BACKGROUND As the most common biliary malignancy,gallbladder cancer(GC)is an elderlybiased disease.Although extensive studies have elucidated the molecular mechanism of microRNA 182(miR-182)and reversion-inducing-cyst...BACKGROUND As the most common biliary malignancy,gallbladder cancer(GC)is an elderlybiased disease.Although extensive studies have elucidated the molecular mechanism of microRNA 182(miR-182)and reversion-inducing-cysteine-rich protein with kazal motifs(RECK)in various cancers,the specific role of exosomal miR-182 and RECK in GC remains poorly understood.AIM To explore the relationship between exosomal miR-182/RECK and metastasis of GC.METHODS Paired GC and adjacent normal tissues were collected from 78 patients.Quantitative polymerase chain reaction was employed to detect miR-182 and exosomal miR-182 expression,and Western blotting was conducted to determine RECK expression.In addition,the effects of exosomal miR-182/RECK on the biological function of human GC cells were observed.Moreover,the double luciferase reporter gene assay was applied to validate the targeting relationship between miR-182 and RECK.RESULTS Compared with normal gallbladder epithelial cells,miR-182 was highly expressed in GC cells,while RECK had low expression.Exosomal miR-182 could be absorbed and transferred by cells.Exosomal miR-182 inhibited RECK expression and promoted the migration and invasion of GC cells.CONCLUSION Exosomal miR-182 can significantly promote the migration and invasion of GC cells by inhibiting RECK;thus miR-182 can be used as a therapeutic target for GC.展开更多
BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the ...BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.展开更多
Fiber Fabry-Perot (FFP) filters have been widely used in optical fiber communications, and insertion loss (IL) is one of its important characteristics. Based on theoretically analysis, factors related to IL were discu...Fiber Fabry-Perot (FFP) filters have been widely used in optical fiber communications, and insertion loss (IL) is one of its important characteristics. Based on theoretically analysis, factors related to IL were discussed. In order to investigate the IL of different structures, simulations are carried out with finite-difference time-domain (FDTD) algorithm. Comparisons are made between the optimized structure and full-size-mirror FFP filter, and fiber-inserted FFP filter as well. Simulation results demonstrated that the finite- size-mirror structure can confine the mode size of the open resonator, hence reduce the IL of FFP filter.展开更多
Background:Wilson's disease(WD)is an autosomal recessive genetic disorder of copper metabolism,caused by mutations in the ATP7B gene,resulting in copper accumulation in the liver,brain,kidney,and cornea and leadin...Background:Wilson's disease(WD)is an autosomal recessive genetic disorder of copper metabolism,caused by mutations in the ATP7B gene,resulting in copper accumulation in the liver,brain,kidney,and cornea and leading to significant disability or death if untreated.Early diagnosis and proper therapy usually predict a good prognosis,especially in pre-symptomatic WD.Genetic testing is the most accurate and effective diagnostic method for early diagnosis.Methods:The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported.The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing.Hundred healthy children with the same ethnic background served as controls.Bioinformatic tools(polymorphism phenotyping-2,sorting intolerant from tolerant,protein analysis through evolutionary relationships,and predictor of human deleterious single nucleotide polymorphisms)were combined and used to predict the functional effects of mutations.Results:We identified 2 novel ATP7B mutations(p.Leu692Pro and p.Asn728Ser)and 3 known mutations(p.Met769fs,p.Arg778Leu and p.Vall216Met)in these Chinese WD families.These mutations were not observed in the 100 normal controls.The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic.Conclusions:Our research enriches the mutation spectrum of the ATP7B gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of ATP7B in the Chinese population.Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy,reduce damage to the liver and brain,and improve prognosis.展开更多
文摘BACKGROUND As the most common biliary malignancy,gallbladder cancer(GC)is an elderlybiased disease.Although extensive studies have elucidated the molecular mechanism of microRNA 182(miR-182)and reversion-inducing-cysteine-rich protein with kazal motifs(RECK)in various cancers,the specific role of exosomal miR-182 and RECK in GC remains poorly understood.AIM To explore the relationship between exosomal miR-182/RECK and metastasis of GC.METHODS Paired GC and adjacent normal tissues were collected from 78 patients.Quantitative polymerase chain reaction was employed to detect miR-182 and exosomal miR-182 expression,and Western blotting was conducted to determine RECK expression.In addition,the effects of exosomal miR-182/RECK on the biological function of human GC cells were observed.Moreover,the double luciferase reporter gene assay was applied to validate the targeting relationship between miR-182 and RECK.RESULTS Compared with normal gallbladder epithelial cells,miR-182 was highly expressed in GC cells,while RECK had low expression.Exosomal miR-182 could be absorbed and transferred by cells.Exosomal miR-182 inhibited RECK expression and promoted the migration and invasion of GC cells.CONCLUSION Exosomal miR-182 can significantly promote the migration and invasion of GC cells by inhibiting RECK;thus miR-182 can be used as a therapeutic target for GC.
文摘BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.
文摘Fiber Fabry-Perot (FFP) filters have been widely used in optical fiber communications, and insertion loss (IL) is one of its important characteristics. Based on theoretically analysis, factors related to IL were discussed. In order to investigate the IL of different structures, simulations are carried out with finite-difference time-domain (FDTD) algorithm. Comparisons are made between the optimized structure and full-size-mirror FFP filter, and fiber-inserted FFP filter as well. Simulation results demonstrated that the finite- size-mirror structure can confine the mode size of the open resonator, hence reduce the IL of FFP filter.
基金supported by grants from the National Natural Science Fundation of China(81100848)the Natural Science Fundation of Zhejiang Province(LY14H090007)+1 种基金the Zhejiang Health Bureau Fund(2014KYA126)the Population and Family Planning Fund of Zhejiang Province(2014kyb335)
文摘Background:Wilson's disease(WD)is an autosomal recessive genetic disorder of copper metabolism,caused by mutations in the ATP7B gene,resulting in copper accumulation in the liver,brain,kidney,and cornea and leading to significant disability or death if untreated.Early diagnosis and proper therapy usually predict a good prognosis,especially in pre-symptomatic WD.Genetic testing is the most accurate and effective diagnostic method for early diagnosis.Methods:The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported.The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing.Hundred healthy children with the same ethnic background served as controls.Bioinformatic tools(polymorphism phenotyping-2,sorting intolerant from tolerant,protein analysis through evolutionary relationships,and predictor of human deleterious single nucleotide polymorphisms)were combined and used to predict the functional effects of mutations.Results:We identified 2 novel ATP7B mutations(p.Leu692Pro and p.Asn728Ser)and 3 known mutations(p.Met769fs,p.Arg778Leu and p.Vall216Met)in these Chinese WD families.These mutations were not observed in the 100 normal controls.The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic.Conclusions:Our research enriches the mutation spectrum of the ATP7B gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of ATP7B in the Chinese population.Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy,reduce damage to the liver and brain,and improve prognosis.
