Dyslipidemia is a hallmark of obstructive sleep apnea (OSA)-induced metabolic syndrome, yet the mechanisms remain poorly understood. We conducted a genome-wide association study on lipid traits in the OSA cohorts, identifying the SNP rs3745683 in ANGPTL8, significantly associated with reductions in multiple lipid traits. ANGPTL8, an essential lipogenic hormone and potential therapeutic target for metabolic syndrome, showed elevated expression in OSA patients compared to healthy controls, strongly correlated with increased insulin levels. Notably, ANGPTL8 expression can be upregulated by insulin stimulation, indicating it as an insulin-responsive hormone regulating dyslipidemia in OSA. Mechanistically, SNP rs3745683 attenuated ANGPTL8 transcription by inhibiting its binding to transcription factor YBX1. Insulin prompted AKT1 to phosphorylate YBX1 at Ser102, facilitating YBX1's nuclear translocation and subsequent regulation of ANGPTL8 expression and lipid synthesis. Specific knockdown of YBX1 in mouse liver confirmed its necessity for ANGPTL8 expression and hepatic lipid synthesis in vivo. Our findings highlight ANGPTL8 as a critical regulator of dyslipidemia in OSA patients, offering a promising therapeutic avenue for managing metabolic syndrome in OSA.
血脂异常是阻塞性睡眠呼吸暂停（OSA）诱发的代谢综合征的特征之一，但对其机制仍知之甚少。我们对 OSA 队列中的血脂特征进行了全基因组关联研究，发现 ANGPTL8 中的 SNP rs3745683 与多种血脂特征的降低显著相关。ANGPTL8是一种重要的致脂激素，也是代谢综合征的潜在治疗靶点，与健康对照组相比，它在OSA患者中的表达升高，与胰岛素水平的升高密切相关。值得注意的是，ANGPTL8的表达可因胰岛素刺激而上调，这表明它是一种胰岛素反应性激素，可调节OSA患者的血脂异常。从机理上讲，SNP rs3745683通过抑制ANGPTL8与转录因子YBX1的结合，减弱了ANGPTL8的转录。胰岛素促使 AKT1 在 Ser102 处磷酸化 YBX1，促进 YBX1 的核转位，进而调节 ANGPTL8 的表达和脂质合成。在小鼠肝脏中特异性敲除 YBX1 证实了其对 ANGPTL8 表达和体内肝脂合成的必要性。我们的研究结果突出表明，ANGPTL8 是 OSA 患者血脂异常的关键调节因子，这为控制 OSA 代谢综合征提供了一条很有前景的治疗途径。
{"title":"Insulin-AKT1-YBX1 Regulation of ANGPTL8 Promote Lipogenesis in OSA-Associated Dyslipidemia","authors":"Feng Liu, Yuenan Liu, Haolin Yuan, Anzhao Wang, Shengming Wang, Xu Xu, Junhui Hu, Jinhong Shen, Yiming Hu, Xinyi Li, Niannian Li, Zhenfei Gao, Xiaoxu Zhang, Xiaoman Zhang, Yupu Liu, Huajun Xu, Hongliang Yi, Jian Guan, Zhiqiang Li, Yongxu Zhao, Shankai Yin","doi":"10.1101/2024.06.23.24309370","DOIUrl":"https://doi.org/10.1101/2024.06.23.24309370","url":null,"abstract":"Dyslipidemia is a hallmark of obstructive sleep apnea (OSA)-induced metabolic syndrome, yet the mechanisms remain poorly understood. We conducted a genome-wide association study on lipid traits in the OSA cohorts, identifying the SNP rs3745683 in ANGPTL8, significantly associated with reductions in multiple lipid traits. ANGPTL8, an essential lipogenic hormone and potential therapeutic target for metabolic syndrome, showed elevated expression in OSA patients compared to healthy controls, strongly correlated with increased insulin levels. Notably, ANGPTL8 expression can be upregulated by insulin stimulation, indicating it as an insulin-responsive hormone regulating dyslipidemia in OSA. Mechanistically, SNP rs3745683 attenuated ANGPTL8 transcription by inhibiting its binding to transcription factor YBX1. Insulin prompted AKT1 to phosphorylate YBX1 at Ser102, facilitating YBX1's nuclear translocation and subsequent regulation of ANGPTL8 expression and lipid synthesis. Specific knockdown of YBX1 in mouse liver confirmed its necessity for ANGPTL8 expression and hepatic lipid synthesis in vivo. Our findings highlight ANGPTL8 as a critical regulator of dyslipidemia in OSA patients, offering a promising therapeutic avenue for managing metabolic syndrome in OSA.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1101/2024.06.18.24308570
Arne Kildahl-Andersen, Erlend Fagertun Hofstad, Ole-Vegard Solberg, Hanne Sorger, Tore Amundsen, Thomas Langø, Håkon Olav Leira
Background and objective: Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data. Methods: The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings. Results: The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm. Conclusion: Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.
