1.miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1
Keyan CHENG ; Jialei CUI ; Wenli ZHOU ; Huiqiang LIU ; Taotao YANG ; Yonghong WANG
Maternal-Fetal Medicine 2022;04(4):238-244
Objective::The objective of this study was to investigate the expression levels of microRNA-141-5p(miRNA-141-5p), MAPK1 and neutrophil elastase in patients with and without preeclampsia (PE), and the relationship between miRNA-141-5p and MAPK1 with respect to the secretion of elastase by neutrophils in patients with PE.Methods::Thirty patients with PE and 30 healthy pregnant (HP) women were recruited from The Second Hospital of Shanxi Medical University, Taiyuan, China, between February 2017 and July 2018. Neutrophils were isolated from 8 mL peripheral blood samples and cultured. We recorded neutrophil count and morphology during culture. Apoptosis was detected by flow cytometry in different groups at 0, 24, and 48 h. The expression levels of elastase were detected in neutrophils by enzyme-linked immunosorbent assay, whereas the expression levels of miRNA-141-5p in peripheral blood neutrophils were detected by real-time polymerase chain reaction. We used TargetScanHuman Release 7.2 to analyze the target genes of miRNA-141-5p. The expression of MAPK1 in peripheral blood neutrophils was detected by western blotting. Data were analyzed by SPSS version 21.0 software, and comparisons between groups were carried out with the Student t test. Results::There was no significant difference between the PE and HP groups ( P > 0.050) with regard to age or body mass index. The weight of newborns in the PE group (2846.00 ± 600.00 g) was significantly lower than that in the HP group (3055.00 ± 230.68 g). The number of neutrophilic granulocytes(NGs) in blood samples from the PE group was significantly higher than that in the HP group ( P = 0.003). There was no significant difference between the groups with regard to morphology. Apoptosis in the PE group was delayed when compared with the HP group at different time points. The P value of apoptosis in the PE and HP groups were respectively 0.790, < 0.001 and 0.030 at 0 h, 24 h and 48 h. The expression levels of miRNA-141-5p in the PE group were significantly lower than those in the HP group ( P < 0.050). The expression levels of MAPK1 in neutrophils from the PE group were significantly higher than those in the HP group ( P < 0.050) by western blot. The expression levels of elastase in neutrophils from the PE group were significantly higher than those in the HP group ( P < 0.050). Furthermore, the number of NGs in peripheral blood from the PE group was higher than that of the HP group; however, the levels of apoptosis were lower. The expression levels of miRNA-141-5p in NGs decreased, the expression of MAPK1 increased, and the secretion of neutrophil elastase in the NG medium increased in the PE group than those in the HP group. Conclusion::Collectively, our analysis suggested that miRNA-141-5p may be involved in the pathogenesis of PE by regulating the MAPK1 signaling pathway to activate neutrophils and increase the secretion of elastase.
2.miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1
Keyan CHENG ; Jialei CUI ; Wenli ZHOU ; Huiqiang LIU ; Taotao YANG ; Yonghong WANG
Maternal-Fetal Medicine 2022;04(4):238-244
Objective::The objective of this study was to investigate the expression levels of microRNA-141-5p(miRNA-141-5p), MAPK1 and neutrophil elastase in patients with and without preeclampsia (PE), and the relationship between miRNA-141-5p and MAPK1 with respect to the secretion of elastase by neutrophils in patients with PE.Methods::Thirty patients with PE and 30 healthy pregnant (HP) women were recruited from The Second Hospital of Shanxi Medical University, Taiyuan, China, between February 2017 and July 2018. Neutrophils were isolated from 8 mL peripheral blood samples and cultured. We recorded neutrophil count and morphology during culture. Apoptosis was detected by flow cytometry in different groups at 0, 24, and 48 h. The expression levels of elastase were detected in neutrophils by enzyme-linked immunosorbent assay, whereas the expression levels of miRNA-141-5p in peripheral blood neutrophils were detected by real-time polymerase chain reaction. We used TargetScanHuman Release 7.2 to analyze the target genes of miRNA-141-5p. The expression of MAPK1 in peripheral blood neutrophils was detected by western