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Radiation-induced lung injury （RILI）， one of the common complications caused by radiotherapy， encompasses two phases： an early phase known as radiation pneumonitis （RP） and a late phase called radiation fibrosis （RF）， threatening the life and life quality of patients， with poor prognosis. Accumulating evidence has shown that the occurrence of RILI is related to a variety of cytokines and signaling pathways. This paper summarized the research on the effects of Chinese medicine on RILI from the perspective of cytokines and signaling pathways. Cytokines include transforming growth factor-β1 （TGF-β1）， interleukins （ILs）， tumor necrosis factor-α （TNF-α）， platelet-derived growth factor （PDGF）， vascular endothelial growth factor （VEGF）， and high mobility group box-1 （HMGB1）. Related signaling pathways are phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， Wnt/β-catenin signaling pathway， Notch1/Jagged1 signaling pathway， and nuclear factor-E2-related factor2/antioxidant response element （Nrf2/ARE） signaling pathway. Cytokines may interfere with RILI progression by initiating various downstream signaling pathways， such as TGF-β1/Smads signaling pathway， TGF-β1/VEGF signaling pathway， TNF-α/nuclear factor-κB （NF-κB） signaling pathway， and HMGB1/Toll-like receptor 4 （TLR4） signaling pathway. In recent years， many scholars have attempted to delay RILI progression by down-regulating the expression of cytokines， antagonizing the effect of cytokines or regulating signaling pathways. It has been verified that many Chinese medicines， Chinese medicine monomers， and compound Chinese medicine prescriptions can inhibit the release of some cytokines or regulate some signaling pathways to reduce the incidence/severity of RILI， with satisfactory therapeutic effects， which have attracted the interest of scholars.
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ObjectiveTo explore the mechanism of antidepressant effect of lily polysaccharide （LLP）and astragalus polysaccharide（APS）. MethodSixty KM mice were randomly divided into blank group， model group， fluoxetine hydrochloride （8 mg·kg-1）group， LLP （0.2 g·kg-1）group， APS （0.2 g·kg-1）group and polysaccharide combination （LLP+APS，0.1 g·kg-1+0.1 g·kg-1）group， with 10 mice in each group. Except the blank group， the other groups were given chronic unpredictable mild stress （CUMS） induced mouse depression model. On the 29th day of modeling，fluoxetine hydrochloride group was given corresponding dose of fluoxetine hydrochloride， and polysaccharide groups were given corresponding drug. The depressive behavior of mice was evaluated by behavioral indexes such as body mass change， open field test. The morphological changes of hippocampal CA1 neurons were observed by Nissl staining. The contents of 5-hydroxytryptamine （5-HT）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT）， in brain tissue and plasma were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of related proteins in adenylate cyclase/cyclic adenylate phosphate/protein kinase A （AC/cAMP/PKA） signal pathway. ResultCompared with the blank group， mice in the model group gained weight slowly， the total distance， central distance and sugar water preference rate decreased significantly （P<0.01）， the depressive behavior was significant， the hippocampal neurons were seriously damaged， the content of 5-HT decreased （P<0.01）， the contents of ACTH and CORT increased significantly （P<0.01）， adenylate cyclase 6（ADCY6）， PKA and cAMP response element binding protein-1 （CREB-1） and brain-derived neurotrophic factor （BDNF） protein expression decreased significantly （P<0.01）. Compared with the model group， depressive behavior of mice in LLP group， APS group and LLP+APS group was significantly improved （P<0.01）. The antidepressant effect of LLP+APS was better than that of LLP and APS. Each administration group could alleviate the damage of hippocampal neurons in varying degrees， significantly increase the content of 5-HT in brain tissue （P<0.01）， and reduce the levels of ACTH and CORT in plasma （P<0.05）. The protein levels of ADCY6， PKA， CREB-1 and BDNF were significantly increased （P<0.05）. ConclusionThe antidepressant effect of LLP+APS is significantly enhanced and has a synergistic effect. The mechanism may be closely related to affecting the content of neurotransmitters， inhibiting HPA axis activity and activating AC/cAMP/PKA signal transduction pathway.
