Publications by authors named "Yan-Jie Jia"

37 Publications

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Neural Regen Res 2022 Jan;17(1):194-202

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 10 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.
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http://dx.doi.org/10.4103/1673-5374.314323DOI Listing
January 2022

The risk factors and prognosis of delayed perihematomal edema in patients with spontaneous intracerebral hemorrhage.

CNS Neurosci Ther 2019 10 22;25(10):1189-1194. Epub 2019 Sep 22.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Purpose: We hypothesize delayed perihematomal edema (DHE) leads to secondary injury after spontaneous intracerebral hemorrhage (sICH) with a poor prognosis. Hence, we need to investigate the risk factors of DHE and identify whether DHE will predict the poor outcome of sICH.

Methods: We retrospectively recruited 121 patients with sICH admitted to the Department of Neurology from January 2014 to August 2018. After dividing all these patients into DHE group and non-DHE group, we analyzed the potential risk factors and outcome of DHE using a multivariate logistic regression model.

Results: We conclude DHE after sICH associates with age, hospitalization time, hematoma shape, blood pressure upon admission, alcohol consumption, blood sodium level, and baseline hematoma volume within 24 hours after symptom onset, among which differences were statistically significant (P < .05). Logistic regression analysis finally identified that age (OR = 0.958, 95% CI = 0.923-0.995) and the baseline hematoma volume (OR = 1.161, 95% CI = 1.089-1.238) were the most significant risk factors for DHE, and moreover, the DHE (OR = 3.062, 95% CI = 1.196-7.839) was also a risk factor for poor prognosis in sICH patients.

Conclusion: We suggest DHE is a clinical predictor of secondary injury following sICH and poor prognosis. In addition, age and baseline hematoma volume are considered significant high-risk factors for DHE in patients with sICH.
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http://dx.doi.org/10.1111/cns.13219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776736PMC
October 2019

Correlation between tumor necrosis factor alpha mRNA and microRNA-155 expression in rat models and patients with temporal lobe epilepsy.

Brain Res 2018 12 11;1700:56-65. Epub 2018 Jul 11.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing 100050, PR China. Electronic address:

Accumulative evidence demonstrates that there is an inseparable connection between inflammation and temporal lobe epilepsy (TLE). Some recent studies have found that the multifunctional microRNA-155 (miR-155) is a key regulator in controlling the neuroinflammatory response of TLE rodent animals and patients. The aim of the present study was to investigate the dynamic expression pattern of tumor necrosis factor alpha (TNF-α) as a pro-inflammatory cytokine and miR-155 as a posttranscriptional inflammation-related miRNA in the hippocampus of TLE rat models and patients. We performed real-time quantitative PCR (qRT-PCR) on the rat hippocampus 2 h, 7 days, 21 days and 60 days following kainic acid-induced status epilepticus (SE) and on hippocampi obtained from TLE patients and normal controls. To further characterize the relationship between TNF-α and miR-155, we examined the effect of antagonizing miR-155 on TNF-α secretion using its antagomir. Here, we found that TNF-α secretion and miR-155 expression levels were correlated after SE. The expression of TNF-α reached peak levels in the acute phase (2h post-SE) of seizure and then gradually decreased; however, it rose again in the chronic phase (60 days post-SE). miR-155 expression started to increase 2 h post-SE, reached peak levels in the latent phase (7 days post-SE) of seizure and then gradually decreased. The variation in the trend of miR-155 lagged behind that of TNF-α. In patients with TLE, the expression levels of both TNF-α and miR-155 were also significantly increased. Furthermore, antagonizing miR-155 inhibited the production of TNF-α in the hippocampal tissues of TLE rat models. Our findings demonstrate a critical role for miR-155 in the physiological regulation of the TNF-α pro-inflammatory response and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, regulation of the miR-155/TNF-α axis may be a new therapeutic target for TLE.
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http://dx.doi.org/10.1016/j.brainres.2018.07.013DOI Listing
December 2018

The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy.

Dis Model Mech 2018 03 23;11(3). Epub 2018 Mar 23.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China

Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells. We found that enhancive miR-146a could upregulate the expression of IL-1β and downregulate the expression of CFH, whereas reductive miR-146a could downregulate the expression of IL-1β and upregulate the expression of CFH, in hippocampi of chronic TLE rat models. Meanwhile, enhancive miR-146a could increase the abnormal wave forms in the chronic TLE rat models. Additionally, enhancive IL-1β could feedback downregulate the expression of CFH, upregulate the expression of miR-146a and increase the abnormal wave forms in chronic TLE rat models. After gene knockdown in U251 cells, enhancive miR-146a did not upregulate the expression of IL-1β. In summary, this study shows that enhancive miR-146a can upregulate the inflammatory factor IL-1β in chronic TLE by downregulating CFH, and that upregulation of IL-1β plays an important feedback-regulating role in the expression of miR-146a and CFH, forming a miR-146a-CFH-IL-1β loop circuit that initiates a cascade of inflammation and then leads to the perpetuate inflammation in TLE. Therefore, modulation of the miR-146a-CFH-IL-1β loop circuit could be a novel therapeutic target for TLE.
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http://dx.doi.org/10.1242/dmm.031708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897725PMC
March 2018

Modulation of liver regeneration via myeloid PTEN deficiency.

