Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

BACKGROUND/OBJECTIVES: Cultural and environmental factors may affect dietary habits and intake, regardless of age. As recent assessments of dietary habits of adults 95 yrs and older are absent, we aimed to determine dietary habits, diet quality, and intake of adults 95 yrs and older and test if they vary by region. SUBJECTS/METHODS: Adults 95 yrs and older residing in rural areas (Gurye-gun, Goksung-gun, and Sunchang-gun [GuGokSun]; n = 46), a near-city area (Hwasun-gun, and Damyang-gun [HwaDam]; n = 77), and a metropolitan city (Gwangju Metropolitan City [Gwangju]; n = 32) were surveyed. Dietary habits and quality were surveyed using the Nutrition Quotient for the Elderly (NQ-E). Participants (n = 20) recorded videos of their meals, which were subsequently analyzed for food and nutrient intake and compared with intakes of participants of the Korea National Health and Nutrition Examination Survey (KNHANES) aged ≥ 80 yrs (n = 1,769), which were assessed via 24-h recall. RESULTS: Most participants (85.2%) consumed similar amounts of food at meals; however, only 65.1% ingested meals at regular times. The mean NQ-E score was 48.0 ± 11.9 and did not differ among regions. In Gwangju participants, subjective income was positively associated with diet quality. The mean energy and grain intakes per meal were lower, whereas the percent energy intake from protein and intakes of seaweed, meat and poultry, and iron were higher in GuGokSun and HwaDam participants with meal recordings than in KNHANES participants. CONCLUSION Among Korean adults aged ≥ 95 yrs, few regional variations exist in dietary quality and habits, although associations with diet quality vary within regions. Adults 95 yrs and older exhibit lower energy intake but higher intakes of seaweed, meat and poultry, and iron than adults aged ≥ 80 yrs. Notwithstanding, further longitudinal studies on centenarians are warranted.

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

BACKGROUND/OBJECTIVES: Cultural and environmental factors may affect dietary habits and intake, regardless of age. As recent assessments of dietary habits of adults 95 yrs and older are absent, we aimed to determine dietary habits, diet quality, and intake of adults 95 yrs and older and test if they vary by region. SUBJECTS/METHODS: Adults 95 yrs and older residing in rural areas (Gurye-gun, Goksung-gun, and Sunchang-gun [GuGokSun]; n = 46), a near-city area (Hwasun-gun, and Damyang-gun [HwaDam]; n = 77), and a metropolitan city (Gwangju Metropolitan City [Gwangju]; n = 32) were surveyed. Dietary habits and quality were surveyed using the Nutrition Quotient for the Elderly (NQ-E). Participants (n = 20) recorded videos of their meals, which were subsequently analyzed for food and nutrient intake and compared with intakes of participants of the Korea National Health and Nutrition Examination Survey (KNHANES) aged ≥ 80 yrs (n = 1,769), which were assessed via 24-h recall. RESULTS: Most participants (85.2%) consumed similar amounts of food at meals; however, only 65.1% ingested meals at regular times. The mean NQ-E score was 48.0 ± 11.9 and did not differ among regions. In Gwangju participants, subjective income was positively associated with diet quality. The mean energy and grain intakes per meal were lower, whereas the percent energy intake from protein and intakes of seaweed, meat and poultry, and iron were higher in GuGokSun and HwaDam participants with meal recordings than in KNHANES participants. CONCLUSION Among Korean adults aged ≥ 95 yrs, few regional variations exist in dietary quality and habits, although associations with diet quality vary within regions. Adults 95 yrs and older exhibit lower energy intake but higher intakes of seaweed, meat and poultry, and iron than adults aged ≥ 80 yrs. Notwithstanding, further longitudinal studies on centenarians are warranted.

This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at –80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.

Background: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

Purpose: Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex. Materials and Methods: We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities. Results: The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females. Conclusions Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.

BACKGROUND/OBJECTIVES: Cultural and environmental factors may affect dietary habits and intake, regardless of age. As recent assessments of dietary habits of adults 95 yrs and older are absent, we aimed to determine dietary habits, diet quality, and intake of adults 95 yrs and older and test if they vary by region. SUBJECTS/METHODS: Adults 95 yrs and older residing in rural areas (Gurye-gun, Goksung-gun, and Sunchang-gun [GuGokSun]; n = 46), a near-city area (Hwasun-gun, and Damyang-gun [HwaDam]; n = 77), and a metropolitan city (Gwangju Metropolitan City [Gwangju]; n = 32) were surveyed. Dietary habits and quality were surveyed using the Nutrition Quotient for the Elderly (NQ-E). Participants (n = 20) recorded videos of their meals, which were subsequently analyzed for food and nutrient intake and compared with intakes of participants of the Korea National Health and Nutrition Examination Survey (KNHANES) aged ≥ 80 yrs (n = 1,769), which were assessed via 24-h recall. RESULTS: Most participants (85.2%) consumed similar amounts of food at meals; however, only 65.1% ingested meals at regular times. The mean NQ-E score was 48.0 ± 11.9 and did not differ among regions. In Gwangju participants, subjective income was positively associated with diet quality. The mean energy and grain intakes per meal were lower, whereas the percent energy intake from protein and intakes of seaweed, meat and poultry, and iron were higher in GuGokSun and HwaDam participants with meal recordings than in KNHANES participants. CONCLUSION Among Korean adults aged ≥ 95 yrs, few regional variations exist in dietary quality and habits, although associations with diet quality vary within regions. Adults 95 yrs and older exhibit lower energy intake but higher intakes of seaweed, meat and poultry, and iron than adults aged ≥ 80 yrs. Notwithstanding, further longitudinal studies on centenarians are warranted.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.