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@#The incidence of liver disease is increasing year by year. Due to the complex predisposing factors and unclear pathogenesis of liver diseases, the cure rate is still not ideal, so it is urgent to clarify its mechanism to find more effective therapeutic targets and drugs. Long non-coding RNA (lncRNA), as a non-coding RNA with a length of more than 200 nt, is a research hotspot in liver diseases in recent years. Focusing on the main signal transduction pathways in liver diseases, this review mainly summarizes the latest research progress of lncRNA in regulating liver disease-related signaling pathways, and elaborates that lncRNAs participate in various physiological processes such as cell proliferation, apoptosis, invasion, and migration by regulating key signaling pathways in liver diseases, thereby promoting the occurrence and development of liver diseases. This review provides new ideas for studying the mechanism of liver diseases, and new directions for finding new targets and biomarkers for the treatment of liver diseases.
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BACKGROUND: Regular exercise training possesses health promotion effect. Low-to-moderate intensity continuous aerobic exercise has been an important strategy for primary and secondary prevention of chronic diseases such as hypertension; however, the effect of high-intensity interval training is still debated. OBJECTIVE: To explore the effects of high-intensity interval training on pathological cardiac hypertrophy and investigate the possible mechanism in spontaneously hypertensive rats. METHODS: Thirty male spontaneously hypertensive rats were randomly assigned into a control group and a training group. Fifteen Wistar-Kyoto rats were used as normotensive group. Rats in the normotensive and control group were housed at rest, while those in the training group were subjected to a high-intensity interval training lasting for 8 weeks. After experiment, blood pressure was detected using a non-invasive blood pressure tester, and cardiac structure and function were measured by echocardiogram. Histopathological detection was performed by hematoxylin-eosin and Masson staining to determine myocardial cross-sectional area. mRNA expression of fetal genes including atrial natriuretic peptide and brain natriuretic peptide were detected by RT-PCR. Protein expression of PI3-K, Akt, CnAβ and NFATc3 was detected using western blot assay. RESULTS AND CONCLUSION: Compared with the normotensive group, the blood pressure level was significantly elevated (P 0.05) in the control group. Compared with the control group, the blood systolic pressure was lowered (P 0.05). Therefore, the 8-week high-intensity interval training can induce the transfer from pathological hypertrophy to physiological hypertrophy and enhance heart function in spontaneously hypertensive rats via the activation of PI3-K/Akt signal transduction pathway; however, the Cn/NFAT pathway cannot be inhibited.
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@#Autophagy is a “self-devouring” biological process of the degradation of organelles and proteins by lysosomes in eukaryotic cells. In the past few years, some results revealed that autophagy played an important role in the regulation of vascular calcification. This review summarized the recent studies on autophagy in the process of vascular calcification, and discussed the effects of electrolyte imbalance, matrix vesicle release, oxidative stress, inflammatory reaction of vascular endothelial cells, and lipid metabolism in autophagy. The research progress of β-catenin/AMPK/CREB/Nrf2-ARE/Erα signal transduction pathways in autophagy induction was reviewed.
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Objective To investigate the effect of Jiaotai Pills on antidepressants in chronic mildly unpredictable stress (CUMS) depression model rats based on nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signal transduction pathway. Methods The depression model of rats was induced by CUMS. On day 21 of the experiment, the rats in each group were treated with continuous ig administration for 14 d. The concentrations of NO and cGMP in hippocampus and plasma of rats were detected by Elisa method. The mRNA expression of NO synthase (including iNOS and nNOS) and NMDA receptor subunits NR1, NR2A, and NR2B in rat hippocampus was detected by RT-PCR. Results Compared with the control group, the levels of NO and cGMP in the hippocampus and plasma in the model group were significantly increased. The expressions of iNOS mRNA, nNOS mRNA, NR1 mRNA, NR2A mRNA, and NR2B mRNA in the hippocampus were significantly increased in the model group. Compared with the model group, Jiaotai Pills high, medium, and low dose and positive drug administration reversed the above changes. Conclusion Jiaotai Pills have the antidepressant effect on depression rats with CUMS by regulating NO-cGMP signal transduction pathway.
