1.Cross-talk between nuclear factor-κB and other signaling pathways
Xian LI ; Changren ZHOU ; Shengli NIE
Chinese Journal of Pathophysiology 2010;26(1):181-187
Transcription factor NF-κB has attracted attention due to its important role in the regulation of the expression of a number of cellular genes involved in host defense, inflammation/immune responses, cytokine and growth factor regulation, cell survival, proliferation, and also in embryonic development and programmed cell death. In this review, we provide an overview of established TNF-α, TLR/IL-1R, TCR and BCR signaling pathways to NF-κB, the alternative NF-κB pathway, and the regulation of NF-κB transcriptional activity. Furthermore, we discuss on emphasis the cross-talks between NF-κB and other signaling pathways (TGF-β, p53, nuclear receptor family, Ras/MEK/MAPK...), which are very complex and remain to be understood. The activation or inhibition of NF-κB has effect on other signaling pathways. They compose a complex signaling network, in which many regulatory signals integrate systematically and coordinate transcriptional responses to the stimulations. So when NF-κB is used as an important target of drugs in human diseases, the pathological and physiological functions of related signal pathways also should be understood sufficiently.
2.Glial cell line-derived neurotrophic factor engineered neural stem cell transplantation as a therapeutic approach for Parkinson' s disease in rat model
Shengli XU ; Ming ZHOU ; Biao CHEN
Chinese Journal of Geriatrics 2010;29(1):58-62
Objective To explore the therapeutic effects of human glial cell line-derived neurotrophic factor (GDNF)-engineered rat neural stem cell (NSC) transplantation in rat model of Parkinson's disease ( PD) . Methods SD rats received a single injection of 24 μg of 6-hydroxydopamine (6-OHDA) at two sites in right striatum. Then 10 days after surgery, the successful animal models of PD were divided into 3 groups: PD model group ( 2 μl transplantation media was injected in right striatum), NSC group (transplanted were 2×10~5 NSCs infected by bare lentivirus) and GDNF group (transplanted were 2×10~5 GDNF-engineered NSCs). The rotation scores were assessed 5 weeks, 7 weeks and 9 weeks after transplantation. The dopaminergic neurons in substantia nigra ( SN ) were analyzed quantitatively using immunohistochemistry for tyrosine hydroxylase (TH), and the dopamine and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were analyzed 9 weeks after transplantation by high performance liquid chromatography ( HPLC) . Results GDNF-engineered NSC transplantation could effectively improve the behavioral performance in rats. At the 5th week after cell transplantation, the rotation turns within 90 min were (993. 9±159. 1) turns, (956. 7±136. 3) turns and (433. 6±100. 9) turns in PD model group, NSC group and GDNF group respectively (F=95. 694, P = 0. 000). At the 7th week, the rotation turns within 90 min were (964. 2 ± 152.0) turns, (909. 2 ± 136. 3) turns and (399. 4±84. 4) turns in PD model group, NSC group and GDNF group respectively (F = 106. 134, P=0. 000). At the 9th week, the rotation turns within 90 min were (909. 5±152. 2) turns, (865. 5± 129. 1) turns and (312. 2±63. 7) turns in PD model group, NSC group and GDNF group respectively (F= 151. 100, P = 0.000). GDNF-engineered NSC transplantation could significantly increase the levels of dopamine and its metabolites in injured striatum. The concentrations of dopamine in injured striatum was higher in GDNF group than that in PD model group and NSC group C(7. 5±0. 8) ng/mg vs. (3.3±0.3) ng/mg and (3. 7±1. 3) ng/mg, F=59. 543, P = 0. 0003. The level of DOPAC was higher in GDNF group than that in PD model group and NSC group C(0. 9±0. 1) ng/mg vs. (0. 5± 0. 1) ng/mg and (0. 6±0. 2) ng/mg, F= 17. 293, P=0. 000]. The concentration of HVA in injured striatum was higher in GDNF group than that in PD model group and NSC group [(0. 9±0. 1) ng/mg vs. (0.5±0. 1) ng/mg and (0. 6±0. 2) ng/mg, F=35.175, P = 0.000]. Conclusions engineered NSC transplantation improves the function of dopamine system in SN and striatum, and GDNF gene therapy has potential clinical value.
3.Establishment of an in vitro system evaluating neurotoxicity using neural differentiation of human ES cells and amniotic fluid stem cells
Junmei ZHOU ; Shengli ZHANG ; Fang CHEN
Journal of Clinical Pediatrics 2011;(2):101-105
Objective A lot of drugs have side effects on the central nerves system. Especially in children. In vivo neurotoxicity tests are time-consuming and expensive. The neural differentiation of human embryonic stem cells and amniotic fluid stem cells provides all ideal in vitro system that Can be applied to evaluate neurotoxicity of drugs. This study was to try to establish such a system. The kainie acid was selected to test the neurotoxicity. Methods The human embryonic stem cells and amniotic fluid stem cells were indueed to differentiate into neural cells by a chemically defined neural induction medium. The induced neural cells were propagated in the presence of basic fibroblast growth factor. Immunocytochemical staining Was applied to confirm these cells' neural identity. The induced cells were propagated under different concentration of kainic acid, then the gosh curve were made based on the cell numbers. Results Both of the human embryonic stem cells and amniotic fluid stem cells could be efficiently induced to be differentiated into neural cells. The neural differentiation efficiency of human embryonic stem cells is higher than that of human amniotic fluid stem cells. The kainic acid has neurotoxieity to the indueed neural cells. Conclusions The neural differentiation of human embryonic stem cells and amniotic fluid stem cells were proved to provide a rapid and convenient approach for estimating the neurotoxlcity of drugs.