Cell Death Dis 2017 05 25;8(5):e2827. Epub 2017 May 25.

Liver Immunology Laboratory, Institute of Immunology, Hefei, China.

Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells. In addition, PTEN-deficient Kupffer cells secrete additional factors that facilitate the proliferation of hepatocytes. In conclusion, PTEN is critical for inhibiting M2-like polarization of Kupffer cells after partial hepatectomy, resulting in NK cell activation and thus the inhibition of liver regeneration. Furthermore, PTEN reduces growth factor secretion by Kupffer cells. Our results suggest that targeting PTEN on Kupffer cells may be useful in altering liver regeneration in patients undergoing liver resection.
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http://dx.doi.org/10.1038/cddis.2017.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520744PMC
May 2017

Circular RNA: a new star in neurological diseases.

Int J Neurosci 2017 Aug 5;127(8):726-734. Epub 2016 Oct 5.

b Department of Neurology, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR. China ; China National Clinical Research Center for Neurological Diseases , Beijing , PR. China.

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. In this review, we summarize a number of the latest theories regarding the biogenesis, properties and functions of circRNAs. Specifically, we focus on the advancing characteristics and functions of circRNAs in the brain and neurological diseases. CircRNAs exhibit the characteristics of species conservation, abundance and tissue/developmental-stage-specific expression in the brain. We also describe the relationship between circRNAs and several neurological diseases and highlight their functions in neurological diseases.
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http://dx.doi.org/10.1080/00207454.2016.1236382DOI Listing
August 2017

[Clinical analysis of anti-NMDA receptor encephalitis complicated by paroxysmal sympathetic hyperactivity].

Zhongguo Dang Dai Er Ke Za Zhi 2016 Apr;18(4):376-8

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390083PMC
April 2016

Successful treatment of murine autoimmune cholangitis by parabiosis: Implications for hematopoietic therapy.

J Autoimmun 2016 Jan 1;66:108-17. Epub 2015 Oct 1.

Liver Immunology Laboratory, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China. Electronic address:

There is a significant unmet need in the treatment of primary biliary cirrhosis (PBC) despite significant data on the effector pathways that lead to biliary duct damage. We focused attention on a murine model of PBC, the dominant negative transforming growth factor β receptor II (Tg) mice. To further define the pathways that lead to biliary pathology in these mice, we developed Tg mice deleted of CD4 cells (CD4(-/-)Tg). Interestingly, these mice developed more severe cholangitis than control Tg mice. These mice, which lack CD4 cells, manifested increased levels of IFN-γ produced by effector CD8 cells. It appears that increased cholangitis is due to the absence of CD4 Treg cells. Based on these data, we parabiosed CD4(-/-)Tg mice with established disease at 8-9 weeks of age with C57BL/6 control mice. Such parabiotic "twins" had a significant reduction in autoimmune cholangitis, even though they had established pathology at the time of surgery. We prepared mixed bone marrow chimera mice constructed from CD4(-/-)Tg and CD8(-/-) mice and not only was cholangitis improved, but a decrease in terminally differentiated CD8(+) T effector cells in the presence of wild type CD4 cells was noted. In conclusion, "correcting" the CD4 T cell subset, even in the presence of pathogenic CD8 T cells, is effective in treating autoimmune cholangitis.
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http://dx.doi.org/10.1016/j.jaut.2015.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829433PMC
January 2016

[Effect of p65 gene inhibited by siRNA on differention of rat marrow mesenchymal stem cells into neurons].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2015 May;31(3):254-8

Objective: To investigate the effect of p65 gene inhibited by siRNA on neuronic differentiation in the marrow mesenchymal stem cells (MSCs).

Methods: The MSCs were transfected with Rn-p65-siRNA. Fasudil hydrochloride induced MSCs differentiating into neurons. The non-transfected group and negative control group (transfected with negative control siRNA marked by Cy3) were used as controls. The fluorescence expressed by transfected MSCs were observed under inverted fluorescence microscope at 24 h,48 h and 72 h after transfected with negative control siRNA. The viability of MSCs was detected by MTT at 24 h, 48 h and 72 h after transfected with Rn-p65-siRNA. The expressions of p65 mRNA and protein in MSCs were detected by RT-PCR and Western blot respectively. The expressions of p65 protein, NSE, MAP-2 and glial fibrillary acidic protein (GFAP) were detected by immunocytochemical method after transfection for 6 h.

