Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment targets.Here,we...Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment targets.Here,we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16(SNHG16)in CRC.The expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription PCR.The functions of SNHG16 were explored by a series of in vitro and in vivo assays(colony formation assay,flow cytometry assay,and xenograft model).Bioinformatics analysis,RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of SNHG16.SNHG16 was found to be significantly elevated in human CRC tissues and cell lines.Functional studies suggested that SNHG16 promoted CRC cell growth both in vitro and in vivo.Mechanistically,we identified that SNHG16 is expressed predominantly in the cytoplasm.SNHG16 could interact with miR-214-3p and up-regulated its target ABCB1.This study indicated that SNHG16 plays an oncogenic role in CRC,suggesting it could be a novel biomarker and therapeutic target in CRC.展开更多
Background:Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds.MicroRNAs(miRNAs)are also considere...Background:Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds.MicroRNAs(miRNAs)are also considered promising targets for the development of effective therapies against skin wounds.However,further research in this field is anticipated.This study aims to identify and provide a new peptide drug candidate,as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.Methods:A combination of Edman degradation,mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide thatwas fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography.The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide(PI)double staining against human keratinocytes(HaCaT cells),hemolytic activity against mice blood cells and acute toxicity against mice.The stability of the peptide in plasma was also evaluated.The prohealing potency of the peptide was determined by MTS,scratch healing and a Transwell experiment against HaCaT cells,full-thickness injury wounds and scald wounds in the dorsal skin of mice.miRNA transcriptome sequencing analysis,enzyme-linked immunosorbent assay,real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.Results:A novel peptide homodimer(named OA-GL17d)that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence‘GLFKWHPRCGEEQSMWT’was identified.Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity,but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice.Mechanistically,OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1(TGF-β1)and activate the subsequent TGF-β1/Smad signaling pathway,thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.Conclusions:Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair.This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81972806)Jiangsu Provincial Key Research and Development Plan(Grant No.BE2019614),Key Project of Science and Technology Development of Nanjing Medicine(ZKX21042)+1 种基金Elderly Health Research Project of Jiangsu Province(Grant No.LR2021017)Specialized Cohort Research Project of Nanjing Medical University(Grants No.NMUC2020035 and NMUC2021013A).
文摘Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment targets.Here,we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16(SNHG16)in CRC.The expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription PCR.The functions of SNHG16 were explored by a series of in vitro and in vivo assays(colony formation assay,flow cytometry assay,and xenograft model).Bioinformatics analysis,RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of SNHG16.SNHG16 was found to be significantly elevated in human CRC tissues and cell lines.Functional studies suggested that SNHG16 promoted CRC cell growth both in vitro and in vivo.Mechanistically,we identified that SNHG16 is expressed predominantly in the cytoplasm.SNHG16 could interact with miR-214-3p and up-regulated its target ABCB1.This study indicated that SNHG16 plays an oncogenic role in CRC,suggesting it could be a novel biomarker and therapeutic target in CRC.
基金supported by grants from the National Natural Science Foundation of China(81760648,32060212 and 82160159)Yunnan Applied Basic Research Project Foundation(2019FB128)+4 种基金Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202101AY070001-006 and 2019FE001(-183))Program for Innovative Research Team in Ministry of Education of China(IRT17-R49)Science and Technology Leadership Talent Project in Yunnan China(2017HA010)Endocrine Clinical Medical Center of Yunnan Province(ZX2019-02-02)the Innovative Team of Precise Prevention and Treatment against Metabolic Diseases of Yunnan University,Scientific Research Fund Projects from the Department of Education of Yunnan Province(2021 J0205).
文摘Background:Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds.MicroRNAs(miRNAs)are also considered promising targets for the development of effective therapies against skin wounds.However,further research in this field is anticipated.This study aims to identify and provide a new peptide drug candidate,as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.Methods:A combination of Edman degradation,mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide thatwas fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography.The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide(PI)double staining against human keratinocytes(HaCaT cells),hemolytic activity against mice blood cells and acute toxicity against mice.The stability of the peptide in plasma was also evaluated.The prohealing potency of the peptide was determined by MTS,scratch healing and a Transwell experiment against HaCaT cells,full-thickness injury wounds and scald wounds in the dorsal skin of mice.miRNA transcriptome sequencing analysis,enzyme-linked immunosorbent assay,real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.Results:A novel peptide homodimer(named OA-GL17d)that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence‘GLFKWHPRCGEEQSMWT’was identified.Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity,but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice.Mechanistically,OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1(TGF-β1)and activate the subsequent TGF-β1/Smad signaling pathway,thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.Conclusions:Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair.This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.
