Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Background and Objectives: Among various emerging catheter-based treatments for severe tricuspid regurgitation (TR), the spacer device can reduce the regurgitation orifice without manipulating the valve leaflet. However, its clinical application has been hampered by traumatic anchoring to the myocardium and the coaxial alignment of the balloon resulting in insufficient TR reduction. This study aimed to evaluate the early-stage safety, technical feasibility, and preliminary efficacy of the novel atraumatic vertical spacer in patients with isolated severe TR. Methods: All procedures were guided by fluoroscopy and transthoracic echocardiography.The maximum device placement time with an inflated balloon was 24 hours. Changes in the amount of TR, right ventricular function, and patient hemodynamics were measured during balloon deployment. Results: A total of 7 patients (median age 74), underwent successful device implantation without procedure-related complications. During balloon inflation (median 25 minutes), there were no symptoms or signs indicative of TR intolerance. TR was reduced by 1 grade or greater in all patients, with 2 patients exhibiting a reduction of 3 grades, from torrential TR to a moderate degree. Mild TR after balloon inflation was achieved in 3 patients with baseline severe TR. The TR reduction observed during initial balloon deployment was sustained during the subsequent balloon maintenance period. Conclusions The Pivot-balloon procedure was safe, technically feasible, and effective in reducing TR in patients with severe TR. No periprocedural complications or adverse cardiovascular events were reported during device placement with TR reduction observed in all patients. However, longer-term follow-up is needed to confirm safety and treatment effect.

RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.

Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

This study introduces a novel biportal endoscopic foraminal decompression technique that minimizes bone removal while ensuring safe and effective nerve root decompression. Leveraging the accessory process as a key surgical landmark, this technique enables precise navigation and controlled turn-down of the ligamentum flavum (LF). A key advantage of this technique is its reduced requirement for bone resection, differing from traditional microscopic or uniportal endoscopic surgeries that often necessitate resection of the lateral isthmus or superior articular process. This technique is particularly beneficial for foraminal and extraforaminal herniated nucleus pulposus cases, where bony decompression needs are relatively lower compared to foraminal stenosis. Using the accessory process as a landmark also enhances surgical precision and reduces the risk of nerve root injury, providing a valuable advantage for less experienced surgeons. Despite these advantages, challenges exist, particularly at the L5–S1 level, where the less prominent accessory process and limited workspace due to anatomical constraints can pose difficulties. In cases of severe bony compression, additional bone removal may be necessary to achieve adequate decompression. In conclusion, the Non-facetectomy LF turn-down technique (non-facetectomy foraminal decompression) offers a safe and effective minimally invasive alternative for treating various foraminal pathologies.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients. Materials and Methods: We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into ‘Mild PD’ and ‘Significant PD’ based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories. Results: Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ −35.48%; significant PD > −35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both). Conclusion Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.