目的观察和分析外周血microRNA-23b作为胃癌筛查分子标志物的应用价值。方法选取100例接受胃镜病理活检者作为研究对象,根据检查结果将其分为三组,确诊为胃癌者列为胃癌组,共纳入46例;确诊为胃癌前病变者列为癌前病变组,共纳入28例;胃...目的观察和分析外周血microRNA-23b作为胃癌筛查分子标志物的应用价值。方法选取100例接受胃镜病理活检者作为研究对象,根据检查结果将其分为三组,确诊为胃癌者列为胃癌组,共纳入46例;确诊为胃癌前病变者列为癌前病变组,共纳入28例;胃粘膜检查结果基本正常者列为对照组,共纳入26例。应用定量real time PCR检测技术对三组研究对象外周血样本中的miRNA-23b表达水平进行检测和比较。结果对照组研究对象的外周血样本的Log2△Ct值显著高于癌前病变组(P<0.05),而且癌前病变组的Log2△Ct值显著高于胃癌组(P<0.05);胃癌组、癌前病变组和对照组研究对象外周血样本中的miRNA-23b表达阳性率分别为71.7%、32.1%和3.8%,胃癌组的阳性率显著高于癌前病变组(P<0.05),癌前病变组显著高于对照组(P<0.05)。与胃镜活检结果对比,其阳性预测值为76.7%,阴性预测值为77.2%。结论胃癌患者外周血中miRNA-23b表达水平可反映患者病情的进展程度,且其诊断效率较高,有望成为用于胃癌早期筛查的新型分子标志物。展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
目的探讨表达CD23的弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的临床病理特点及可能的肿瘤相关免疫微环境。方法回顾性分析12例表达CD23的DLBCL临床病理资料,分析其临床、病理特点并研究其临床相关性及肿瘤相关免疫浸...目的探讨表达CD23的弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的临床病理特点及可能的肿瘤相关免疫微环境。方法回顾性分析12例表达CD23的DLBCL临床病理资料,分析其临床、病理特点并研究其临床相关性及肿瘤相关免疫浸润。结果表达CD23的DLBCL约占所有DLBCL的9.45%;男女性各6例;平均发病年龄64.83岁;发生于淋巴结内者4例,结外者8例;9例为进展期(Ⅲ~Ⅳ期),3例为早期(Ⅰ~Ⅱ期);3例患者诊断后未经治疗且失访;1例患者手术后病情恶化死亡;8例患者经化疗后,2例死亡、1例进展、5例部分缓解。镜下肿瘤细胞均为弥漫浸润并破坏正常组织结构,可观察到肿瘤细胞呈现中心母细胞、免疫母细胞及间变性大细胞形态,其形态学均未见母细胞变及浆细胞样分化。Hans分型:除1例为GCB表型,其余11例均为非GCB表型。生物信息学研究发现CD23表达与调节性T细胞、NK细胞、浆细胞样树突细胞呈正相关,与中性粒细胞呈负相关。结论表达CD23的DLBCL患者主要为中老年人,以发生于淋巴结外为主,多为进展期(Ⅲ~Ⅳ期),随访结果显示其预后较差。形态学上相对于一般的DLBCL并无特殊,Hans分型提示肿瘤组织大多数为非GCB亚型,CD23表达对DLBCL的免疫微环境可能有一定的影响。展开更多
Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug lo...Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.展开更多
文摘目的观察和分析外周血microRNA-23b作为胃癌筛查分子标志物的应用价值。方法选取100例接受胃镜病理活检者作为研究对象,根据检查结果将其分为三组,确诊为胃癌者列为胃癌组,共纳入46例;确诊为胃癌前病变者列为癌前病变组,共纳入28例;胃粘膜检查结果基本正常者列为对照组,共纳入26例。应用定量real time PCR检测技术对三组研究对象外周血样本中的miRNA-23b表达水平进行检测和比较。结果对照组研究对象的外周血样本的Log2△Ct值显著高于癌前病变组(P<0.05),而且癌前病变组的Log2△Ct值显著高于胃癌组(P<0.05);胃癌组、癌前病变组和对照组研究对象外周血样本中的miRNA-23b表达阳性率分别为71.7%、32.1%和3.8%,胃癌组的阳性率显著高于癌前病变组(P<0.05),癌前病变组显著高于对照组(P<0.05)。与胃镜活检结果对比,其阳性预测值为76.7%,阴性预测值为77.2%。结论胃癌患者外周血中miRNA-23b表达水平可反映患者病情的进展程度,且其诊断效率较高,有望成为用于胃癌早期筛查的新型分子标志物。
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘目的探讨表达CD23的弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的临床病理特点及可能的肿瘤相关免疫微环境。方法回顾性分析12例表达CD23的DLBCL临床病理资料,分析其临床、病理特点并研究其临床相关性及肿瘤相关免疫浸润。结果表达CD23的DLBCL约占所有DLBCL的9.45%;男女性各6例;平均发病年龄64.83岁;发生于淋巴结内者4例,结外者8例;9例为进展期(Ⅲ~Ⅳ期),3例为早期(Ⅰ~Ⅱ期);3例患者诊断后未经治疗且失访;1例患者手术后病情恶化死亡;8例患者经化疗后,2例死亡、1例进展、5例部分缓解。镜下肿瘤细胞均为弥漫浸润并破坏正常组织结构,可观察到肿瘤细胞呈现中心母细胞、免疫母细胞及间变性大细胞形态,其形态学均未见母细胞变及浆细胞样分化。Hans分型:除1例为GCB表型,其余11例均为非GCB表型。生物信息学研究发现CD23表达与调节性T细胞、NK细胞、浆细胞样树突细胞呈正相关,与中性粒细胞呈负相关。结论表达CD23的DLBCL患者主要为中老年人,以发生于淋巴结外为主,多为进展期(Ⅲ~Ⅳ期),随访结果显示其预后较差。形态学上相对于一般的DLBCL并无特殊,Hans分型提示肿瘤组织大多数为非GCB亚型,CD23表达对DLBCL的免疫微环境可能有一定的影响。
基金the National Natural Science Foundation of China(32271319 and 32071267)the Science and Technology Department of Jilin Province(YDZJ202301ZYTS537 and 20240402035GH)+1 种基金the Development and Reform Commission of Jilin Province(2023C015)the“Medicine+X”cross-innovation team of Bethune Medical Department of Jilin University“Leading the Charge with Open Competition”construction project(2022JBGS04).
文摘Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
