1.Shikonin Promotes Skin Cell Proliferation and Inhibits Nuclear Factor-κB Translocation via Proteasome Inhibition In Vitro.
Yan YAN ; Minao FURUMURA ; Takako GOUYA ; Atsufumi IWANAGA ; Kwesi TEYE ; Sanae NUMATA ; Tadashi KARASHIMA ; Xiao-Guang LI ; Takashi HASHIMOTO
Chinese Medical Journal 2015;128(16):2228-2233
BACKGROUNDShikonin is a major active chemical component extracted from Lithospermi Radix, an effective traditional herb in various types of wound healing. Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue. The purpose of the study was to investigate its mechanism of action in human skin cells.
METHODSMTS assay was used to measure cell growth. The collagen type I (COL1 ) mRNA expression and procollagen type I C-peptide (PIP) production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-κB (NF-κB) signaling pathway. Cell-based proteasome activity assay was used to determine proteasome activity.
RESULTSIn this study, we found that 10 μmol/L shikonin stimulated the growth of normal human keratinocytes and 1 μmol/L shikonin promoted growth of human dermal fibroblasts. However, shikonin did not directly induce COL1 mRNA expression and PIP production in dermal fibroblasts in vitro. In addition, 1 μmol/L shikonin inhibited translocation of NF-κB p65 from cytoplasm to nucleus induced by tumor necrosis factor-α stimulation in dermal fibroblasts. Furthermore, shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation of phosphorylated inhibitor κB-α in dermal fibroblasts.
CONCLUSIONSThese results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome. Thus, shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases.
Cell Proliferation ; drug effects ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; drug effects ; Humans ; Keratinocytes ; drug effects ; NF-kappa B ; metabolism ; Naphthoquinones ; pharmacology ; Polymerase Chain Reaction ; Proteasome Endopeptidase Complex ; drug effects ; Skin ; cytology
2.Schwannoma in the extremity: clinical features and microscopic intra-capsular enucleation
Keiichi MURAMATSU ; Yasuhiro TANI ; Tetsuya SETO ; Ryuta IWANAGA ; Atsushi MIHARA ; Koichiro IHARA ; Takashi SAKAI
Journal of Rural Medicine 2021;16(4):184-190
Objective: Schwannomas are the most common type of neoplasm of the peripheral nerves. Enucleation is a standard surgical procedure; however, it occasionally results in iatrogenic nerve injury, even with atraumatic procedures. Herein, we present the clinical characteristics of schwannoma arising in the extremities and discuss the clinical outcomes of extra- and intra-capsular enucleation.Patients and Methods: We reviewed 122 schwannomas treated at our institute. Schwannomas arising from the minor nerve (n=30) or intramuscularly (n=15) were operated using the extra-capsular technique. Of the 77 major nerve schwannomas, 62 schwannomas were treated using the intra-capsular technique and 15 schwannomas using the extra-capsular technique.Results: Neurological deficits following enucleation were significantly lower using the intra-capsular technique than with the extra-capsular technique. The patient age, duration of symptoms, maximum tumor diameter, and site of occurrence were not associated with subsequent neurological deficits. With both techniques, no tumor recurrence was observed at the final follow-up.Conclusion: These results support the use of intra-capsular micro-enucleation as a safe and reliable treatment for every type of schwannoma. To minimize the risk of nerve injury, en bloc resection should not be used because the main purpose of schwannoma surgery is the relief of symptoms, not tumor resection.
3.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
4.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
5.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
6.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
7.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.