背景和目的：疑似肺癌患者接受支气管内超声支气管镜检查（EBUS）是为了诊断和分期。对于推定可治愈的患者，EBUS 支气管镜检查是根据计算机断层扫描（CT）图像和正电子发射断层扫描（PET）的图像和数据来计划的。我们的研究旨在评估用于 EBUS 支气管镜检查的多模态电磁导航平台的可行性，该平台整合了超声、分段 CT 和 PET 扫描成像数据：这项概念验证研究的对象包括疑似肺癌患者，以及在 CT 和 PET 扫描中均发现病理纵隔/肺门淋巴结的患者。对从这两种方式获得的图像进行分割，以划定目标淋巴结，然后将其纳入 CustusX 导航平台。EBUS 支气管镜配备了一个传感器，经过校准后固定在支气管镜顶端的 3D 打印点击装置上。术后使用超声记录测量导航准确性：该研究共招募了三名患者，他们都是纵隔淋巴结转移（N1-3）的疑似患者。在 EBUS 手术过程中，导航平台显示了所有 PET 阳性淋巴结。共采集了五个不同淋巴结的样本，其中三个淋巴结采集到恶性细胞，其余两个淋巴结采集到淋巴细胞。导航系统的中位精确度为 7.7 毫米：我们的研究介绍了一种可行的多模态电磁导航平台，该平台将术中超声与术前分割 CT 和 PET 成像数据相结合，用于 EBUS 淋巴结分期检查。这种创新方法有望提高 EBUS 手术的准确性和有效性。
{"title":"Navigated ultrasound bronchoscopy with integrated positron emission tomography - A human feasibility study","authors":"Arne Kildahl-Andersen, Erlend Fagertun Hofstad, Ole-Vegard Solberg, Hanne Sorger, Tore Amundsen, Thomas Langø, Håkon Olav Leira","doi":"10.1101/2024.06.18.24308570","DOIUrl":"https://doi.org/10.1101/2024.06.18.24308570","url":null,"abstract":"Background and objective: Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.\u0000Methods: The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings.\u0000Results: The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.\u0000Conclusion: Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.30.24308242
Tiejun Wu, Tao Wang, Jinjiao Jiang, Yue Tang, Lina Zhang, Zhiming Jiang, Fen Liu, Guiqing Kong, Tingfa Zhou, Ruijin Liu, Haipeng Guo, Jie Xiao, Wenqing Sun, Yuye Li, Yingying Zhu, Quan Liu, Weifeng Xie, Yan Qu, Xiaozhi Wang
Objectives Neutrophil elastase (NE) plays an important role in the development of acute respiratory distress syndrome (ARDS). Sivelestat sodium, as a selective NE inhibitor, may improve the outcomes of patients with sepsis-induced ARDS in previous studies, but there is a lack of solid evidence. This trial aimed to evaluate the effect of sivelestat sodium on oxygenation in patients with sepsis-induced ARDS.
{"title":"Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) on Oxygenation in Patients with Sepsis Induced Acute Respiratory Distress Syndrome","authors":"Tiejun Wu, Tao Wang, Jinjiao Jiang, Yue Tang, Lina Zhang, Zhiming Jiang, Fen Liu, Guiqing Kong, Tingfa Zhou, Ruijin Liu, Haipeng Guo, Jie Xiao, Wenqing Sun, Yuye Li, Yingying Zhu, Quan Liu, Weifeng Xie, Yan Qu, Xiaozhi Wang","doi":"10.1101/2024.05.30.24308242","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308242","url":null,"abstract":"<strong>Objectives</strong> Neutrophil elastase (NE) plays an important role in the development of acute respiratory distress syndrome (ARDS). Sivelestat sodium, as a selective NE inhibitor, may improve the outcomes of patients with sepsis-induced ARDS in previous studies, but there is a lack of solid evidence. This trial aimed to evaluate the effect of sivelestat sodium on oxygenation in patients with sepsis-induced ARDS.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.29.24308131
Emmanuelle Bardin, Hélène Salvator, Camille Roquencourt, Elodie Lamy, Nicolas Hunzinger, Isabelle Sermet-Gaudelus, Sandra De Miranda, Dominique Grenet, Philippe Devillier, Stanislas Grassin-Delyle
Background The combination of CFTR modulators ivacaftor/tezacaftor/elexacaftor (ETI) achieves unprecedented improvements in clinical symptoms and respiratory function of people with cystic fibrosis. Yet, evaluation is difficult in people with high baseline lung function and the sweat test may vary depending on the type of CFTR mutation. Exhaled breath is a non-invasive sample, rich in personalised metabolic information and breathomics has emerged as a promising tool to monitor and assess therapeutic response. We hypothesised that ETI induces alterations in the breath composition and that these changes may correlate with clinical readouts.
