Young Charles Jang

Background/Objectives: Body mass index (BMI) cannot distinguish fat mass (FM) from fat-free mass (FFM). The fat-free mass index (FFMI = FFM/height²) and fat mass index (FMI = FM/height²) decompose BMI into lean and fat components. We aimed to establish the first nationally representative, BIA-based FFMI and FMI reference values for Korean adults, visualize body composition trajectories, and classify obesity subtypes using the body composition chart. Methods: Cross-sectional data from 10,140 participants (4508 men, 5632 women; aged 10–80 years) from KNHANES IX (2022–2023) were analyzed. Multifrequency BIA (InBody 970) measured FFM and FM. Obesity subtypes (%BF ≥ 25% men, ≥35% women) were classified as underlean (FFMI < P5), proportional (P5–P95), or heavy (>P95) relative to an 18–59-year-old reference. Results: In men, FFMI peaked at 19.1 kg/m² (30–49 years), declining 9.7% by 70–80 years, while FMI remained stable. In women, FMI increased 44% with stable FFMI. Underlean obesity in men rose from 0.7% (30–39 years) to 17.4% (70–80 years), undetected by BMI or waist circumference. Conclusions: These reference values and body composition chart provide practical tools for identifying underlean obesity and assessing body composition beyond BMI in Korean adults.

Parkinson's disease (PD) is the second most common neurodegenerative disease that affects movement and cognitive function, resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neurons. It affects nearly one million people in the United States and 8.5 million worldwide. While there are some pharmacological and surgical options available, they only provide symptomatic relief, as there is currently no cure for PD. In contrast, exercise training, a non-pharmacological intervention, has emerged as a powerful strategy to enhance the psychological, cognitive, and physiological (motor) impairments associated with PD. Given that the beneficial effects of exercise differ based on the intensity and type of training, gaining a thorough understanding of the molecular mechanisms underlying exercise-induced protection is crucial for developing innovative therapies that improve the quality of life for PD patients around the globe. This review discusses PD pathogenesis and pathophysiology and provides recent clinical evidence of neuroprotective benefits from various exercise modalities and intensity. Furthermore, the molecular mechanisms of exercise in PD pathogenesis (e.g., modulations on neurotrophic factors, oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, and autophagy) will be emphasized.

SUMMARY: Mesenchymal stromal cells (MSCs) exert regenerative and immunomodulatory effects largely through secreted paracrine factors and extracellular vesicles (EVs), which transfer proteins, lipids, and nucleic acids to recipient cells. Lipid composition critically influences EV stability, uptake, and bioactivity. Sphingomyelinase (SMase), an enzyme that hydrolyzes sphingomyelin into ceramide, regulates EV biogenesis by inducing membrane curvature and initiating inward membrane budding. Here, MSCs were treated with SMase, and EVs were isolated and characterized by nanoparticle tracking analysis, miRNA sequencing, lipidomics, and proteomics. SMase treatment increased EV yield and altered lipid, protein, and miRNA cargo linked to TNF-α signaling, wound healing, and angiogenesis. Functionally, SMase-EVs suppressed TNF-α in macrophages, showed trending increased HUVEC tubular formation, and altered T-cell populations following local delivery in a critical murine oral wound defect model. These findings highlight how enzymatic lipid remodeling modifies MSC-EVs, enhancing their therapeutic potential and informing strategies for optimized EV-based therapies and scalable production.

Mesenchymal stromal cells (MSCs) are widely studied for their immunomodulatory and tissue reparative capabilities, but clinical translation has been hampered by inconsistent efficacy and limited standardization in manufacturing. While cytokine-based priming methods, such as interferon-gamma (IFN-γ) stimulation, have shown promise in enhancing MSC potency, alternative approaches targeting distinct biological metabolism integral to secretome and membrane architecture have not been explored in MSCs. In this study, we investigate sphingomyelinase (SMase), an enzyme that generates ceramide from sphingomyelin, as a novel lipid-based priming strategy to modulate MSC function. Here, human MSCs were treated with SMase and high-content imaging and morphological profiling revealed that SMase-treated cells adopted a phenotype overlapping with IFN-γ–licensed MSCs, including increased cell compactness and solidity. Lipidomic analysis showed broad alterations in sphingolipid species, and dynamic flux estimation (DFE) modeling predicted distinct metabolic shifts in SMase-treated cells compared to untreated controls. These changes were sustained up to 35 hours post-stimulation, indicating stable metabolic reprogramming. SMase priming also altered the MSC secretome, enriching for factors implicated in immune regulation. Functionally, SMase-primed MSCs retained the ability to suppress T-cell activation and promote anti-inflammatory macrophage phenotypes. Collectively, these findings demonstrate that SMase stimulation induces a durable, immunomodulatory-like state in MSCs through coordinated changes in lipid metabolism and secretory activity. This lipid-centric priming approach represents a promising alternative to cytokine-based licensing strategies and may support therapeutic MSC products.

