https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/3 Sun, 05 Apr 2026 06:32:29 GMT 2026-04-05T06:32:29Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79436 Title: Therapeutic reprogramming of circulating myeloid cells via signal regulatory protein a extracellular vesicles in acute kidney injury Authors: Shin, Dong-U; Jo, Min Kyoung; Kwon, Minjeong; Jeong, Yewon; Cho, Bogyeong; Kim, Seong A.; Choi, Ga-Eun; Kim, Seohyun; Song, Seok Ho; Joo, Hyemin; KIM, Hyun Jung; Lee, Jung Pyo; Lee, Jeonghwan; Kim, In-San; Nam, Gi Hoon Abstract: Introduction: Acute kidney injury (AKI) presents significant clinical challenges, with high mortality and progression risk to chronic kidney disease. Mechanisms remain incompletely understood and disease-specific therapies are lacking. Recent evidence highlights the pivotal role of infiltrating myeloid cells in perpetuating kidney inflammation. CD47, a key cell surface immune checkpoint protein, is upregulated in inflammation and regulates myeloid cell infiltration, making it an attractive therapeutic target. Methods: Single-cell RNA sequencing and CD47 protein staining were used to identify CD47 expressions in human AKI specimens and two mouse models (cis-platin and bilateral ischemia/reperfusion). To therapeutically exploit this, we engineered extracellular vesicles (EVs) from human bone marrow mesenchymal stem cells to express a high-affinity signal regulatory protein a (SIRP alpha) variant (SIRP-EVs), the ligand for CD47. The efficacy of SIRP-EVs was evaluated in murine AKI models. Results: CD47 expression was significantly elevated in myeloid populations, particularly macrophages, in both human AKI tissues and mouse models. A single systemic administration of SIRP-EVs in murine AKI models exhibited therapeutic effects, including improved kidney function markers, reduced pro-inflammatory cytokine production, and ameliorated kidney histopathology. Mechanistically, SIRP-EVs preferentially localize to circulating myeloid cells, modulate CD47 expression, and subsequently inhibit their migration into injured kidney tissue. Moreover, single cell transcriptomics revealed that SIRP-EV treatment reprograms circulating macrophages toward pro-resolving phenotypes, characterized by upregulation of genes associated with tissue repair. Conclusions: Targeting CD47 on circulating myeloid cells with SIRP-EVs provides a systemic, blood-focused immunomodulatory strategy that precedes tissue infiltration, contrasting with conventional tissue-centric approaches. Our findings support SIRP-EVs as a promising therapeutic option for AKI and potentially other inflammation-driven diseases through selective modulation and reprogramming of peripheral myeloid cells. Sun, 01 Mar 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79436 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78750 Title: NDST3-Induced Epigenetic Reprogramming Reverses Neurodegeneration in Parkinson's Disease Authors: Chang, Yujung; Na, Yongwoo; Im, Hyeonjoo; Yang, Garam; Yang, Seungseon; Shim, Hyun-soo; Kim, Chunggoo; Kim, Gyeung Yun; Park, Hyeok-ju; Kim, Hee-young; Lee, Seungeun; Lee, Wonwoong; Ha, Yoon; Park, Sungho; Kim, Jieun; Cho, Won-young; Sun, Woong; Kim, Jong Seo; Yoo, Junsang Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons (DN) in the substantia nigra and disruption of cellular maintenance. Here, we demonstrate that NDST3-mediated epigenetic reprogramming halts neuronal degeneration and restores motor function in an animal model of PD. Following NDST3 administration, the DN and its associated circuits in the substantia nigra and striatum showed marked revitalization, accompanied by a considerable alleviation of PD-like motor deficits. Integrative single-cell and spatial RNA sequencing with CUT&RUN revealed that NDST3-driven reactivation of pathways is linked to neuronal survival, synaptic integrity, and steering of compromised cells toward a resilient phenotype. By recalibrating the epigenetic landscape, NDST3 promotes cellular maintenance and functional recovery in key motor circuits. These findings highlight NDST3's therapeutic potential as an epigenetic modulator of PD. These findings provide insights into the mechanisms underlying neuronal revitalization and highlight the potential of NDST3 as a novel agent for restoring brain function in neurodegenerative conditions. © 2025 Stand up Therapeutics and The Author(s). Advanced Science published by Wiley-VCH GmbH. Sun, 01 Mar 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78750 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79496 Title: The Inhibition of ROCK2 Mediates the