背景 CFTR调节剂ivacaftor/tezacaftor/elexacaftor（ETI）的组合能前所未有地改善囊性纤维化患者的临床症状和呼吸功能。然而，对于基线肺功能较高的患者来说，评估工作十分困难，而且出汗试验会因 CFTR 突变类型的不同而有所差异。呼出的气体是一种非侵入性样本，含有丰富的个性化代谢信息，呼吸组学已成为监测和评估治疗反应的一种有前途的工具。我们假设 ETI 会引起呼气成分的改变，而这些改变可能与临床读数相关。
{"title":"Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: an open-label proof-of-concept study","authors":"Emmanuelle Bardin, Hélène Salvator, Camille Roquencourt, Elodie Lamy, Nicolas Hunzinger, Isabelle Sermet-Gaudelus, Sandra De Miranda, Dominique Grenet, Philippe Devillier, Stanislas Grassin-Delyle","doi":"10.1101/2024.05.29.24308131","DOIUrl":"https://doi.org/10.1101/2024.05.29.24308131","url":null,"abstract":"<strong>Background</strong> The combination of CFTR modulators ivacaftor/tezacaftor/elexacaftor (ETI) achieves unprecedented improvements in clinical symptoms and respiratory function of people with cystic fibrosis. Yet, evaluation is difficult in people with high baseline lung function and the sweat test may vary depending on the type of CFTR mutation. Exhaled breath is a non-invasive sample, rich in personalised metabolic information and breathomics has emerged as a promising tool to monitor and assess therapeutic response. We hypothesised that ETI induces alterations in the breath composition and that these changes may correlate with clinical readouts.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.30.24308215
Linh T. Ngo, Michaella J. Rekowski, Devin C. Koestler, Takafumi Yorozuya, Atsushi Saito, Imaan Azeem, Alexis Harrison, M. Kristen Demoruelle, Jonathan Boomer, Bryant R. England, Paul Wolters, Philip L. Molyneaux, Mario Castro, Joyce S. Lee, Joshua J. Solomon, Koji Koronuma, Michael P. Washburn, Scott M. Matson
Background Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).
{"title":"Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease","authors":"Linh T. Ngo, Michaella J. Rekowski, Devin C. Koestler, Takafumi Yorozuya, Atsushi Saito, Imaan Azeem, Alexis Harrison, M. Kristen Demoruelle, Jonathan Boomer, Bryant R. England, Paul Wolters, Philip L. Molyneaux, Mario Castro, Joyce S. Lee, Joshua J. Solomon, Koji Koronuma, Michael P. Washburn, Scott M. Matson","doi":"10.1101/2024.05.30.24308215","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308215","url":null,"abstract":"<strong>Background</strong> Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and Objectives Cough is a common symptom of respiratory diseases and change in the cough sound can reflect a pathological condition in the lungs. Recent advancement on the analysis of the cough sound has suggested that it has the potential to be used as a non-invasive marker for screening respiratory conditions, such as Asthma, Chronic Pulmonary Obstructive Disease (COPD), Interstitial Lung Disease (ILD) and Bronchiectasis. The energy envelope is distinguishable for normal subjects versus subjects with respiratory conditions. Peak analysis of the energy envelope helps in quantifying the feature variation for these conditions.
