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Article: Modulation of experimental acute lung injury by exosomal miR-7704 from mesenchymal stromal cells acts through M2 macrophage polarization.

Lin, Wei-Ting / Wu, Hao-Hsiang / Lee, Chien-Wei / Chen, Yu-Fan / Huang, Lawrence / Hui-Chun Ho, Jennifer / Kuang-Sheng Lee, Oscar

Molecular therapy. Nucleic acids

2023 Volume 35, Issue 1, Page(s) 102102

Abstract: Acute lung injury (ALI) is a life-threatening condition with limited treatment options. The pathogenesis of ALI involves macrophage-mediated disruption and subsequent repair of the alveolar barriers, which ultimately results in lung damage and ... ...

Abstract	Acute lung injury (ALI) is a life-threatening condition with limited treatment options. The pathogenesis of ALI involves macrophage-mediated disruption and subsequent repair of the alveolar barriers, which ultimately results in lung damage and regeneration, highlighting the pivotal role of macrophage polarization in ALI. Although exosomes derived from mesenchymal stromal cells have been established as influential modulators of macrophage polarization, the specific role of exosomal microRNAs (miRNAs) remains underexplored. This study aimed to elucidate the role of specific exosomal miRNAs in driving macrophage polarization, thereby providing a reference for developing novel therapeutic interventions for ALI. We found that miR-7704 is the most abundant and efficacious miRNA for promoting the switch to the M2 phenotype in macrophages. Mechanistically, we determined that miR-7704 stimulates M2 polarization by inhibiting the MyD88/STAT1 signaling pathway. Notably, intra-tracheal delivery of miR-7704 alone in a lipopolysaccharide-induced murine ALI model significantly drove M2 polarization in lung macrophages and remarkably restored pulmonary function, thus increasing survival. Our findings highlight miR-7704 as a valuable tool for treating ALI by driving the beneficial M2 polarization of macrophages. Our findings pave the way for deeper exploration into the therapeutic potential of exosomal miRNAs in inflammatory lung diseases.
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2023.102102
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Article ; Online: Clinical Efficacy of Omidenepag Isopropyl for Primary Open-Angle Glaucoma, Normal Tension Glaucoma, or Ocular Hypertension: A Meta-Analysis.

Kuo, Hou-Ting / Yeh, Cyuan-Yi / Hsu, Alan Y / Ho, Jennifer Hui-Chun / Lin, Chun-Ju / Tsai, Yi-Yu

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

2023 Volume 39, Issue 10, Page(s) 705–715

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Humans ; Aged ; Low Tension Glaucoma/drug therapy ; Glaucoma, Open-Angle/drug therapy ; Intraocular Pressure ; Glaucoma/drug therapy ; Ocular Hypertension/drug therapy ; Treatment Outcome ; Antihypertensive Agents/pharmacology ; Antihypertensive Agents/therapeutic use
Chemical Substances	omidenepag isopropyl (G0G0H52U6K) ; Antihypertensive Agents
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Systematic Review ; Meta-Analysis ; Journal Article
ZDB-ID	1237021-6
ISSN	1557-7732 ; 1080-7683
ISSN (online)	1557-7732
ISSN	1080-7683
DOI	10.1089/jop.2023.0058
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Article ; Online: Performance and Limitation of Machine Learning Algorithms for Diabetic Retinopathy Screening: Meta-analysis.

Wu, Jo-Hsuan / Liu, T Y Alvin / Hsu, Wan-Ting / Ho, Jennifer Hui-Chun / Lee, Chien-Chang

Journal of medical Internet research

2021 Volume 23, Issue 7, Page(s) e23863

Abstract: Background: Diabetic retinopathy (DR), whose standard diagnosis is performed by human experts, has high prevalence and requires a more efficient screening method. Although machine learning (ML)-based automated DR diagnosis has gained attention due to ... ...

