The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

and Relevance: This case is the first instance of using tracheal stenting to effectively manage tracheal stenosis in a cat, successfully resolving a respiratory emergency, and ensuring long-term care.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Heart failure (HF) is a major cause of mortality and morbidity in South Korea, imposing substantial physical, emotional, and financial burdens on patients and society. Despite the high burden of symptom and complex care needs of HF patients, palliative care and hospice services remain underutilized in South Korea due to cultural, institutional, and knowledge-related barriers. This position statement from the Korean Society of Heart Failure emphasizes the need for integrating palliative and hospice care into HF management to improve quality of life and support holistic care for patients and their families. By clarifying the role of palliative care in HF and proposing practical referral criteria, this position statement aims to bridge the gap between HF and palliative care services in South Korea, ultimately improving patient-centered outcomes and aligning treatment with the goals and values of HF patients.

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.

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.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.