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Objective To explore the mechanism of hypertonic salt solution (HS) alleviates lung injury of rats at the early stage of severe scald.Methods Thirty-two female Sprague-Dawley (SD) rats were randomly assigned to sham group, lactated Ringer solution (LR) group, HS200 group (200 mmol/L HS group, 1 L 200 mmol/L HS contained 955 mL LR and 45 mL 10％ NaCl) and HS400 group (400 mmol/L HS group, 1 L 400 mmol/L HS contained 846 mL LR and 154 mL 10％ NaCl), with 8 rats in each group. A 30％ total body surface area (TBSA)Ⅲ degree scalded model was reproduced by scalded on the back with 98℃ boiling water for 12 seconds, whereas those in the sham group were exposed to 37 ℃ water without liquid resuscitation. Rats in the three drug intervention groups were resuscitated with LR, 200 mmol/L HS and 400 mmol/L HS by caudal vein according to the Parkland formula, respectively. All rats were sacrificed at 8 hours after scald injury to harvest abdominal aorta blood and lung tissues. Interleukins (IL-6, IL-10 and IL-17) in serum were determined by enzyme-linked immunosorbent assay (ELISA). Samples from the lung tissue were used to measure malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ultraviolet spectrophotometer. Expressions of p38 mitogen-activated protein kinase (p38MAPK) and extracellular regulated protein kinase 1/2 (ERK1/2) in the lung were determined by Western Blot. The lung tissue was stained with hematoxylin and eosin (HE), and the pathological changes were observed with a light microscope.Results Compared with the sham group, the lung tissues in the LR group were damage obviously, which accompanied with more inflammatory cell infiltration, cell edema and pulmonary septum thickening, and the levels of IL-6, IL-10, IL-17 in serum and MDA content, the phosphorylation of p38MAPK and ERK1/2 in lung tissues were increased whereas the activity of SOD was decreased. Compared with the LR group, the lung injury was significantly alleviated, the levels of IL-6, IL-17 in serum and MDA content and the phosphorylation of p38MAPK and ERK1/2 were decreased, and the levels of IL-10 and SOD were increased in both HS groups with a dose-dependent manner. There were significant difference in above parameters between HS400 group and LR group [serum IL-6 (ng/L): 3.76±0.12 vs. 6.72±0.90, serum IL-10 (ng/L): 33.76±3.71 vs. 16.77±3.19, serum IL-17 (ng/L): 103.52±2.78 vs. 124.96±4.96, lung MDA (nmol/mg): 5.59±0.24 vs. 7.09±0.39, lung SOD (U/mg):226.7±3.9 vs. 172.7±3.4, lung phosphorylation of p38MAPK (p-p38MAPK)/p38MAPK: 0.15±0.09 vs. 0.35±0.19, lung phosphorylation of ERK1/2 (p-ERK1/2)/ERK1/2: 0.27±0.01 vs. 0.70±0.01, allP < 0.01].Conclusion HS protected against lung injury induced by severe burns in rats with a dose-dependent manner, and it was better than LR, and its possible mechanism was related with reducing the expression of p38MAPK and ERK1/2 pathway in lung tissue, increasing the level of anti-inflammatory cytokines and decreasing the release of pro-inflammatory cytokines, thus inhibiting excessive inflammation and oxidative stress injury in lung.
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Cannabinoid receptor (CBR) has two subtypes,type 1 cannabinoid receptor (CB 1 receptor,CB1R) and type 2 cannabinoid receptor(CB2 receptor,CB2R).CB2R widely is found distributing in the central nervous system and playing important functions.Cannabis can regulate CB2R signal pathway to protect central nervous system in CNS diseases.
