This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Objective: To assess the performance of novel qualitative diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to identify the pathologic complete response (pCR) of primary tumors in esophageal cancer after neoadjuvant chemoradiation (nCRT). Materials and Methods: Patients who underwent nCRT, subsequent MRI, positron emission tomography/computed tomography (PET/CT), endoscopy, or esophagectomy for esophageal cancer between October 2021 and October 2023 were retrospectively analyzed. The DCE-MRI response of primary tumors was interpreted using five grades by thoracic radiologists as follows: G1 (compatible with CR), G2 (probable CR), G3 (probable partial response [PR]), G4 (compatible with PR), and G5 (stable or progressive disease). The performances of MRI, PET/CT, endoscopy, and their combinations in diagnosing pCR in primary tumors were calculated. Results: A total of 52 patients (male:female, 46:6; age, 61.2 ± 8.0 years) were included. Surgical specimens revealed pCR (ypT0) in 34 patients. G1 as the MRI criterion for pCR of primary tumors yielded a positive predictive value (PPV), specificity of 100% (18/18), and low sensitivity (23.5% [8/34]). Combining G1 and G2 as the MRI criteria increased the sensitivity to 73.5% (25/34), with a specificity of 88.9% (16/18), accuracy of 78.8% (41/52), and PPV of 92.6% (25/27). Adding the DCEMRI results (G1-2) significantly improved accuracy for both PET/CT (from 65.4% [34/52] to 80.8% [42/52], P = 0.03) and endoscopy (from 55.8% [29/52] to 76.9% [40/52], P = 0.005), with increase in sensitivity (from 55.9% [19/34] to 82.4% [28/34] for PET/CT-based evaluation [P = 0.008] and from 47.1% [16/34] to 82.4% [28/34] for endoscopy-based evaluation [P = 0.001]). Conclusion DCE-MRI-based grading shows high diagnostic performance for identifying pCR in primary tumors, particularly in terms of PPV and specificity, and enhances response evaluation when combined with PET/CT and endoscopy.

The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Objective: To assess the performance of novel qualitative diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to identify the pathologic complete response (pCR) of primary tumors in esophageal cancer after neoadjuvant chemoradiation (nCRT). Materials and Methods: Patients who underwent nCRT, subsequent MRI, positron emission tomography/computed tomography (PET/CT), endoscopy, or esophagectomy for esophageal cancer between October 2021 and October 2023 were retrospectively analyzed. The DCE-MRI response of primary tumors was interpreted using five grades by thoracic radiologists as follows: G1 (compatible with CR), G2 (probable CR), G3 (probable partial response [PR]), G4 (compatible with PR), and G5 (stable or progressive disease). The performances of MRI, PET/CT, endoscopy, and their combinations in diagnosing pCR in primary tumors were calculated. Results: A total of 52 patients (male:female, 46:6; age, 61.2 ± 8.0 years) were included. Surgical specimens revealed pCR (ypT0) in 34 patients. G1 as the MRI criterion for pCR of primary tumors yielded a positive predictive value (PPV), specificity of 100% (18/18), and low sensitivity (23.5% [8/34]). Combining G1 and G2 as the MRI criteria increased the sensitivity to 73.5% (25/34), with a specificity of 88.9% (16/18), accuracy of 78.8% (41/52), and PPV of 92.6% (25/27). Adding the DCEMRI results (G1-2) significantly improved accuracy for both PET/CT (from 65.4% [34/52] to 80.8% [42/52], P = 0.03) and endoscopy (from 55.8% [29/52] to 76.9% [40/52], P = 0.005), with increase in sensitivity (from 55.9% [19/34] to 82.4% [28/34] for PET/CT-based evaluation [P = 0.008] and from 47.1% [16/34] to 82.4% [28/34] for endoscopy-based evaluation [P = 0.001]). Conclusion DCE-MRI-based grading shows high diagnostic performance for identifying pCR in primary tumors, particularly in terms of PPV and specificity, and enhances response evaluation when combined with PET/CT and endoscopy.

Objective: This study aimed to compare the efficacy and safety of romosozumab, a bone anabolic agent, versus vertebroplasty, a conventional surgical intervention, in treating osteoporotic vertebral compression fractures (OVCFs). Methods: A retrospective analysis included 86 thoracic/lumbar compression fracture patients from 2014 to 2022 at a medical center. Forty-two patients received romosozumab (monthly injections for 1 year) followed by 1 year of denosumab, while 44 underwent vertebroplasty followed by denosumab injections biannually for 2 years. Outcomes were assessed using the Numerical Rating Scale (NRS) for pain, bone mineral density (BMD), vertebral compression ratio, and Cobb angle over 12 months. Results: At 12 months, the romosozumab group showed a greater reduction in NRS scores (4.90 ± 1.01 vs. 4.27 ± 1.34, p = 0.015) and a higher increase in lumbar BMD (0.8 ± 0.5 vs. 0.5 ± 0.3, p = 0.000) compared to the vertebroplasty group. There were no significant differences in changes in hip total BMD and femur neck BMD (p = 0.190, p = 0.167, respectively). Radiographic assessments showed no significant differences in vertebral compression ratio (14.7% vs. 14.8%; p = 0.960) or Cobb angle (4.2° vs. 4.9°; p = 0.302). The incidence of major osteoporotic fractures was lower in the romosozumab group (7.1% vs. 25.0%, p = 0.051), with similar rates of cardiovascular events in both groups (4.8% vs. 9.1%, p = 0.716). Conclusion Romosozumab has demonstrated superior pain reduction and lumbar BMD improvement compared to vertebroplasty at 12 months, with no significant differences in radiographic outcomes or adverse events, suggesting it as an alternative to vertebroplasty for OVCF.

The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Background: The aim of this study was to examine various patient factors affecting first programmed embryo transfer (ET) outcomes under the freeze-all policy at a single tertiary university infertility center. Methods: This retrospective observational study reviewed the medical records of 243 couples who underwent their first ET using blastocysts collected under the freeze-all antagonist-controlled ovarian stimulation (COS) protocol from 2015 to 2023. Patients were grouped into pregnant and nonpregnant groups, and their data, including demographics, COS and ET outcomes, and embryo storage duration, were analyzed. Results: Patient body mass index, cause of infertility, follicle-to-oocyte index, distribution of blastocyst grades, number of transferred embryos, and embryo storage duration were not significantly different between the groups. In a simple comparative analysis, patients with successful clinical pregnancy tended to have significantly lower female and male age (33.83±3.67 and 35.32±4.54 years vs. 37.07±4.15 and 39.33±5.60 years, respectively), higher anti-Müllerian hormone levels (6.27±5.32 ng/mL vs. 4.14±3.82 ng/mL) and antral follicle counts (14.20±8.26 vs. 10.04±5.75), and higher numbers of retrieved oocytes and metaphase II oocytes (13.74±6.92 and 9.64±6.19 vs. 11.21±6.04 and 7.53±5.56, respectively). Multivariate logistic regression analysis of these variables revealed that only male age was a significant factor for successful clinical pregnancy (odds ratio, 4.768; 95% confidence interval, 1.252–18.162; p=0.022). Conclusion During the first programmed ET using blastocysts collected under the freeze-all antagonist COS protocol, male age and correspondingly the quality of gametes for fertilization were crucial for successful pregnancy, having more importance than calculated female ovarian reserve and embryo storage duration.