BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
目的分析幽门螺杆菌(H.pylori,Hp)相关胃癌中miR-145的表达及临床意义。方法选取本院2019年6月—2022年12月接诊的86例胃癌患者,根据是否存在Hp感染将其分为两组,56例Hp阳性患者为观察组,30例Hp阴性患者为对照组。取患者癌组织及癌旁组...目的分析幽门螺杆菌(H.pylori,Hp)相关胃癌中miR-145的表达及临床意义。方法选取本院2019年6月—2022年12月接诊的86例胃癌患者,根据是否存在Hp感染将其分为两组,56例Hp阳性患者为观察组,30例Hp阴性患者为对照组。取患者癌组织及癌旁组织,检测miR-145表达,比较两组患者癌组织及癌旁组织中miR-145表达量,比较不同病理特征Hp阳性患者的miR-145表达量。抽取两组患者空腹静脉血5 mL,检测血清C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平,绘制接受者操作特征(ROC)曲线,计算曲线下面积(AUC),比较CRP、TNF-α、miR-145对Hp阳性胃癌的诊断价值。Pearson分析miR-145与CRP、TNF-α的相关性。随访3年,比较存活组、死亡组miR-145表达量。采用Kaplan-Meier法进行生存分析,Graph Pad Prism 8.0绘制miR-145高表达组、低表达组生存曲线。结果观察组患者癌组织及癌旁组织中miR-145的表达量均显著低于对照组(P<0.05)。不同性别、年龄、肿瘤大小的Hp阳性胃癌患者miR-145表达量比较,差异无统计学意义(P>0.05),远处转移、淋巴结转移、浸润深度T3~T4、Ⅲ~Ⅳ期Hp阳性胃癌患者miR-145表达量均显著低于无远处转移、无淋巴结转移、浸润深度T1~T2、Ⅰ~Ⅱ期患者(P<0.05)。观察组患者血清CRP、TNF-α水平均显著高于对照组(P<0.05)。miR-145与CRP、TNF-α的表达均呈负相关(r=-0.493,P<0.05;r=-0.482,P<0.05)。ROC曲线显示:miR-145的诊断灵敏度(90.24%)、特异度(89.28%)明显高于CRP(75.82%,76.28%)和TNF-α(77.37%,78.17%)(P<0.05)。随访3年,86例患者无脱落病例,中位生存时间30.52个月,3年生存率为58.14%。存活组患者癌组织及癌旁组织中miR-145表达量显著高于死亡组(P<0.05),miR-145高表达组患者生存率高于miR-145低表达组(P<0.05)。结论胃癌患者miR-145表达量较低,尤其是感染Hp的患者,miR-145表达量更低;Hp相关胃癌患者的临床病理特征、炎症反应与miR-145表达存在一定关系,临床可通过检测miR-145表达量评估疾病进程和炎症反应,提高诊断灵敏度、特异度;miR-145低表达可能影响Hp相关胃癌患者疾病转归与预后。展开更多
染料是一种结构复杂、具有剧毒的有机化合物,对人体毒害作用大。本研究制备了一种基于活性赤泥(activated red mud,ARM)和聚合吡咯(polypyrrole,PPy)的吸附剂,并应用于水溶液中染料的吸附脱除。通过吸附实验研究了溶液pH、吸附剂种类、...染料是一种结构复杂、具有剧毒的有机化合物,对人体毒害作用大。本研究制备了一种基于活性赤泥(activated red mud,ARM)和聚合吡咯(polypyrrole,PPy)的吸附剂,并应用于水溶液中染料的吸附脱除。通过吸附实验研究了溶液pH、吸附剂种类、吸附时间、添加量和染料初始浓度对吸附过程的影响,并对ARM-PPy复合材料进行分析表征,阐明了活性黄染料-145(RYD-145)的吸附作用机制。RYD-145在ARM-PPy上的吸附过程与三种吸附等温线关联极好(R2>0.99),其中Langmuir吸附最合适。根据Langmuir吸附模型的拟合结果,RYD-145的最大吸附量是442.5 mg/g。热力学研究表明,RYD-145分子在ARM-PPy的吸附过程中,焓变(ΔH)和熵变(ΔS)均增加,这表明该过程为吸热过程,且表面RYD-145分子排列具有随机性。研究表明,ARM-PPy具有高效处理阴离子和阳离子染料污染废水的能力,且具有较好的成本效益。展开更多
Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise ...Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.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