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Objective To investigate the influence of bushenhuoxue drug-containing serum on PI3K and Akt signaling pathway in purified retinal ganglion cell (RGCs) in vitro of Sprague-Dawley (SD) rats,and to explore the protective mechanisms of bushenhuoxue recipe on RGCs.Methods At first,bushenhuoxue drug-containing serum was prepared,and the RGCs of SD rats were purified;after the apoptotic model of pressurized and purified RGCs was established successfully in vitro using open pressure control system,RGCs were dealt with 50 g · L-1,100 g · L-1,200 g · L-1 concentration gradient of bushenhuoxue drug-containing serum.Then the subjected cells were divided into normal culture group (N group),control group (C group),50 g · L-1 bushenhuoxue group (50 g · L-1 BSHX group),100 g · L-1 bushenhuoxue group (100 g · L-1 BSHX group),200 g · L-1 bushenhuoxue group (200 g · L-1 BSHX group).Finally,cell apoptotic rate was detected by Annexin V-FITC/PI staining,while real-time quantitative PCR (qRT-PCR) and Western blot were used to detect the mRNA and protein expression of PI3K and Akt in each group respectively.Results The results of qRT-PCR detection showed that PI3K,Akt mRNA expression level in C group (0.04 ±0.01) was decreased compared with N group (1.00 ± 0.04),and the difference was statistically significant (all P＜0.05),while PI3K,Akt mRNA levels in 50 g · L-1,100 g · L-1 and 200 g · L-1 BXHX group (0.18 ±0.01,0.21 ±0.02,0.22 ±0.01,0.36 ±0.01,0.84 ±0.10,1.07 ± 0.17) were increased compared with the C group,and the difference was statistically significant (all P ＜0.05).The Western blot results of each group showed that PI3K,Akt protein expression level in C group was decreased compared with N group,with statistical difference (all P ＜ 0.05),while PI3 K,Akt protein expression levels in 50 g · L-1,100 g · L-1 and 200 g · L-1 BSHX group were increased compared with C group,with staffstical difference (all P ＜ 0.05).Conclusion Bushenhuoxue drug-containing serum may inhibit the RGCs apoptosis induced by pressure,which may be related to the activation of PBK/Akt signal transduction pathway.
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Objective To investigate the effects of three different concentrations of hypertonic sodium salt (HS) resuscitation on liver injury of rats at the early stage of severe burned.Methods 104 female Sprage-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24), 600, 800, 1000 mmol/L HS groups (HS600, HS800, and HS1000 groups,n = 24). Rats in LR group and HS groups were subjected to full-thickness scald with 30% total body surface area (TBSA), and then given liquid resuscitation treatment with LR and the corresponding HS. These rats were sacrificed at 2, 8 and 24 hours post injury to collect blood and liver tissue. Rats in sham group were given simulation of burns without resuscitation, which were immediately sacrificed and the specimens were harvested. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemical analyzer. The levels of liver tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by ultraviolet spectrophotometry. The expression of liver tissue p38 mitogen-actirated protein kinase (p38MARK) was detected by Western Blot.Results Compared with sham group, the levels of ALT, AST, MDA and p38MAPK were increased, and the activities of SOD were decreased in LR group and different degrees in HS groups at each time point after injury. Compared with LR group, the levels of ALT, AST, MDA and p38MAPK were decreased and the activities of SOD were increased in different degrees with HS groups, among which HS600 group changed most significantly [ALT (U/L): 147±52 vs. 227±60 at 8 hours, 138±47 vs. 191±41 at 24 hours; AST (U/L):288±79 vs. 548±237 at 2 hours, 567±167 vs. 841±338 at 8 hours, 515±180 vs. 712±159 at 24 hours; MDA (nmol/mg): 0.287±0.036 vs. 0.395±0.041 at 2 hours, 0.298±0.030 vs. 0.392±0.018 at 8 hours, 0.278±0.033 vs. 0.422±0.036 at 24 hours; SOD (U/mg): 230±16 vs. 159±30 at 2 hours, 251±14 vs. 194±15 at 8 hours, 296±8 vs. 243±11 at 24 hours; p-p38MAPK/p38MAPK (A value): 0.778±0.040 vs. 1.065±0.066 at 2 hours, 0.791±0.046 vs. 0.967±0.041 at 8 hours, 0.733±0.027 vs. 1.020±0.043 at 24 hours; allP < 0.05]. The levels of ALT and AST in HS600 group were significantly lower than those in HS1000 group at 2 hours and in HS800 group at 8 hours. The levels of MDA and p38MAPK in HS600 group were significantly lower than those of HS800 group and HS1000 group, and the level of SOD in HS600 group was significantly higher than that in HS800 group and HS1000 group at each time point after injury. There were no significant differences in all test indicators between HS800 group and HS1000 group at each time point after injury.Conclusions High concentration of HS can reduce the early liver injury in severely scalded rats, of which the curative effect of HS 600 mmol/L is best.