Volumetric muscle loss (VML) injuries result in chronic fibrosis, inflammation, and persistent functional deficits. Fibro-adipogenic progenitor (FAP) cells are a heterogeneous, muscle-resident stromal cell population that play a crucial role in muscle regeneration, but also contribute to fibrosis in muscle disease. The role of FAPs in VML is not well established and may be critical target to ensure functional muscle regeneration after VML. We utilized a VML model in the mouse quadriceps to study the location, secretome, surface marker distribution, gene expression, and single-cell transcriptional profile of FAPs after VML. After VML, a subpopulation of FAPs highly expressed β1-integrin and were elevated in the post-VML muscle tissue; these FAPs had increased fibrotic gene expression and increased myofibroblast differentiation potential. Transforming growth factor-β1 (TGF-β1) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) were identified as secreted proteins from VML derived FAPs that produced both pro-fibrotic and anti-myogenic signaling. These data establish an aberrant FAP sub-population that are elevated in VML injury and provides novel targets for future scarless muscle regeneration in VML.

Cellular senescence, a process that induces irreversible cell cycle arrest in response to diverse stressors, is a primary contributor to aging and age-related diseases. Currently, exposure to hydrogen peroxide is a widely used technique for establishing in vitro cellular senescence models; however, this traditional method is inconsistent, laborious, and ineffective in vivo. To overcome these limitations, we have developed a hydrogen peroxide-releasing hydrogel that can readily and controllably induce senescence in conventional 2-dimensional cell cultures as well as advanced 3-dimensional microphysiological systems. Notably, we have established 2 platforms using our hydrogen peroxide-releasing hydrogel for investigating senolytics, which is a promising innovation in anti-geronic therapy. Conclusively, our advanced model presents a highly promising tool that offers a simple, versatile, convenient, effective, and highly adaptable technique for inducing cellular senescence. This innovation not only lays a crucial foundation for future research on aging but also markedly accelerates the development of novel therapeutic strategies targeting age-related diseases.

Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formation, persistent pain, and permanent functional deficits. The aberrant healing response is preceded by acute inflammation and immune cell infiltration which does not resolve. We analyzed the biosynthesis of inflammatory and specialized pro-resolving lipid mediators (SPMs) after VML injury in two different models; muscle with critical-sized defects had a decreased capacity to biosynthesize SPMs, leading to dysregulated and persistent inflammation. We developed a modular poly(ethylene glycol)-maleimide hydrogel platform to locally release a stable isomer of Resolvin D1 (AT-RvD1) and promote endogenous pathways of inflammation resolution in the two muscle models. The local delivery of AT-RvD1 enhanced muscle regeneration, improved muscle function, and reduced pain sensitivity after VML by promoting molecular and cellular resolution of inflammation. These findings provide new insights into the pathogenesis of VML and establish a pro-resolving hydrogel therapeutic as a promising strategy for promoting functional muscle regeneration after traumatic injury.

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring. This scalable system includes a low-profile, label-free thin-film sensor array and electronics integrated with a flexible cell bag, allowing for simultaneous assessment of culture properties such as pH, dissolved oxygen, glucose, and temperature, to receive real-time feedback for up to 30 days. The experimental results show the accurate monitoring of time-dynamic and spatial variations of stem cells and myoblast cells with adjustable carriers from a plastic dish to a 2-liter cell bag. These advances open up the broad applicability of the smart sensing system for large-scale, lower-cost, reproducible, and high-quality engineered cell manufacturing for broad clinical use.