blotting. Data were analyzed by SPSS version 21.0 software, and comparisons between groups were carried out with the Student t test. Results::There was no significant difference between the PE and HP groups ( P > 0.050) with regard to age or body mass index. The weight of newborns in the PE group (2846.00 ± 600.00 g) was significantly lower than that in the HP group (3055.00 ± 230.68 g). The number of neutrophilic granulocytes(NGs) in blood samples from the PE group was significantly higher than that in the HP group ( P = 0.003). There was no significant difference between the groups with regard to morphology. Apoptosis in the PE group was delayed when compared with the HP group at different time points. The P value of apoptosis in the PE and HP groups were respectively 0.790, < 0.001 and 0.030 at 0 h, 24 h and 48 h. The expression levels of miRNA-141-5p in the PE group were significantly lower than those in the HP group ( P < 0.050). The expression levels of MAPK1 in neutrophils from the PE group were significantly higher than those in the HP group ( P < 0.050) by western blot. The expression levels of elastase in neutrophils from the PE group were significantly higher than those in the HP group ( P < 0.050). Furthermore, the number of NGs in peripheral blood from the PE group was higher than that of the HP group; however, the levels of apoptosis were lower. The expression levels of miRNA-141-5p in NGs decreased, the expression of MAPK1 increased, and the secretion of neutrophil elastase in the NG medium increased in the PE group than those in the HP group. Conclusion::Collectively, our analysis suggested that miRNA-141-5p may be involved in the pathogenesis of PE by regulating the MAPK1 signaling pathway to activate neutrophils and increase the secretion of elastase.
3.MR imaging features of vessel walls at the beginning of the middle cerebral artery in patients with moyamoya disease: a follow up study
Keyan WANG ; Jingliang CHENG ; Jing HAN ; Shuman LI ; Sheng GUAN
Chinese Journal of Neuromedicine 2019;18(5):475-480
Objective To investigate the MR imaging features and changes of arterial walls at the beginning of the middle cerebral artery in patients with moyamoya disease during the natural course.Methods Nineteen patients with moyamoya disease,admitted to our hospital from January 2014 to December 2015,were chosen prospectively in the study.The MR imaging manifestations and clinical symptoms of the initial vascular walls of the unilateral middle cerebral artery in each patient were observed.Results Two patients were classified as Suzuki grading Ⅱ,9 were classified as Suzuki grading Ⅲ,and 8 were classified as Suzuki grading Ⅳ.The maximum cross-sectional area of patients with moyamoya disease was (5.7±1.4) mm2,and the maximum thickness was (0.9±0.2) mm;15 patients showed wall non-enhancement,two showed wall slight enhancement,and two showed wall obvious enhancement.Concentric thickening was noted in 17 patients and eccentric thickening in two.Two patients with Suzuki grading Ⅲ presented concentric thickening and slight enhancement;two patients with Suzuki grading Ⅲ presented concentric thickening and obvious enhancement;one patient with Suzuki grading Ⅱ and one with Suzuki grading Ⅳ presented eccentric thickening and non-enhancement;one patient with Suzuki grading Ⅱ,5 with Suzuki grading Ⅲ and 7 with Suzuki grading Ⅳ presented concentric thickening and non-enhancement.After the follow up for a median time of 38.7 months,the maximum cross-sectional area was (5.5±1.2) mm2 and the maximum thickness was (1.0±0.3) mm,which showed no significant differences as compared with those at admission (P>0.05).Two patients with Suzuki grading Ⅱ progressed to Suzuki grading Ⅲ (the vessel wall developed from non-enhancement to slight or obvious enhancement).No obvious differences in Suzuki grading,enhancement or thickening styles were noted in the other patients during the follow up.Six patients had recurrent cerebral ischemia during follow-up,4 were with wall enhancement,and two were with wall non-enhancement.Conclusions Patients with moyamoya disease at Suzuki grading Ⅱ-Ⅳ commonly present concentric thickening without enhancement.Moyamoya disease progresses slowly,a few patients with moyamoya disease may present enhancement when it is in progress,and patients with wall enhancement are more likely to have recurrent attack of cerebral ischemia.
