Bronchiectasis has traditionally been characterized as a neutrophil-driven disease, yet emerging evidence suggested inflammatory heterogeneities. The prognostic significance of elevated serum immunoglobulin E (IgE) in patients without peripheral eosinophilia remains unclear. We conducted a multicenter prospective cohort study between 2017 and 2020 across 16 institutions in Taiwan. Individuals with bronchiectasis but without allergic bronchopulmonary aspergillosis were included. Patients were stratified by baseline absolute eosinophil count (cutoff 300 /uL) and serum IgE level (≤ 100, 100–500, > 500 IU/mL). The primary endpoint was severe exacerbations resulting in hospitalization at one year. Secondary endpoints included all-cause mortality, distribution of sputum pathogen, imaging pattern, and lung function. A total of 579 individuals were enrolled. Nontuberculous mycobacteria (10.7
Dermal fibroblasts are pivotal in maintaining skin integrity through extracellular matrix (ECM) production, a process compromised during aging due to oxidative stress from excessive reactive oxygen species (ROS). Salvia miltiorrhiza Bunge (Danshen, DS), a medicinal plant rich in bioactive compound-rich dried roots, has demonstrated broad therapeutic potential. This study investigates the anti-aging properties of Danshen callus (DSC)-an undifferentiated cell mass derived from leaf tissue culture, as a sustainable and controlled source of bioactive compounds. Using hydrogen peroxide (H2O2)-induced premature aging and chronological aging models in human dermal fibroblasts (HDFs), we evaluated DSC effects on redox homeostasis and senescence. Pretreatment and posttreatment with DSC significantly enhanced HDF viability, restored ECM synthesis, suppressed MMP-1 secretion, and reduced senescence-associated markers in H2O2-induced premature aging HDFs. Mechanistically, DSC activated the Nrf2/ARE pathway, mitigating ROS accumulation and reinforcing antioxidant defenses. Crucially, comparative analysis revealed DSC superior efficacy over native Danshen (DS) in both aging paradigms. These findings highlight DSC potential as a novel, plant-based therapeutic agent for anti-aging cosmetic formulations, leveraging agricultural waste for sustainable skincare solutions.
Ease of access to big data and automated analysis tools can facilitate the rapid generation of poorly designed epidemiological studies, which collectively pose a risk to the quality of medical literature. Member organizations of the TriNetX network have the ability to mass-produce retrospective cohort studies at speed using the federated data network’s statistical power and streamlined analytics pipeline. This exploratory meta-research study collated 13 published TriNetX-based retrospective cohort studies that claim to have used a design that is, in fact, impossible on the platform (the setting of a pseudo-index event on the TriNetX platform). Of these, 8 studies described their analysis as being conducted on the platform alone, making their description of the index event impossible. When we queried seven different generative artificial intelligence (AI) tools for advice on how to set an index event on TriNetX, six tools suggested at least one strategy that cannot be implemented on the platform. Unlike previously documented errors in TriNetX-based studies, we argue that the reporting of impossible index event designs in the identified publications likely constitute either distortion of the reported methods or the uncritical adoption of false AI-generated methodological advice. In an age of accelerating and increasingly automated medical research, editors and peer-reviewers must be informed of limitations with emerging epidemiological datasets and analytic tools.
Osteoarthritis (OA) is a degenerative joint disease with chronic inflammation, causing joint damage and function loss. Current treatments relieve symptoms but don't halt disease progression, highlighting the need for new therapies. Research shows mesenchymal stem cells (MSCs) can repair joints and reduce inflammation, but direct MSC injection may cause immune rejection, making MSC-derived exosomes a promising alternative. Artemisia argyi (AA) has antioxidant, anti-inflammatory, and anti-ageing effects that enhance stem cell function and cellular stability, making it a potential therapy for OA. This study explores whether AA extract can enhance exosomes from Wharton's jelly stem cells (WJSCs) for OA treatment. Results revealed that AA promoted WJSCs proliferation and increased both the yield and size of exosomes. Furthermore, AA-enhanced exosomes significantly suppressed NF-κB pathway related proteins (p-IKKα/β and p-NF-κB) and the matrix degrading protein MMP13 while increasing the expression of the cartilage extracellular matrix protein COL2A1, resulting in a greater reduction of NF-κB signaling proteins and MMP13 expression, along with increased COL2A1 levels. Additionally, these exosomes effectively reversed H₂O₂-induced ROS accumulation, with antioxidant effects surpassing those of untreated exosomes. Further studies using NF-κB activators confirmed that the therapeutic effects of these exosomes were primarily mediated by inhibition of the NF-κB signalling pathway. In conclusion, AA-enhanced WJSCs exosomes improved the proliferation, anti-inflammatory, and antioxidant capacities of C28/I2 chondrocytes under oxidative stress. These findings highlight their potential to reduce ROS levels, regulate pro-inflammatory proteins, and inhibit the NF-κB pathway, offering a promising strategy for protecting cartilage against damage caused by inflammatory joint diseases.
Background & Aims TZX4 is an enhancement platform designed to preserve stemness, mitigate cellular aging, and improve the therapeutic potential of stem cells. AeviStem® is a TZX4-enhanced stem cell product developed for neurodegenerative disorders such as Alzheimer’s disease (AD), where neuroregenerative capacity and cellular resilience are compromised. Methodology Mesenchymal stem cells (MSCs) were manufactured using TZX4 under defined conditions to ensure phenotypic consistency, multipotency, and product quality, and were subsequently released as AeviStem® for experimental use. Results To evaluate anti-aging efficacy, AeviStem® were compared with conventionally cultured, non-TZX4-treated cells under conditions of accelerated aging. Following near-infrared (NIR) photobiomodulation, control cells exhibited reduced viability, increased DNA damage, and altered aging-associated gene expression and DNA methylation patterns. In contrast, AeviStem® preserved youthful epigenomic states, maintaining age-related transcriptional and DNA methylation patterns, and mitigated DNA damage. Epigenetic clock analysis further supported reversal of NIR-accelerated biological aging. Extracellular vesicles derived from AeviStem® (AeviStem®-EVs) exhibited enhanced neurotrophic and neuroprotective effects in vitro compared with EVs from conventional stem cells. In neurons derived from AD patient-specific induced pluripotent stem cells (AD-iPSCs), treatment with AeviStem®-EVs improved cell survival, promoted neurite outgrowth, increased synaptic protein expression, and effectively reduced amyloid-β(1-42) and phosphorylated tau (pTau231). In vivo, AeviStem®-EVs significantly improved hippocampal-dependent learning and memory in 3xTg-AD mice relative to EVs from conventional stem cells, indicating TZX4-mediated enhancement of the stem cell therapeutic effect. Conclusion AeviStem® is a next-generation stem cell product in which TZX4 enhancement mitigates aging and enhances neuroregenerative capacity. The efficacy of the cells and their extracellular vesicles underscores a promising regenerative approach for Alzheimer’s disease, with implications for both cell-based and cell-free therapies.
