Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were d...Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 （MEG3 overexpression plasmid） and GV144 （control plasmid） were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues （P〈0.05） and RCC cell lines （P〈0.05）. The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h （P〈0.05）. Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h （P〈0.05）. Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm （P〈0.05）. Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression （P〈0.05）. It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.展开更多
BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucida...BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.展开更多
BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic canc...BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.展开更多
The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and funct...The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lnc RNAs in enterovirus infection. We profiled lnc RNAs and m RNA expression in CVB3-infected He La cells by lnc RNA-m RNA integrated microarrays. As a result, 700 differentially expressed lnc RNAs(431 up-regulated and 269 down-regulated) and665 differentially expressed m RNAs(299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lnc RNA-m RNA integrated pathway analysis to identify potential functional impacts of the differentially expressed m RNAs, in which lnc RNA-m RNA correlation network was built. According to lnc RNA-m RNA correlation, we found that XLOC-001188, an lnc RNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 m RNA,an anti-CVB3 gene reported previously. This interaction was supported by q PCR detection following si RNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 m RNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lnc RNAs, SNHG11, RP11-145 F16.2, RP11-1023 L17.1 and RP11-1021 N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2 BP1. In all, our studies reveal the alteration of lnc RNA expression in CVB3 infection and its potential influence on CVB3 replication,providing useful information for future studies of enterovirus infection.展开更多
[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mo...[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.展开更多
Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is deter...Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is determined, incorporating with previous deep geophysical data. In the upper crust, a positive anomaly velocity zone exists in the Sichuan basin, whereas a negative anomaly velocity zone exists in the western Sichuan plateau. The boundary between the positive and negative anomaly zones is the Longmenshan fault zone. The images of lower crust and upper mantle in the Longmenshan fault, Xianshuihe fault, Honghe fault and others show the characteristic of tectonic boundary, indicating that the faults likely penetrate the Moho discontinuity. The negative velocity anomalies at the depth of 50 km in the Tengchong volcanic area and the Panxi tectonic zone appear to be associated with the temperature and composition variations in the upper mantle. The overall features of the crustal and the upper mantle structures in the SichuanYunnan region are the lower average velocity in both crust and uppermost mantle, the large crustal thickness variations, and the existence of high conductivity layer in the crust or/and upper mantle, and higher geothermal value. All these features are closely related to the collision between the India and the Asia plates. The crustal velocity in the SichuanYunnan rhombic block generally shows normal value or positive anomaly, while the negative anomaly exists in the area along the large strike-slip faults as the block boundary. It is conducive to the crustal block side-pressing out along the faults. In the major seismic zones, the seismicity is relative to the negative anomaly velocity. Most strong earthquakes occurred in the upper-mid crust with positive anomaly or normal velocity, where the negative anomaly zone generally exists below.展开更多
BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secr...BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown. AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells. METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a. CONCLUSION Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.展开更多
AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric...AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material.Antimicrobial susceptibility was determined by the agar dilution method.Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping(cagA,vacA alleles s and m),Glu-Pro-Ile-Tyr-Ala(EPIYA)polymerase chain reaction and random amplified polymorphic DNA(RAPD).Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5program.Cluster analyses was done using SPSS 15.0statistical package,where each of the fingerprint bands were denoted as variables.Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H.pylori isolates was calculated with the squared Euclidean distance.RESULTS:Resistance rates were 4%for amoxicillin and 2.7%for clarithromycin with 2%double resistances.Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1.The 3’region of cagA gene was successfully amplified in 92.3%(12/13)of the baseline resistant isolates and in 60%(36/60)of the resistant isolates growing in antibiotic dilutions.Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates,it was found that in 61.5%(8/13)of the baseline isolates,a change in the number of EPIYA repetitions lowered antibiotic pressure.The gain and loss of EPIYA motifs resulted in a diversity of H.pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure.RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions.CONCLUSION:Antibiotic pressure does not induce loss of the cag pathogenicity island,but it can leadin most cases-to genetic rearrangements within the3’region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.展开更多
The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbe...The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.展开更多
