急性缺血性脑卒中患者血清miR-103,miR-29b的表达水平变化及其临床意义

目的 探讨急性缺血性脑卒中(AIS)患者血清miR-103,miR-29b的表达水平变化及其临床意义。方法 收集2016年1月-2019年12月本院神经内科收治的126例AIS患者(AIS组),根据美国国立卫生研究院卒中量表(NIHSS)评分将其分为轻度组(45例)、中度组(57例)和重度组(24例),根据改良Rankin量表(mRS)评分将其分为预后良好组(78例)和预后不良组(48例),另选择56例同期于本院门诊体检健康者为对照组,检测血清miR-103,miR-29b表达水平,Spearman秩相关性分析miR-103,miR-29b表达水平与NIHSS,mRS评分的相关性,受试者工作特征曲线(ROC)分析miR-103,miR-29b表达水平对神经功能预后的预测价值。结果 AIS组血清miR-103表达水平高于对照组(P<0.05),miR-29b表达水平低于对照组(P<0.05),血清miR-103表达水平随着AIS患者神经缺损程度加重而升高(P<0.05),miR-29b表达水平则降低(P<0.05)。预后不良组血清miR-103表达水平高于预后良好组(P<0.05),miR-29b表达水平低于预后良好组(P<0.05)。Spearman秩相关性分析显示AIS患者血清miR-103表达水平与NIHSS评分、mRS评分呈正相关(r₂=0.636、0.794,P<0.05),miR-29b表达水平与NIHSS评分、mRS评分呈负相关(r₂=-0.664、-0.659,P<0.05)。ROC分析显示miR-103,miR-29b表达水平预测AIS患者神经功能预后的曲线下面积(AUC)为0.713、0.741,联合miR-103,miR-29b表达水平预测AIS患者神经功能预后的AUC为0.918,高于单独miR-103,miR-29b表达水平(P<0.05)。结论 AIS患者血清miR-103表达水平升高,miR-29b表达水平降低,miR-103表达上调、miR-29b表达缺失均与AIS患者神经功能缺损程度和神经功能恶化有关,可以为患者神经功能预后评估提供参考。     

IL-33/ST2信号通路在纤维化疾病中的作用

Interleukin (IL)-33 is a member of IL-1 family. It is identified as a functional ligand for ST2 which is an IL-1 receptor-like protein. IL-33/ST2 signaling is involved in T-cell-mediated immune responses. Increasing evidence indicates that IL-33 has different roles in different diseases. Recently, some studies have demonstrated that IL-33 may be related to the genesis and development of fibrosis diseases. We review current knowledge of the biological characteristics of IL-33 and the role of IL-33/ST2 signaling pathway in fibrosis diseases.     