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This study was aimed to observe the effects of gymnema sylvestre total saponins (GA) on insulin resistance (IR) in adipose tissues of KKay mice,in order to discuss the action mechanism from the PI3K/AKT signal transduction pathway.A total of 27 KKay mice were randomly divided into the model group (DM),Pioglitazone group (BG) and GA group.Nine normal C57BL/6J mice were used as the normal control group (NC).Intragastric administration of drugs was given for eight weeks.The bodyweight and food intake of all mice were tested each week.After the experiment was completed,fasting plasma insulin (Fins) and fasting plasma glucose (FPG) were detected and the insulin sensitive index (ISI) was calculated.Expressions of PDK-1,AKT,P-AKT (Ser473),P-AKT (Thr308) in adipose tissues of epididymis in mice were detected.And expressions of PI3K-p85 mRNA,PTEN mRNA,APN mRNA were also measured.The results showed that compared with DM group,bodyweight of BG and GA groups were decreased (P＜0.05,P＜0.05);FPG and Fins level of BG and GA groups were decreased (P＜0.05,P＜0.05,P＜0.05,P＜0.05),ISI increased (P＜0.05,P＜0.05);APN mRNA increased in BG and GA group (P＜0.01,P＜0.01);PI3K-p85 mRNA increased in GA group (P＜0.05);P-AKT (Thr308) protein expression increased in BG and GA group (P＜0.05,P＜0.01);P-AKT (Ser473) protein expression increased in GA group (P＜0.05);the phosphorylation of AKT (Thr 308) was enhanced in BG and GA group (/9＜0.01,P＜ 0.01);the phosphorylation of AKT (Ser473) was enhanced in GA group (P＜0.01,P＜0.01).PDK-1 protein expression was decreased in BG and GA group (P＜0.05);PTEN mRNA decreased in BG and GA group (P＜0.05,P＜0.01).It was concluded that GA can ameliorate IR by sensitizing PI3κ/AKT signal pathway in adipose tissues of KKAy mice.
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Background Retinal ischemia reperfusion injury (RIRI) is a common pathological process of many retinal vascular diseases with comprehensive pathogenesis mechanism.Researches showed that apoptosis of retinal cells and nerve fiber loss is the finally common pathway of RIRI,and Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway is a newly discovered signal transcript channel in recent years,which is involved in varieties of pathological processes.However,whether JAK-STAT pathway is associated with RIRI is still unelucidated.Objective This study was to investigate the time course of activation of JAK-STAT signal pathway and its significance during RIRI.Methods Forty clear adult male Sprague-Dawley rats were randomized into RIRI 6-hour,12-hour,24-hour and 48-hour groups.RIRI models were induced in lateral eyes of the rats by perfusing normal saline solution into the anterior chamber to elevate intraocular pressure (IOP) to 110 mmHg for 60 minutes and then allowing reperfusion,and the fellow eyes of the rats served as normal control group.The rats were sacrificed and the eyeballs were enucleated at 6,12,24 and 48 hours after reperfusion.The expressions of JAK2 and STAT3 protein (absorbance) in the retinas were located and detected by immunohistochemistry,and the relative expression levels of JAK2 and STAT3 mRNA in the retinas were detected by real-time fluorescence quantitative PCR.The use and care of the rats followed the ARVO Statement.Results Immunohistochemistry showed that JAK2 and STAT3 were faintly expressed in inner nuclear layer and retinal ganglion cells (RGCs) in the normal control group and strongly expressed in various RIRI groups.Significant differences were found in the expression intensities of JAK2 and STAT3 protein among the five groups (F =88.735,96.625,both at P ＜ 0.01).Compared with the normal control group,the expression intensities of JAK2 and STAT3 were enhanced in RIRI groups,with the peak values in RIRI 12-hour group (JAK2:t=4.308,5.559,5.315,4.726;all at P＜0.01.STAT3:t=5.047,7.843,6.281,4.887;all at P＜0.01).The thickening of inner retinal layer,loosening of retinal tissue,vacuolus degeneration of cells and decrease of RGCs were seen in the RIRI eyes.The relative expressing levels of the JAK2 mRNA and STAT3 mRNA in the retinas were significantly different among the groups (F =111.239,129.539;both at P＜0.01),and the relative expressing levels of JAK2 mRNA and STAT3 mRNA in the retinas were significantly increased in RIRI 6-hour,12-hour,24-hour and 48-hour groups in comparison with the normal control group (JAK2 mRNA:t=3.504,5.102,4.679,4.213;all at P＜0.01.STAT3 mRNA:t =6.541,8.787,5.693,5.898;all at P＜0.01).Conclusions The retinal morphology appears to be abnormal and RGCs are evidently decreased in rat eyes with RIRI,and the expressions of JAK2 and STAT3 in the retinas are simultaneously up-regulated,indicating that JAK-STAT signal pathway is involved during the RIRI process.
