Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address ...Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.展开更多
BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia ...BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.展开更多
The leaves of Eucalyptus are abundant in natural resources as a novel potential antioxidant and have broad market prospect.Four of characteristic hydrolysable tannins from Eucalyptus leaves have been demonstrated grea...The leaves of Eucalyptus are abundant in natural resources as a novel potential antioxidant and have broad market prospect.Four of characteristic hydrolysable tannins from Eucalyptus leaves have been demonstrated great application potential as natural antioxidants in our previous research.In this study,the bioactive activities of another hydrolysable tannin isolated and identified as oenothein B(OEB)were evaluated.Content of bioactive compound(hydrolysable tannin)from different Eucalyptus species and regions in southern China were investigated.The results showed that OEB not only exerted anti-proliferative activity against HepG2 cell,but also showed higher cellular antioxidant activity than some common antioxidants.Generally,content of characteristic hydrolysable tannins decreased in the order of OEB>tellimagrandin I(T1)>pedunculagin>gemin D>pentagalloyl glucose(PGG).E.grandis×E.urophylla GL9 and E.urophylla×E.grandis could be recommended as new natural sources to exploit hydrolysable tannins because of high content,widely plantation and strong adaptability.This study supplied first insight on introduction of high cellular antioxidant activity of OEB and selecting the species and region to exploit natural antioxidants.It will promote the increasing of economic value of Eucalyptus.展开更多
A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites(1-14)including eight sesquiterpenoids(1-8)and six polyphenols...A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites(1-14)including eight sesquiterpenoids(1-8)and six polyphenols(9-14).Compounds1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy,high resolution mass spectrometry(HRMS)and electronic circular dichroism(ECD)data.All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells,and cellular antioxidant activity.Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus(SARS-CoV-2)activity.As a result,compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%,62.7%,33.7%and 21.4%at the dose of 50μmol·L^(-1),respectively.Compounds 9-12 also showed good cellular antioxidant activities with CAA_(50)values of 12.23,23.11,5.31 and 16.04μmol·L^(-1),respectively.Molecular docking between COVID-19 M^(pro)and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds.This work provides new insights for the potential role of the medicinal mushroom S.sanghuang as drugs and functional foods.展开更多
Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,CD85j),we have selected a range of mutants with binding affinities enhanced b...Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(MHC)class I molecules.Produced in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of MHC I-positive cells of many hours.The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and in a dose-dependent manner.As a selective inhibitor of CD8^(+)CTL responses,the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.展开更多
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2020-I2M-C&T-A-004National High Level Hospital Clinical Research Funding,No.2022-PUMCH-A-210,No.2022-PUMCH-B-041,and No.2022-PUMCH-C-025and National Key R&D Program of China,No.2020YFE0201600.
文摘Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.
基金Supported by The Shandong Provincial Natural Science Foundation,No.ZR2021MH059。
文摘BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.
基金supported by the General project of the Natural Science Foundation of Guangdong Province,China(2022A1515010907)the National Key R&D Program(2016YFD0600806)National Natural Science Foundation of China(31700501).
文摘The leaves of Eucalyptus are abundant in natural resources as a novel potential antioxidant and have broad market prospect.Four of characteristic hydrolysable tannins from Eucalyptus leaves have been demonstrated great application potential as natural antioxidants in our previous research.In this study,the bioactive activities of another hydrolysable tannin isolated and identified as oenothein B(OEB)were evaluated.Content of bioactive compound(hydrolysable tannin)from different Eucalyptus species and regions in southern China were investigated.The results showed that OEB not only exerted anti-proliferative activity against HepG2 cell,but also showed higher cellular antioxidant activity than some common antioxidants.Generally,content of characteristic hydrolysable tannins decreased in the order of OEB>tellimagrandin I(T1)>pedunculagin>gemin D>pentagalloyl glucose(PGG).E.grandis×E.urophylla GL9 and E.urophylla×E.grandis could be recommended as new natural sources to exploit hydrolysable tannins because of high content,widely plantation and strong adaptability.This study supplied first insight on introduction of high cellular antioxidant activity of OEB and selecting the species and region to exploit natural antioxidants.It will promote the increasing of economic value of Eucalyptus.
基金supported by the National Key R&D Program of China(No.2018YFD0400203)the National Natural Science Foundation of China(No.81673334)。
文摘A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites(1-14)including eight sesquiterpenoids(1-8)and six polyphenols(9-14).Compounds1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy,high resolution mass spectrometry(HRMS)and electronic circular dichroism(ECD)data.All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells,and cellular antioxidant activity.Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus(SARS-CoV-2)activity.As a result,compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%,62.7%,33.7%and 21.4%at the dose of 50μmol·L^(-1),respectively.Compounds 9-12 also showed good cellular antioxidant activities with CAA_(50)values of 12.23,23.11,5.31 and 16.04μmol·L^(-1),respectively.Molecular docking between COVID-19 M^(pro)and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds.This work provides new insights for the potential role of the medicinal mushroom S.sanghuang as drugs and functional foods.
基金This work was funded by MediGene AG,Munich,Germany.Authors declare noconflict of interest associated with this work.
文摘Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(MHC)class I molecules.Produced in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of MHC I-positive cells of many hours.The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and in a dose-dependent manner.As a selective inhibitor of CD8^(+)CTL responses,the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
