Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collect...Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.展开更多
Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is incre...Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.展开更多
Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation...Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.展开更多
Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rat...Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.展开更多
Rhesus monkey embryonic stem（rES） cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,wh...Rhesus monkey embryonic stem（rES） cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,which are composed of cholangiocytes.However,little is known about the role of Notch signaling in cholangiocytic commitment of ES cells.We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells.About 80% of definitive endoderm（DE） cells were generated from rES cells after treatment with activin A.After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium,rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins（CK7,CK18,CK19,CK20,and OV-6） and genes（GSTPi,IB4,and HNF1β）.At the same time,expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation,as well as their downstream target genes such as Hes 1 and Hes 5.Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes.In addition,the proportion of cholangiocyte-like cells declined from ～90% to ～20%.These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.展开更多
Traffic wave theory is used to study the critical conditions for traffic jams according to their features. First, the characteristics of traffic wave propagation is analyzed for the simple signal-controlled lane and t...Traffic wave theory is used to study the critical conditions for traffic jams according to their features. First, the characteristics of traffic wave propagation is analyzed for the simple signal-controlled lane and the critical conditions for oversaturation is established. Then, the basic road is decomposed into a series of one-way links according to its topological characteristics. Based on the decomposition, traffic wave propagation under complex conditions is studied. Three complicated factors are considered to establish the corresponding critical conditions of jam formation, namely, dynamic and insufficient split, channelized section spillover and endogenous traffic flow. The results show that road geometric features, traffic demand structures and signal settings influence the formation and propagation of traffic congestion. These findings can serve as a theoretical basis for future network jam control.展开更多
Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the ag...Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal＇ s life-span control machinery, as well as the dauer formation control.展开更多
For orthogonal frequency division multiplexing (OFDM) wireless communication, the system throughput and data rate are usually limited by pilots, especially in a high mobility environment. In this paper, an enhanced it...For orthogonal frequency division multiplexing (OFDM) wireless communication, the system throughput and data rate are usually limited by pilots, especially in a high mobility environment. In this paper, an enhanced iterative joint channel estimation and symbol detection algorithm is proposed to enhance the system throughput and data rate. With lower pilot power, the proposed scheme increases system throughput firstly, and then the channel estimation and symbol detection proceed iteratively within one OFDM symbol to improve the BER performance. In the proposed algorithm, the original channel estimate of each OFDM symbol is based on the channel estimate of the previous OFDM symbol, thus the variation of the mobile channel is traced efficiently, so the number of pilots in the time domain can be reduced greatly. Besides reducing the system overhead, the proposed algorithm is also shown by simulation to give much better BER performance than the conventional iterative algorithm does.展开更多
The c-Jun N-terminal kinases （JNKs） are important regulators of a variety of physiological and pathological processes both in the central and in the peripheral nervous systems. JNKs are considered as crucial mediato...The c-Jun N-terminal kinases （JNKs） are important regulators of a variety of physiological and pathological processes both in the central and in the peripheral nervous systems. JNKs are considered as crucial mediators of neuronal cell death in response to stress and injury. However, recent studies have provided substantial evidence that the JNK pathway plays an important role in neuronal migration. Here, we will give a brief introduction of the JNK signaling pathway and put more emphasis on its role in nettronal migration.展开更多
MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPI(families have been characterized: extracellular si...MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPI(families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.展开更多
AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polyme...AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.展开更多
In our previous study, five homologous feeder cell lines, Monkey ear skin fibroblasts （MESFs）, clonally derived fibroblasts from the MESFs （CMESFs）, monkey oviductal fibroblasts （MOFs）, monkey follicular granulo...In our previous study, five homologous feeder cell lines, Monkey ear skin fibroblasts （MESFs）, clonally derived fibroblasts from the MESFs （CMESFs）, monkey oviductal fibroblasts （MOFs）, monkey follicular granulosa fibroblast-like （MFGs） cells, monkey follicular granulosa epithelium-like （MFGEs） cells, were developed for the maintenance of rhesus embryonic stem cells （rESCs）. We found that MESFs, CMESFs, MOFs and MFGs, but not MFGEs, support the growth of rhesus embryonic stem cells. Moreover, we detected some genes that are upregulated in supportive feeder cell lines by semi-quantitative PCR. In the present study, we applied the GeneChip Rhesus Macaque Genome Array of Affymetrix Corporation to study the expression profiles of these five feeder cell lines, in purpose to find out which cytokines and signaling pathways were important in maintaining the rESCs, mRNAs of eight genes, including GREM2, bFGF, KITLG, DKK3, GREM1, AREG, SERPINF1 and LTBP1, were found to be upregulated in supportive feeder cell lines, but not in MFGE. The results indicate that many signaling pathways may play redundant roles in supporting the undifferentiated growth and maintenance of pluripotency in rESCs.展开更多
AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, ...AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.展开更多
文摘Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.