The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background o...The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background of strong earthquakes in China's Mainland and to predict future strong earthquake risk zones.Studies of the structural environment and physical characteristics of the deep structure in this area are helpful to explore deep dynamic effects and deformation field characteristics,to strengthen our understanding of the roles of anisotropy and tectonic deformation and to study the deep tectonic background of the seismic origin of the block's interior.In this paper,the three-dimensional(3D)P-wave velocity structure of the crust and upper mantle under the southeastern margin of the Qinghai-Tibet Plateau is obtained via observational data from 224 permanent seismic stations in the regional digital seismic network of Yunnan and Sichuan Provinces and from 356 mobile China seismic arrays in the southern section of the north-south seismic belt using a joint inversion method of the regional earthquake and teleseismic data.The results indicate that the spatial distribution of the P-wave velocity anomalies in the shallow upper crust is closely related to the surface geological structure,terrain and lithology.Baoxing and Kangding,with their basic volcanic rocks and volcanic clastic rocks,present obvious high-velocity anomalies.The Chengdu Basin shows low-velocity anomalies associated with the Quaternary sediments.The Xichang Mesozoic Basin and the Butuo Basin are characterised by low-velocity anomalies related to very thick sedimentary layers.The upper and middle crust beneath the Chuan-Dian and Songpan-Ganzi Blocks has apparent lateral heterogeneities,including low-velocity zones of different sizes.There is a large range of low-velocity layers in the Songpan-Ganzi Block and the sub-block northwest of Sichuan Province,showing that the middle and lower crust is relatively weak.The Sichuan Basin,which is located in the western margin of the Yangtze platform,shows high-velocity characteristics.The results also reveal that there are continuous low-velocity layer distributions in the middle and lower crust of the Daliangshan Block and that the distribution direction of the low-velocity anomaly is nearly SN,which is consistent with the trend of the Daliangshan fault.The existence of the low-velocity layer in the crust also provides a deep source for the deep dynamic deformation and seismic activity of the Daliangshan Block and its boundary faults.The results of the 3D P-wave velocity structure show that an anomalous distribution of high-density,strong-magnetic and high-wave velocity exists inside the crust in the Panxi region.This is likely related to late Paleozoic mantle plume activity that led to a large number of mafic and ultra-mafic intrusions into the crust.In the crustal doming process,the massive intrusion of mantle-derived material enhanced the mechanical strength of the crustal medium.The P-wave velocity structure also revealed that the upper mantle contains a low-velocity layer at a depth of 80-120 km in the Panxi region.The existence of deep faults in the Panxi region,which provide conditions for transporting mantle thermal material into the crust,is the deep tectonic background for the area's strong earthquake activity.展开更多
The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation ...The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.展开更多
The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover...The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover types in the key area of SGN, where the returning cropland to tree/grass project has been carried out since 1999. The modified new land cover types include desert, forest, shrub and grass. They represent degraded, improved, and maintained vegetation cover with natural canopy in the key area. Results from three individual case studies show that the land cover change causes changes in temperature and terrestrial water variables especially within the key area, while changes in precipitation are found for a larger area. The strongest changes appear where the cropland is degraded to bare soil, leading to increasing temperature and decreases in rainfall, evaporation and soil water. Opposite changes occur when cropland changed into forests, especially with strong increases in soil water. When cropland changed to grass and shrub land, the climatic changes are closer to those with forest cover. This shows the importance of improving and maintaining the vegetation in SGN for the ecosystem and regional climate.展开更多
In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve ...In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.展开更多
Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are ...Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are the most difficult problems for constructing the system. Based on the current 3D GIS technique, some basic problems in establishing the system are discussed in this paper, including 3D spatial data model, 3D geological modeling, and visu- alization of 3D geological data. A kind of 3D vector data model based on boundary representation for geological object and its topology was developed in order to model and visualize complex geological structures. In addition, some key techniques are pointed out for further study.展开更多
Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted usin...Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.展开更多
Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stres...Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits as well as sustained cerebral iniurv in the adult hippocampus.展开更多
The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological,structural,geochemical,geophysical,and borehole data.Luanc...The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological,structural,geochemical,geophysical,and borehole data.Luanchuan,the case study area,southwestern Henan Province,is an important molybdenum-tungsten-lead-zinc polymetallic belt in China.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81001132,81172423,and 81272816)
文摘Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 （MEG3 overexpression plasmid） and GV144 （control plasmid） were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues （P〈0.05） and RCC cell lines （P〈0.05）. The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h （P〈0.05）. Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h （P〈0.05）. Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm （P〈0.05）. Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression （P〈0.05）. It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.
