The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of...The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.展开更多
AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood m...AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.展开更多
A series of true-triaxial compression tests were performed on red sandstone cubic specimens with a circular hole to investigate the influence of depth on induced spalling in tunnels.The failure process of the hole sid...A series of true-triaxial compression tests were performed on red sandstone cubic specimens with a circular hole to investigate the influence of depth on induced spalling in tunnels.The failure process of the hole sidewalls was monitored and recorded in real-time by a micro-video monitoring equipment.The general failure evolution processes of the hole sidewall at different initial depths(500 m,1000 m and 1500 m)during the adjustment of vertical stress were obtained.The results show that the hole sidewall all formed spalling before resulting in strain rockburst,and ultimately forming a V-shaped notch.The far-field principal stress for the initial failure of the tunnel shows a good positive linear correlation with the depth.As the depth increases,the stress required for the initial failure of the tunnels clearly increased,the spalling became more intense;the size and mass of the rock fragments and depth and width of the V-shaped notches increased,and the range of the failure zone extends along the hole sidewall from the local area to the entire area.Therefore,as the depth increases,the support area around the tunnel should be increased accordingly to prevent spalling.展开更多
Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cer...Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups： in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-hep-arinized blood into the Brain. In the acupuncture group, modeled rats had Baihui （DU20） and Qubin （GBT） acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution （10 mL） infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch 1 and Hesl protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by in- hibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.展开更多
AIM: To perform a meta-analysis to quantitatively summarize the evidence for the association between the Notch signaling pathway and gastric cancer ( GC). METHODS: An electronic search of the MEDLINE, EMBASE and Chine...AIM: To perform a meta-analysis to quantitatively summarize the evidence for the association between the Notch signaling pathway and gastric cancer ( GC). METHODS: An electronic search of the MEDLINE, EMBASE and Chinese National Knowledge Infrastructure, which contain articles published from 1966 onwards, was conducted to select studies for this meta-analysis. RESULTS: Fifteen studies with a total of 1547 gastric cancer cases and 450 controls were included in this meta-analysis. Overall, the expression of Notch1, Notch2, Delta-like 4 and Hes1 was significantly higher in tumor tissues of GC compared to normal tissues. Specifically, stratified analyses showed that significantly increased expression of Notch1 was associated with non-cardia location, > 5 cm size, diffuse type, positive lymphovascular invasion and distal metastasis. Statistically significant higher expression of Notch3 was found in diffuse type GC. Jagged1 was also significantly over-expressed in diffuse type and poor differentiation type of GC. DLL4 was significantly over-expressed in advanced T stage, N stage and TNM stage in GC patients. However, the stratified analysis showed that there was no statistically significant difference in Hes1 expression between different subgroups. Sporadic reports showed that Notch1 and Jagged1 were independent poor prognostic predictors in GC. CONCLUSION: The Notch signaling pathway plays an important role in tumor progression of gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present stu...OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present study.A rat model of CAG was successfully established using the combined active immunization/ethanol/sodium deoxycholate method.BXD was prepared from a mixture of seven Chinese herbs,and was intragastrically administered to CAG rats at three different doses(6,12,and 24 g·kg^-1·d^-1).Af-ter 24 weeks,the rats were euthanized,and gastric tissue specimens were collected.Gastric mucosal specimens were stained with hematoxylin and eosin for histological examination to evaluate the degree of inflammation and morphological changes.Immunohistochemical staining was performed to examine the mucosal expression of proliferating cell nuclear antigen.Serum gastrin levels were measured using radioimmunoassay.The expression of Notch signaling-associated genes was examined by quantitative polymerase chain reaction and Western blot assay.RESULTS:BXD at all three doses significantly reversed the adverse effects generated by CAG in rats.Compared with control rats,the CAG rats who were administered BXD had an accelerated growth rate,reduced inflammatory cell infiltration,improved gastric mucosal morphology,augmented thickness of the gastric mucosa,increased number of gastric glands,enhanced mucosal expression of proliferating cell nuclear antigen,and elevated serum gastrin levels.展开更多