Neuroprotection via BRSK1 Signaling Pathway in Ischemic Stroke Authors: Kim, Dongjoon; Meraj, Munazzah; Kim, Nami; Hwang, Seo-kyoung; Ahn, Yong-Joo; Lee, Seeun; Jun, Yonghyun; Kim, Hwewon; Cho, Suin; Lim, Chiyeon; Lim, Sehyun; Elsayed, Mahmoud; Moon, Hyunmae; Kim, Daeki; Choi, Minseok; Kim, Hyeon Soo; You, Zerong; Chen, John; Atochin, Dmitriy; Kim, Hyung-Hwan Abstract: Background and Purpose: Brain specific kinases 1 and 2 (BRSK1/2, also named SAD-B/A kinases) are serine-threonine kinases and are specifically expressed in mammalian forebrain and are implicated in various processes including cell polarity and cell cycle regulation. ROCKs (ROCK1 and ROCK2) regulate cell polarity, cell cycle, and cell migration predominantly through enhancing actomyosin contraction and focal adhesions. Increased ROCK activity is found after ischemic stroke, and inhibition of ROCK2 in the brain is an important therapeutic target for ischemic stroke. To determine the interplay between BRSKs and ROCKs in ischemic stroke, we investigated the functions of ROCK2, AMPKalpha, BRSK1, and BRSK2 after experimental ischemic stroke. We hypothesize that the inhibition of ROCK2 mediates BRSK1 signaling pathway and plays an important role in mitigating ischemic stroke damage. Methods: Using ROCK1 and ROCK2 siRNA in mouse hippocampal neuronal cell line (HT-22 cells), we investigated the roles ROCK1/ROCK2 and BRSK1/BRSK2 in brain ischemia. To determine the role of BRSK1/2 in transient focal cerebral ischemia, isoflurane-anesthetized WT (C57Bl/6), ROCK1+/- and ROCK2+/- mice (20-22g) underwent 2 h focal cerebral ischemia (Middle Cerebral Artery Occlusion; MCAO) induced with an 8-0 nylon monofilament coated with a silicone resin/hardener mixture introduced into the left internal carotid artery up to the anterior cerebral artery. We measured Sirt1, AMPKalpha, BRSK1, BRSK2, and GAPDH protein levels by western blotting analysis in both in vitro and in vivo experiments. Results: After the ischemic stroke, expression levels of Sirt1, AMPKalpha, BRSK1, and BRSK2 decreased. The Inhibition of ROCK by fasudil (10 mg/kg, i.p.) and KD025 (100 mg/kg, p.o.) significantly reduced infarction volume and increased AMPKalpha, BRSK1, and BRSK2 expression levels in the brain after ischemic stroke compared to those of WT mice. ROCK2 deficient mice showed increased BRSK1 expression, decreased infarction volume and improved neurological deficit score. Conclusions: These findings indicate that ROCK2 deficiency decreased infarction volume in vivo via BRSK1 signaling pathways. These results suggest that inhibition of ROCK2 and activation of BRSK1 may have therapeutic benefits in ischemic stroke. Thu, 05 Feb 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79496 2026-02-05T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79305 Title: Analytical evaluation of intact human tissues using mid-frequency scanning acoustic microscopy at the mesoscopic scale Authors: Kim, Dasom; Koo, Jeongmo; Kim, Dai Hyun; Kim, Nam-Woon; Yu, Hyunung; Rhyu, Im Joo Abstract: Conventional histological examination requires irreversible sectioning, consuming tissue and precluding three-dimensional analysis. This limitation is particularly problematic for archival specimens and forensic investigations. Scanning acoustic microscopy (SAM) enables non-destructive tissue visualization through acoustic impedance contrast without sectioning or staining, offering a complementary approach to conventional histology. We investigated mid-frequency (50 MHz) SAM imaging of intact, formalin-fixed human tissue blocks representing diverse anatomical structures, including skull table, pineal gland, cerebellum, and scalp. SAM successfully delineated histologically meaningful microarchitectural features, including trilaminar skull organization with diploic channels; pineal calcifications (corpora arenacea); cerebellar cortical lamination with identifiable Purkinje cells; and stratified scalp architecture. Multifocal image integration and stereoscopic reconstruction enabled extended depth-of-field imaging and three-dimensional visualization of intact specimens. Corresponding hematoxylin-eosin and Masson's trichrome histology confirmed close structural agreement with SAM-derived contrasts. This non-destructive imaging approach preserves tissue integrity while generating digital datasets suitable for volumetric reconstruction and downstream computational analysis, supporting applications in anatomical education, tissue banking, pathology training, and biomedical research. Sun, 01 Feb 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79305 2026-02-01T00:00:00Z