{"title":"Identification of Respiratory Diseases using Peak Energy Analysis of Acoustic Cough","authors":"Sujith Thomas Chandy, Balamugesh Thangakunam, Gowrisree Rudraraju, Narayana Rao Sripada, Jayanthy Govindaraj, Charishma Gottipulla, Baswaraj Mamidgi, Shubha Deepti Palreddy, Nikhil kumar Reddy Bhoge, Harsha Vardhan Reddy Narreddy, Prasanna Samuel P, Devasahayam Jesudas Christopher, Venkat Yechuri","doi":"10.1101/2024.05.29.24308077","DOIUrl":"https://doi.org/10.1101/2024.05.29.24308077","url":null,"abstract":"<strong>Background and Objectives</strong> Cough is a common symptom of respiratory diseases and change in the cough sound can reflect a pathological condition in the lungs. Recent advancement on the analysis of the cough sound has suggested that it has the potential to be used as a non-invasive marker for screening respiratory conditions, such as Asthma, Chronic Pulmonary Obstructive Disease (COPD), Interstitial Lung Disease (ILD) and Bronchiectasis. The energy envelope is distinguishable for normal subjects versus subjects with respiratory conditions. Peak analysis of the energy envelope helps in quantifying the feature variation for these conditions.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.31.24308236
Bedado Dulo, Gamachu Hinsene, Ephrem Mannekulih
Background Acute viral origins account for around 80% of respiratory illnesses globally. The influenza virus, respiratory syncytial virus, coronavirus, adenovirus, and rhinovirus are the main viruses that cause these illnesses. All ages are susceptible to severe acute respiratory infections, which have a high rate of morbidity and mortality.
{"title":"Viral etiology of respiratory infections among patients at Adama Hospital Medical College, a facility-based surveillance site in Oromia, Ethiopia","authors":"Bedado Dulo, Gamachu Hinsene, Ephrem Mannekulih","doi":"10.1101/2024.05.31.24308236","DOIUrl":"https://doi.org/10.1101/2024.05.31.24308236","url":null,"abstract":"<strong>Background</strong> Acute viral origins account for around 80% of respiratory illnesses globally. The influenza virus, respiratory syncytial virus, coronavirus, adenovirus, and rhinovirus are the main viruses that cause these illnesses. All ages are susceptible to severe acute respiratory infections, which have a high rate of morbidity and mortality.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-28DOI: 10.1101/2024.05.28.24307995
Yunli Zhao, Ya Gao, Gordon Guyatt, Timothy M. Uyeki, Ping Liu, Ming Liu, Yanjiao Shen, Xiaoyan Chen, Shuyue Luo, Xingsheng Li, Rongzhong Huang, Qiukui Hao
Background To support an update of WHO influenza guidelines, we performed a systematic review and network meta-analysis of the evidence on antiviral drugs for prophylaxis of influenza.
{"title":"Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis","authors":"Yunli Zhao, Ya Gao, Gordon Guyatt, Timothy M. Uyeki, Ping Liu, Ming Liu, Yanjiao Shen, Xiaoyan Chen, Shuyue Luo, Xingsheng Li, Rongzhong Huang, Qiukui Hao","doi":"10.1101/2024.05.28.24307995","DOIUrl":"https://doi.org/10.1101/2024.05.28.24307995","url":null,"abstract":"<strong>Background</strong> To support an update of WHO influenza guidelines, we performed a systematic review and network meta-analysis of the evidence on antiviral drugs for prophylaxis of influenza.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141197182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-10DOI: 10.1101/2024.05.10.24307167
Ziyue Wang, Vadim Farztdinov, Ludwig Roman Sinn, Pinkus Tober-Lau, Daniela Ludwig, Anja Freiwald, Fatma Amari, Kathrin Textoris-Taube, Agathe Niewienda, Anna Sophie Welter, Alan An Jung Wei, Luise Luckau, Florian Kurth, Matthias Selbach, Johannes Hartl, Michael Mülleder, Markus Ralser
The role of plasma and serum proteomics in characterizing human disease, identifying biomarkers, and advancing diagnostic technologies is rapidly increasing. However, there is an ongoing need to improve proteomic workflows in terms of accuracy, reproducibility, platform transferability, and cost-effectiveness. Here, we present the Charité Open Peptide Standard for Plasma Proteomics (OSPP), a panel of 211 extensively pre-selected, stable-isotope labeled peptides combined in an open, versatile, and cost-effective internal standard for targeted and untargeted plasma and serum proteomics studies. The selected peptides show consistent quantification properties in human studies, across platforms and matrices, are well suited for chemical synthesis, and distribute homogeneously over proteomics-typical chromatographic gradients. Being derived from proteins that function in a wide range of biological processes, including several that are routinely used in clinical tests or are targets of FDA-approved drugs, the OSPP quantifies proteins that are important for human disease. On an acute COVID-19 in-patient cohort, we demonstrate the application of the OSPP to i) achieve patient classification and biomarker identification, ii) generate comparable quantitative proteome data with both targeted and untargeted proteomic approaches, and iii) estimate absolute peptide quantities to achieve cross-platform alignment across targeted, data-dependent and data-independent acquisition (DIA) proteomic methods on different instrument platforms. The OSPP adds only cents of cost per proteome sample, thus making the use of an internal standard cost-effective and accessible. In addition to the standards, corresponding spectral libraries and optimized acquisition methods for several platforms are made openly available.
