Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional p...Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.展开更多
目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖...目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。展开更多
目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医...目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医院住院治疗的汉族(对照组)和壮族(试验组)非心源性轻型缺血性卒中患者。所有患者在CYP2C19基因检测结果指导下进行抗血小板治疗:对于基因表型为氯吡格雷快代谢的患者,抗血小板药物选择硫酸氢氯吡格雷;对于中间代谢或慢代谢的患者,抗血小板药物选择阿司匹林肠溶片或替格瑞洛片。随访90 d,记录mRS评分、日常生活能力量表(activity of daily living scale,ADL)评分、NIHSS评分以及90 d缺血性卒中累积复发率。结果共纳入1036例缺血性卒中患者,对照组743例,CYP2C19基因检测结果显示,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为299例(40.24%)、345例(46.43%)和99例(13.32%)。试验组293例,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为107例(36.52%)、161例(54.95%)和25例(8.53%)。两组不同CYP2C19基因表型的比例差异无统计学意义。随访90 d,两组间的mRS评分、ADL评分、NI HSS评分差异无统计学意义。对照组和试验组的90 d缺血性卒中累积复发率分别为5.52%(41/743)和5.12%(15/293),差异无统计学意义。结论基于CYP2C19基因检测指导的抗血小板治疗在汉族和壮族的缺血性卒中患者人群中,预防缺血性卒中复发的效果相似。展开更多
本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速...本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测,结果为中间代谢型,提示应用氯吡格雷的效果可能不佳。基于这一检测结果调整抗血小板治疗方案,选择替格瑞洛联合阿司匹林作为替代治疗。治疗后,患者病情稳定,预后较好。本病例报道提示,在非轻型卒中患者中,快速CYP2C19基因检测可帮助选择抗血小板治疗策略,改善患者预后。展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
基金jointly funded by projects supported by the National Natural Science Foundation of China(Grant No.41872150)the Joint Funds of the National Natural Science Foundation of China(Grant No.U19B6003)Major Scientific and Technological Projects of CNPC during the 13th five-year plan(No.2019A-02-10)。
文摘Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.
文摘目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。
文摘目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医院住院治疗的汉族(对照组)和壮族(试验组)非心源性轻型缺血性卒中患者。所有患者在CYP2C19基因检测结果指导下进行抗血小板治疗:对于基因表型为氯吡格雷快代谢的患者,抗血小板药物选择硫酸氢氯吡格雷;对于中间代谢或慢代谢的患者,抗血小板药物选择阿司匹林肠溶片或替格瑞洛片。随访90 d,记录mRS评分、日常生活能力量表(activity of daily living scale,ADL)评分、NIHSS评分以及90 d缺血性卒中累积复发率。结果共纳入1036例缺血性卒中患者,对照组743例,CYP2C19基因检测结果显示,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为299例(40.24%)、345例(46.43%)和99例(13.32%)。试验组293例,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为107例(36.52%)、161例(54.95%)和25例(8.53%)。两组不同CYP2C19基因表型的比例差异无统计学意义。随访90 d,两组间的mRS评分、ADL评分、NI HSS评分差异无统计学意义。对照组和试验组的90 d缺血性卒中累积复发率分别为5.52%(41/743)和5.12%(15/293),差异无统计学意义。结论基于CYP2C19基因检测指导的抗血小板治疗在汉族和壮族的缺血性卒中患者人群中,预防缺血性卒中复发的效果相似。
文摘本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测,结果为中间代谢型,提示应用氯吡格雷的效果可能不佳。基于这一检测结果调整抗血小板治疗方案,选择替格瑞洛联合阿司匹林作为替代治疗。治疗后,患者病情稳定,预后较好。本病例报道提示,在非轻型卒中患者中,快速CYP2C19基因检测可帮助选择抗血小板治疗策略,改善患者预后。
