This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion throug...This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.展开更多
CONSTANS(CO)and CONSTANS-LIKE(COL)transcription factors are known to regulate a series of cellular processes,including the transition from vegetative growth to flower development in plants.However,their role in regula...CONSTANS(CO)and CONSTANS-LIKE(COL)transcription factors are known to regulate a series of cellular processes,including the transition from vegetative growth to flower development in plants.However,their role in regulating the fruit chlorophyll content is poorly understood.In this study,SlCOL1,the tomato(Solanum lycopersicum)ortholog of Arabidopsis CONSTANS,was shown to play key roles in controlling fruit chlorophyll.The suppression of SlCOL1 expression led to a reduction in the chlorophyll content of immature green fruit,while the overexpression of SlCOL1 increased it.An analysis of protein-protein interactions indicated that SlCOL1 forms a complex with GOLDEN2-LIKE(GLK2),which promotes the stability of its protein.The overexpression of SlCOL1in the glk2 null mutation background of tomato failed to promote chlorophyll accumulation in the immature green fruit,which suggests that GLK2 is required for the function of SlCOL1 in regulating chlorophyll content.These results shed new light on the mechanisms used by COL1 and GLK2 to regulate fruit development and chlorophyll accumulation in tomato.展开更多
Dermatofibrosarcoma protuberans(DFSP)is a rare cutaneous intermediate-grade soft tissue tumor characterized by COL1A1::PDGFB fusion in most cases.This fusion drives tumorigenesis and forms the basis for imatinib treat...Dermatofibrosarcoma protuberans(DFSP)is a rare cutaneous intermediate-grade soft tissue tumor characterized by COL1A1::PDGFB fusion in most cases.This fusion drives tumorigenesis and forms the basis for imatinib treatment,which acts by blocking platelet-derived growth factor receptor-beta kinase activity.Apart from this canonical fusion,there is an expanding spectrum of rare fusions,including COL6A3::PDGFD,EMILIN::PDGFD,TNC::PDGFD,etc.,through mole-cular profiling.These atypical rearrangements may be encountered in morpho-logically classic DFSP,unusual anatomic sites,or diagnostically challenging variants such as fibrosarcomatous DFSP.Their recognition is clinically relevant,as they may influence tumor biology,response to targeted therapy,and eligibility for clinical trials.This newly documented DFSP involving the lacrimal sac was initially misdiagnosed as a solitary fibrous tumor,emphasizing the diagnostic pitfalls in anatomically constrained regions and the importance of integrated diagnosis combining histology,immunohistochemistry,and molecular testing.In this editorial commentary,we briefly highlight the ever-growing genomic land-scape of DFSP,report rare fusions and their biological implications,and examine the role of expanded molecular diagnostics in refining diagnosis,guiding therapy,and informing prognosis.Incorporating comprehensive fusion analysis into routine workup may be critical for accurate classification,especially in unusual presentations where reliance on morphology alone risks misdiagnosis.展开更多
BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old femal...BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.展开更多
目的:观察高糖刺激下人肾小球系膜细增殖分化及Col IV、MCP-1 mRNA和蛋白活性表达变化,探究益气解毒活络中药有效成分防治糖尿病肾病的分子机制,讨论正交配伍中最优药物组合。方法:以体外培养人肾小球系膜细胞株,传代3~5代后接种于96孔...目的:观察高糖刺激下人肾小球系膜细增殖分化及Col IV、MCP-1 mRNA和蛋白活性表达变化,探究益气解毒活络中药有效成分防治糖尿病肾病的分子机制,讨论正交配伍中最优药物组合。方法:以体外培养人肾小球系膜细胞株,传代3~5代后接种于96孔培养板,采用4因素3水平分为正常对照组,高糖模型组、中药1、2、3、4、5、6、7、8、9组,以相应药物对HMCs干预24、48、72 h。MTT法检测24、48、72 h各时间点HMCs增殖分化情况;以qRT-PCR法检测48 h Col IV、MCP-1 mRNA表达;以ELISA法检测48 h Col IV、MCP-1蛋白活性表达。结果:(1)高糖环境刺激作用下HMCs及胞外基质均能够显著增殖,且在48 h达到顶峰;(2)益气解毒活络中药有效成分药防治DN作用机制与通过下调高糖作用下HMCs Col IV、MCP-1 mRNA及蛋白活性表达,进而抑制高糖刺激HMCs增殖相关;(3)益气解毒活络中药有效,最佳配伍为黄芪甲苷低剂量、盐酸小檗碱低剂量、水蛭素低剂量、木犀草苷低剂量。展开更多
文摘This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.
