BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres...BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.展开更多
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio...Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.展开更多
Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2...Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2012）.Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system（CNS）,while mutations in FOXP1 have been implicated in cognitive abnormalities（Bacon and Rappold, 2012）.展开更多
AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genist...AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.展开更多
FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3...FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关.展开更多
文摘BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.
基金This work was supported by the National Natural Science Foundation of China(82071779 and 81901626)the Science Fund for Creative Research Groups of Chongqing Municipal Education Commission of China,the grants from the Talent Foundation of Army Medical University(to Shuang-Shuang Dai)+1 种基金the Scientific Research Grant(ALJ22J003)the Chongqing Natural Science Foundation of China(CSTB2022NSCQ-MSX0177).
文摘Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.
文摘Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2012）.Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system（CNS）,while mutations in FOXP1 have been implicated in cognitive abnormalities（Bacon and Rappold, 2012）.
基金National Natural Science Foundation of China, No. 81172375Hunan Provincial Natural Science Foundation, No. 03JJY5009
文摘AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.
文摘FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关.
