Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory respons...Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.展开更多
Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cellbased immunotherapy for liver cancer.Ho...Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cellbased immunotherapy for liver cancer.However,abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control.Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation,we proposed a strategy using nanoemulsion-loaded obeticholic acid(OCA),a clinically approved selective farnesoid X receptor(FXR)agonist,for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy.The OCA-nanoemulsion(OCA-NE)was prepared via ultrasonic emulsification method,with a diameter of 184 nm and good stability.In vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer cells.As a result,OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model,which performed much better than oral medication of free OCA.Immunologic analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-g,as well as increased NKT cell populations inside the tumor.Overall,our research provides a new evidence for the antitumor effect of receptors for primary bile acids,and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy.展开更多
This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and pointed out the potential risk factors associated ...This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and pointed out the potential risk factors associated with fatal outcomes.Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology,Wuhan,China was analyzed.Demographics,clinical detection,laboratory findings,and treatments of the deceased were collected and analyzed.The average time between onset of symptoms and admission to the hospitals was 11±5 days of hospitalization.Among the deceased,60%were with co-morbidities.All of them were having fever and bilateral pneumonia on computed tomography,abnormal infection-related biomarkers,and renal impairment.Abnormal blood coagulation parameters that appeared in more than half of them,were consistent with disseminated intravascular coagulation.All of the patients were treated in the ICU.Based on the fact that SARS-CoV-2 infection carries a risk of mortality,we may infer a few older male patients with underlying comorbidities are likely to have the increased risk.Impaired consciousness level,markers of renal impairment and coagulation abnormalities may be poor prognostic factors.展开更多
基金Ministry of Science and Technology of China,Grant/Award Number:2022YFE0110200Natural Science Foundation of Jilin Province,Grant/Award Number:20230101037JCNational Natural Science Foundation of China,Grant/Award Numbers:52203198,52025035。
文摘Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.
基金financially supported by the National Natural Science Foundation of China(51673189,51973215,51833010and 51520105004)Ministry of Science and Technology of China(Project 2018ZX09711003-012)+1 种基金the Program of Scientific Development of Jilin Province(20170101100JC,20180520207JH,20190103112JH,China)supported by NIH grant CA198999(USA)
文摘Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cellbased immunotherapy for liver cancer.However,abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control.Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation,we proposed a strategy using nanoemulsion-loaded obeticholic acid(OCA),a clinically approved selective farnesoid X receptor(FXR)agonist,for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy.The OCA-nanoemulsion(OCA-NE)was prepared via ultrasonic emulsification method,with a diameter of 184 nm and good stability.In vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer cells.As a result,OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model,which performed much better than oral medication of free OCA.Immunologic analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-g,as well as increased NKT cell populations inside the tumor.Overall,our research provides a new evidence for the antitumor effect of receptors for primary bile acids,and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy.
基金supported by grants from the Epidemiology,Early Warning,and Response Techniques of Major Infectious Diseases in the Belt and Road Initiative(#2018ZX10101002)National Natural Science Foundation of China(#81871699)Foundation of Jilin Province Science and Technology Department(#172408GH010234983).
文摘This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and pointed out the potential risk factors associated with fatal outcomes.Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology,Wuhan,China was analyzed.Demographics,clinical detection,laboratory findings,and treatments of the deceased were collected and analyzed.The average time between onset of symptoms and admission to the hospitals was 11±5 days of hospitalization.Among the deceased,60%were with co-morbidities.All of them were having fever and bilateral pneumonia on computed tomography,abnormal infection-related biomarkers,and renal impairment.Abnormal blood coagulation parameters that appeared in more than half of them,were consistent with disseminated intravascular coagulation.All of the patients were treated in the ICU.Based on the fact that SARS-CoV-2 infection carries a risk of mortality,we may infer a few older male patients with underlying comorbidities are likely to have the increased risk.Impaired consciousness level,markers of renal impairment and coagulation abnormalities may be poor prognostic factors.