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Background Researches showed that microRNA (miRNA) is involved in the pathogenesis and development of many tumors and plays a cancer-suppressing-gene like role or cancer-gene like action.Uveal melanoma (UM) is a common ocular malignant tumor in aduh,and the mechanism of UM pathogenesis and metastasis is still not elucidated.Understanding the differential expression of miRNAs in UM is expected to provide a basis for targeting treatment of UM.Objective This study was to screen and compare the expression profiles of miRNAs in epithelial type and spindle type of UM.Methods The use of specimens of UM and donor eyes was approved by Ethic Commission of Capital Medical University.The specimens of epithelial type (4 specimens) and spindle type (4 specimens) of UM confirmed by histopathology and immunochemistry were collected in Beijing Tongren Hospital from March 2013 to October 2015.The expression profile of miRNA was assayed by miRNA array.Normal uveal specimens were obtained from 8 donors as controls.The differentially expressing miRNAs were screened by intergroup differential folds of ≥2.The genes targeting differentially expressed miRNAs were predicted using multiples online software and the potential signal pathway was further analyzed by bioinformatics method.The microarray outcomes were validated by real-time quantitative PCR.Results Spindle cell type and epithelial cell type of UMs were verified by hematoxylin and eosin staining.Immunochemistry showed that HMB45,melanin-A and S-100 were positively expressed in the two types of UM.Compared with the normal uveal tissue,109 differentially expressed miRNAs,including 29 up-regulated and 80 down-regulated miRNAs were seen in the spindle cell type of UM,and in the epithelial cell type of UM,50 differentially expressed miRNAs were found,including 23 up-regulated and 27 down-regulated miRNAs.In spindle cell type of UM,the up-regulated miRNAs were miR-146a-5p,miR-25-3p and miR-29b-l-5p,and down-regulated ones were miR-126-5p,miR-183-5p and miR-96-5p.In epithelial cell type of UM,the up-regulated miRNAs were miR-155-5p,miR-210 and miR-378a-5p,and down-regulated ones were miR-199a-5p,miR-143-3p and miR-143-5p.In addition,the mutual up-regulated miRNA in both spindle cell type of UM and epithelial cell type of UM were miR-132-3p,miR-21-5p,miR-34a-5p and miR-34b-5p,and mutual down-regulated ones were miR-125b-2-3p,miR-126-3p,miR-199a-3p and miR-214-3p.Bioinformatics analysis showed that the targeting genes predicted by differentially expressed miRNAs participated in a number of biological pathways,including cancer-related pathway,mitogenactivated protein kinase (MAPK) pathway,Wnt signal pathway and intercellular adhesion,endocytosis,prostatic cancer,colorectal cancer pathways.Conclusions Many differentially expressed miRNAs exist among spindle cell type of UM,epithelial cell type of UM and normal uveal tissue.These miRNAs participate in or regulate the biological behaviour of UM via different signal pathways.