Results: The fluorescence of MSCs was mostly displayed after transfection of 72 hours and the efficiency of transfection was up to 83.3% ± 3.8%. Meanwhile, the p65 mRNA and p65 protein expressed by MSCs of transfected group were significantly decreased (P < 0.05); MTT displayed that the viability of MSCs was also significantly reduced (P < 0.05). The best efficiency of induction was observed in the transfected group. There were higher expressions of NSE and MAP-2 than the other group (P < 0.05).

Conclusion: The p65 gene inhibited by siRNA can promote the marrow mesenchymal stem cells to differentiate into neurons.
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May 2015

MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy.

Neural Regen Res 2015 Feb;10(2):314-20

Rehabilitation and Treatment Center for Children with Cerebral Palsy of Henan Province, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

MicroRNA-9 (miR-9) has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3)-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9(+) group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.
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http://dx.doi.org/10.4103/1673-5374.143439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392682PMC
February 2015

Systems biologic analysis of T regulatory cells genetic pathways in murine primary biliary cirrhosis.

J Autoimmun 2015 May 17;59:26-37. Epub 2015 Feb 17.

Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China. Electronic address:

CD4(+)Foxp3(+) regulatory T cells (Tregs) play a non-redundant role in control of excessive immune responses, and defects in Tregs have been shown both in patients and murine models of primary biliary cirrhosis (PBC), a progressive autoimmune biliary disease. Herein, we took advantage of a murine model of PBC, the dominant negative transforming growth factor β receptor II (dnTGFβRII) mice, to assess Treg genetic defects and their functional effects in PBC. By using high-resolution microarrays with verification by PCR and protein expression, we found profound and wide-ranging differences between dnTGFβRII and normal, wild type Tregs. Critical transcription factors were down-regulated including Eos, Ahr, Klf2, Foxp1 in dnTGFβRII Tregs. Functionally, dnTGFβRII Tregs expressed an activated, pro-inflammatory phenotype with upregulation of Ccl5, Granzyme B and IFN-γ. Genetic pathway analysis suggested that the primary effect of loss of TGFβ pathway signaling was to down regulate immune regulatory processes, with a secondary upregulation of inflammatory processes. These findings provide new insights into T regulatory genetic defects; aberrations of the identified genes or genetic pathways should be investigated in human PBC Tregs. This approach which takes advantage of biologic pathway analysis illustrates the ability to identify genes/pathways that are affected both independently and dependent on abnormalities in TGFβ signaling. Such approaches will become increasingly useful in human autoimmunity.
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http://dx.doi.org/10.1016/j.jaut.2015.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829434PMC
May 2015

[A preliminary study of plasma microRNA levels in children with methylmalonic acidemia].

Zhongguo Dang Dai Er Ke Za Zhi 2014 Jun;16(6):629-33

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: To screen out differentially expressed microRNAs (miRNAs) in the plasma of children with methylmalonic acidemia (MMA), to determine the expression of miR-9-1 in plasma and to preliminarily evaluate the significance of miR-9-1 as a biomarker in MMA.

Methods: Plasma was obtained from 17 MMA children, 10 hyperhomocysteinemia (HHcy) children without MMA (HHcy group), and 10 normal controls. Of 17 MMA children, 12 had HHcy (MMA+HHcy group), and 5 had no HHcy (MMA group). The differentially expressed miRNAs were screened out by miRNA microarray. Differentially expressed miR-9-1 was selected, and plasma miR-9-1 levels were determined by RT-PCR. Urine was collected from MMA patients who received vitamin B12 treatment, and plasma miR-9-1 levels were determined by RT-PCR after treatment.

Results: The miRNA microarray analysis showed that 26 miRNAs were differentially expressed, among which 16 miRNAs (including miR-9-1) were down-regulated over 2 times, while 10 miRNAs were up-regulated over 2 times. The MMA+HHcy , MMA and HHcy groups had significantly down-regulated miR-9-1 compared with the normal control group (P<0.01). The patients who showed a good response to vitamin B12 treatment had significantly increased plasma miR-9-1 levels, without significant difference compared with the normal control group.

Conclusions: Plasma miR-9-1 is significantly down-regulated in MMA patients, but it is significantly up-regulated after vitamin B12 treatment, suggesting that miR-9-1 may act as a biomarker in monitoring the progression of MMA.
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June 2014

Effects of resveratrol on apoptosis in a rat model of vascular dementia.

Exp Ther Med 2014 Apr 13;7(4):843-848. Epub 2014 Feb 13.

Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China.

Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.
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http://dx.doi.org/10.3892/etm.2014.1542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961111PMC
April 2014

[Mental symptoms as the first presentation of late-onset methylmalonic acidemia: report of 3 cases].

Zhongguo Dang Dai Er Ke Za Zhi 2014 Jan;16(1):85-6

Department of Internal Medicine, First Hospital, Zhengzhou Univesity, Zhengzhou 450052, China.