基金National Natural Science Foundation of China,No. 30700773,No. 81070378,and No. 81270561Sichuan Outstanding Youth Fund Project,No. 2015JQ0060。
文摘BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
基金National Natural Science Foundation of China,No.81974372.
文摘BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.
基金supported by the National Natural Science Foundation of China (81101234 to Lei Tong 81571999, 81871652 to Zhaohua Zhong+9 种基金 31470260 to Xingyi Ge 81672007 to Wenran Zhao 81772188 to Yan Wang)the Foundation of Heilongjiang Provincial Postdoctor of China (LBH-Z11076 to Lei Tong)the China Postdoctoral Science Foundation (2015M580269 to Lexun Lin)the Research Foundation of Education Bureau of Heilongjiang Province (12511176 to Lei Tong)the Hu-Xiang Youth Talents Scholar Program of Hunan Province (2017RS3017 to Xingyi Ge)Health and Family Planning Commission of Heilongjiang Province (2016-165 to Lexun Lin)the Provincial Natural Science Foundation of Hunan Province (Grant Number 2019JJ50035 to Ye Qiu)the Fundamental Research Funds for the Central Universities of China (Grant Number 531107051162 to Ye Qiu)
文摘The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lnc RNAs in enterovirus infection. We profiled lnc RNAs and m RNA expression in CVB3-infected He La cells by lnc RNA-m RNA integrated microarrays. As a result, 700 differentially expressed lnc RNAs(431 up-regulated and 269 down-regulated) and665 differentially expressed m RNAs(299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lnc RNA-m RNA integrated pathway analysis to identify potential functional impacts of the differentially expressed m RNAs, in which lnc RNA-m RNA correlation network was built. According to lnc RNA-m RNA correlation, we found that XLOC-001188, an lnc RNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 m RNA,an anti-CVB3 gene reported previously. This interaction was supported by q PCR detection following si RNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 m RNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lnc RNAs, SNHG11, RP11-145 F16.2, RP11-1023 L17.1 and RP11-1021 N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2 BP1. In all, our studies reveal the alteration of lnc RNA expression in CVB3 infection and its potential influence on CVB3 replication,providing useful information for future studies of enterovirus infection.
文摘[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.
基金Foundation item: National Scientific and Technological Development Program (95-973-02-02) the Climb Program (95-S-05-01) of National Scientific and Technological Ministry of China and the State Natural Sciences Foundation of China (49874021).