Abstract	Background: Diabetic retinopathy (DR), whose standard diagnosis is performed by human experts, has high prevalence and requires a more efficient screening method. Although machine learning (ML)-based automated DR diagnosis has gained attention due to recent approval of IDx-DR, performance of this tool has not been examined systematically, and the best ML technique for use in a real-world setting has not been discussed. Objective: The aim of this study was to systematically examine the overall diagnostic accuracy of ML in diagnosing DR of different categories based on color fundus photographs and to determine the state-of-the-art ML approach. Methods: Published studies in PubMed and EMBASE were searched from inception to June 2020. Studies were screened for relevant outcomes, publication types, and data sufficiency, and a total of 60 out of 2128 (2.82%) studies were retrieved after study selection. Extraction of data was performed by 2 authors according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), and the quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis of diagnostic accuracy was pooled using a bivariate random effects model. The main outcomes included diagnostic accuracy, sensitivity, and specificity of ML in diagnosing DR based on color fundus photographs, as well as the performances of different major types of ML algorithms. Results: The primary meta-analysis included 60 color fundus photograph studies (445,175 interpretations). Overall, ML demonstrated high accuracy in diagnosing DR of various categories, with a pooled area under the receiver operating characteristic (AUROC) ranging from 0.97 (95% CI 0.96-0.99) to 0.99 (95% CI 0.98-1.00). The performance of ML in detecting more-than-mild DR was robust (sensitivity 0.95; AUROC 0.97), and by subgroup analyses, we observed that robust performance of ML was not limited to benchmark data sets (sensitivity 0.92; AUROC 0.96) but could be generalized to images collected in clinical practice (sensitivity 0.97; AUROC 0.97). Neural network was the most widely used method, and the subgroup analysis revealed a pooled AUROC of 0.98 (95% CI 0.96-0.99) for studies that used neural networks to diagnose more-than-mild DR. Conclusions: This meta-analysis demonstrated high diagnostic accuracy of ML algorithms in detecting DR on color fundus photographs, suggesting that state-of-the-art, ML-based DR screening algorithms are likely ready for clinical applications. However, a significant portion of the earlier published studies had methodology flaws, such as the lack of external validation and presence of spectrum bias. The results of these studies should be interpreted with caution.
MeSH term(s)	Algorithms ; Diabetes Mellitus ; Diabetic Retinopathy/diagnosis ; Diagnostic Techniques, Ophthalmological ; Humans ; Machine Learning ; Neural Networks, Computer
Language	English
Publishing date	2021-07-03
Publishing country	Canada
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2028830-X
ISSN	1438-8871 ; 1439-4456
ISSN (online)	1438-8871
ISSN	1439-4456
DOI	10.2196/23863
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Article ; Online: Mesenchymal stem cells prolong survival and prevent lethal complications in a porcine model of fulminant liver failure.

Lin, Niang-Cheng / Wu, Hao-Hsiang / Ho, Jennifer Hui-Chun / Liu, Chin-Su / Lee, Oscar Kuang-Sheng

Xenotransplantation

2019 Volume 26, Issue 6, Page(s) e12542

Abstract: Background: Fulminant liver failure (FLF) is a life-threatening disease.: Methods: Lethal FLF was induced by ischemia-reperfusion (I-R) injury in mini-pigs, and MSCs were infused via splenic vein after reperfusion.: Results: Accumulated survival ... ...

Abstract	Background: Fulminant liver failure (FLF) is a life-threatening disease. Methods: Lethal FLF was induced by ischemia-reperfusion (I-R) injury in mini-pigs, and MSCs were infused via splenic vein after reperfusion. Results: Accumulated survival within 28 days was significantly improved by MSCs (P = 0.0348). Notably, MSCs maintained blood-gas homeostasis in the first 24 hours and prevented FLF-induced elevation of prothrombin time, international normalized ratio, and creatinine and ammonia levels in the first 3 days. With MSCs, serum levels of liver enzymes gradually decreased after 3 days, and platelet count was back to normal at 1 week of FLF. MSCs promoted liver regeneration within 2 weeks and differentiated into functional hepatocytes at 2-4 weeks after transplantation, evidenced by increase in Ki67-positive cells, detectable human hepatocyte growth factor, human vascular endothelial growth factor, human hepatocyte-specific antigen, and human albumin-expressing cells in the liver at different time points. Reactive oxidative species (ROS) were accumulated after FLF and eliminated at 4 weeks after MSC transplantation. Conclusions: Together, MSCs prolong the survival and prevent lethal sequelae of I-R injury-induced FLF by maintenance of liver-function homeostasis and rescue of ROS in the acute stage and by homing and differentiation into hepatocytes in the subacute stage.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Cells, Cultured ; Hepatocytes/cytology ; Liver/cytology ; Liver Failure, Acute/therapy ; Male ; Mesenchymal Stem Cells/cytology ; Swine ; Transplantation, Heterologous/methods ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2019-06-20
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12542
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Article ; Online: Mesenchymal stem cells restore the sperm motility from testicular torsion-detorsion injury by regulation of glucose metabolism in sperm

Chi-Hao Hsiao / Andrea Tung-Qian Ji / Chih-Cheng Chang / Ming-Hsien Chien / Liang-Ming Lee / Jennifer Hui-Chun Ho

Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Background Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of ... ...

