1.Photodynamic performance and anti-lung cancer effect of novel chlorin compounds
Yan QIU ; Hao WU ; Yafen DONG ; Ye CHEN ; Jian WANG ; Hui JIN
Journal of Pharmaceutical Practice and Service 2026;44(1):39-45
<b>Objectiveb> To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) acetic acid(<b>D1b>)and 4-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) butanoic acid (<b>D2b>). <b>Methodsb> The ultraviolet visible absorption spectrum and fluorescence spectrum of <b>D1 b>and <b>D2 b>were determined. The singlet oxygen generation capacity of <b>D1b> and <b>D2b> was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of <b>D2b> in nude mice, its distribution in tumor tissue and skin tissue were further detected. <b>Resultsb> <b>D1b> and <b>D2b> had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. <b>D1 b>and <b>D2b> had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, <b>D1b> and <b>D2b> showed significant antitumor activity in vivo and in vitro (P<0.01). However, <b>D2b> could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. <b>Conclusionb> <b>D2b> had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.
2.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.
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.Erratum to: Advantages of contrast-enhanced ultrasound in the localization and diagnostics of sentinel lymph nodes in breast cancer.
Qiuhui YANG ; Yeqin FU ; Jiaxuan WANG ; Hongjian YANG ; Xiping ZHANG
Journal of Zhejiang University. Science. B 2025;26(3):302-302
The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.
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.
8.Bioisosterism-driven design of orally active, safe, and broad-spectrum biphenyl-DAPY derivatives as highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
Xiao-Mei CHEN ; Qing-Qing HAO ; Christophe PANNECOUQUE ; Erik DE CLERCQ ; Shuai WANG ; Fen-Er CHEN
Acta Pharmaceutica Sinica B 2025;15(8):4115-4136
This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound <b>A12b> demonstrated exceptional efficacy against both WT HIV-1 (EC50 = 1.9 nmol/L) and seven mutant strains (EC50 = 1.7-157 nmol/L), surpassing that of the lead compound <b>6b> and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC50 = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC50 > 4.6 μmol/L, SI > 1436) and rilpivirine (CC50 = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC50 = 6.99-25 μmol/L) and hERG (IC50 > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, <b>A12b> exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T 1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that <b>A12b> could serve as a promising drug candidate for HIV treatment.
9.Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand.
Xin ZHOU ; Jiahui CHEN ; Jimmy S PATEL ; Wenqing RAN ; Yinlong LI ; Richard S VAN ; Mostafa M H IBRAHIM ; Chunyu ZHAO ; Yabiao GAO ; Jian RONG ; Ahmad F CHAUDHARY ; Guocong LI ; Junqi HU ; April T DAVENPORT ; James B DAUNAIS ; Yihan SHAO ; Chongzhao RAN ; Thomas L COLLIER ; Achi HAIDER ; David M SCHUSTER ; Allan I LEVEY ; Lu WANG ; Gabriel CORFAS ; Steven H LIANG
Acta Pharmaceutica Sinica B 2025;15(10):5036-5049
Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its 18F-isotopologue ([18F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [18F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [18F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.
10.Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management.
Zheng ZHAO ; Zhiwei CHEN ; Jacques CROMMEN ; Shengfeng HUANG ; Qiqin WANG ; Zhengjin JIANG
Acta Pharmaceutica Sinica B 2025;15(11):5632-5662
Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

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