AIM： To investigate whether Notch signaling is involved in liver fibrosis by regulating the activation of hepatic stellate cells （HSCs）.METHODS： Immunohistochemistry was used to detect the expression of Notch3 in ...AIM： To investigate whether Notch signaling is involved in liver fibrosis by regulating the activation of hepatic stellate cells （HSCs）.METHODS： Immunohistochemistry was used to detect the expression of Notch3 in fibrotic liver tissues of patients with chronic active hepatitis. The expression of Notch3 in HSC-T6 cells treated or not with transforming growth factor （TGF）-β1 was analyzed by iramunofluorescence staining, The expression of Notch3 and myofibroblastic marker （z-smooth muscle actin （（z-SMA） and collagen 1 in HSC-T6 cells transfected with pcDNA3. I-N3ICD or control vector were detected by Western blotting and immunofluorescence staining. Moreover, effects of Notch3 knockdown in HSC-T6 by Notch3 siRNA were investigated by Western blotting and immunofluorescence staining.RESULTS： The expression of Notch3 was significantly up-regulated in fibrotic liver tissues of patients withchronic active hepatitis, but not detected in normal liver tissues. Active Notch signaling was found in HSC-T6 cells. TGF-β1 treatment led to up-regulation of Notch3 expression in HSC-T6 cells, and over-expression of Notch3 increased the expression of α-SMA and collagen I in HSC-T6 without TGF-β1 treatment. Interestingly, transient knockdown of Notch3 decreased the expression of myofibroblastic marker and antagonized TGF-β1 induced expression of α-SMA and collagen I in HSC-T6.CONCLUSION： Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti -fibrotic strategy in hepatic fibrosis.展开更多
文摘The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
基金Supported by the Natural Science Foundation of Shandong Province,No.2014ZRB01466
文摘AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.
基金Projects(41877272,41472269)supported by the National Natural Science Foundation of ChinaProject(2017zzts167)supported by the Fundamental Research Funds for the Central Universities,China。
文摘A series of true-triaxial compression tests were performed on red sandstone cubic specimens with a circular hole to investigate the influence of depth on induced spalling in tunnels.The failure process of the hole sidewalls was monitored and recorded in real-time by a micro-video monitoring equipment.The general failure evolution processes of the hole sidewall at different initial depths(500 m,1000 m and 1500 m)during the adjustment of vertical stress were obtained.The results show that the hole sidewall all formed spalling before resulting in strain rockburst,and ultimately forming a V-shaped notch.The far-field principal stress for the initial failure of the tunnel shows a good positive linear correlation with the depth.As the depth increases,the stress required for the initial failure of the tunnels clearly increased,the spalling became more intense;the size and mass of the rock fragments and depth and width of the V-shaped notches increased,and the range of the failure zone extends along the hole sidewall from the local area to the entire area.Therefore,as the depth increases,the support area around the tunnel should be increased accordingly to prevent spalling.
基金supported by the National Natural Science Foundation of China,No.81273824,30772840Ministry of Education Doctoral Fund in China,No.20102327110003+1 种基金the Natural Science Foundation of Heilongjiang Province in China,No.ZD201204Special funds for Technological Innovation Research of Harbin,China,No.2012RFXXS062
文摘Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups： in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-hep-arinized blood into the Brain. In the acupuncture group, modeled rats had Baihui （DU20） and Qubin （GBT） acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution （10 mL） infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch 1 and Hesl protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by in- hibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.
