BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essenti...BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.展开更多
AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA(HOTAIR) in gastric cancer(GC) migration and invasion.METHODS Quantitative real-time polymerase chain reaction(qp CR) was used to detect the expr...AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA(HOTAIR) in gastric cancer(GC) migration and invasion.METHODS Quantitative real-time polymerase chain reaction(qp CR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve(AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qp CR,western blot and immunohistochemistry were used to evaluate the m RNA and protein expression of E-cadherin. RNAbinding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin.RESULTS The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues(p < 0.001). Its over-expression was correlated with tumor-node-metastasis(TNM) stage(p = 0.024),tumor invasion(p = 0.018),lymph node metastasis(p = 0.023),and poor prognosis(p < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival(p = 0.033),together with TNM stage(p = 0.002) and lymph node metastasis(p = 0.002). The AUCROC was up to 0.709(95%CI: 0.623-0.785,p < 0.001). Knockdown of HOTAIR by si RNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines,and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.展开更多
The engineering of plants with enhanced tolerance to abiotic stresses typically involves complex multigene networks and may therefore have a greater potential to introduce unintended effects than the genetic modificat...The engineering of plants with enhanced tolerance to abiotic stresses typically involves complex multigene networks and may therefore have a greater potential to introduce unintended effects than the genetic modification for simple monogenic traits. For this reason, it is essential to study the unintended effects in transgenic plants engineered for stress tolerance. We selected drought-and salt-tolerant transgenic wheat overexpressing the transcription factor, GmDREB1, to investigate unintended pleiotropic effects using RNA-seq analysis. We compared the transcriptome alteration of transgenic plants with that of wild-type plants subjected to salt stress as a control. We found that GmDREB1 overexpression had a minimal impact on gene expression under normal conditions.GmDREB1 overexpression resulted in transcriptional reprogramming of the salt response,but many of the genes with differential expression are known to mitigate salt stress and contribute incrementally to the enhanced stress tolerance of transgenic wheat. GmDREB1 overexpression did not activate unintended gene networks with respect to gene expression in the roots of transgenic wheat. This work is important for establishing a method of detecting unintended effects of genetic engineering and the safety of such traits with the development of marketable transgenic crops in the near future.展开更多
Somatic nuclear transfer technology has become increasingly promising in biomedicine and agriculture.Whereas the approach remains inefficient and underlying mechanisms remain ambiguous.Although cloned embryos have sim...Somatic nuclear transfer technology has become increasingly promising in biomedicine and agriculture.Whereas the approach remains inefficient and underlying mechanisms remain ambiguous.Although cloned embryos have similar in vitro developmental capacity as in vitro fertilized（IVF） embryos before implantation,they appeared to have much lower full-term developmental efficiency in pig and cattle,and thus it would be reasonable to postulate that profound distinction at the molecular level should exist between them.Herein,RNA sequencing technique was used to screen differentially expressed genes in cloned and IVF blastocysts,and in total 628 differentially expressed transcripts were obtained,among which,280 transcripts are up-regulated and 348 transcripts are down-regulated in cloned blastocysts.Moreover,one statistically significant pathway associated with endoplasmic reticulum（ER） protein processing was enriched,and some ER-stress markers such as ATF4,ATF6,PDIA3,HSPA1 B,HSP40 and HSP90 between cloned and IVF blastocysts were suggested.Additionally,some developmentally important genes such as lipid metabolism related genes（MGLL,DDHD2 and FADS2） and epigenetic modification genes（DNMT1,KDM5 C and MBD3L5） were found differentially expressed between cloned and IVF embryos.展开更多
文摘BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.
基金Supported by the Shandong Provincial Natural Science Foundation of China,No.ZR2016HQ08Shandong Province Medical Science and Technology Development Projects of China,No.2016WS0151the Jining Municipal Project on Science and Technology Development of China,No.2013jnwk58
文摘AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA(HOTAIR) in gastric cancer(GC) migration and invasion.METHODS Quantitative real-time polymerase chain reaction(qp CR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve(AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qp CR,western blot and immunohistochemistry were used to evaluate the m RNA and protein expression of E-cadherin. RNAbinding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin.RESULTS The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues(p < 0.001). Its over-expression was correlated with tumor-node-metastasis(TNM) stage(p = 0.024),tumor invasion(p = 0.018),lymph node metastasis(p = 0.023),and poor prognosis(p < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival(p = 0.033),together with TNM stage(p = 0.002) and lymph node metastasis(p = 0.002). The AUCROC was up to 0.709(95%CI: 0.623-0.785,p < 0.001). Knockdown of HOTAIR by si RNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines,and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.
基金supported by the National Transgenic Key Project of the Ministry of Agriculture of China(2016ZX08011-003)the Agricultural Science and Technology Program for Innovation Team on Identification and excavation of Elite Crop Germplasm,CAAS
文摘The engineering of plants with enhanced tolerance to abiotic stresses typically involves complex multigene networks and may therefore have a greater potential to introduce unintended effects than the genetic modification for simple monogenic traits. For this reason, it is essential to study the unintended effects in transgenic plants engineered for stress tolerance. We selected drought-and salt-tolerant transgenic wheat overexpressing the transcription factor, GmDREB1, to investigate unintended pleiotropic effects using RNA-seq analysis. We compared the transcriptome alteration of transgenic plants with that of wild-type plants subjected to salt stress as a control. We found that GmDREB1 overexpression had a minimal impact on gene expression under normal conditions.GmDREB1 overexpression resulted in transcriptional reprogramming of the salt response,but many of the genes with differential expression are known to mitigate salt stress and contribute incrementally to the enhanced stress tolerance of transgenic wheat. GmDREB1 overexpression did not activate unintended gene networks with respect to gene expression in the roots of transgenic wheat. This work is important for establishing a method of detecting unintended effects of genetic engineering and the safety of such traits with the development of marketable transgenic crops in the near future.
基金supported by a grant from the NationalHigh-Technology Research and Development Program of China(2011AA100304)two grants from Guangdong Provincial Department of Science and Technology,China(2011A090700016 and 2011A020102003)
文摘Somatic nuclear transfer technology has become increasingly promising in biomedicine and agriculture.Whereas the approach remains inefficient and underlying mechanisms remain ambiguous.Although cloned embryos have similar in vitro developmental capacity as in vitro fertilized（IVF） embryos before implantation,they appeared to have much lower full-term developmental efficiency in pig and cattle,and thus it would be reasonable to postulate that profound distinction at the molecular level should exist between them.Herein,RNA sequencing technique was used to screen differentially expressed genes in cloned and IVF blastocysts,and in total 628 differentially expressed transcripts were obtained,among which,280 transcripts are up-regulated and 348 transcripts are down-regulated in cloned blastocysts.Moreover,one statistically significant pathway associated with endoplasmic reticulum（ER） protein processing was enriched,and some ER-stress markers such as ATF4,ATF6,PDIA3,HSPA1 B,HSP40 and HSP90 between cloned and IVF blastocysts were suggested.Additionally,some developmentally important genes such as lipid metabolism related genes（MGLL,DDHD2 and FADS2） and epigenetic modification genes（DNMT1,KDM5 C and MBD3L5） were found differentially expressed between cloned and IVF embryos.