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January 2014

[Function of autophagy on differentiation of rat bone marrow mesenchymal stem cells into neurons].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2013 Sep;29(5):389-90, 394

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September 2013

[miR-124-1 promotes neural differentiation of rat bone marrow mesenchymal stem cells].

Zhongguo Dang Dai Er Ke Za Zhi 2012 Mar;14(3):215-20

Department of Radiology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.

Objective: To study the effects of miR-124-1 on neuronal differentiation of rat bone marrow mesenchymal stem cells (MSCs).

Methods: MSCs cells were assigned into three groups: control (uninfected and untransfected), miR-124-1+ (infected with miR-124-1), and miR-124-1- (transfected with Anti-rno-miR-124* Inhibitor). MSCs were induced by β-mercaptoethanol (β-ME) to differentiate into neurons. The fluorescence expressed by infected MSCs was observed under an inverted fluorescence microscope. MTT method was used to measure cell survival rate after transfection or infection. Immunocytochemistry, RT-PCR and Western blot methods were used to detect the expression of β3 tubulin, MAP-2 and GFAP 6 days after β-ME induction.

Results: The expression of miR-124-1 in the miR-124-1+ group was significantly higher 2 days after infection of lentivirus vector compared with the control group (P<0.01). In the miR-124-1- group, the cell survival rate and the miR-124-1 expression level decreased significantly 24 hrs after transfection of anti-rno-miR-124* inhibitor (P<0.01). After 6 days of β-ME induction, the protein and mRNA expression levels of β3 tubulin and MAP-2 in the miR-124-1+ group were much higher than the other two groups (P<0.01); while the expression levels of β3 tubulin and MAP-2 in the miR-124-1-group were lower than the control group (P<0.01). The expression of GFAP in the three groups was weak (<1%).

Conclusions: miR-124 might promote neuronal differentiation of rat MSCs.
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March 2012

[Significance of soluble DLL1 in diagnosis of intracranial infectious diseases in children].

Zhongguo Dang Dai Er Ke Za Zhi 2011 Mar;13(3):205-7

Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.

Objective: To investigate the significance of soluble DLL1 (Delta-like-1) levels of cerebrospinal fluid (CSF) and serum in the diagnosis of intracranial infection in children.

Methods: Fifty children with intracranial infection, including 20 cases of tuberculous meningitis (TM), 20 cases of viral meningitis (VM) and 10 cases of purulent meningitis (PM), and 20 children without intracranial infection (control group) were enrolled. The levels of soluble DLL1 in CSF and serum were measured using ELISA.

Results: The level of CSF soluble DLL1 in the TM group was significantly higher than that in the VM, PM and control groups (2.89 ± 1.72 ng/mL vs 0.14 ± 0.14 ng/mL, 0.27 ± 0.21 ng/mL, 0.13 ± 0.12 ng/mL; P<0.01). The level of serum soluble DLL1 in the TM group was also significantly higher than that in the VM, PM and control groups (12.61 ± 6.45 ng/mL vs 2.28 ± 2.27 ng/mL, 2.38 ± 1.79 ng/mL, 2.26 ± 2.10 ng/mL; P<0.01). The levels of soluble DLL1 in the CSF and serum in the VM and PM groups were not significantly different from those in the control group.

Conclusions: Soluble DLL1 as a novel indicator might have potentially important value in the diagnosis of TM.
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March 2011

[Effect of notch signaling on differentiation of rat marrow mesenchymal stem cells into neurons induced by fasudil hydrochloride].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2010 Nov;26(4):428-32

Department of Neurology, Hainan Provincial People's Hospital, Haikou 570311, China.

Objective: To investigate the effect of notch signaling on differentiation of rat bone marrow mesenchymal stem cells (MSCs) into neurons induced by fasudil hydrochloride.

Methods: The experiments were divided into non-transfected group, transfected group (transfected with Rn-Notch1-siRNA), positive control group (transfected with Rn-MAPK-1 Control siRNA) and negative control group (transfected with negative control siRNA). Fasudil hydrochloride induced MSCs differentiating into neurons. The fluorescence expressed by transfected MSCs were observed under inverted fluorescence microscope. The expression of notch1 mRNA, Hes1 mRNA and MAPK1 mRNA in MSCs was detected by RT-PCR. The expression of Notch1 protein, NSE, neurofilament M (NF-M) and glial fibrillary acidic protein(GFAP)was detected by immunocytochemical method. The viability of MSCs was detected by MTT.

Results: (1) The fluorescence of MSCs was mostly displayed after transfection for 72 h and the efficiency of transfection was up to 91.3% +/- 4.2%. Meanwhile, the notch1 mRNA and Hes1 mRNA expressed by MSCs of transfected group were significantly decreased (P < 0.05) and MTT displayed that the viability of MSCs was also significantly reduced (P < 0.05). (2) Fasudil hydrochloride could induce MSCs differentiate into neurons and the best efficiency of induction was observed in the transfected group. There was higher expression of NSE and neurofilament-M (NF-M) than the other groups (P < 0.05).

