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.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

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.

OBJECTIVE: Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). METHODS: This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. RESULTS: A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. CONCLUSION: The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. TRIAL REGISTRATION Clinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).
Humans ; Feasibility Studies ; Prospective Studies ; Pilot Projects ; Acupuncture Therapy/methods* ; Research Design ; Treatment Outcome

The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

Background: Most of the studies that have examined the association between the sub-factors of occupational stress and depressive symptoms have used cross-sectional data. However, our study has longitudinally measured the occupational stress and depressive symptoms of Korean workers of a semiconductor manufacturing company across six years to intending to investigate the associations between the sub-factors of occupational stress and depressive symptoms using longitudinal data. Methods: Data collected from the workers of a semiconductor manufacturing company.Out of 1,013 recruited workers, 405 (40.0%) completed the survey questionnaires at 3 and 6-year follow-ups. Occupational stress was measured using a shorter version of the Korean Occupational Stress Scale (KOSS), whereas depressive symptoms were assessed using the Korean version of the Center for Epidemiological Studies-Depressive Symptoms Scale (CES-D). The data of male and female participants independently analyzed. Longitudinal associations were analyzed using panel data analysis with fixed effects. Results: In panel data analysis with fixed effects, job insecurity (B = 0.048, p-value = 0.004) was associated with depressive symptoms among male workers. In female workers, inadequate social support (B = 0.080, p-value < 0.001), job insecurity (B = 0.039, p-value = 0.004), lack of reward (B = 0.059, p-value = 0.004) and discomfort in occupational climate (B = 0.074, p-value < 0.001) were associated with depressive symptoms among female workers. Conclusions Temporal changes in the sub-factors of occupational stress were associated with changes in depressive symptoms within the same period. There was a gender difference in occupational stress sub-factors related to depressive symptoms.

Background: The global labor market is moving towards increasing job instability. Relatively few studies have examined the relationship between precarious employment and subjective well-being using quantitative scales. We evaluated the association between wage workers' employment status and their subjective well-being through the Cantril ladder scale using Korean Welfare Panel Survey data (KOWEPS). Methods: This study used KOWEPS data. A total of 4,423 wage workers were divided into permanently employed workers, temporarily employed workers and daily employed workers.The relationship between precarious employment and subjective well-being was analyzed by multiple linear regression adjusted for potential confounding factors. Results: The more unstable the employment status, the lower the subjective well-being, which can be expressed by the Cantril ladder scale. The mean score of both temporarily employed and daily employed workers were statistically significantly lower (B = −0.454, p < 0.001; B = −0.994, p < 0.001, respectively) than permanently employed workers. This appeared to be the same when occupational and sociodemographic factors were adjusted (B = −0.153, p = 0.002 for temporarily employed, B = −0.610, p < 0.001 for daily employed). Conclusions The more unstable the employment status, the lower the subjective well-being score according to the Cantril ladder scale.