5.Predictive value of the metabolic tumor volume ratio of cardiac mass to maximal extra cardiac mass for the origin of cardiac tumors
Keyan WANG ; Jingliang CHENG ; Xingmin HAN ; Xinli XIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(3):178-181
Objective To explore the value of metabolic volume of cardiac tumor (MTV1 to that of the maximum extracardiac tumor (MTV2) ratio in predicating the cardiac tumor origin.Methods A total of 35 consecutive cases (19 males,16 females,age range:18-68 years) with multiple cardiac and extracardiac tumors were enrolled in this retrospective analysis.All of them were confirmed by pathology or clinical follow-up results and examined by 18F-fluorodeoxyglucose PET/CT from January 2010 to February 2016.Maximum standardized uptake value (SUVmax) 3.63 was used as the background threshold.MTV1 and MTV2 were automatically obtained by PETVCRA software.Receiver operating characteristic (ROC) curve was drawn to obtain the diagnostic threshold of MTV1/MTV2 ratio for cardiac tumors,and the sensitivity,specificity and accuracy were calculated.Mann-Whitney u test was used to analyze the data.Results Twelve patients were confirmed to have primary cardiac malignant tumors (PCMT),and 23 cases were metastatic cardiac malignant tumors (MCMT).There was statistical difference of MTV1 between PCMT and MCMT patients:52.9(33.3,703.4) cm3vs 8.1(1.2,24.6) cm3(z=-3.70,P<0.05).MTV2 was 11.7(1.8,38.4) cm3 in PCMT patients,which was lower than that in MCMT patients (182.0(100.1,238.0) cm3;z=-4.17,P< 0.05).MTV1/MTV2 ratio of PCMT was 16.20(9.40,71.80),which was significantly higher than that of MCMT (0.10(0.01,0.60),z=-4.66,P<0.05).When MTV1/MTV2 ratio=1.2 was selected as the cut-off value,the sensitivity,specificity and accuracy were 12/12,91.30%(21/23),94.29%(33/35) respectively.Conclusion It may be an important criterion for the diagnosis of PCMT that MTV 1 is greater than MTV2.
6.The value of high-resolution MRI in the differential diagnosis of Moyamoya disease and atherosclerosis-related Moyamoya syndrome
Keyan WANG ; Jingliang CHENG ; Yong ZHANG ; Shuman LI
Chinese Journal of Radiology 2017;51(1):3-7
Objective To explore the value of high-resolution MRI(HR-MRI) on clinical application in the differential diagnosis between Moyamoya disease(MMD) and atherosclerosis-related Moyamoya syndrome (A-MMS). Methods Seventeen cases of patients with MMD and 18 cases of patients with A-MMS in our hospital from January 2014 to September 2015 were prospectively enrolled in the study. Record the clinical data and the proximal middle cerebral artery (M1 portion) performance on HR-MRI, the max-vessel area, the min-vessel area, the max-lumen area, the min-lumen area, the wall max-thickness, the styles of M1 portion thickening (eccentric or concentric), whether the wall was enhanced or not, and analysis the recorded data statistically, t test and χ2 test were used for the statistical analysis. Results The wall max-thickness of MMD group was (0.94 ± 0.17) mm, which was smaller than that in A-MMS group (1.23 ± 0.42) mm, there was statistic significance (t=-2.977, P=0.006). The cases of M1 portion non-enhancement was 15, slight enhancement 2, strong enhancement 0 in MMD group, and non-enhancement 5, slight enhancement 5, strong enhancement 8 in the A-MMS group, the difference was significant statistically (χ2=9.794, P=0.001). The cases of M1 portion concentric thickening was 16, 9 cases in the A-MMS group, there was statistic difference between them (χ2=6.317, P=0.012). Wall concentric thickening diagnose the MMD with a sensitivity of 94.1% (16/17), specificity of 50.0% (9/18), accuracy of 71.4%(25/35). Wall strong enhancement appear in the A-MMS with a sensitivity of 44.4%(8/18), specificity of 100%(17/17), accuracy of 71.4%(25/35).With a cut-off the maximum wall thickness of 1.2 mm could be used to noninvasively differential diagnose the MMD and A-MMS with a sensitivity of 55.6%(10/18), specificity of 88.2%(15/17), accuracy of 71.4%(25/35). Conclusion HR-MRI is a good tool for the differential diagnosis between MMD and A-MMS.
