Background/Aims: Serum gastrin levels may be elevated following proton pump inhibitor (PPI) therapy. We aim to elucidate the predictors for the development of hypergastrinemia in maintenance treatment for mild gastroesophageal reflux disease (GERD) using a half-dose PPI. Methods: This study analyzed data from a prospective randomized trial to compare continuous versus on-demand maintenance treatment modalities in patients with mild GERD. Age, sex, body mass index, Helicobacter pylori infection, serum gastrin levels, pepsinogen (PG) I/II ratios, total days of PPI intake, and weight-based PPI dosage (mg/kg) were evaluated. Results: Data from 293 patients who completed a randomized trial were analyzed (continuous group, n = 147 vs on-demand group, n = 146). In univariate analysis, age (P < 0.001), H. pylori infection (P = 0.012), baseline gastrin levels (P < 0.001), and baseline PG ratios (P = 0.016) significantly correlated with post-treatment gastrin levels. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with final serum gastrin levels. In univariate analysis, age (P = 0.018), H. pylori infection (P = 0.028), baseline gastrin levels (P = 0.011), and baseline PG ratios (P = 0.031) significantly correlated with the development of hypergastrinemia. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with the development of hypergastrinemia. Conclusion Old age, high baseline serum gastrin levels, and low baseline PG ratios are significant predictors of the development of hypergastrinemia in maintenance treatment for mild GERD using a half-dose PPI.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Vertebral arteriovenous fistula (VAVF) is a rare lesion characterized by an abnormal connection between the extracranial vertebral artery and the surrounding venous plexus. It typically arises due to penetrating injury, although it can occasionally result from blunt trauma. Brachial plexus injury (BPI) is also infrequently associated with VAVF. We present a rare case of VAVF caused by blunt trauma, which resulted in BPI. The patient, who had previously sustained a C2 fracture and C2–3 myelopathy from a bicycle accident, presented with new-onset weakness in the right upper extremity. His previous clinical history led to an initial suspicion of either an exacerbation of a pre-existing lesion or a shoulder injury. However, electromyography indicated that the weakness was due to BPI. Further evaluations later revealed VAVF to be the primary cause of the BPI. VAVF must be recognized as a rare potential reason for BPI, as timely intervention is essential for improving patient recovery and prognosis.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Background/Aims: Serum gastrin levels may be elevated following proton pump inhibitor (PPI) therapy. We aim to elucidate the predictors for the development of hypergastrinemia in maintenance treatment for mild gastroesophageal reflux disease (GERD) using a half-dose PPI. Methods: This study analyzed data from a prospective randomized trial to compare continuous versus on-demand maintenance treatment modalities in patients with mild GERD. Age, sex, body mass index, Helicobacter pylori infection, serum gastrin levels, pepsinogen (PG) I/II ratios, total days of PPI intake, and weight-based PPI dosage (mg/kg) were evaluated. Results: Data from 293 patients who completed a randomized trial were analyzed (continuous group, n = 147 vs on-demand group, n = 146). In univariate analysis, age (P < 0.001), H. pylori infection (P = 0.012), baseline gastrin levels (P < 0.001), and baseline PG ratios (P = 0.016) significantly correlated with post-treatment gastrin levels. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with final serum gastrin levels. In univariate analysis, age (P = 0.018), H. pylori infection (P = 0.028), baseline gastrin levels (P = 0.011), and baseline PG ratios (P = 0.031) significantly correlated with the development of hypergastrinemia. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with the development of hypergastrinemia. Conclusion Old age, high baseline serum gastrin levels, and low baseline PG ratios are significant predictors of the development of hypergastrinemia in maintenance treatment for mild GERD using a half-dose PPI.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Background/Aims: Serum gastrin levels may be elevated following proton pump inhibitor (PPI) therapy. We aim to elucidate the predictors for the development of hypergastrinemia in maintenance treatment for mild gastroesophageal reflux disease (GERD) using a half-dose PPI. Methods: This study analyzed data from a prospective randomized trial to compare continuous versus on-demand maintenance treatment modalities in patients with mild GERD. Age, sex, body mass index, Helicobacter pylori infection, serum gastrin levels, pepsinogen (PG) I/II ratios, total days of PPI intake, and weight-based PPI dosage (mg/kg) were evaluated. Results: Data from 293 patients who completed a randomized trial were analyzed (continuous group, n = 147 vs on-demand group, n = 146). In univariate analysis, age (P < 0.001), H. pylori infection (P = 0.012), baseline gastrin levels (P < 0.001), and baseline PG ratios (P = 0.016) significantly correlated with post-treatment gastrin levels. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with final serum gastrin levels. In univariate analysis, age (P = 0.018), H. pylori infection (P = 0.028), baseline gastrin levels (P = 0.011), and baseline PG ratios (P = 0.031) significantly correlated with the development of hypergastrinemia. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with the development of hypergastrinemia. Conclusion Old age, high baseline serum gastrin levels, and low baseline PG ratios are significant predictors of the development of hypergastrinemia in maintenance treatment for mild GERD using a half-dose PPI.

Background and Objectives: Metformin, a commonly used antidiabetic drug, has been reported to exhibit promising anticancer effects across various tumor types. This study investigated the effectiveness of combining metformin with radiotherapy (RT) to treat head and neck squamous cell carcinoma (HNSCC).Materials and Method In vitro experiments were conducted in which FaDu and SCC-25 cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated by MTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/ propidium iodide, followed by flow cytometry. Western blotting was performed to evaluate changes in apoptotic markers. In vivo experiments were performed using a murine AT-84 allograft model, where tumor volume was measured and serum samples were collected to assess the level of vascular endothelial growth factor (VEGF). Results: The combination of metformin and RT significantly reduced cell proliferation in a dose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompanied by the upregulation of cleaved caspase-8 and FoxO3, and the downregulation of Bcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reduced hypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelial cells. The combined therapy in the mouse model led to marked decrease in tumor volume and the serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation, triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These results support the use of metformin as an adjunct to RT for the treatment of HNSCC.

Purpose: Human breast milk (HBM) contains immune components that produced and delivered from the mother along with nutrients necessary for the baby. MicroRNA (miRNA) is a small noncoding RNA molecule, that is used as an ideal biomarker for diagnosis and prognosis of various diseases and are more abundant in HBM. We analyzed and compared the immune components and miRNAs of HBM. Methods: HBM were collected from 20 healthy breastfeeding mothers. We measured the amount of lactoferrin, lysozyme, and immunoglobulin A (IgA) and extracted the miRNAs from each breast milk samples. Next, the top 5 and bottom 5 expressed miRNAs were compared and analyzed based on the amounts of the 3 immune components. Results: The mean levels and ranges of lactoferrin, lysozyme, and IgA were 6.33 (2.24–14.77)×106 ng/mL, 9.90 (1.42–17.59)×107 pg/mL, and 6.64 (0.48–20.01)×105 ng/mL, respectively. The miRNAs concentration per 1 mL of skim milk was 40.54 (14.95–110.01) ng/μL. Comparing the bottom 5 and top 5 groups of each immune component, 19 miRNAs were significantly upregulated (6, 9, and 4 targeting lactoferrin, lysozyme, and IgA, respectively) and 21 were significantly downregulated (4, 9, and 8 targeting lactoferrin, lysozyme, and IgA, respectively). There were no miRNAs that were expressed significantly higher or lower in common to all 3 components.However, 2 and 3 miRNAs were commonly overexpressed and underexpressed, in the top 5 groups of lysozyme and IgA concentrations. Conclusion We identified the immune components and miRNAs in breast milk and found that each individual has different ingredients.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.