血清IL-32、IL-33、IL-35在不同亚型Hp感染者及胃癌患者中的水平及意义

目的观察血清白细胞介素-32(interleukin-32,IL-32)、白细胞介素-33(interleukin-33,IL-33)、白细胞介素-35(interleukin-35,IL-35)水平与不同亚型幽门螺杆菌(Helicobacter pylori,Hp)感染之间的关系,并探讨胃癌患者血清IL-32、IL-33、IL-35水平的变化及意义。方法选取胃癌(GC)患者46例、慢性萎缩性胃炎(CAG)患者40例及慢性非萎缩性胃炎(CNAG)患者114例作为研究对象。采用酶联免疫吸附试验(ELISA)定量检测患者血清IL-32、IL-33、IL-35水平。比较各组患者血清IL-32、IL-33、IL-35水平与Hp感染率及其亚型之间的关系。结果1)3组患者血清IL-32、IL-33、IL-35水平的比较:GC组患者血清IL-32、IL-33、IL-35水平均明显高于CAG组及CNAG组(P<0.01);CAG组患者血清IL-32、IL-33水平均明显高于CNAG组患者(P<0.05);CAG组患者血清IL-35水平与CNAG组患者比较无明显差异(P>0.05)。2)3组患者Hp感染率的比较:GC组患者Hp感染率及Ⅰ型Hp感染率均明显高于CNAG患者(P<0.05),Hp感染率及Ⅰ型Hp感染率在GC组与CAG组、CAG组与CNAG组之间比较无显著统计学差异(P>0.05)。3)血清IL-32、IL-33、IL-35水平与不同亚型Hp感染之间的关系:在3组患者中,Ⅰ型Hp感染组血清IL-32、IL-33、IL-35水平均明显高于Ⅱ型Hp感染组及Hp阴性组(P<0.05),Ⅱ型Hp感染组血清IL-32、IL-33水平与Hp阴性组比较均无明显差异(P>0.05)。在CNAG组患者中,Ⅱ型Hp感染组血清IL-35水平明显高于Hp阴性组(P<0.05)。结论1)Ⅰ型Hp感染者发生GC的风险增加。2)在CNAG、CAG及GC患者中,Ⅰ型Hp感染者血清IL-32、IL-33、IL-35水平均显著升高。3)血清IL-32、IL-33、IL-35水平在GC患者中明显升高,其水平变化有利于提高GC的确诊率。     

MiR-183 regulates the differentiation of osteoblasts in the development of osteoporosis by targeting Smad4

ObjectiveTo discuss the effect of miR-183 on osteoblast differentiation in the osteoporosis progression via targeting Smad4.MethodsOsteoporosis models were constructed on ovariectomized (OVX) mice to determine the expression of miR-183 and Smad4. Then, MC3T3-E1 cells and primary osteoblasts were divided into Mock, miR-control, miR-183 mimic, miR-183 inhibitor, siSmad4 and miR-183 inhibitor + siSmad4 groups. Alkaline phosphatase (ALP) staining were performed to determine ALP activity, alizarin red staining to evaluate the calcium deposit, while qRT-PCR and Western blotting were used to determine the expression of related molecules. Besides, MC3T3-E1 cells transfected with miR-control or miR-183 mimic were cultured with or without TGF-β1 to verify whether miR-183 regulates the TGF-β signaling pathway.ResultsMiR-183 was up-regulated with decreased Smad4 in the femur of OVX mice, and dual luciferase reporter gene assay showed that Smad4 was a target of miR-183. As compared to Mock group, MC3T3-E1 cells and primary osteoblasts in the miR-183 mimic group and siSmad4 group had significant reductions of OCN, OPN, Runx2 and Osx, as well as decreased ALP activity and calcium deposit. Contrarily, miR-183 and Smad4 were up-regulated and down-regulated respectively. However, cells in the miR-183 inhibitor group manifested the opposite changes. Besides, osteoblast differentiation in the miR-183 inhibitor + siSmad4 group was weakened evidently when compared to miR-183 inhibitor group. Pathway analysis indicated that miR-183 regulated osteogenic differentiation via TGF-β signaling pathway.ConclusionMiR-183 was up-regulated in osteoporosis, and miR-183 overexpression can inhibit osteoblast differentiation by targetedly down-regulating TGF-β pathway member Smad4 to trigger osteoporosis.     

β3-integrin Leu33Pro gain of function variant does not modulate inflammatory activity in human derived macrophages in diabetes

Objective: We aimed to investigate the association between the Leu33Pro (rs5918) polymorphism in β3-integrin with diabetic complications and inflammatory function of macrophages depending on the genotype in subjects with diabetes mellitus.Material and methods: We determined the Leu33Pro polymorphism in 186 diabetic subjects and collected laboratory data. Monocytes from 24 patients were collected for macrophage differentiation to determine the inflammatory activity by treating with different stimulants.Results: We could demonstrate that human derived differentiated macrophages expressed β3‑integrin. Their secretory capacity upon inflammatory stimulation did not reveal any differences depending on the Leu33Pro variant. We found trends for an association of the polymorphism with the presence of diabetic nephropathy (p = 0.071), as well as with creatinine [1.32 mg/dL (1) vs. 0.98 mg/dL (0)] (p = 0.029 in recessive model) and glomerular filtration rate [75.6 ml/min ± 22 vs. 62.3 ml/min ± 25] (p = 0.076 in recessive model) as quantitative markers of kidney function.Conclusion: Despite the expression of β3‑integrin in human macrophages, the Leu33Pro polymorphism in β3‑integrin does not modify the inflammatory response upon stimulation but might play a role in the progression of diabetic nephropathy. Further studies are necessary to substantiate such a hypothesis.     