7.Effects of androgen deficiency on visceral fat accumulation and inflammatory gene expression in miniature pigs fed a high-fat diet
Zhaowei CAI ; Yun LING ; Yueqin CAI ; Keyan ZHU ; Cheng CHEN
Acta Laboratorium Animalis Scientia Sinica 2017;25(1):74-78,84
Objective The aim of this study was to explore the effect of androgen deficiency on serum hormone levels, visceral fat accumulation and inflammatory gene expression in miniature pigs fed a high-fat diet ( HFD) . Methods Sexually mature male Chinese Wuzhishan miniature pigs were divided into three groups ( animals/group) as follows:intact male pigs ( SHAM) , castrated male pigs ( CAS) and castrated male pigs plus testosterone treatment ( CAS+T) . The pigs were fed a HFD diet for 12 weeks. Serum levels of testosterone and leptin were measured and visceral fat were dissected and weighted. qRT?PCR was performed to determine the mRNA expression levels of lipogenic, lipolysis and inflammation relat?ed genes. Results (1) Serum testosterone levels were significantly decreased but serum leptin levels were significantly in?creased in the castrated pigs. These effects were recovered after testosterone treatment. ( 2 ) Visceral fat percentage was significantly increased in the castrated pigs, and testosterone treatment reduced the increased visceral fat in the castrated pigs. (3) Castration and testosterone treatment had no significant effects on the expression levels of lipogenic genes (FAS and ACC) and lipolysis genes (HSL and ATGL) in pigs fed a HFD. (5) Castration significantly induced the expressions of inflammatory genes including Leptin, CD68, CCL16, CCL23 and SAA, and testosterone treatment recovered the expres?sions of the above genes in the castrated pigs. Conclusions Castration?induced testosterone deficiency promotes visceral fat accumulation and upregulates the expression levels of inflammatory genes in miniature pigs fed a HFD. Moreover, tes?tosterone treatment ameliorates castration?induced visceral fat accumulation and inflammatory response in HFD?fed pigs.
8.Study on the protective effect of Guanxinning Tablet on myocardial ischemia reperfusion injury in rats
Fei HU ; Yili RONG ; Keyan ZHU ; Hong LU ; Cheng CHEN ; Minli CHEN ; Yongming PAN
Chinese Journal of Comparative Medicine 2017;27(5):76-82
Objective To observe the effect of Guanxinning Tablet (GXNT) on myocardial infarction and cardiac autonomic nervous function in rats with myocardial ischemia reperfusion injury (MI/RI).Methods Seventy SD rats were divided into 7 groups randomly (n=10);the sham group, the MI/RI group, 75 mg/kg, 150 mg/kg, 300 mg/kg and 600 mg/kg GXNT groups and 300 mg/kg Compound Danshen Tablets (DST) group.All rats were administered orally for 7 days, and then the MI/RI model was made by ligating the left anterior descending branch of coronary artery in rats.The changes of electrocardiogram were recorded and the electrocardiogram of J points and heart rate variability (HRV) parameters were analyzed.At the end of reperfusion, the myocardial infarct size was measured by using Evans blue and tetrazolium chloride (TTC) double staining, and pathological changes of myocardium were observed by HE staining.The changes of serum lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) and nitric oxide (NO) levels were also detected.Results Compared with MI/RI group, GXNT and DST groups were significantly reduced myocardial infarct size and inhibited the rising of serum LDH and CK activities (P < 0.05, P < 0.01), and also reduced the total or average value of J point during reperfusion (P < 0.05, P < 0.01).Meanwhile, GXNT and DST groups were markedly increased HRV and serum NO level as well as decreased serum MDA content (P < 0.05, P < 0.01), and improved myocardial tissue pathology.Conclusions GXNT can reduce the myocardial infarction in rats with MI/RI, and also improve the cardiac autonomic nervous function.
