Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Background and Objectives: The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience. Methods: Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored. Results: The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA. Conclusions The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.

Background and Objectives: The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments. Methods: In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments. Results: We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied). Conclusion Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.

Background and Objectives: The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments. Methods: In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments. Results: We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied). Conclusion Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.

Background and Objectives: The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments. Methods: In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments. Results: We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied). Conclusion Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.