Abstract	Abstract Background Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of spermatogenesis. We previously reported that mesenchymal stem cells (MSCs), through local injection upon testicular torsion-detorsion, restored the spermatogenesis without differentiation into sperm. In this study, molecular mechanisms of MSCs in regulating germ cell activity induced by testicular torsion-detorsion were investigated. Methods Sixteen male Sprague-Dawley rats 6–8 weeks old received left testis 720° torsion for 3 h followed by detorsion with or without MSCs. Right inguinal skin incision without testicular torsion served as control. MSCs with 3 × 104 cells were locally injected into left testis 30 min before detorsion. Three days after the surgery, orchiectomy was executed and the testis, epididymis, and sperm were separated to each other. Functional assessments on sperm included counting sperm amount and sperm motility, staining F-actin, and quantifying adenosine triphosphate (ATP) content. The hallmarks of glycogenesis and glycolysis in each tissue segment were measured by Western blot. Results Testicular torsion-detorsion significantly decreased the amount of sperm, inhibited the motility, declined the F-actin expression, and reduced the content of ATP in sperm. Local injection of MSCs improved sperm function, particularly in sperm motility. With MSCs, ATP content and F-actin were preserved after testicular torsion-detorsion. MSCs significantly reversed the imbalance of glycolysis in sperm and testis induced by testicular torsion-detorsion, as evidenced by increasing the expression of phosphoglycerate kinase 2 and glyceraldehyde-3-phosphate dehydrogenase-spermatogenic, activating Akt, and increasing glycogen synthase kinase 3 (GSK3), which led to the increase in glycolysis cascades and ATP production. Human stem cell factor contributed the activation of ...
Keywords	Glycolysis ; Infertility ; Mesenchymal stem cells ; Sperm motility ; Testicular torsion-detorsion ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	572
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study.

Chemaly, Roy F / Marty, Francisco M / Wolfe, Cameron R / Lawrence, Steven J / Dadwal, Sanjeet / Soave, Rosemary / Farthing, Jason / Hawley, Stephen / Montanez, Paul / Hwang, Jimmy / Ho, Jennifer Hui-Chun / Lewis, Stanley / Wang, George / Boeckh, Michael

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue 3, Page(s) e773–e781

Abstract: Background: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.: Methods: Adult immunocompromised patients diagnosed with ... ...

Abstract	Background: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.
MeSH term(s)	Adult ; Animals ; Humans ; Immunocompromised Host ; Lung ; Paramyxoviridae Infections ; Recombinant Fusion Proteins ; Respiratory Tract Infections/drug therapy
Chemical Substances	Recombinant Fusion Proteins ; oplunofusp (227R1C272Q)
Language	English
Publishing date	2021-02-07
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab113
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mesenchymal stem cells restore the sperm motility from testicular torsion-detorsion injury by regulation of glucose metabolism in sperm.

Hsiao, Chi-Hao / Ji, Andrea Tung-Qian / Chang, Chih-Cheng / Chien, Ming-Hsien / Lee, Liang-Ming / Ho, Jennifer Hui-Chun

Stem cell research & therapy

2019 Volume 10, Issue 1, Page(s) 270

Abstract: Background: Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of spermatogenesis. ...

