Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel...Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus(2019-nCoV), an ongoing novel coronavirus that causes pneumonia.Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database.Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion(ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction.In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response.Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.展开更多
The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients f...The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.展开更多
Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening...Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening applications.Emerging organ-on-a-chip(OoC)microfluidic technologies represent promising new approach methodologies(NAMS)and a real alternative to animal testing.While tissue-specific decellularized extracellular matrix(ECM)can recapitulate in vivo-like microenvironments,its application in SG-on-a-chip(SGoC)is still underexplored.This study developed an injectable porcine decellularized submandibular gland(dSMG)hydrogel for bioengineering an SG MEC tissue chip.dSMG was prepared using a chemical and enzymatic decellularization process with 0.1%or 1%sodium dodecyl sulfate(SDS).Both treatments effectively removed DNA content while preserving key ECM components,including collagens,glycoproteins,and mucins.Proteomic analysis revealed that 1%SDS-treated dSMG contained a greater abundance of ECM components involved in matrix assembly and cell-ECM interactions compared to the 0.1%group.The 1%SDS-treated dSMG was subsequently digested with a pepsin-based buffer to form hydrogels.At 5 mg/mL,dSMG hydrogel exhibited nanofibrous architecture,thermo-responsive gelation,injectability into microfluidic devices,and minimal batch-to-batch biological variations.In static conditions,dSMG hydrogel significantly enhanced SG cell viability and mitochondria-dependent proliferation compared to Matrigel.Under gravity-driven flow,dSMG hydrogel promoted a ductal phenotype on human SG MEC cells,unlike on Matrigel.Additionally,dSMG hydrogel supported cholinergic-specific signaling and functional activity.These findings demonstrate the potential of dSMG hydrogel as a physiologically relevant matrix for SG cancer modeling towards drug screening applications in SGoC microfluidic systems.展开更多
Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vi...Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.展开更多
基金supported by Shanghai Leading Talent Grants in Medicine(No.2019LG26)Shanghai Traditional Chinese Medicine Content Construction Innovation Project(No.ZY3-CCCX-3-7001)Postdoctoral Funding of Shanghai Gongil Hospital(No.GLBH2017002).
文摘Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus(2019-nCoV), an ongoing novel coronavirus that causes pneumonia.Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database.Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion(ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction.In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response.Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.
基金This work was supported by Xiangyang Science and Technology Bureau(2020YL10,2020YL14,2020YL17,and 2020YL39)National Natural Science Foundation of China(31501116)+2 种基金Shenzhen Science and Technology Innovation Commission(JCYJ20190809100005672)Shenzhen Sanming Project of Medicine(SZSM201911013)US Department of Veterans Affairs(5I01BX001353).
文摘The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
文摘Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening applications.Emerging organ-on-a-chip(OoC)microfluidic technologies represent promising new approach methodologies(NAMS)and a real alternative to animal testing.While tissue-specific decellularized extracellular matrix(ECM)can recapitulate in vivo-like microenvironments,its application in SG-on-a-chip(SGoC)is still underexplored.This study developed an injectable porcine decellularized submandibular gland(dSMG)hydrogel for bioengineering an SG MEC tissue chip.dSMG was prepared using a chemical and enzymatic decellularization process with 0.1%or 1%sodium dodecyl sulfate(SDS).Both treatments effectively removed DNA content while preserving key ECM components,including collagens,glycoproteins,and mucins.Proteomic analysis revealed that 1%SDS-treated dSMG contained a greater abundance of ECM components involved in matrix assembly and cell-ECM interactions compared to the 0.1%group.The 1%SDS-treated dSMG was subsequently digested with a pepsin-based buffer to form hydrogels.At 5 mg/mL,dSMG hydrogel exhibited nanofibrous architecture,thermo-responsive gelation,injectability into microfluidic devices,and minimal batch-to-batch biological variations.In static conditions,dSMG hydrogel significantly enhanced SG cell viability and mitochondria-dependent proliferation compared to Matrigel.Under gravity-driven flow,dSMG hydrogel promoted a ductal phenotype on human SG MEC cells,unlike on Matrigel.Additionally,dSMG hydrogel supported cholinergic-specific signaling and functional activity.These findings demonstrate the potential of dSMG hydrogel as a physiologically relevant matrix for SG cancer modeling towards drug screening applications in SGoC microfluidic systems.
基金funded by the National Research Council of Thailand(NRCT)and Chulalongkorn University with project number:N42A670176 to JNF(main PI)and to RC(Co-I)supported by the International Association for Dental,Oral and Craniofacial Research(IADR)2022 Innovation in Oral Care Award funded by GlaxoSmithKline to JNF,CHLH,KST,SY and WP+5 种基金supported by Thailand Science Research and Innovation Fund Chulalongkorn University to JNFRC.Center of Excellence and Innovation for Oral Health and Healthy Longevity is funded by the Ratchadaphiseksomphot Endowment Fund,Chulalongkorn University(Grant number:CE68_003_3200_001)supported by a Chulalongkorn University scholarship from Graduate Scholarship Program for ASEAN or Non-ASEAN Countriessupported by the 90th Anniversary of Chulalongkorn University Scholarship under Ratchadapisek Somphot Endowment Fund(Grant number:GCUGR1125662098M)the IADR-Southeast Asia Mentor-Mentee Funding provided to TTTT under the mentorship of JNF and OMsupported by the Second Century Fund(C2F),Chulalongkorn University provided to TVP.
文摘Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.