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Background Idiopathic orbital inflammatory pseudotumor (IOIP) is a commom orbital disease,with serious eye symptoms and replase tendency,and its pathogenesis is still unclear.Nuclear factor-κB (NF-κB)-related proteins participate in many important pathophysiological process,however,whether NF-κB plays a role in the IOIP process is worthy of attention.Objective This study was to explore the roles of NF-κB pathway in IOIP pathogenesis.Methods Twenty-four IOIP specimens were collected during surgery in Beijing Tongren Hospital from September 2010 to May 2016.The histopathological characteristics of IOIP were examined by hematoxylin and eosin staining.The expression and location of NF-κB/p65,p-p65,p50 and inhibitor of κB (IκB-ot) were detected by immunohistochemistry and verified by immunocytochemistry and Western blot assay.Results The histopathological features of IOIP were numerous small lymphocyte infiltraion and fibrous tissue proliferation,and a lot of epithelioid cells were seen in lacrimal gland-involved specimens.NF-κB/p65 was positively expressed in the cytoplasm of all 24 specimens and the nucleus in 15 specimens with the expressing rate of 62.5％.p50 was expressed in the cytoplasm in 22 specimens with the expressing rate of 91.7％ and in the nucleus in 17 specimens with the expressing rate of 70.8％.The positive expression of p-p65 was found in 22 specimens with the expressing rate of 91.7％,and IκB-α was expressed in the cytoplasm of 11 specimens with the expressing rate of 45.8％.These results were confirmed by immunocytochemistry and Western blot assay.Conclusions NF-κB pathway is activiated during IOIP process,and NF-κB pathway may be involved in the pathogenesis of IOIP.
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Objective To predict signal transduction pathways of the integrin adhesome via bioinformatics method, so as to provide references for experimental study on the mechanism of integrin-related signal transduction pathways. Methods First, the interaction network between the interactive integrin adhesome was constructed, and the confidence probability of each interaction was used as its link weight, respectively. Secondly, the pathways of the minimum weight were identified via a standard dynamic programming algorithm. Finally, all pathways calculated by the algorithm were aggregated into some probable networks. Results Seven signal transduction pathways were obtained from the integrin adhesome interaction network that contained 147 components with 736 interactions. In every predicted signal transduction pathway, the coverage rate of the proteins with Gene Ontology annotation was calculated. Conclusions By research on signal transduction pathways the pathogenesis of some diseases can be explored at the molecular level. Several possible signal transduction pathways obtained in this study have some reference value for exploring disease mechanism in basic medical sciences, and also provide some useful information for such exploration under the stimulation of external signals including mechanical or chemical signals.
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Curcumin is one of the polyphenolic compounds, which is the biological active ingredient of Curcuma longa. Studies indicate a beneficial role of curcumin in terms of anti-oxidant, anti-tumourgenic, and anti-inflammatory properties. And H-atom transfer is a preferred anti-oxidant mechanism of curcumin. Curcumin activates the Nrf2-ARE, NF-κB, NADPH oxidase/ROS, Notch, AMPK/eNOS, and MAPK signal transduction pathways, induces or inhibits signaling molecules and functional gene, modulates the protein expression, increases anti-oxidant enzyme activities, and counteracts oxidative stress.
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Objective:To study the inhibition of astragaloside on the proliferation of human keloid fibroblasts. Methods: Com-pared with that of normal skin, the expression of transforming growth factor-β( TGF-β) and its transduction factors Smad in the human keloid fibroblasts was detected. The optimal concentration was screened by MTT after HFF-1 human skin fibroblast was infected with astragaloside at different concentrations. The mRNA expression of Smad2, Smad3, Smad4 and Smad7 in the fibroblasts was studied by using real-time. The protein expression of TGF-βRⅡ, Smad2, Smad3, Smad4 and Smad7 in the fibroblasts was detected by using Western blot. Results: Compared with that of normal skin tissue, the expression of Smad protein was significantly increased ( P 0. 05). The optimal concentration of astragaloside was 0. 5μg·ml-1 . The expression level of Smad2 protein in the two groups was significantly increased, and the level of Smad3 expression was significantly decreased (P<0. 05). Conclusion:Astragaloside can inhibit the formation of fi-broblast possibly through Smad2 over-expression and Smad3 inhibition in the TGF-β/Smad signal transduction pathway.
