https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/564 Sat, 04 Apr 2026 09:47:14 GMT 2026-04-04T09:47:14Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77622 Title: Gene expression network analysis identified CDK1 and KIF11 as possible key molecules in the development of colorectal cancer from normal tissues Authors: Lee, Soo Bin; Noh, Young Seon; Moon, Ji-Wook; Sim, Soohyun; Han, Sung Won; Kim, Eun Sun; Lee, Ji-Yun Abstract: Background: Colorectal cancer (CRC) is one of the most common malignancies and the second most common cause of cancer-related mortality worldwide. Despite extensive research, the mechanism underlying CRC development remains unclear. This study aimed to understand the development and progression of CRC. Methods: Gene network analysis of tumors with their paired normal tissues was performed using the differentially expressed genes dataset for CRC from the Cancer Genome Atlas. Further investigation of the regulatory relationship between hub genes and tumor development was conducted by protein–protein interaction network, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses using the selected hub genes. Results: The network was more centered, and a common hub as well as a hub of hub genes were more connected to each other in the tumor than in the normal tissue, indicating changes in the network from normal to tumor. Eight downregulated and two upregulated hub genes (CDK1 and KIF11) in the tumor were identified. Further, the regulatory pathway was altered, especially in cell cycle and cell division. All R implementation codes are available on the journal website as supplementary materials. Conclusions: Our findings may help understand the biological processes underlying tumor development and progression and suggest CDK1 and KIF11 as possible key molecules in the development of CRC. © The Author(s) 2025. Mon, 01 Dec 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77622 2025-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78445 Title: Meso-macroporous hydrogel for direct litre-scale isolation of extracellular vesicles Authors: Kim, Junbeom; Kang, Minjin; Han, Geonhee; Hyung, Sujin; Kim, Mina; Jang, Minjeong; Lee, Han Kyul; Seo, Yunhee; Gil, Ki Cheol; Kim, Changheon; Song, Sojin; Jeong, Seonghyeok; Kim, Seongchan; Kim, Min Soo; Shim, Ji Sung; Kang, Sung Gu; Lee, Young Chan; Chung, Seok; Cho, Il-Joo; Shim, Tae Soup; Song, Kwang Hoon; Min, Jouha; Seong, Hyejeong; Lee, Kyungeun; Lee, Jeeyun; Lee, Cheolju; Kim, Hong Nam; Lee, Hyojin; Kim, Sun Hwa; Kang, Ji Yoon; Bong, Ki Wan; Choi, Nakwon Abstract: Extracellular vesicles are cell-originated lipid bilayer membrane vesicles that play vital roles in cell-to-cell communications. While extracellular vesicles hold substantial biomedical potential, conventional methodologies for isolating extracellular vesicles require elaborate preprocessing and, therefore, remain labour intensive and limited by throughput. To overcome these challenges, we present a facile fabrication route for generating a meso-macroporous hydrogel matrix with pores of similar to 400 nm for customizable extracellular vesicle isolation. By combining surface charge-selective capture of extracellular vesicles within the hydrogel matrix and their recovery by high ionic strength, we report direct extracellular vesicle isolation with a throughput range from microlitre to litre scales, without preprocessing, for various biofluids, including whole blood, plasma, ascites, saliva, urine, bovine milk and cell culture media. Furthermore, we demonstrate that the meso-macroporous hydrogel also serves as a solid-phase matrix for preserving extracellular vesicles for on-demand downstream analyses, making it applicable for therapeutics, cosmeceuticals and disease diagnostics. Sat, 01 Nov 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78445 2025-11-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78165 Title: Alpha-Ketoisocaproate Attenuates Muscle Atrophy in Cancer Cachexia Models Authors: Lim, Pooreum; Woo, Sang-woo; Han, Jihye; Lee, Young-lim; Lim, Jin-ju; Kang, Yeonghoon; Moon, Ji-wook; Nam, Jeong-min; Kim, Jeong-hyeon; Kim, Donghun; Shim, Jae Ho; Kim, Hyeon Soo Abstract: Background: Cancer-associated cachexia (CAC) is a