Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

OBJECTIVES: Electrocardiogram (ECG) data are important for the study of cardiovascular disease and adverse drug reactions. Although the development of analytical techniques such as machine learning has improved our ability to extract useful information from ECGs, there is a lack of easily available ECG data for research purposes. We previously published an article on a database of ECG parameters and related clinical data (ECG-ViEW), which we have now updated with additional 12-lead waveform information. METHODS: All ECGs stored in portable document format (PDF) were collected from a tertiary teaching hospital in Korea over a 23-year study period. We developed software which can extract all ECG parameters and waveform information from the ECG reports in PDF format and stored it in a database (meta data) and a text file (raw waveform). RESULTS: Our database includes all parameters (ventricular rate, PR interval, QRS duration, QT/QTc interval, P-R-T axes, and interpretations) and 12-lead waveforms (for leads I, II, III, aVR, aVL, aVF, V1, V2, V3, V4, V5, and V6) from 1,039,550 ECGs (from 447,445 patients). Demographics, drug exposure data, diagnosis history, and laboratory test results (serum calcium, magnesium, and potassium levels) were also extracted from electronic medical records and linked to the ECG information. CONCLUSIONS: Electrocardiogram information that includes 12 lead waveforms was extracted and transformed into a form that can be analyzed. The description and programming codes in this case report could be a reference for other researchers to build ECG databases using their own local ECG repository.
Calcium ; Cardiovascular Diseases ; Demography ; Diagnosis ; Drug-Related Side Effects and Adverse Reactions ; Electrocardiography* ; Electronic Health Records ; Hospitals, Teaching ; Korea ; Machine Learning ; Magnesium ; Potassium

BACKGROUND/OBJECTIVES: Fermentation can increase functional compounds in fermented soybean products, thereby improving antioxidant and/or anti-inflammatory activities. We investigated the changes in the contents of phenolics and isoflavones, antioxidant activity and anti-inflammatory activity of Doenjang during fermentation and aging. MATERIALS/METHODS: Doenjang was made by inoculating Aspergillus oryzae and Bacillus licheniformis in soybeans, fermenting and aging for 1, 3, 6, 8, and 12 months (D1, D3, D6, D8, and D12). Doenjang was extracted using ethanol, and sequentially fractioned by hexane, dichloromethane (DM), ethylacetate (EA), n-butanol, and water. The contents of total phenolics, flavonoids and isoflavones, 2,2-diphenyl-1 picryl hydrazyl (DPPH) radical scavenging activity, and ferric reducing antioxidant power (FRAP) were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2 and pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions were also measured using LPS-treated RAW 264.7 macrophages. RESULTS: Total phenolic and flavonoid contents showed a gradual increase during fermentation and 6 months of aging and were sustained thereafter. DPPH radical scavenging activity and FRAP were increased by fermentation. FRAP was further increased by aging, but DPPH radical scavenging activity was not. Total isoflavone and glycoside contents decreased during fermentation and the aging process, while aglycone content and its proportion increased up to 3 or 6 months of aging and then showed a slow decrease. DM and EA fractions of Doenjang showed much higher total phenolic and flavonoid contents, and DPPH radical scavenging activity than the others. At 100 microg/mL, DM and EA fractions of D12 showed strongly suppressed NO production to 55.6% and 52.5% of control, respectively, and PGE2 production to 25.0% and 28.3% of control with inhibition of iNOS or COX-2 protein expression in macrophages. CONCLUSIONS: Twelve month-aged Doenjang has potent antioxidant and anti-inflammatory activities with high levels of phenolics and isoflavone aglycones, and can be used as a beneficial food for human health.
1-Butanol ; Aging ; Aspergillus oryzae ; Bacillus ; Dinoprostone ; Ethanol* ; Fermentation ; Flavonoids ; Humans ; Inflammation ; Isoflavones ; Macrophages* ; Methylene Chloride ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phenol ; Prostaglandin-Endoperoxide Synthases ; Soybeans ; Water