文摘Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.
基金National Natural Science Foundation of China(82104836 and 82104793)Science and Technology Talent Promotion Project of Hunan Province(2023TJ-N22).
文摘Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.
文摘Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.
基金supported by research grants from Zhejiang Natural Sciences Foundation of China (Y2110911 Y2080996)the National Key Technologies R&D Program of China (2007CB947701)
文摘Rhesus monkey embryonic stem（rES） cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,which are composed of cholangiocytes.However,little is known about the role of Notch signaling in cholangiocytic commitment of ES cells.We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells.About 80% of definitive endoderm（DE） cells were generated from rES cells after treatment with activin A.After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium,rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins（CK7,CK18,CK19,CK20,and OV-6） and genes（GSTPi,IB4,and HNF1β）.At the same time,expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation,as well as their downstream target genes such as Hes 1 and Hes 5.Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes.In addition,the proportion of cholangiocyte-like cells declined from ～90% to ～20%.These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.
基金The National Basic Research Program of China(973 Program)(No.2006CB705505)the Basic Scientific Research Fund of Jilin University(No.200903209)
文摘Traffic wave theory is used to study the critical conditions for traffic jams according to their features. First, the characteristics of traffic wave propagation is analyzed for the simple signal-controlled lane and the critical conditions for oversaturation is established. Then, the basic road is decomposed into a series of one-way links according to its topological characteristics. Based on the decomposition, traffic wave propagation under complex conditions is studied. Three complicated factors are considered to establish the corresponding critical conditions of jam formation, namely, dynamic and insufficient split, channelized section spillover and endogenous traffic flow. The results show that road geometric features, traffic demand structures and signal settings influence the formation and propagation of traffic congestion. These findings can serve as a theoretical basis for future network jam control.
文摘Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal＇ s life-span control machinery, as well as the dauer formation control.
文摘For orthogonal frequency division multiplexing (OFDM) wireless communication, the system throughput and data rate are usually limited by pilots, especially in a high mobility environment. In this paper, an enhanced iterative joint channel estimation and symbol detection algorithm is proposed to enhance the system throughput and data rate. With lower pilot power, the proposed scheme increases system throughput firstly, and then the channel estimation and symbol detection proceed iteratively within one OFDM symbol to improve the BER performance. In the proposed algorithm, the original channel estimate of each OFDM symbol is based on the channel estimate of the previous OFDM symbol, thus the variation of the mobile channel is traced efficiently, so the number of pilots in the time domain can be reduced greatly. Besides reducing the system overhead, the proposed algorithm is also shown by simulation to give much better BER performance than the conventional iterative algorithm does.
基金This work was supported in part by the National Natural Sciences Foundation of China (No.30530660)the Chinese Academy of Sciences Knowledge Innovation Program (No.KSCX1-YW-R-62)the National Basic Research of China (No.2006CB504100 and No. 2006CB500701).
文摘The c-Jun N-terminal kinases （JNKs） are important regulators of a variety of physiological and pathological processes both in the central and in the peripheral nervous systems. JNKs are considered as crucial mediators of neuronal cell death in response to stress and injury. However, recent studies have provided substantial evidence that the JNK pathway plays an important role in neuronal migration. Here, we will give a brief introduction of the JNK signaling pathway and put more emphasis on its role in nettronal migration.
基金supported by the Major StateBasic Research Project (Grant No. G1999053901).
文摘MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPI(families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.
基金Supported by The University of Mainz Project Grant
文摘AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.
文摘In our previous study, five homologous feeder cell lines, Monkey ear skin fibroblasts （MESFs）, clonally derived fibroblasts from the MESFs （CMESFs）, monkey oviductal fibroblasts （MOFs）, monkey follicular granulosa fibroblast-like （MFGs） cells, monkey follicular granulosa epithelium-like （MFGEs） cells, were developed for the maintenance of rhesus embryonic stem cells （rESCs）. We found that MESFs, CMESFs, MOFs and MFGs, but not MFGEs, support the growth of rhesus embryonic stem cells. Moreover, we detected some genes that are upregulated in supportive feeder cell lines by semi-quantitative PCR. In the present study, we applied the GeneChip Rhesus Macaque Genome Array of Affymetrix Corporation to study the expression profiles of these five feeder cell lines, in purpose to find out which cytokines and signaling pathways were important in maintaining the rESCs, mRNAs of eight genes, including GREM2, bFGF, KITLG, DKK3, GREM1, AREG, SERPINF1 and LTBP1, were found to be upregulated in supportive feeder cell lines, but not in MFGE. The results indicate that many signaling pathways may play redundant roles in supporting the undifferentiated growth and maintenance of pluripotency in rESCs.
基金grants from National Natural Science Foundation of China, No. 30228031, No. 30671072
文摘AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.
