This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Background and Objectives: Studies investigating the correlation between papillary thyroid carcinoma (PTC) tumor size and the prevalence of the B-type Raf kinase (BRAF) mutation have yielded conflicting results. Therefore, we evaluated the prevalence of BRAF mutation according to tumor size in a large cohort of PTC patients to clarify this association. Materials and Methods: We retrospectively analyzed 6,438 patients with surgically diagnosed classic PTC between January 2009 and December 2017 at Samsung Medical Center, Seoul, Republic of Korea.During the study period, BRAF mutation testing was attempted on all fine-needle aspiration specimens, except for a small number of inadequate specimens. All other histologic subtypes were excluded. The prevalence of BRAF mutation was assessed based on tumor size, and further analyzed by age group and sex according to tumor size. Results: The overall prevalence of BRAF mutation was 79.2%. When PTCs ≤1 cm were excluded, the prevalence was 77.2%. The prevalence significantly decreased with increasing tumor size (p for trend ＜0.001). It was significantly higher in men than in women (p=0.013), but did not differ by age. The inverse correlation between tumor size and prevalence was prominent in patients aged 20-49 years but was less distinct in those aged 50 years and older. Conclusion In this large cohort of patients with PTC, the prevalence of BRAF mutation significantly decreased with increasing tumor size. These findings suggest that BRAF mutation is enriched in smaller surgically treated classic PTCs and may provide a hypothesis-generating clue regarding its role in early PTC development, although selection bias cannot be excluded.

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases.However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H 2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+ ) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+ -dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+ -mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Epidural adhesions cause pain by interfering with the free movement of the spinal nerves and increasing neural sensitivity as a consequence of neural compression. To remove adhesions and deliver injected drugs to target sites, percutaneous epidural adhesiolysis (PEA) is performed in patients who are unresponsive to conservative treatments. We describe four patients who were treated with a newly developed inflatable balloon catheter for more effective PEA and relief of stenosis. In the present patients, treatments with repetitive epidural steroid injection and/or PEA with the Racz catheter or the NaviCath did not yield long-lasting effects or functional improvements. However, PEA and decompression with the inflatable balloon catheter led to maintenance of pain relief for more than seven months and improvements in the functional status with increases in the walking distance. The present case series suggests that the inflatable balloon catheter may be an effective alternative to performing PEA when conventional methods fail to remove adhesions or sufficiently relieve stenosis.
Catheters* ; Constriction, Pathologic ; Decompression* ; Humans ; Peas ; Spinal Nerves ; Spinal Stenosis ; Walking

No abstract available.
Cytarabine* ; Cytosine* ; Drug Therapy, Combination* ; Idarubicin* ; Leukemia, Myeloid, Acute*