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Objective Bone morphogenetic protein 4 ( BMP4) induces rat myocardial hypertrophy in H9c2 cells, but the spe-cific mechanism remains unclear .The study aimed to elucidate the role of autophagy in myocardial hypertrophy and its relationship with extracellular signal regulating kinase ( ERK1/2) signal transduction pathway . Methods H9c2 cardiomyocytes were randomly divided into 4 groups:control group, BMP4 group, BMP4+PD98059 (ERK1/2 signal pathway inhibitor) group and BMP4+3MA (autophagy inhibitor) group.With PD98059(50μmol/L) and 3MA(5mmol/L) blocking for 30min, BMP4 (50μg/L) were added.Expressions of tiny tube related proteins 1 light chain 3 (LC3) and p-ERK1/2 were detec-ted after culturing for 30min.48h later, measurements were made on cell surface area , average protein content and α-smooth muscle actin (α-SMA ) protein expression level .Cell morphology and size were measured respectively by inverted microscope and Image J software .Total protein content was detected by BCA , and western blot was used to measure the expressions of LC3, ERK1/2, p-ERK1/2 and α-SMA. Resul ts 30min later, the expressions of LC3 and p-ERK1/2 were significantly higher in BMP4 group than in control group [(1.54 ±0.05) vs (1.95 ±0.11),(0.94 ±0.04) vs (1.33 ± 0.06),P0.05). Conclusion Autophagy may participate in BMP4-induced rat myo-cardial hypertrophy in H9c2 cells through ERK1/2 signal transduction pathway .The clinical treatment of myocardial hypertrophy may benefit from the blocking of autophagy or ERK 1/2 signal transduction pathway .
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Objective To study the inhibitory effects of GANT61, as an inhibitor of Gli, on the growth of human esophageal adenocarcinoma cell lines OE19 and OE33, and their mechanisms thereof. Methods After treating with different concentrations of GANT61(30,20,13.333 3,8.888 8,5.925 9,3.950 6,2.633 7,1.755 8,1.170 5μmol/L),the cell viabilities of OE19 and OE33 were detected by MTS method, which expressed by IC50. The Gli1and Gli2 mRNA expressions treated with GANT61(10 μmol/L GANT61) or DMSO for 24 h were detected in OE19 and OE33 cell lines by real time fluorescence quantitative PCR. The protein expressions of Gli1, Gli2 and CyclinD1 treated with GANT61 or DMSO for 24 h were detected in OE19 and OE33 cell lines by Western blot assay. Transwell invasion assay was performed to evaluate the inhibiting effect on OE19 and OE33 cell invasion by the treatment of GANT61 or DMSO. Results The IC50 of GANT61 was 8.08μmol/L in OE19 and 9.65μmol/L in OE33 cells. Compared with DMSO group, Gli1 and Gli2 mRNA expressions and Gli1,Gli2 and CyclinD1 protein expressions were significantly decreased in OE19 and OE33 cells of GANT61 group (P<0.05). The number of penetrating cells was significantly reduced in OE19 and OE33 cells of GANT61 group compared with that of DMSO group (P<0.01). Conclusion GANT61 can inhibit the growth and invasion of esophageal neoplasms cells by down-regulating Gli1 and Gli2 mRNA expression,which indicates that Hedgehog signaling pathway may play an important role in carcinogenesis and progression of esophageal adenocarcinoma.
ABSTRACT
Ischemic stroke, gravely affecting human health with its increasing incidence rate , is a common disease of old age . JAK/STAT way , a recently discovered signaling pathway , is not only widely involved in processes of cell growth ,differentiation, and apoptosis ,but also closely related to the pathophysiology of stroke.However,the pathway function and mechanism in ische-mic cerebral stroke has not yet been fully elucidated .We will review the role and mechanism of JAK/STAT signal transduction pathway in ischemic stroke ,and scientifically draw network chart between various related signal molecules in the process of ische-mic stroke neuropathy combining both domestic and foreign re-search reported in this paper , in order to better understand the pathological mechanism process of brain stroke , find new drugs for the treatment of cerebral ischemic diseases ,then provide more systematic scientific literature support .