Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tum...Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tumors.Previously,we described the preferential existence of a novel endothelial projection with trafficking vesicles in PCs,referring to basal microvilli.However,whether the basal microvilli microvessels have good perfusion or deliver nutrients to the tumor milieu is unknown.Here,we perfused multiple endothelial markers and nutrients to autochthonous PC-bearing mice to study the nutrient trafficking and perfusion status of the basal microvilli microvasculature.展开更多
Huntington's disease(HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein(m HTT) forms abnormal aggregates and intranuclear inclusions ...Huntington's disease(HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein(m HTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here,we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected m HTT in Neuro-2 a cells and endogenous m HTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected m HTT in Neuro-2 a cells, endogenous m HTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose-and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal m HTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.展开更多
文摘Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tumors.Previously,we described the preferential existence of a novel endothelial projection with trafficking vesicles in PCs,referring to basal microvilli.However,whether the basal microvilli microvessels have good perfusion or deliver nutrients to the tumor milieu is unknown.Here,we perfused multiple endothelial markers and nutrients to autochthonous PC-bearing mice to study the nutrient trafficking and perfusion status of the basal microvilli microvasculature.
基金supported by the National Key Research and Development Program of China (2018YFA0108004)the National Natural Science Foundation of China (81271259)
文摘Huntington's disease(HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein(m HTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here,we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected m HTT in Neuro-2 a cells and endogenous m HTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected m HTT in Neuro-2 a cells, endogenous m HTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose-and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal m HTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.
