Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we ident...Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.展开更多
Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a r...Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine展开更多
Malonyl-CoA synthetases may modulate cell responses to abiotic stress by regulating stress-related signaling transduction pathways or activating expression of transcription factors.However,the molecular mechanism of c...Malonyl-CoA synthetases may modulate cell responses to abiotic stress by regulating stress-related signaling transduction pathways or activating expression of transcription factors.However,the molecular mechanism of cold stress tolerance enhanced by malonyl-CoA synthetase is not fully understood.Here,we report that overexpression of the Arabidopsis thaliana malonyl-CoA synthetase gene AAE13.1 resulted in increased cell viability and growth rate and decreased thiobarbituric acid reactive substances under cold stress in rice(Oryza sativa L.),tobacco(Nicotiana tabacum),and slash pine(Pinus elliottii Engelm.).AAE13.1 was associated with cold stress tolerance by increasing the activity of ascorbate peroxidase,catalase,polyphenol oxidase,and peroxidase and the accumulation of acid phosphatase and alkaline phosphatase.Among six rice mitogenactivated protein kinase(MAPK)genes examined,AAE13.1 overexpression increased the expression of OsMAPK genes during cold stress.AAE13.1 activated expression of stressresponse genes OsMAPK1,OsMAPK2,and OsMAPK3,indicating that AAE13.1 enhances cold stress tolerance by regulating expression of MAPK genes in plant cells.These results increase our understanding of cold stress tolerance in species of monocotyledons,dicotyledons,and gymnosperms.展开更多
We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors(TLR)2 and 4.The downstream transcription factors signal transducer and activator of transcription 3(STA...We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors(TLR)2 and 4.The downstream transcription factors signal transducer and activator of transcription 3(STAT3)and nuclear factor kappa B(NF-κB)are also affected by argon and may play a role in neuroprotection.It also has been demonstrated that argon treatment could mitigate brain damage,reduce excessive microglial activation,and subsequently attenuate brain inflammation.Despite intensive research,the further exact mechanism remains unclear.In this study,human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours(to mimic cerebral ischemia and reperfusion damage),followed by a 2-hour post-conditioning with argon(75%).In a separate in vivo experiment,retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour.Upon reperfusion,argon was administered by inhalation for 2 hours.Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3,nuclear factor kappa B,activator protein 1,and nuclear factor erythroid 2-related factor 2,which are involved in regulation of neuronal damage.Flow cytometry analysis showed that argon downregulated the Fas ligand.Some transcription factors were regulated by toll-like receptors;therefore,their effects could be eliminated,at least in part,by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine(OxPAPC).Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury.Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin(IL-1α),IL-1β,IL-6,tumor necrosis factorα,and inducible nitric oxide synthase.Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation.Argon has no known side effects o展开更多
Anthocyanin is abundant in a few vegetables,including eggplant.It protects plants from abiotic stress and benefits human health,making the research of anthocyanin biosynthesis increasingly important.Flowering time is ...Anthocyanin is abundant in a few vegetables,including eggplant.It protects plants from abiotic stress and benefits human health,making the research of anthocyanin biosynthesis increasingly important.Flowering time is an important reference for judging reproduction and adaptability,which can guide plant production.In this study,SmbHLH13 from eggplant was identified.Yeast one-hybrid and dual-luciferase assays showed that SmbHLH13 binded and activated the expression of structural genes SmCHS and SmF3H in anthocyanin biosynthesis and it also was bound to the promoter of the key gene SmFT in flowering.Furthermore,genetic transformation of Arabidopsis revealed that overexpression of SmbHLH13 enhanced anthocyanin accumulation and delayed flowering.These results demonstrated that SmbHLH13 might promote anthocyanin accumulation through positive regulation of SmCHS and SmF3H.Moreover,SmbHLH13 might have a role in delaying eggplant flowering.展开更多
The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative st...The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.展开更多
基金This study was supported by Shanghai Changning District Committee of Science and Technology(CNKW2016Y01)Shanghai Tongren Hospital Project(TRYJ201501)+3 种基金Suzhou Science and Technology Development Program(SYS201717)the Second Affiliated Hospital of Soochow University Advance Research Program of the Natural Science Foundation of China Grants(SDFEYGJ1705)Open project of Jiangsu State Key Laboratory of Radiation Medicine and Projection(GJS1963)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.