文摘Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is determined, incorporating with previous deep geophysical data. In the upper crust, a positive anomaly velocity zone exists in the Sichuan basin, whereas a negative anomaly velocity zone exists in the western Sichuan plateau. The boundary between the positive and negative anomaly zones is the Longmenshan fault zone. The images of lower crust and upper mantle in the Longmenshan fault, Xianshuihe fault, Honghe fault and others show the characteristic of tectonic boundary, indicating that the faults likely penetrate the Moho discontinuity. The negative velocity anomalies at the depth of 50 km in the Tengchong volcanic area and the Panxi tectonic zone appear to be associated with the temperature and composition variations in the upper mantle. The overall features of the crustal and the upper mantle structures in the SichuanYunnan region are the lower average velocity in both crust and uppermost mantle, the large crustal thickness variations, and the existence of high conductivity layer in the crust or/and upper mantle, and higher geothermal value. All these features are closely related to the collision between the India and the Asia plates. The crustal velocity in the SichuanYunnan rhombic block generally shows normal value or positive anomaly, while the negative anomaly exists in the area along the large strike-slip faults as the block boundary. It is conducive to the crustal block side-pressing out along the faults. In the major seismic zones, the seismicity is relative to the negative anomaly velocity. Most strong earthquakes occurred in the upper-mid crust with positive anomaly or normal velocity, where the negative anomaly zone generally exists below.
基金Supported by Tianjin Clinical Research Center for Organ Transplantation Project,No.15ZXLCSY00070The Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2018PT32021
文摘BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown. AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells. METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a. CONCLUSION Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.
基金Supported by The Administrative Department on Science and Innovation of the Republic of Colombia-COLCIENCIAS,No.RC-1106-408-20549,RC-1106-493-26237its program:Jóvenes Investigadores e Innovadores"Virginia Gutiérrez de Pineda",and by the Universidad del Valle,Cali,Colombia
文摘AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material.Antimicrobial susceptibility was determined by the agar dilution method.Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping(cagA,vacA alleles s and m),Glu-Pro-Ile-Tyr-Ala(EPIYA)polymerase chain reaction and random amplified polymorphic DNA(RAPD).Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5program.Cluster analyses was done using SPSS 15.0statistical package,where each of the fingerprint bands were denoted as variables.Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H.pylori isolates was calculated with the squared Euclidean distance.RESULTS:Resistance rates were 4%for amoxicillin and 2.7%for clarithromycin with 2%double resistances.Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1.The 3’region of cagA gene was successfully amplified in 92.3%(12/13)of the baseline resistant isolates and in 60%(36/60)of the resistant isolates growing in antibiotic dilutions.Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates,it was found that in 61.5%(8/13)of the baseline isolates,a change in the number of EPIYA repetitions lowered antibiotic pressure.The gain and loss of EPIYA motifs resulted in a diversity of H.pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure.RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions.CONCLUSION:Antibiotic pressure does not induce loss of the cag pathogenicity island,but it can leadin most cases-to genetic rearrangements within the3’region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.
文摘The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.
基金supported by China earthquake scientific array exploration Southern section of North South seismic belt(201008001)Northern section of North South seismic belt(20130811)+1 种基金National Natural Science Foundation of China(41474057)Science for Earthquake Resllience of China Earthquake Administration(XH15040Y)
文摘The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background of strong earthquakes in China's Mainland and to predict future strong earthquake risk zones.Studies of the structural environment and physical characteristics of the deep structure in this area are helpful to explore deep dynamic effects and deformation field characteristics,to strengthen our understanding of the roles of anisotropy and tectonic deformation and to study the deep tectonic background of the seismic origin of the block's interior.In this paper,the three-dimensional(3D)P-wave velocity structure of the crust and upper mantle under the southeastern margin of the Qinghai-Tibet Plateau is obtained via observational data from 224 permanent seismic stations in the regional digital seismic network of Yunnan and Sichuan Provinces and from 356 mobile China seismic arrays in the southern section of the north-south seismic belt using a joint inversion method of the regional earthquake and teleseismic data.The results indicate that the spatial distribution of the P-wave velocity anomalies in the shallow