Abstract	Background: Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of spermatogenesis. We previously reported that mesenchymal stem cells (MSCs), through local injection upon testicular torsion-detorsion, restored the spermatogenesis without differentiation into sperm. In this study, molecular mechanisms of MSCs in regulating germ cell activity induced by testicular torsion-detorsion were investigated. Methods: Sixteen male Sprague-Dawley rats 6-8 weeks old received left testis 720° torsion for 3 h followed by detorsion with or without MSCs. Right inguinal skin incision without testicular torsion served as control. MSCs with 3 × 10 Results: Testicular torsion-detorsion significantly decreased the amount of sperm, inhibited the motility, declined the F-actin expression, and reduced the content of ATP in sperm. Local injection of MSCs improved sperm function, particularly in sperm motility. With MSCs, ATP content and F-actin were preserved after testicular torsion-detorsion. MSCs significantly reversed the imbalance of glycolysis in sperm and testis induced by testicular torsion-detorsion, as evidenced by increasing the expression of phosphoglycerate kinase 2 and glyceraldehyde-3-phosphate dehydrogenase-spermatogenic, activating Akt, and increasing glycogen synthase kinase 3 (GSK3), which led to the increase in glycolysis cascades and ATP production. Human stem cell factor contributed the activation of Akt/GSK3 axis when sperm suffered from testicular torsion-detorsion-induced germ cell injury. Conclusions: Local injection of MSCs into a testis damaged by testicular torsion-detorsion restores sperm function mainly through the improvement of sperm motility and energy. MSCs reversed the imbalance of glycogenesis and glycolysis in sperm by regulating Akt/GSK3 axis. Thus, MSCs may potentially rescue torsion-detorsion-induced infertility via local injection.
MeSH term(s)	Actins/metabolism ; Animals ; Germ Cells/metabolism ; Glucose/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Isoenzymes/metabolism ; Male ; Mesenchymal Stem Cells/metabolism ; Phosphoglycerate Kinase/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism ; Sperm Motility/physiology ; Spermatic Cord Torsion/metabolism ; Spermatogenesis/physiology ; Spermatozoa/metabolism ; Testis/metabolism
Chemical Substances	Actins ; Isoenzymes ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (EC 1.2.1.12) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Phosphoglycerate Kinase (EC 2.7.2.3) ; phosphoglycerate kinase, testis specific (EC 2.7.2.3) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2019-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-019-1351-5
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Article ; Online: Control of matrix stiffness promotes endodermal lineage specification by regulating SMAD2/3 via lncRNA LINC00458.

Chen, Yu-Fan / Li, Yi-Shuan J / Chou, Chih-Hung / Chiew, Men Yee / Huang, Hsien-Da / Ho, Jennifer Hui-Chun / Chien, Shu / Lee, Oscar K

Science advances

2020 Volume 6, Issue 6, Page(s) eaay0264

Abstract: During endoderm formation, cell identity and tissue morphogenesis are tightly controlled by cell-intrinsic and cell-extrinsic factors such as biochemical and physical inputs. While the effects of biochemical factors are well studied, the physical cues ... ...

Abstract	During endoderm formation, cell identity and tissue morphogenesis are tightly controlled by cell-intrinsic and cell-extrinsic factors such as biochemical and physical inputs. While the effects of biochemical factors are well studied, the physical cues that regulate cell division and differentiation are poorly understood. RNA sequencing analysis demonstrated increases of endoderm-specific gene expression in hPSCs cultured on soft substrate (Young's modulus, 3 ± 0.45 kPa) in comparison with hard substrate (Young's modulus, 165 ± 6.39 kPa). Further analyses revealed that multiple long noncoding RNAs (lncRNAs) were up-regulated on soft substrate; among them,
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Line ; Cell Lineage/genetics ; Cells, Cultured ; Endoderm/cytology ; Endoderm/metabolism ; Extracellular Matrix ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Humans ; Mice ; Models, Biological ; Organ Specificity/genetics ; RNA Interference ; RNA, Long Noncoding/genetics ; Smad2 Protein/genetics ; Smad3 Protein/genetics ; Transcriptome
Chemical Substances	CAHM long non-coding RNA, human ; RNA, Long Noncoding ; SMAD2 protein, human ; SMAD3 protein, human ; Smad2 Protein ; Smad3 Protein
Language	English
Publishing date	2020-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.aay0264
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Article ; Online: Cardiovascular protection of magnolol: cell-type specificity and dose-related effects.

Ho, Jennifer Hui-Chun / Hong, Chuang-Ye

Journal of biomedical science

2012 Volume 19, Page(s) 70

Abstract: Magnolia officinalis has been widely used in traditional Chinese medicine. Magnolol, an active component isolated from Magnolia officinalis, is known to be a cardiovascular protector since 1994. The multiplex mechanisms of magnolol on cardiovascular ... ...

