability was analyzed, and cardiomyocyte efficiency was assessed through the expression of cardiac-specific markers. Additionally, electrophysiological function was evaluated by examining drug-induced responses. RESULTS: The lactate treatment led to a significant decrease in the viability of non-cardiomyocytes (pMEF-LAC), while CiCMs (CiCM-LAC) showed minimal cell death. Specifically, the expression of all cardiac-related markers was increased in CiCM-LAC. Metabolically purified CiCMs exhibited enhanced contractile force and increased contraction frequency compared to non-purified CiCMs, as well as an elevated responsiveness to drugs. CONCLUSION This study demonstrates that lactate-based metabolic selection is an effective and practical approach for enriching CiCMs, offering a cost-effective alternative to other purification methods. The application of this strategy could potentially broaden the accessibility and utility of reprogrammed cardiomyocytes in cardiac regeneration and therapeutic development.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.