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
文摘目的分析幽门螺杆菌(H.pylori,Hp)相关胃癌中miR-145的表达及临床意义。方法选取本院2019年6月—2022年12月接诊的86例胃癌患者,根据是否存在Hp感染将其分为两组,56例Hp阳性患者为观察组,30例Hp阴性患者为对照组。取患者癌组织及癌旁组织,检测miR-145表达,比较两组患者癌组织及癌旁组织中miR-145表达量,比较不同病理特征Hp阳性患者的miR-145表达量。抽取两组患者空腹静脉血5 mL,检测血清C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平,绘制接受者操作特征(ROC)曲线,计算曲线下面积(AUC),比较CRP、TNF-α、miR-145对Hp阳性胃癌的诊断价值。Pearson分析miR-145与CRP、TNF-α的相关性。随访3年,比较存活组、死亡组miR-145表达量。采用Kaplan-Meier法进行生存分析,Graph Pad Prism 8.0绘制miR-145高表达组、低表达组生存曲线。结果观察组患者癌组织及癌旁组织中miR-145的表达量均显著低于对照组(P<0.05)。不同性别、年龄、肿瘤大小的Hp阳性胃癌患者miR-145表达量比较,差异无统计学意义(P>0.05),远处转移、淋巴结转移、浸润深度T3~T4、Ⅲ~Ⅳ期Hp阳性胃癌患者miR-145表达量均显著低于无远处转移、无淋巴结转移、浸润深度T1~T2、Ⅰ~Ⅱ期患者(P<0.05)。观察组患者血清CRP、TNF-α水平均显著高于对照组(P<0.05)。miR-145与CRP、TNF-α的表达均呈负相关(r=-0.493,P<0.05;r=-0.482,P<0.05)。ROC曲线显示:miR-145的诊断灵敏度(90.24%)、特异度(89.28%)明显高于CRP(75.82%,76.28%)和TNF-α(77.37%,78.17%)(P<0.05)。随访3年,86例患者无脱落病例,中位生存时间30.52个月,3年生存率为58.14%。存活组患者癌组织及癌旁组织中miR-145表达量显著高于死亡组(P<0.05),miR-145高表达组患者生存率高于miR-145低表达组(P<0.05)。结论胃癌患者miR-145表达量较低,尤其是感染Hp的患者,miR-145表达量更低;Hp相关胃癌患者的临床病理特征、炎症反应与miR-145表达存在一定关系,临床可通过检测miR-145表达量评估疾病进程和炎症反应,提高诊断灵敏度、特异度;miR-145低表达可能影响Hp相关胃癌患者疾病转归与预后。
文摘染料是一种结构复杂、具有剧毒的有机化合物,对人体毒害作用大。本研究制备了一种基于活性赤泥(activated red mud,ARM)和聚合吡咯(polypyrrole,PPy)的吸附剂,并应用于水溶液中染料的吸附脱除。通过吸附实验研究了溶液pH、吸附剂种类、吸附时间、添加量和染料初始浓度对吸附过程的影响,并对ARM-PPy复合材料进行分析表征,阐明了活性黄染料-145(RYD-145)的吸附作用机制。RYD-145在ARM-PPy上的吸附过程与三种吸附等温线关联极好(R2>0.99),其中Langmuir吸附最合适。根据Langmuir吸附模型的拟合结果,RYD-145的最大吸附量是442.5 mg/g。热力学研究表明,RYD-145分子在ARM-PPy的吸附过程中,焓变(ΔH)和熵变(ΔS)均增加,这表明该过程为吸热过程,且表面RYD-145分子排列具有随机性。研究表明,ARM-PPy具有高效处理阴离子和阳离子染料污染废水的能力,且具有较好的成本效益。
基金This work was supported by Nantong Science and Technology Project(MS22022012,MS12021039,MS12018020,MS12018041,JC2020040)Jiangsu Provincial Laboratory Animal Association(DWXH202116)+1 种基金the Doctoral Scientific Research Foundation of Nantong University(135420505015,135422505037)National College Students’Innovation and Entrepreneurship Training Program(202110304036Z).
文摘Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.
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.