Abstract	Magnolia officinalis has been widely used in traditional Chinese medicine. Magnolol, an active component isolated from Magnolia officinalis, is known to be a cardiovascular protector since 1994. The multiplex mechanisms of magnolol on cardiovascular protection depends on cell types and dosages, and will be reviewed and discussed in this article. Magnolol under low and moderate dosage possesses the ability to protect heart from ischemic/reperfusion injury, reduces atherosclerotic change, protects endothelial cell against apoptosis and inhibits neutrophil-endothelial adhesion. The moderate to high concentration of magnolol mainly acts on smooth muscle cells and platelets. Magnolol induces apoptosis in vascular smooth muscle cells at moderate concentration and inhibits proliferation at moderate and high concentration. High concentration of magnolol also abrogates platelet activation, aggregation and thrombus formation. Magnolol also serves as an smooth muscle relaxant only upon the high concentration. Oral intake of magnolol to reach the therapeutic level for cardiovascular protection is applicable, thus makes magnolol an agent of great potential for preventing cardiovascular diseases in high-risk patients.
MeSH term(s)	Apoptosis/drug effects ; Biphenyl Compounds/chemistry ; Biphenyl Compounds/therapeutic use ; Cardiovascular System/drug effects ; Drugs, Chinese Herbal/chemistry ; Humans ; Inflammation/prevention & control ; Lignans/chemistry ; Lignans/therapeutic use ; Magnolia/chemistry ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Myocytes, Smooth Muscle/cytology ; Myocytes, Smooth Muscle/drug effects
Chemical Substances	Biphenyl Compounds ; Drugs, Chinese Herbal ; Lignans ; magnolol (001E35HGVF)
Language	English
Publishing date	2012-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/1423-0127-19-70
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Article ; Online: Resolution of Coronavirus Disease 2019 Infection and Pulmonary Pathology With Nebulized DAS181: A Pilot Study.

Ho, Jennifer Hui-Chun / Zhao, Yang / Liu, Zhenlian / Zhou, Xiaoyang / Chen, Xiaobei / Xianyu, Yunyan / Lewis, Stanley / Fan, Liya / Tian, Yuan / Chang, Nancy / Gong, Zuojiong / Hu, Ke

Critical care explorations

2020 Volume 2, Issue 10, Page(s) e0263

Abstract: Objectives: Severe acute respiratory syndrome coronavirus 2 infections commonly lead to respiratory failure and potentially fatal systemic inflammation and organ failure. Nebulized DAS181, a host-directed biologics with sialidase activity, is an ... ...

Abstract	Objectives: Severe acute respiratory syndrome coronavirus 2 infections commonly lead to respiratory failure and potentially fatal systemic inflammation and organ failure. Nebulized DAS181, a host-directed biologics with sialidase activity, is an investigational drug with antiviral activities on parainfluenza and influenza under phase 3 and phase 2 development. The objective of this study (NCT04324489) is to investigate the safety and effects of nebulized DAS181 on hypoxic coronavirus disease 2019 patients. Design: Single-center, prospective, open-label, compassionate use. Setting: Renmin Hospital of Wuhan University, Department of Respiratory and Critical Care Medicine and Department of Infectious Diseases. Subjects: Patients 18 to 70 years old who met Chinese criteria for severe coronavirus disease 2019 pneumonia and required supplemental oxygen but not on mechanical ventilator at screening. Interventions: Nebulized DAS181 (4.5 mg) twice a day for 10 days. Measurements and main results: Three male coronavirus disease 2019 hypoxic patients with bilateral lung involvement completed DAS181 treatment for 10 days. By day 14, all achieved return to room air (primary endpoint) and their nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus 2. Clinical severity improved from severe coronavirus disease 2019 at baseline to moderate or mild disease by day 5, consistent with rapid reduction of inflammatory cytokines by days 2-3 and radiologic improvement by days 5-10. No DAS181-related adverse events were reported. Conclusions: Inhalation of DAS181 was well tolerated and potential clinical benefit of DAS181 on hypoxic coronavirus disease 2019 is the reduction of supplemental oxygen need. Efficacy and safety, including pharmacokinetics and viral studies of DAS181 in severe, hypoxic coronavirus disease 2019, should be examined by a double-blind, randomized controlled study.
Keywords	covid19
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000000263
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