upper crust is closely related to the surface geological structure,terrain and lithology.Baoxing and Kangding,with their basic volcanic rocks and volcanic clastic rocks,present obvious high-velocity anomalies.The Chengdu Basin shows low-velocity anomalies associated with the Quaternary sediments.The Xichang Mesozoic Basin and the Butuo Basin are characterised by low-velocity anomalies related to very thick sedimentary layers.The upper and middle crust beneath the Chuan-Dian and Songpan-Ganzi Blocks has apparent lateral heterogeneities,including low-velocity zones of different sizes.There is a large range of low-velocity layers in the Songpan-Ganzi Block and the sub-block northwest of Sichuan Province,showing that the middle and lower crust is relatively weak.The Sichuan Basin,which is located in the western margin of the Yangtze platform,shows high-velocity characteristics.The results also reveal that there are continuous low-velocity layer distributions in the middle and lower crust of the Daliangshan Block and that the distribution direction of the low-velocity anomaly is nearly SN,which is consistent with the trend of the Daliangshan fault.The existence of the low-velocity layer in the crust also provides a deep source for the deep dynamic deformation and seismic activity of the Daliangshan Block and its boundary faults.The results of the 3D P-wave velocity structure show that an anomalous distribution of high-density,strong-magnetic and high-wave velocity exists inside the crust in the Panxi region.This is likely related to late Paleozoic mantle plume activity that led to a large number of mafic and ultra-mafic intrusions into the crust.In the crustal doming process,the massive intrusion of mantle-derived material enhanced the mechanical strength of the crustal medium.The P-wave velocity structure also revealed that the upper mantle contains a low-velocity layer at a depth of 80-120 km in the Panxi region.The existence of deep faults in the Panxi region,which provide conditions for transporting mantle thermal material into the crust,is the deep tectonic background for the area's strong earthquake activity.
基金the grants from the National Natural Science Foundation of China(U1805232,31770156,and 32172365)the China Postdoctoral Science Foundation(2021M690637)。
文摘The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.
基金supported by the Spe-cial Research Program for Public-Welfare Forestry(No.200804001)Meteorology(No.GYHY2011060114-3)the 863 Project(No.2009AA122005)
文摘The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover types in the key area of SGN, where the returning cropland to tree/grass project has been carried out since 1999. The modified new land cover types include desert, forest, shrub and grass. They represent degraded, improved, and maintained vegetation cover with natural canopy in the key area. Results from three individual case studies show that the land cover change causes changes in temperature and terrestrial water variables especially within the key area, while changes in precipitation are found for a larger area. The strongest changes appear where the cropland is degraded to bare soil, leading to increasing temperature and decreases in rainfall, evaporation and soil water. Opposite changes occur when cropland changed into forests, especially with strong increases in soil water. When cropland changed to grass and shrub land, the climatic changes are closer to those with forest cover. This shows the importance of improving and maintaining the vegetation in SGN for the ecosystem and regional climate.
基金supported by the National Natural Science Foundation of China,No.30472241,90709031 and 30973796the Ministry of Science and Technology of China("973"Project),No.2007CB512505+1 种基金provided by the Foundation of Hainan Province,No.310054the Health Department of Hainan Province,Qiong-Wei-45
文摘In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.
基金Project 2001AA135170 supported by the National High-Tech Research and Development 863 Program of China
文摘Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are the most difficult problems for constructing the system. Based on the current 3D GIS technique, some basic problems in establishing the system are discussed in this paper, including 3D spatial data model, 3D geological modeling, and visu- alization of 3D geological data. A kind of 3D vector data model based on boundary representation for geological object and its topology was developed in order to model and visualize complex geological structures. In addition, some key techniques are pointed out for further study.
基金supported by grants from the National Natural Science Foundation of China(No.81773980)Project of Science and Technology Commission of Shanghai Municipality(No.15401902600)。
文摘Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.
基金the Natural Science Research Project from Bureau of Public Health of Sichuan Province,No. 090194the Natural Science Research Project of Science Technology Bureau of Luzhou,No. 090102
文摘Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits as well as sustained cerebral iniurv in the adult hippocampus.
文摘The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological,structural,geochemical,geophysical,and borehole data.Luanchuan,the case study area,southwestern Henan Province,is an important molybdenum-tungsten-lead-zinc polymetallic belt in China.