{"title":"Cross-platform Clinical Proteomics using the Charité Open Standard for Plasma Proteomics (OSPP)","authors":"Ziyue Wang, Vadim Farztdinov, Ludwig Roman Sinn, Pinkus Tober-Lau, Daniela Ludwig, Anja Freiwald, Fatma Amari, Kathrin Textoris-Taube, Agathe Niewienda, Anna Sophie Welter, Alan An Jung Wei, Luise Luckau, Florian Kurth, Matthias Selbach, Johannes Hartl, Michael Mülleder, Markus Ralser","doi":"10.1101/2024.05.10.24307167","DOIUrl":"https://doi.org/10.1101/2024.05.10.24307167","url":null,"abstract":"The role of plasma and serum proteomics in characterizing human disease, identifying biomarkers, and advancing diagnostic technologies is rapidly increasing. However, there is an ongoing need to improve proteomic workflows in terms of accuracy, reproducibility, platform transferability, and cost-effectiveness. Here, we present the Charité <em><span>O</span>pen Peptide <span>S</span>tandard for <span>P</span>lasma <span>P</span>roteomics</em> (OSPP), a panel of 211 extensively pre-selected, stable-isotope labeled peptides combined in an open, versatile, and cost-effective internal standard for targeted and untargeted plasma and serum proteomics studies. The selected peptides show consistent quantification properties in human studies, across platforms and matrices, are well suited for chemical synthesis, and distribute homogeneously over proteomics-typical chromatographic gradients. Being derived from proteins that function in a wide range of biological processes, including several that are routinely used in clinical tests or are targets of FDA-approved drugs, the OSPP quantifies proteins that are important for human disease. On an acute COVID-19 in-patient cohort, we demonstrate the application of the OSPP to i) achieve patient classification and biomarker identification, ii) generate comparable quantitative proteome data with both targeted and untargeted proteomic approaches, and iii) estimate absolute peptide quantities to achieve cross-platform alignment across targeted, data-dependent and data-independent acquisition (DIA) proteomic methods on different instrument platforms. The OSPP adds only cents of cost per proteome sample, thus making the use of an internal standard cost-effective and accessible. In addition to the standards, corresponding spectral libraries and optimized acquisition methods for several platforms are made openly available.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140939501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The comparison between traditional Chinese medicine Jinzhen Oral Liquid (JZOL) and western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This head to head randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1 and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels was the key mechanism of action.
{"title":"Depicting the regulatory role of JZOL on TRP channels in the treatment of Acute Bronchitis based on the combination of clinical trials, computational analysis and in vivo experiments","authors":"Qinhua Fan, Chongming Wu, Yawei Du, Boyang Wang, Yanming Xie, Zeling Zhang, Wenquan Su, Zizhuo Wang, Changchang Xu, Xueke Li, Ying Ding, Xinjiang An, Jing Chen, Yunying Xiao, Rong Yu, Nan Li, Juan Wang, Yiqun Teng, Hongfen Lv, Nian Yang, Yuling Wen, Xiaoli Huang, Wei Pan, Yufeng Liu, Xueqin Xi, Qianye Zhao, Changshan Liu, Jian Xu, Haitao Zhang, Lie Zhuo, Qiangquan Rong, Yu Xia, Qin Shen, Shao Li, Junhong Wang, Shengxian Wu","doi":"10.1101/2024.05.07.24306993","DOIUrl":"https://doi.org/10.1101/2024.05.07.24306993","url":null,"abstract":"The comparison between traditional Chinese medicine Jinzhen Oral Liquid (JZOL) and western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This head to head randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1 and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels was the key mechanism of action.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140939500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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