基金This study was supported by the National Natural Science Foundation of China,Nos.81871193(to XD),81671532(to BS),81771625&81701490(to XF),81801505(to MG)Jiangsu Provincial Medical Youth Talent of China,Nos.QNRC2016763(to XD),QNRC2016758(to LXX),QNRC2016762(to ML)+7 种基金the Science and Technology Project of Suzhou City of China,No.SS201709(to XD)the Natural Science Foundation of Jiangsu Province of China,No.BK20180205(to XD)the Training Program Foundation for Health Talents of Gusu of China,No.GSWS2019049(to XD)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Jiangsu Province Women and Children Health Research Project of China,No.F201750(to LXX)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)Suzhou Industrial Technology Innovation Project of China,No.SYS201765(to LZ)the Project of Suzhou Science,Education and Health and Technology,China,No.KJXW2018018(to ML).
文摘Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine
文摘Malonyl-CoA synthetases may modulate cell responses to abiotic stress by regulating stress-related signaling transduction pathways or activating expression of transcription factors.However,the molecular mechanism of cold stress tolerance enhanced by malonyl-CoA synthetase is not fully understood.Here,we report that overexpression of the Arabidopsis thaliana malonyl-CoA synthetase gene AAE13.1 resulted in increased cell viability and growth rate and decreased thiobarbituric acid reactive substances under cold stress in rice(Oryza sativa L.),tobacco(Nicotiana tabacum),and slash pine(Pinus elliottii Engelm.).AAE13.1 was associated with cold stress tolerance by increasing the activity of ascorbate peroxidase,catalase,polyphenol oxidase,and peroxidase and the accumulation of acid phosphatase and alkaline phosphatase.Among six rice mitogenactivated protein kinase(MAPK)genes examined,AAE13.1 overexpression increased the expression of OsMAPK genes during cold stress.AAE13.1 activated expression of stressresponse genes OsMAPK1,OsMAPK2,and OsMAPK3,indicating that AAE13.1 enhances cold stress tolerance by regulating expression of MAPK genes in plant cells.These results increase our understanding of cold stress tolerance in species of monocotyledons,dicotyledons,and gymnosperms.
基金This work was financially supported by the Department of Anesthesiology and Critical Care,Medical Center-University of Freiburg,GermanyThe article processing charge was funded by the Baden-Württemberg Ministry of Science,Research and Art and the University of Freiburg in the funding programme Open Access Publishing.
文摘We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors(TLR)2 and 4.The downstream transcription factors signal transducer and activator of transcription 3(STAT3)and nuclear factor kappa B(NF-κB)are also affected by argon and may play a role in neuroprotection.It also has been demonstrated that argon treatment could mitigate brain damage,reduce excessive microglial activation,and subsequently attenuate brain inflammation.Despite intensive research,the further exact mechanism remains unclear.In this study,human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours(to mimic cerebral ischemia and reperfusion damage),followed by a 2-hour post-conditioning with argon(75%).In a separate in vivo experiment,retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour.Upon reperfusion,argon was administered by inhalation for 2 hours.Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3,nuclear factor kappa B,activator protein 1,and nuclear factor erythroid 2-related factor 2,which are involved in regulation of neuronal damage.Flow cytometry analysis showed that argon downregulated the Fas ligand.Some transcription factors were regulated by toll-like receptors;therefore,their effects could be eliminated,at least in part,by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine(OxPAPC).Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury.Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin(IL-1α),IL-1β,IL-6,tumor necrosis factorα,and inducible nitric oxide synthase.Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation.Argon has no known side effects o
基金The project was supported by the National Natural Science Foundation of China(Grant No.31872944)Science and Technology Committee of Shanghai(Grant No.18391900500).
文摘Anthocyanin is abundant in a few vegetables,including eggplant.It protects plants from abiotic stress and benefits human health,making the research of anthocyanin biosynthesis increasingly important.Flowering time is an important reference for judging reproduction and adaptability,which can guide plant production.In this study,SmbHLH13 from eggplant was identified.Yeast one-hybrid and dual-luciferase assays showed that SmbHLH13 binded and activated the expression of structural genes SmCHS and SmF3H in anthocyanin biosynthesis and it also was bound to the promoter of the key gene SmFT in flowering.Furthermore,genetic transformation of Arabidopsis revealed that overexpression of SmbHLH13 enhanced anthocyanin accumulation and delayed flowering.These results demonstrated that SmbHLH13 might promote anthocyanin accumulation through positive regulation of SmCHS and SmF3H.Moreover,SmbHLH13 might have a role in delaying eggplant flowering.
基金supported by the National Natural Science Foundation of China, Nos.81471238, 81771327(both to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No.PXM2020_026280_000002(to BYL)。
文摘The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.