Conclusion: There may be notch1 signaling and Rho/Rho GTPase signaling synergy on differentiation of rat bone marrow stromal cell into neurons induced by fasudil hydrochloride and they jointly promote the differentiation of MSCs into neurons.
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November 2010

Expression and significance of DSCAM in the cerebral cortex of APP transgenic mice.

Neurosci Lett 2011 Mar 15;491(2):153-7. Epub 2011 Jan 15.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, Henan Province 450052, China.

Down syndrome cell adhesion molecule (DSCAM) plays important roles in the regulation of synaptogenesis, neurite outgrowth, axon guidance and synapse formation. Overexpression of DSCAM in Down syndrome (DS) may be involved in the pathogenesis of mental retardation through an inhibitory action on synaptogenesis/neurite outgrowth, and in the precocious dementia associated with an amyloid precursor protein (APP) dosage effect with enhanced plaque formation. In this report we examined the expression of DSCAM in the cerebral cortex of APP transgenic mice versus age-matched wild-type mice. We found that the level of DSCAM expression increased with increasing age in both groups of mice, up to a maximum at 3 months old. The level of DSCAM expression in APP transgenic mice was significantly higher than in the age-matched wild types. We propose that overexpression of DSCAM in the cerebral cortex might play an important role in the learning and memory defects of APP transgenic mice.
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http://dx.doi.org/10.1016/j.neulet.2011.01.028DOI Listing
March 2011

[Clinical analysis of 322 cases of non-epileptic cerebral palsy].

Zhongguo Dang Dai Er Ke Za Zhi 2010 Dec;12(12):933-5

Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China. Email:

Objective: To study the clinical features of non-epileptic seizures associated with cerebral palsy (CP) in children.

Methods: A total of 1 198 children with CP (age: 9 months to 6 years) were enrolled. The children with paroxysmal events were monitored by 24 hrs video-EEG (VEEG) to make sure the seizures were epileptic or non-epileptic. The symptoms, age, CP types and EEG features were observed in children with non-epileptic CP.

Results: Five hundred and seventy-eight children (48.24%) presented paroxysmal events. The seizures were epileptic in 231 children (19.28%) and non-epileptic in 322 cases (26.88%). In the 322 cases of non-epileptic CP, the paroxysmal events were of various kinds, including non-epileptic seizure tonic, seizure shake head, shrug shoulder or head hypsokinesis, cry or scream, panic attacks, sleep myoclonic and stereotyped movement. One hundred and fifty-eight (49.1%) out of the 322 children demonstrated nonspecific EEG abnormalities. One hundred and eleven children (34.5%) were misdiagnosed as epilepsy in primary hospitals. The CP children less than one year old showed higher frequency of non-epileptic seizures than the age groups over 1 year and 3 to 6 years. The frequency of non-epileptic seizures was the highest in children with spastic CP (168 cases, 52.2%), followed by dyskinetic CP (69 cases, 21.4%) and mixed type CP (65 cases, 20.2%).

Conclusions: The paroxysmal events in children with CP partially are non-epileptic seizures and it is important to differentiate non-epileptic from epileptic seizures. The frequencies of non-epileptic seizures may be associated with a child's age and CP type.
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December 2010

[Protective effect of musk extract on rat's cerebral cortical neurons with inflammatory injury].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2010 Jun;30(6):625-9

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou.

Objective: To investigate the protective effects of musk extract (ME) and its possible mechanism on rat's cerebral cortical neurons with inflammatory injury induced by lipopolysaccharide (LPS).

Methods: Neurons and astrocytes from newborn rat cerebral cortex were cultured in vitro respectively, and the astrocyte conditioned medium (ACM), obtained by treating astrocytes with 10 mg/L LPS and different concentrations of ME for 24 h, was added in the culture fluid of neurons. The survival rate and apoptotic rate of neurons were measured by MTT method and AO/EB stain; and the changes of inflammatory factors in the ACM were determined by ELISA.

Results: The survival rate (%) of neurons treated by ACM with ME in concentrations of 18 mg/L, 36 mg/L, 72 mg/L and 144 mg/L was 52.55 +/- 3.52, 55.77 +/- 2.36, 64.89 +/- 3.45 and 73.67 +/- 1.80, respectively, significantly higher than that in the model neurons (43.62 +/- 4. 51, P < 0.05), while the apoptotic rate (%) in them, 68.11 +/- 2.16, 44.27 +/- 3.68, 32.56 +/- 2.14 and 21.89 +/- 2.46, respectively, was significantly lower than that in model neurons (71.33 +/- 3.25, P < 0.05 or P < 0.01). Level of IL-6 was decreasing along with the raising of ME concentration in the ACM, showing a concentration-dependent state.