multifactorial syndrome characterised by progressive loss of muscle mass with limited Food and Drug Administration treatments. Although emerging evidence suggests that l-leucine and β-hydroxy-β-methyl butyrate (HMB) have potential for treating CAC, the role of α-ketoisocaproate (KIC), a metabolite of l-leucine, remains unclear. Therefore, this study explored the use of KIC as a therapeutic agent for CAC-induced muscle atrophy by targeting myostatin. Methods: We evaluated the effect of KIC on muscle atrophy using BALB/c mice and C2C12 myotubes as models of C26- and 4T1-induced CAC. Male and female mice were injected with C26 and 4T1 cells, respectively. Grip strength was measured weekly, and mice were sacrificed 4 weeks post-injection for muscle collection. C2C12 myotubes were treated with conditioned media (CM) derived from C26 or 4T1 cells. Results: KIC suppressed mRNA expression of myostatin, a key regulator of muscle atrophy, more effectively than did l-leucine (−26.37 ± 4.11%, p < 0.01). KIC enhanced protein turnover in C2C12 myotubes and maintained 50% cell viability at high concentrations (KIC: 4.68 mM, HMB: 3.11 mM). Following CM treatment, KIC suppressed MuRF1 and MAFbx expression in a myostatin-dependent manner, thereby reducing their polyubiquitination. KIC restored Akt-FoxO3a phosphorylation, leading to improved myotube diameter (+63.8 ± 25.71%, p < 0.05) and fusion index (+51.9 ± 22.6%, p < 0.05). Immunofluorescence and nuclear fractionation revealed that KIC reduced FoxO3a nuclear accumulation. CM reduced p-Akt–FoxO3a interaction, which was rescued by KIC. In vivo, KIC administration increased body weight (11.11 ± 8.53%), grip strength (24.76 ± 10.58%), and skeletal muscle mass (p < 0.001) in C26 tumour-bearing mice. Protein expression of myostatin in the tibialis anterior (TA) muscle (−23.57 ± 12.22%, p < 0.05) and serum (−52.11 ± 3.56%, p < 0.001) was lower in KIC-treated mice (n = 12) compared with that in the controls. KIC increased the mean fibre cross-sectional area in TA (24.51 ± 14.14%, p < 0.01). In 4T1 tumour-bearing mice, KIC improved body weight (13.10 ± 10.76%) and grip strength (7.42 ± 4.33%) (p < 0.001, n = 10). Serum myostatin levels (−57.43 ± 9.46%, p < 0.001) and skeletal muscle weight were reduced in KIC-treated mice (n = 10). Conclusion: Our findings demonstrate that KIC improves muscle function in CAC-induced muscle atrophy by regulating myostatin expression in skeletal muscle via the Akt–FoxO3a pathway. Thus, KIC has been proposed as a potential therapeutic agent against CAC. © 2025 Elsevier B.V., All rights reserved. Fri, 01 Aug 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78165 2025-08-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/76813 Title: Effects of D-alanine analog on muscle atrophy through regulation of myostatin expression Authors: Oh, Joo Yeon; Moon, Ji Wook; Kang, Min Ju; Wu, Sang Woo; Lim, Pooreum; Shim, Jae Ho; Kim, Hyeon Soo Abstract: Sarcopenia is an aging process characterized by the loss of skeletal muscle mass and function. Although this condition primarily affects older adults, it is also associated with various diseases, physical inactivity, and nutritional deficiencies. Effective preventive measures include regular exercise, and adequate nutrition and protein intake to mitigate muscle atrophy. In this study, we investigated the effects of alanine on muscle tissue. Alanine supplementation increases physical performance and muscle function during physiological exercise in humans. To further explore its potential, we synthesized a D-alanine analog, D-Ala-Oi-pr-HCl, which demonstrated the ability to prevent muscle atrophy and increase muscle mass by downregulating myostatin expression both in vitro and in vivo. Furthermore, D-Ala-Oi-pr-HCl promoted the phosphorylation of Akt and ERK, both of which are associated with cell proliferation. However, the underlying mechanisms remain unclear. Notably, myostatin was inhibited by a D-alanine analog. These findings suggest that D-alanine analogs may serve as new therapeutic agents for muscle atrophy, providing valuable insights for future biomedical applications. © 2025 Thu, 01 May 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/76813 2025-05-01T00:00:00Z