4.Cross-talk between nuclear factor-?B and other signaling pathways
Xian LI ; Changren ZHOU ; Shengli NIE
Chinese Journal of Pathophysiology 1986;0(01):-
Transcription factor NF-?B has attracted attention due to its important role in the regulation of the expression of a number of cellular genes involved in host defense,inflammation/immune responses,cytokine and growth factor regulation,cell survival,proliferation,and also in embryonic development and programmed cell death. In this review,we provide an overview of established TNF-?,TLR/IL-1R,TCR and BCR signaling pathways to NF-?B,the alternative NF-?B pathway,and the regulation of NF-?B transcriptional activity. Furthermore,we discuss on emphasis the cross-talks between NF-?B and other signaling pathways (TGF-?,p53,nuclear receptor family,Ras/MEK/MAPK...),which are very complex and remain to be understood. The activation or inhibition of NF-?B has effect on other signaling pathways. They compose a complex signaling network,in which many regulatory signals integrate systematically and coordinate transcriptional responses to the stimulations. So when NF-?B is used as an important target of drugs in human diseases,the pathological and physiological functions of related signal pathways also should be understood sufficiently.
5.Value of dual source CT iodine concentration in the evaluation of pathological grades of esophageal carcinoma
Xiaojing LIU ; Shengli ZHOU ; Chongchang MIAO
Chinese Journal of Radiology 2016;50(6):436-438
Objective To investigate the value of dual source CT iodine concentration in the assessment of pathological grade of esophageal carcinoma. Methods Retrospective review was performed on 60 cases with pathologically?confirmed esophageal carcinoma. Among them, 17 tumors were well differentiated, 24 were moderately differentiated and 19 were poorly differentiated. The dual?energy plain scan and double phase enhanced scan of dual?source CT were performed on all 60 cases. Normalized iodine concentration (NIC) and the enhancement degree of the esophageal carcinoma in the arterial and venous phase were measured. The difference of NIC and enhancement degree among different grades of esophageal carcinoma were analyzed by analysis of variance. To evaluate the efficiency of NIC and enhancement degree in differentiating the well?moderately differentiated esophageal carcinoma from poorly differentiated esophageal carcinoma, ROC curve was plotted. Results The NIC values of the well differentiated, the moderately differentiated and the poorly differentiated esophageal carcinoma in the arterial phase were (1.54±0.34),(1.72±0.50)and(2.10±0.40)mg/ml, respectively;the NIC values in venous phase were(1.55± 0.52),(1.80±0.62)and(2.18±0.35)mg/ml,respectively, and the degrees of CT enhancement in venous phase were(25.65 ± 4.43),(27.55 ± 6.82)and(30.77 ± 6.38)HU, respectively. The differences between groups were statistically significant(P<0.05). The degrees of CT enhancement of well differentiated, moderately differentiated and poorly differentiated esophageal carcinoma in arterial phase were(14.40 ± 3.91),(14.26 ± 7.35)and(16.17 ± 6.89)HU, respectively, and there were no statistically significant differences(P=0.582). Areas under the ROC curves to differentiate well?moderately differentiated from poorly differentiated esophageal carcinoma for NIC in arterial phase, NIC in venous phase and the degree of CT enhancement in venous phase were 0.801, 0.817 and 0.730. Conclusion The iodine concentration measured on dual source CT has a certain value in evaluating the pathological grades of esophageal carcinoma.