9.Value of high-resolution magnetic resonance imaging in differential diagnoses of moyamoya disease and vasculitis-related moyamoya syndrome
Keyan WANG ; Jingliang CHENG ; Shuman LI ; Yong ZHANG ; Yuming XU
Chinese Journal of Neuromedicine 2017;16(12):1225-1229
Objective To explore the clinical application value of high-resolution magnetic resonance imaging (HR-MRI) in the differential diagnoses of moyamoya disease (MMD) and vasculitis-related moyamoya syndrome (V-MMS). Methods A prospective study of clinical data of 22 patients with MMD and 24 patients with V-MMS, admitted to our hospital from January 2014 to September 2016, was performed. HR-MRI and 3D-time of flight-magnetic resonance angiography (3D-TOF-MRA) were performed in all the patients. The proximal middle cerebral artery performance on HR-MRI was recorded: the max-vessel area, min-vessel area, max-lumen area, min-lumen area, wall max-thickness, styles of stenosis of the proximal middle cerebral artery lumen (eccentric stenosis or concentric stenosis), and wall enhancement or not. Results The max-vessel area, min-vessel area, and wall max-thickness of the V-MMS group were significantly larger than those in the MMD group (P<0.05). As compared with patients from MMD group, those from V-MMS group displayed higher distinct and concentric enhancement in the proximal portion of middle cerebral artery (M1 portion) and perforator vessels in basal ganglia region and small vessels in meninges or groove, with statistically significant differences (P<0.05). The sensitivity, specificity and accuracy of M1 portion wall distinct enhancement in diagnosing V-MMS were 75.0% (18/24), 86.4% (19/22), and 80.4% (37/46). The sensitivity, specificity and accuracy of M1 portion wall distinct enhancement combined with perforator vessels in basal ganglia region or small vessels in meningeal or groove in diagnosing V-MMS were 63.6%(15/24), 90.9%(20/22), and 76.1%(35/46). The sensitivity, specificity and accuracy of M1 portion wall distinct enhancement combined with perforator vessels in basal ganglia region or small vessels in meningeal or groove in diagnosing V-MMS were 63.6% (15/24), 90.9% (20/22), and 76.1% (35/46). Conclusion HR-MRI is a good tool in the differential diagnoses of MMD and V-MMS.
10.High resolution magnetic resonance imaging features of proximal portion of middle cerebral artery in patients with moyamoya angiopathy
Keyan WANG ; Jinliang CHENG ; Shuman LI ; Xianzhi LIU
Chinese Journal of Neuromedicine 2016;15(12):1260-1266
Objective To observe the high-resolution magnetic resonance imaging (HR-MRI) features of proximal portion of middle cerebral artery (M1 portion) in patients with moyamoya angiopathy (MMA).Methods Forty-six MMA patients and 12 health volunteers,collected in our hospital from January 2014 to September 2015,were chosen in our study;these subjects were performed three dimensional time of flight magnetic resonance angiography (3D-TOF-MRA) and HR-MRI.The quantitative measurements were conducted retrospectively at the minimum cross-sectional area of vessel and maximum thickness of wall;the morphological changes of the vessel wall of the M1 portion and enhancement or not of wall were evaluated.Moreover,general clinical data and vascular risk factors of all patients were evaluated.Results The minimum cross-sectional area of volunteers was (13.71 ± 2.510) mm2,and the maximum thickness was (0.631±0.203) mm;the minimum cross-sectional area of patients with MMA was (2.700±1.511) mm2,remodeling index was (0.209±0.136),and the maximum thickness was (1.078±0.375) mm.Eccentric thickening was noted in 30.4% patients (14/46),concentric thickening in 69.6% patients (32/46).Wall non-enhancement was noted in 45.7% patients (21/46) and wall enhancement in 54.3% patients (25/46).Eccentric thickening patients had significantly elder age,higher maximum thickness of wall and carotid atherosclerosis rate than concentric thickening patients (P<0.05).Multivariate Logistic regression showed that carotid atherosclerosis were independently associated with wall eccentric thickening (OR=4.986,95%CI:1.263-36046,P=0.026).Wall enhancement patients had significantly higher maximum thickness of wall and hypertension level than the wall non-enhancement patients (P<0.05).Logistic regression showed that hypertension was independently associated with wall enhancement (OR=1 1.764,95%CI:2.081-66.51,P=0.005).Hypertension and carotid atherosclerosis were positively related to the wall thickness (r=0.401,P=0.008;r=0.415,P=0.004).Themaximum thickness was significantly higher in hypertension group than that in normal blood pressure group ([1.234±0.4329] mm vs.[0.936±0.2455] mm,P=0.008).Conclusions M1 portion commonly shows concentric thickening,or eccentric thickening when MMA comorbid with atherosclerosis and negative remodeling in MMA patients on HR-MRI.Wall enhancement is associated with wall thickening,and hypertension is an important factor in the wall thickening.

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