Conclusion: ME shows apparent protective effect on neurons against inflammatory injury, especially in a high concentration (144 mg/L), which may be associated with the reduction of IL-6 secreted by astrocytes.
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June 2010

[Expression of microRNA in neonatal rats with hypoxic-ischemic brain damage].

Zhongguo Dang Dai Er Ke Za Zhi 2010 May;12(5):373-6

Department of Neurology, Zhengzhou University, Zhengzhou, China.

Objective: To study the changes of microRNA expression in cortex tissues in neonatal rats with hypoxic-ischemic brain damage (HIBD)and the possible roles of microRNA in the pathogenesis of HIBD. METHODS Rat HIBD model was prepared. The cortex tissues were obtained 14 days after the HIBD event. The microRNA expression profiles were measured using microRNA microarray. Expression of 9 microRNAs (miR-126,-26a,-674-5p,-21,-25,-290, miR-124,-125b-5p and microRNA-9a) was determined by quantitative real-time PCR.

Results: he results of microRNA expression profiles indicated that 27 pieces of microRNA were up-regulated more than 2 folds and 60 pieces were down-regulated more than 2 folds compared with the normal control group. The results of the 9 microRNAs detected by quantitative real-time PCR were consistent with those detected by microRNA microarray.

Conclusions: HIBD rats have significant changes in microRNA expression, suggesting that microRNA expression may play important roles in the pathogenesis of HIBD.
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May 2010

[Effect of non-contact coculture on bone marrow stromal cells and neural stem cells].

Nan Fang Yi Ke Da Xue Xue Bao 2010 Apr;30(4):823-6

Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Objective: To observe the effect of non-contact coculture on bone marrow stromal cells (MSCs) and neural stem cells (NSCs) in neural stem cell culture medium.

Methods: MSCs and NSCs were cultured in non-contact coculture in Transwell plate, and cell morphology and immunocytochemical profile were investigated.

Results: In the coculture, the NSCs showed adhering growth and extended long processes, and the migrating cells formed a network of cells within 7 days. The cells differentiated into neurons, astrocytes and oligodendrocytes as shown by immunocytochemistry. Most of the MSCs grew in a non-adherent manner, giving rise to large spherical cell masses which expressed neuronal, astrocyte, and oligodendrocyte phenotypes. In the control group, the NSCs grew in suspension, some of MSCs formed small non-adherent spherical cell masses, while some cells showed adherent growth.

Conclusion: MSCs and NSCs in the non-contact coculture can mutually promote the cell differentiation into neural cells in neural stem cell culture medium, indicating that both MSCs and NSCs can secrete some neurotrophic factors to provide a microenvironment suitable for survival and differentiation for each other.
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April 2010

[Effects of DSCAM on differentiation of rat marrow mesenchymal stem cells into neurons in vitro].

Zhongguo Dang Dai Er Ke Za Zhi 2009 Jun;11(6):486-9

First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

Objective: To study the effects of Down syndrome cellular adhesion molecule (DSCAM) on differentiation of rat marrow mesenchymal stem cells (MSCs) into neurons in vitro.

Methods: MSCs from Sprague-Dawley rats were induced into neurons by baicalin. The expression of DSCAM before and after induction was evaluated by immunocytochemical staining and Western blot assay. After knockdown of DSCAM by siRNA transfection, the differentiation rate of neurons derived from MSCs was measured.

Results: Before induction, the expression of DSCAM was not detectable in MSCs. After bFGF preinduction for 24 hrs, DSCAM was slightly expressed in MSCs (1.71+/- 0.67%). The DSCAM expression increased 6 hrs after baicalin induction (15.79+/- 4.24%), reached a peak at 3 days (53.16+/- 5.94%) and then decreased gradually. The DSCAM expression 6 days after baicalin induction (28.99+/- 6.72%) was significantly lower than that at 3 days (P<0.01). However, after DSCAM-siRNA transfection, the DSCAM expression in MSCs was significantly reduced. MSCs did not express neuron-specific beta-III-tubulin before induction. After baicalin induction for 6 hrs, 3 days and 6 days, the expression of beta-III-tubulin was 1.40+/- 0.79%, 41.59+/- 3.17% and 59.11+/- 4.76% respectively. But the beta-III-tubulin expression significantly decreased 3 and 6 days after DSCAM-siRNA transfection (28.57+/- 2.91% and 43.90+/- 12.31% respectively).

Conclusions: DSCAM may play an important role in MSCs differentiation into neural cells.
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June 2009

[Clinical analysis of families with generalized epilepsy with febrile seizures plus].

Zhongguo Dang Dai Er Ke Za Zhi 2007 Oct;9(5):436-40

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: To investigate the clinical phenotypes and hereditary patterns of the generalized epilepsy with febrile seizures plus (GEFS+).

