Human brain organoids are 3-dimensional brain-like tissues derived from human pluripotent stem cells and hold promising potential for modeling neurological,psychiatric,and developmental disorders.While the molecular a...Human brain organoids are 3-dimensional brain-like tissues derived from human pluripotent stem cells and hold promising potential for modeling neurological,psychiatric,and developmental disorders.While the molecular and cellular aspects of human brain organoids have been intensively studied,their functional properties such as organoid neural networks(ONNs)are largely understudied.Here,we summarize recent research advances in understanding,characterization,and application of functional ONNs in human brain organoids.We first discuss the formation of ONNs and follow up with characterization strategies including microelectrode array(MEA)technology and calcium imaging.Moreover,we highlight recent studies utilizing ONNs to investigate neurological diseases such as Rett syndrome and Alzheimer’s disease.Finally,we provide our perspectives on the future challenges and opportunities for using ONNs in basic research and translational applications.展开更多
Homoharringtonine (HHT),a plant alkaloid from Cephalotaxus harringtonia,exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s.Tria...Homoharringtonine (HHT),a plant alkaloid from Cephalotaxus harringtonia,exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s.Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens.Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C),whereas patients in arm B were treated with HHTcontaining regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT.From February 2009 to November 2015,59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited.A total of 42 patients achieved a morphologic complete remission (CR) after the first course,with similar rates in both arms (70.6% vs.72.0%).At the end of the follow-up period,40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR,which could not be considered as events but censors.The 5-year event-free survival (EFS) was 60.2%± 9.6% for arm A and 88.0%± 6.5% for arm B (P=0.024).Patients in arm B experienced shorter durations of leukopenia,neutropenia,and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C.Consequently,the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.展开更多
基金supported by the National Institutes of Health(awards DP2AI160242 and U01DA056242).
文摘Human brain organoids are 3-dimensional brain-like tissues derived from human pluripotent stem cells and hold promising potential for modeling neurological,psychiatric,and developmental disorders.While the molecular and cellular aspects of human brain organoids have been intensively studied,their functional properties such as organoid neural networks(ONNs)are largely understudied.Here,we summarize recent research advances in understanding,characterization,and application of functional ONNs in human brain organoids.We first discuss the formation of ONNs and follow up with characterization strategies including microelectrode array(MEA)technology and calcium imaging.Moreover,we highlight recent studies utilizing ONNs to investigate neurological diseases such as Rett syndrome and Alzheimer’s disease.Finally,we provide our perspectives on the future challenges and opportunities for using ONNs in basic research and translational applications.
基金the National Natural Science Foundation of China (No.81270623)the Science and Technology Commission of Shanghai Municipality (No.14411950600)the Public Health 3-Year Project of Shanghai Children's Medical Center(No.GWIV-25).
文摘Homoharringtonine (HHT),a plant alkaloid from Cephalotaxus harringtonia,exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s.Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens.Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C),whereas patients in arm B were treated with HHTcontaining regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT.From February 2009 to November 2015,59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited.A total of 42 patients achieved a morphologic complete remission (CR) after the first course,with similar rates in both arms (70.6% vs.72.0%).At the end of the follow-up period,40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR,which could not be considered as events but censors.The 5-year event-free survival (EFS) was 60.2%± 9.6% for arm A and 88.0%± 6.5% for arm B (P=0.024).Patients in arm B experienced shorter durations of leukopenia,neutropenia,and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C.Consequently,the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.