基金Supported by National Natural Science Foundation of China,No.81071777Sichuan Province Science and Technology Support Program,No.2011SZ0293 and No.2011SZ0087
文摘AIM: To perform a meta-analysis to quantitatively summarize the evidence for the association between the Notch signaling pathway and gastric cancer ( GC). METHODS: An electronic search of the MEDLINE, EMBASE and Chinese National Knowledge Infrastructure, which contain articles published from 1966 onwards, was conducted to select studies for this meta-analysis. RESULTS: Fifteen studies with a total of 1547 gastric cancer cases and 450 controls were included in this meta-analysis. Overall, the expression of Notch1, Notch2, Delta-like 4 and Hes1 was significantly higher in tumor tissues of GC compared to normal tissues. Specifically, stratified analyses showed that significantly increased expression of Notch1 was associated with non-cardia location, > 5 cm size, diffuse type, positive lymphovascular invasion and distal metastasis. Statistically significant higher expression of Notch3 was found in diffuse type GC. Jagged1 was also significantly over-expressed in diffuse type and poor differentiation type of GC. DLL4 was significantly over-expressed in advanced T stage, N stage and TNM stage in GC patients. However, the stratified analysis showed that there was no statistically significant difference in Hes1 expression between different subgroups. Sporadic reports showed that Notch1 and Jagged1 were independent poor prognostic predictors in GC. CONCLUSION: The Notch signaling pathway plays an important role in tumor progression of gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
基金Supported by the Natural Science Foundation of Zhejiang Province(Notch signaling-based Mechanistic Studies on the Therapeutic Role of Banxia Xiexin Decoction in Chronic Atrophic Gastritis,No.LY15H270013)
文摘OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present study.A rat model of CAG was successfully established using the combined active immunization/ethanol/sodium deoxycholate method.BXD was prepared from a mixture of seven Chinese herbs,and was intragastrically administered to CAG rats at three different doses(6,12,and 24 g·kg^-1·d^-1).Af-ter 24 weeks,the rats were euthanized,and gastric tissue specimens were collected.Gastric mucosal specimens were stained with hematoxylin and eosin for histological examination to evaluate the degree of inflammation and morphological changes.Immunohistochemical staining was performed to examine the mucosal expression of proliferating cell nuclear antigen.Serum gastrin levels were measured using radioimmunoassay.The expression of Notch signaling-associated genes was examined by quantitative polymerase chain reaction and Western blot assay.RESULTS:BXD at all three doses significantly reversed the adverse effects generated by CAG in rats.Compared with control rats,the CAG rats who were administered BXD had an accelerated growth rate,reduced inflammatory cell infiltration,improved gastric mucosal morphology,augmented thickness of the gastric mucosa,increased number of gastric glands,enhanced mucosal expression of proliferating cell nuclear antigen,and elevated serum gastrin levels.
基金Supported by The National Natural Science Foundation ofChina,No. 30900663
文摘AIM： To investigate whether Notch signaling is involved in liver fibrosis by regulating the activation of hepatic stellate cells （HSCs）.METHODS： Immunohistochemistry was used to detect the expression of Notch3 in fibrotic liver tissues of patients with chronic active hepatitis. The expression of Notch3 in HSC-T6 cells treated or not with transforming growth factor （TGF）-β1 was analyzed by iramunofluorescence staining, The expression of Notch3 and myofibroblastic marker （z-smooth muscle actin （（z-SMA） and collagen 1 in HSC-T6 cells transfected with pcDNA3. I-N3ICD or control vector were detected by Western blotting and immunofluorescence staining. Moreover, effects of Notch3 knockdown in HSC-T6 by Notch3 siRNA were investigated by Western blotting and immunofluorescence staining.RESULTS： The expression of Notch3 was significantly up-regulated in fibrotic liver tissues of patients withchronic active hepatitis, but not detected in normal liver tissues. Active Notch signaling was found in HSC-T6 cells. TGF-β1 treatment led to up-regulation of Notch3 expression in HSC-T6 cells, and over-expression of Notch3 increased the expression of α-SMA and collagen I in HSC-T6 without TGF-β1 treatment. Interestingly, transient knockdown of Notch3 decreased the expression of myofibroblastic marker and antagonized TGF-β1 induced expression of α-SMA and collagen I in HSC-T6.CONCLUSION： Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti -fibrotic strategy in hepatic fibrosis.