Methods: Detailed family trees were constructed by inquire and physical examinations for the probands of the 15 pedigrees of GEFS+. Some patients received electroencephalography, cranial CT or MRI examination. The seizures and epilepsy syndromes were classified according to the 2001 Seizure International Classification. The clinical data of GEFS+ were reviewed.

Results: The 15 families consisted of 196 individuals. Seventy-five individuals were confirmed with epilepsy. The phenotypes of 64 out of the 75 patients with epilepsy conformed to GEFS+. The 64 patients included 38 males and 26 females (1 deceased) and there was no gender difference in the morbility of GEFS+. The age at onset was all in childhood. GEFS+ had a diversity of phenotypes. Febrile seizures (FS) were confirmed in 44 patients, FS and myoclonic seizure in 1, febrile seizures plus (FS+) in 13, FS+ and absence seizure in 2, FS+ and myoclonic seizure in 1, and FS+ and focal seizure in 3.

Conclusions: The heterogeneity of phenotypes and genetics may be the hallmarks of GEFS+. FS and FS+ are common phenotypes while FS+ and absence seizure, FS+ and myoclonic seizure, and FS+ and focal seizure are rare. If one of the parents is affected in a GEFS+ family, the susceptibility of their children to GEFS+ is the same no matter what gender of their children is. It is speculated that the hereditary pattern of GEFS+ conforms to autosomal dominant inheritance.
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October 2007

[The best site of transplantation of neural stem cells into brain in treatment of hypoxic-ischemic damage: experiment with newborn rats].

Zhonghua Yi Xue Za Zhi 2007 Mar;87(12):847-50

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China.

Objective: To investigate the best site of transplantation of neural stem cells (NSCs) into the brain to treat hypoxic-ischemic damage (HIBD).

Methods: Forty-eight 7-day-old Spraque-Dawley rats underwent ligation of the left common carotid artery and exposure to 8% oxygen at 37 degrees C for 2 hours to establish HIBD models and then were randomly divided into 4 equal groups 3 days later: HIBD control group, HIBD + cortex transplantation group (CT group) undergoing NSC transplantation into the sensorimotor cortex, HIBD + hippocampus transplantation group (HT group) undergoing NSC transplantation into the hippocampus, and HIBD + ventricle transplantation group (VT group), undergoing NSC transplantation into the lateral ventricle. Since the rats were 40-day-old, they underwent radial maze water-seeking test and 4 sensorimotor tests. Then the brains of the rats were taken out to undergo histological examination by Nissl staining and immunohistochemistry to observer the 5-bromodeoxyuridine (BrdU) expression.

Results: The times the rats took to find the water in all 3 arms of the maze were arranged form short to long in the order HT group < VT group < CT group < HIBD group with significant differences between the HT, VT, and CT groups and HIBD group (All P < 0.05) and between the groups HT and VT and the group CT (both P < 0.05). The results of the 4 sensorimotor tests were arranged from the best to the worst in the order CT group > VT group > HT group > HIBD group with significant differences between the groups CT and VT and the group HIBD (both P < 0.05). Nissl staining showed that the number of normal neurons in the cortex area from more to less were arranged in the order CT group > VT group > HT group > HIBD group; and the number of normal neurons in the CAI area from more to less were arranged in the order HT group > VT group > CT group > HIBD group.

Conclusion: Transplantation of NSC attenuates the brain damage and the cognitive and sensorimotor dysfunction after HIBD. Transplantation into the lateral ventricle is the most effective.
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March 2007

[Effects of Notch-1 signaling in bone marrow mesenchymal stem cells differentiating into neurons: experiment in vitro].

Zhonghua Yi Xue Za Zhi 2006 Nov;86(41):2916-21

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: To investigate the role of Notch-1 signaling in bone marrow mesenchymal stem cells (MSCs) differentiating into neurons.

Methods: Mice Notch-1 small hairpin RNA (mNotch-1 shRNA) was constructed and transfected into the MSCs obtained from the tibiae of BALB/c mice. MSCs transfected with glyceraldehyde-3-phosphate hydoxygenase (GADPH) shRNA and untransfected MSCs were used as controls. The cell survival rate was detected by ELISA. The MSCs of different groups were cultured in Neurobasal-A medium so as to be induced to differentiate into neurons. Apoptosis of the MSCs was detected by TUNEL.

Results: After induction of 6 days the MSCs transfected with mNotch-1 shRNA displayed typical neuronal morphology and high expression of neuron-specific markers: nestin, neuron-specific enolase (NSE), neurofilament 200 (NF 200), and Notch-1 protein, however, gilal fibrillary acidic protein (GFAP), the glia-specific marker, was not detected. The percentage of apoptotic cells in the MSCs transfected with mNotch-1 shRNA was 13.3% +/- 2.3%, significantly higher than those of the MSCs transfected with mGAPH shRNA and untransfected MSCs (4.7% +/- 0.5% and 4.5% +/- 0.4%, both P < 0.01).