MicroRNA-33/33* inhibit the activation of MAVS through AMPK in antiviral innate immunity

Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated. As vital orchestrators in cholesterol homeostasis, microRNA-33/33* have been widely investigated in cellular metabolism. However, their role in antiviral innate immunity is largely unknown. Here, we report that VSV stimulation decreased the expression of miR-33/33* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. In addition, miR-33/33* specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein (MAVS) from forming activated aggregates by targeting adenosine monophosphate activated protein kinase (AMPK), subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation. Our findings establish miR-33/33* as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.     

牙周炎宿主转化生长因子-β^+调节性B细胞变化特点

目的:探讨牙周炎时宿主不同组织内转化生长因子β(transforming growth factor-β,TGF-β)+调节性B细胞的变化特点,比较健康个体与牙周炎模型之间的差异,分析其潜在的作用机制,为进一步揭示牙周炎病理机制提供理论支持。方法:采用SD大鼠建立实验性牙周炎病理模型。采用流式细胞术分析各组不同组织内TGF-β^+调节性B细胞占总淋巴细胞的比例,采用实时荧光定量聚合酶链反应(Real-time polymerase chain reaction,Real-time PCR)检测各样本中B细胞发育相关因子B细胞活化因子(B-cellactivatingfactor,BAFF)、增殖诱导配体(aproliferation-inducingligand,APRIL)及白细胞介素-33(interleukin-33,IL-33)的表达水平。结果:与健康组比较,牙周炎大鼠牙龈中TGF-β^+调节性B细胞比例显著上调(P<0.05);而在外周血中两者比较差异无统计学意义(P>0.05)。在牙龈中,牙周炎大鼠各检测基因的相对表达水平与健康组比较差异显著(P<0.05);在外周血中,牙周炎大鼠与健康组各检测基因的相对表达水平比较差异无统计学意义(P>0.05)。结论:牙周炎时宿主牙龈中TGF-β^+调节性B细胞上调,这与局部BAFF、APRIL及IL-33等细胞因子表达水平呈正相关。     

Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma

We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population.     

miR-126 regulated breast cancer cell invasion by targeting ADAM9

Accumulating evidence has shown that microRNAs (miRNAs) deregulation is commonly observed in human malignancies and crucial to cancer metastasis. Herein, we demonstrated that miR-126 play a suppressor role in human breast cancer cells invasion through the direct repression of a disintegrin and metalloprotease 9 (ADAM9). MiR-126 expression was investigated in forty cases of breast cancer specimens by real-time PCR. Transwell assay was conducted to explore the effects of miR-126 on the invasion of human breast cancer cell lines. The impact of miR-126 overexpression on putative target ADAM9 was subsequently confirmed by Western blot analysis. Our results indicated that miR-126 expression was frequently down-regulated in breast cancer specimens compared with adjacent normal tissues (P<0.05). Overexpression of miR-126 significantly reduced (P<0.05) the protein levels of ADAM9, further suppressed (P<0.05) breast cancer cell invasion in vitro. Meanwhile, knockdown of ADAM9 by small interfering RNA (siRNA) also inhibited (P<0.05) breast cancer cell invasion. Thus, our study revealed that miR-126 may act as a tumor suppressor via inhibition of cell invasion by downregulating ADAM9 in breast cancer development.