Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it re...Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.展开更多
The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells.It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs.Here,...The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells.It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs.Here,we demonstrate that mature low-density neutrophils in colorectal cancer patients abnormally accumulate neutral lipids and induce the reactivation of dormant tumor cells,a process regulated by hepatic stellate cells.Mechanistically,activated hepatic stellate cells increased DGAT1/2-dependent lipid droplet synthesis in low-density neutrophils through the secretion of IL33,thereby maintaining the survival and immunosuppressive function of these neutrophils.The uptake of lipids from lipid-laden low-density neutrophils drives dormant tumor cell reactivation through the potentiation ofβ-oxidation and the stimulation of protumorigenic eicosanoid synthesis.In mouse models,targeting IL33 blocked neutrophil lipid synthesis,decreased the colonization of colorectal cancer cells in the liver,and enhanced the efficacy of immunotherapy.Overall,our study revealed that lipid accumulation in mature low-density neutrophils regulates the growth of dormant tumor cells and antitumor immunity to facilitate colorectal cancer liver metastasis.Targeting IL33 could be a promising therapeutic approach for colorectal cancer liver metastases.展开更多
基金supported by the National Natural Science Foundation of China,No.81370445,81061120527,81241082Major Funding from Beijing Hospital,No.BJ-2010-30+4 种基金Key Project of Clinical Disciplines at the Subordinate Hospital,Ministry of Health,No.10120101National Department Public Benefit Research Foundation by the Ministry of Health,No.20130200812th 5-year National Program from Ministry of Scientific Technology,No.2012BAI10B01Science and Technology Development Foundation of Guangxi Zhuang Autonomous Region,No.1355005-62Canadian Institute of Health Research(CIHR),No.109606
文摘Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.
基金supported by the National Natural Science Foundation of China,grants 81802326,82473026 and 81871933。
文摘The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells.It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs.Here,we demonstrate that mature low-density neutrophils in colorectal cancer patients abnormally accumulate neutral lipids and induce the reactivation of dormant tumor cells,a process regulated by hepatic stellate cells.Mechanistically,activated hepatic stellate cells increased DGAT1/2-dependent lipid droplet synthesis in low-density neutrophils through the secretion of IL33,thereby maintaining the survival and immunosuppressive function of these neutrophils.The uptake of lipids from lipid-laden low-density neutrophils drives dormant tumor cell reactivation through the potentiation ofβ-oxidation and the stimulation of protumorigenic eicosanoid synthesis.In mouse models,targeting IL33 blocked neutrophil lipid synthesis,decreased the colonization of colorectal cancer cells in the liver,and enhanced the efficacy of immunotherapy.Overall,our study revealed that lipid accumulation in mature low-density neutrophils regulates the growth of dormant tumor cells and antitumor immunity to facilitate colorectal cancer liver metastasis.Targeting IL33 could be a promising therapeutic approach for colorectal cancer liver metastases.