Conclusion: Block of the Notch signal pathway may increase the differentiation of MSCs into neurons.
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November 2006

[Study on molecular mechanism of inhibitory effect of baicalin on proliferation of insulinoma cell line in rats].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2006 Apr;26(4):337-40

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008.

Objective: To investigate the effect of baicalin on insulinoma cell line and the molecular mechanism involved.

Methods: Light microscope, MTT assay, flow cytometry, gene analysis and Western Blot were applied to investigate the effects of baicalin on the cell proliferation, the cell cycle and the involved molecular mechanism.

Results: After treatment with baicalin, the number of cells in mitotic stage and the survival rate of cells obviously decreased, and cell proliferation was inhibited in a drug concentration- and acting time-dependent manner, with the appearance of apoptotic insulinoma cells. During the apoptotic process, the activity of caspase-3 was elevated by baicalin in a time-dependent manner; with the increase of the concentration of baicalin, the number of cells in S-phase obviously decreased from 38.2% to 9.4%, while the percentage of cells in G0/G1 phase increased from 56.4% to 85.9%, indicating cells were arrested in G1-phase. Meanwhile, the activity of cyclin gene promoter obviously declined, and the expression of cyclin reduced remarkably.

Conclusion: Baicalin could induce apoptosis of insulinoma cells, which might be correlated with the activity of caspase-3, and inhibiting proliferation of insulinoma cells in a concentration- and time-dependent manner, in which the action of baicalin in down-regulating the gene transcription and expression of cyclin may play an important role.
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April 2006

[Effect of hyperbaric oxygenation on neural stem cells and myelin in neonatal rats with hypoxic-ischemic brain damage].

Zhongguo Dang Dai Er Ke Za Zhi 2006 Feb;8(1):33-7

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China.

Objective: This study investigated the effect of hyperbaric oxygenation (HBO) on neural stem cells (NSCs) and myelin in neonatal rats following hypoxic-ischemic brain damage (HIBD) and aimed to explore the possible mechanism of the protective effect of HBO on HIBD.

Methods: Seven-day-old Sprague-Dawley rat pups were randomly assigned into 4 groups: Normal control, HIBD, hyperbaric air (HBA), and HBO groups (n=30 each). The HIBD model was produced by permanent occlusion of the left common carotid artery and 2 hrs hypoxemia exposure (8% O2 at 37 degrees C). HBA and HBO treatment was administered (2 ATA, once daily for 7 days) in the HBA and HBO groups respectively 1 hr after HIBD. BrdU immunohistochemistry was used to detect the NSCs in the sub-ventricle zone (SVZ) of the lateral ventricle and the dentate gyrus (DG) of the hippocampus. The myelin damage was assessed by myelin basic protein (MBP) immunostaining.

Results: The BrdU-positive cells in the SVZ and the DG of the ischemic hemisphere in the HIBD group were dramatically decreased compared with those of the Normal control group at 3 weeks post-HIBD (P < 0.01). The HBO treatment resulted in an increase of BrdU-positive cells in the DG from 153.7 +/- 37.0 to 193.7 +/- 38.8 (P < 0.05). The nestin expression in the HIBD and HBA groups was reduced compared with that in the Normal control group. There was no difference in the nestin expression between the HBO and the Normal control groups. Hypoxia-ischemia (HI) led to marked myelin damage at 1 week post-HIBD. HBO or HBA treatment alleviated the damage.

Conclusions: The HBO treatment can result in the proliferation of BrdU-positive cells and alleviate the myelin damage following HIBD in neonatal rats, thereby offering neuroprotectivity against HI insults.
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February 2006

Intracerebral xenotransplantation of semipermeable membrane- encapsuled pancreatic islets.

World J Gastroenterol 2005 Sep;11(36):5714-7

Neurosurgery Department of Yiwu Central Hospital, 3rd Faculty of Medical College, Zhejiang University, Zhejiang Province, China.

Aim: To identify the decreasing effect of xenotransplantion in combination with privileged sites on rejection and death of biological semipermeable membrane-(BSM) encapsulated implanted islets.

Methods: After the BSM experiment in vitro, BSM-encapsulated SD rat's islet-like cell clusters (ICCs) were xenotransplanted into normal dog's brain. Morphological changes were observed under light and transmission electron microscope. The islets and apoptosis of implanted B cells were identified by insulin-TUNEL double staining.

Results: The BSM used in our study had a favorable permeability, some degree of rigidity, lighter foreign body reaction and toxicity. The grafts consisted of epithelioid cells and loose connective tissue. Severe infiltration of inflammatory cells was not observed. The implanted ICCs were identified 2 mo later and showed typical apoptosis.

Conclusion: BSM xenotransplantation in combination with the privileged site can inhibit the rejection of implanted heterogeneous ICCs, and death of implanted heterogeneous B cells is associated with apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481495PMC
http://dx.doi.org/10.3748/wjg.v11.i36.5714DOI Listing
September 2005