6.Valuation of dynamic MR imaging for diagnosis of pituitary microadenomas
Wu LU ; Shengli ZHOU ; Yucheng LIU ;
Chinese Journal of Radiology 1994;0(06):-
Objective To evaluate the use of keyhole dynamic magnetic resonance (MR) imaging in evaluation of pituitary microadenomas. Methods Fifty three patients with pituitary microadenomas proved by operation or clinical findings such as headache, amenorrhea, lactating, fat or acromegaly were retrospectively studied on dynamic MR, conventional contrast enhanced MR, and unenhanced MR. Then the image data were analyzed by two experienced doctors who didn′t know the details and three degrees were made as follows: grade 0, no evidence of the tumor; gradeⅠ, asymmetry signals in the pituitary; and gradeⅡ, nodulated or sheets signals in the pituitary. The grading data were compared with statistical methods. Results In dynamic MR grading system: grade 0 was revealed in 1 patient, gradeⅠ in 29 patients and gradeⅡ in 23 patients. In conventional enhanced MR: grade 0 in 26 patients, grade Ⅰ in 17 patients and gradeⅡin 10 patients. In conventional unenhanced MR: grade 0 in 39 patients, grade Ⅰin 10 patients and grade Ⅱ in 4 patients. The diagnostic rate of dynamic MR, conventional enhanced MR, and unenhanced MR was 98.1%, 51.9%, and 26.4%, respectively. ( P
7.The diagnostic values of color ultrasound to the stenosis of extracranial carotid arteries
Mingxian TAN ; Jie ZHOU ; Shengli CHEN
Journal of Clinical Neurology 2001;0(05):-
Objective To investigate the diagnostic values of color ultrasound to the stenosis of extracranial carotid arteries.Methods Color ultrasound examination and digital subtraction angiography(DSA)were performed in 145 patients with ischemic cerebravascular disease.The sensitivity and specificity of color ultrasound for the stenosis of extracranial carotid arteries were analyzed according to the golden standard of DSA results.Results The sensitivity and specificity of color ultrasound for stenosis of carotid bifurcation,subclavicular artery and vertebral artery were 96.8%,80.6%,60.0% and 98.7%,33.3%,89.0%.The accuracy of color ultrasound for stenosis of carotid bifurcation,subclavicular artery and vertebral artery were 93.0%,92.8% and 82.1%.Conclusion Color ultrasound examination are effective for the diagnosis of carotid bifurcation sterosis,and less effective for the diagnosis of the subclavicular and vertebral artery stenosis because of the poor sensitivity.
8.Nicotine inhibits the inflammation induced by 6-hydroxydopamine lesion in the striatum of SD rat
Hui DING ; Shengli XU ; Ming ZHOU ; Biao CHEN
Chinese Journal of Geriatrics 2008;27(8):605-609
Objective To explore the mechanism through which nicotine protects dopaminergic neurons against 6-OHDA toxicity in SD rat. Methods Rats received nicotine or saline treatment (two doses tested,0. 2 rag/ kg and 2 rag/ kg, 5 injections i.p. per day at 2-h intervals). On day 8after the treatment, a single injection of 20μg of 6-OHDA was administered into right striatum.Nicotine or saline was administered continuously daily until animals were killed. The dopaminergic neurons and CD3, CD4 and CDS-positive lymphocytes were analyzed quantitatively using immunohistochemistry. Microglia activation was quantified by IBA1 immunofluorescence. Results The loss of dopaminergic neurons induced by 6-OHDA in the substantia nigra was significantly less severe in the nicotine treatment group (at both 0. 2 and 2 mg/kg groups) than that in the saline treated group. In the striatum, we observed that the number of CD3, CD4 and CD8-positive lymphocytes reduced significantly in the nicotine treated animals as compared to saline controls. Otherwise, nicotine inhibited CD4 and CD8-positive lymphocytes infiltration equivalently. Quantitative immunofluorescenee analysis indicated the microglia activation was inhibited obviously in nicotine treatment. Conclusions Our data suggest that nicotine may have a neuroprotective effect against dopaminergic lesion induced by 6-OHDA by inhibiting the inflammation.
9.Endoscopic ultrasonography features of gastric ectopic pancreas
Shengli KUANG ; Bingxi ZHOU ; Yuxiu YANG ; Bing HU
Chinese Journal of Ultrasonography 2011;20(6):499-501
Objective To describe the characteristic endoscopic ultrasonography (EUS) features of gastric ectopic pancreas.Methods Totally 23 patients were diagnosed pathologically as having gastric ectopic pancreas.The EUS images of the lesions were retrospectively reviewed regarding layer of origin,size,growth pattern,margin,and internal echo pattern.Results The coincidence of EUS and pathologic diagnosis was 91%(21/23).EUS revealed that the lesions originated from the second,third,and/or fourth layers of the gastric wall.Most lesions were heterogenous,mainly isoechoic.The borders of the lesions were indistinct in 70%(16/23) patients. Anechoic cystic or tubular structures within the lesions appeared in 10 of the 23 lesions(43%).The mean longest/shortest diameter ratio of ectopic pancreas was 1.7.Conclusions Characteristic EUS features of gastric ectopic pancreases include:mural lateral growth pattern,third layer (submucosa) origin,indistinct margin,intermediate echogenecity,anechoic areas,and fourth-layer thickening.Careful assessment of the EUS findings may be a useful aid in the diagnosis of gastric ectopic pancreas.
10.Effects of Yisui Jiedu Recipe on JAK2-STAT5 signal transduction pathway in bone marrow hematopoietic cells from patients with myelodysplastic syndrome-refractory anemia.
Shengli TIAN ; Yongming ZHOU ; Tao HUANG ; Zhizhong XUE ; Wei HE
Journal of Integrative Medicine 2008;6(2):185-9
To investigate the effect of Yisui Jiedu Recipe (YSJDR), a compound traditional Chinese herbal medicine, on cytokines and their corresponding just another kinase 2-signal transducers and activators of transcription 5 (JAK2-STAT5) signal transduction pathway in bone marrow hematopoietic cells from patients with myelodysplastic syndrome-refractory anemia (MDS-RA).