基金supported by grants from the National Natural Science Foundation of China(32360766,32072595 and 32202512)the Earmarked Fund for CARS(CARS-23-A13)。
文摘CONSTANS(CO)and CONSTANS-LIKE(COL)transcription factors are known to regulate a series of cellular processes,including the transition from vegetative growth to flower development in plants.However,their role in regulating the fruit chlorophyll content is poorly understood.In this study,SlCOL1,the tomato(Solanum lycopersicum)ortholog of Arabidopsis CONSTANS,was shown to play key roles in controlling fruit chlorophyll.The suppression of SlCOL1 expression led to a reduction in the chlorophyll content of immature green fruit,while the overexpression of SlCOL1 increased it.An analysis of protein-protein interactions indicated that SlCOL1 forms a complex with GOLDEN2-LIKE(GLK2),which promotes the stability of its protein.The overexpression of SlCOL1in the glk2 null mutation background of tomato failed to promote chlorophyll accumulation in the immature green fruit,which suggests that GLK2 is required for the function of SlCOL1 in regulating chlorophyll content.These results shed new light on the mechanisms used by COL1 and GLK2 to regulate fruit development and chlorophyll accumulation in tomato.
文摘Dermatofibrosarcoma protuberans(DFSP)is a rare cutaneous intermediate-grade soft tissue tumor characterized by COL1A1::PDGFB fusion in most cases.This fusion drives tumorigenesis and forms the basis for imatinib treatment,which acts by blocking platelet-derived growth factor receptor-beta kinase activity.Apart from this canonical fusion,there is an expanding spectrum of rare fusions,including COL6A3::PDGFD,EMILIN::PDGFD,TNC::PDGFD,etc.,through mole-cular profiling.These atypical rearrangements may be encountered in morpho-logically classic DFSP,unusual anatomic sites,or diagnostically challenging variants such as fibrosarcomatous DFSP.Their recognition is clinically relevant,as they may influence tumor biology,response to targeted therapy,and eligibility for clinical trials.This newly documented DFSP involving the lacrimal sac was initially misdiagnosed as a solitary fibrous tumor,emphasizing the diagnostic pitfalls in anatomically constrained regions and the importance of integrated diagnosis combining histology,immunohistochemistry,and molecular testing.In this editorial commentary,we briefly highlight the ever-growing genomic land-scape of DFSP,report rare fusions and their biological implications,and examine the role of expanded molecular diagnostics in refining diagnosis,guiding therapy,and informing prognosis.Incorporating comprehensive fusion analysis into routine workup may be critical for accurate classification,especially in unusual presentations where reliance on morphology alone risks misdiagnosis.
文摘BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.
文摘目的:观察高糖刺激下人肾小球系膜细增殖分化及Col IV、MCP-1 mRNA和蛋白活性表达变化,探究益气解毒活络中药有效成分防治糖尿病肾病的分子机制,讨论正交配伍中最优药物组合。方法:以体外培养人肾小球系膜细胞株,传代3~5代后接种于96孔培养板,采用4因素3水平分为正常对照组,高糖模型组、中药1、2、3、4、5、6、7、8、9组,以相应药物对HMCs干预24、48、72 h。MTT法检测24、48、72 h各时间点HMCs增殖分化情况;以qRT-PCR法检测48 h Col IV、MCP-1 mRNA表达;以ELISA法检测48 h Col IV、MCP-1蛋白活性表达。结果:(1)高糖环境刺激作用下HMCs及胞外基质均能够显著增殖,且在48 h达到顶峰;(2)益气解毒活络中药有效成分药防治DN作用机制与通过下调高糖作用下HMCs Col IV、MCP-1 mRNA及蛋白活性表达,进而抑制高糖刺激HMCs增殖相关;(3)益气解毒活络中药有效,最佳配伍为黄芪甲苷低剂量、盐酸小檗碱低剂量、水蛭素低剂量、木犀草苷低剂量。
