Pathogenic mutations in 3-keto-dihydrosphingosine reductase(KDSR)gene are associated with keratinization disorders and impaired platelet function.However,no case with both homozygotic mutation of KDSR and hepatic hema...Pathogenic mutations in 3-keto-dihydrosphingosine reductase(KDSR)gene are associated with keratinization disorders and impaired platelet function.However,no case with both homozygotic mutation of KDSR and hepatic hemangioendothelioma has ever been reported due to its low prevalence.Here we report a seven months old Chinese boy with a homozygotic missense mutation in KDSR and both of his parents carry a same heterozygous mutation.He was born with thick plate-like scales overlying erythrodermic skin,but the skin symptoms were resolved spontaneously over the first month of his birth.He was also diagnosed with hepatic hemangioendothelioma at birth and accepted a resection surgery at 2 months old.At birth,his platelet count was severely low(10-20×10~9/L)with recurrent skin and gingival bleeding.Meanwhile,he suffered a mild normocytic,normochromic anemia with normal iron and hematinic levels.The anemia spontaneously recovered over the first 6 months,while the platelet count keeped at a low level(4-20×10~9/L).Treatment with corticosteroids,immunoglobulin or thrombopoietin was all suboptimal.展开更多
[Objective] The paper was to provide new germplasm sources for efficient and economical degradation and utilization of animal keratin.[Method] The keratin-degrading fungus was isolated,screened and primarily identifie...[Objective] The paper was to provide new germplasm sources for efficient and economical degradation and utilization of animal keratin.[Method] The keratin-degrading fungus was isolated,screened and primarily identified by using the combination method of traditional isolation and screening,solid culture-medium degradation and animal test.[Result] A strain of non-pathogenic filamentous fungi with high degradation efficiency was obtained,which was preliminarily identified to be a species in Mucoraceae.[Conclusion] The discovery of the strain enriched the family members of keratin-degrading fungus,and provided new germplasm resources for degradation and utilization of animal keratin.展开更多
As an important evolutionary innovation and unique organ,the rumen has played a crucial role in ruminant adaptation to complex ecological environments.However,the cellular basis of its complex morphology and function ...As an important evolutionary innovation and unique organ,the rumen has played a crucial role in ruminant adaptation to complex ecological environments.However,the cellular basis of its complex morphology and function remains largely unknown.In this study,we identified eight major cell types from seven representative prenatal and postnatal rumen samples using~56600 single-cell transcriptomes.We captured the dynamic changes and high heterogeneity in cellular and molecular profiles before,during,and after the appearance of keratinized stratified squamous epithelium with neatly arranged papillae and functional maturity.Basal cells,keratinocytes,differentiating keratinocytes,terminally differentiated keratinocytes,and special spinous cells provided the cellular basis for rumen epithelium formation.Notably,we obtained clear evidence of two keratinization processes involved in early papillogenesis and papillae keratinization and identified TBX3 as a potential marker gene.Importantly,enriched stratum spinosum cells played crucial roles in volatile fatty acid(VFA)metabolism and immune response.Our results provide a comprehensive transcriptional landscape of rumen development at single-cell resolution,as well as valuable insight into the interactions between dietary metabolism and the rumen.展开更多
2016年10月Nature Genetics在线发表了北京大学第一医院皮肤性病科杨勇、林志淼课题组与清华大学谭旭课题组合作的研究成果,题为＂Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragilit...2016年10月Nature Genetics在线发表了北京大学第一医院皮肤性病科杨勇、林志淼课题组与清华大学谭旭课题组合作的研究成果,题为＂Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility＂。该研究在国际上确定了遗传性大疱性表皮松解症（epidermolysis bullosa,EB）的一种新致病基因KLHL24及其全新发病机制，同时，研究还发现，KLHL24是皮肤结构分化形成及蛋白代谢稳态的重要调节基因，揭示了皮肤角蛋白泛素化的信号传导通路，为角蛋白异常性疾病治疗提供了新途径。展开更多
A new feather-degrading bacterium was isolated from a local feather waste site and identified as Bacillus subtilis based on morphological, physiochemical, and phylogenetic characteristics. Screening for mutants with e...A new feather-degrading bacterium was isolated from a local feather waste site and identified as Bacillus subtilis based on morphological, physiochemical, and phylogenetic characteristics. Screening for mutants with elevated keratinolytic activity using N-methyl-N＇-nitro-N-nitrosoguanidine mutagenesis resulted in a mutant strain KD-N2 producing keratinolytic activity about 2.5 times that of the wild-type strain. The mutant strain produced inducible keratinase in different substrates of feathers, hair, wool and silk under submerged cultivation. Scanning electron microscopy studies showed the degradation of feathers, hair and silk by the keratinase. The optimal conditions for keratinase production include initial pH of 7.5, inoculum size of 2% （v/v）, age of inoculum of 16 h, and cultivation at 23 ℃. The maximum keratinolytic activity of KD-N2 was achieved after 30 h. Essential amino acids like threonine, valine, methionine as well as ammonia were produced when feathers were used as substrates. Strain KD-N2, therefore, shows great promise of finding potential applications in keratin hydrolysis and keratinase production.展开更多
The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion...The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.展开更多
AIM:To reconstruct the lamellar cornea using human amniotic epithelial(HAE) cells and rabbit cornea stroma in vitro using tissue engineering technology.·METHODS:Human amnia taken from uncomplicated caesarean sect...AIM:To reconstruct the lamellar cornea using human amniotic epithelial(HAE) cells and rabbit cornea stroma in vitro using tissue engineering technology.·METHODS:Human amnia taken from uncomplicated caesarean sections were digested by collagenase to obtain HAE cells,and the cells were cultured to proliferate.Rabbit corneal epithelial cells were removed by n-heptanol to make lamellar matrix sheets.The second passage of HAE cells were cultured on the corneal stroma sheets for 1 or 2 days,then transferred to an air-liquid interface environment to culture for 2weeks.Tissue engineered lamellar cornea(TELC)morphology was observed by Hematoxylin-eosin(HE)staining;its ultrastructure was observed by transmission electron microscopy(TEM) and scanning electron microscopy(SEM);corneal epithelial cell-specific keratin3 and keratin 12 were detected with immunofluorescence microscopy.·RESULTS:HAE cells grew on the rabbit corneal stroma,forming a monolayer after 1-2 days.About 4-5 layers of epithelial cells developed after 2 weeks of air-liquid interface cultivation,a result similar to normal corneal epithelium.Rabbit corneal stromal cells were significantly reduced after one week,then almost completely disappeared after 2 weeks.TEM showed desmosomes between the epithelial cells;hemidesmosomes formed between the epithelial cells and the basement membrane.SEM revealed that the HAE cells which grew on the lamellar cornea had abundant microvilli.The tissue-engineered cornea expressed keratin 3 and keratin 12,as detected by immunofluorescence assay.·CONCLUSION:Functional tissue-engineered lamellar corneal grafts can be constructed in vitro using HAE cells and rabbit corneal stroma.展开更多
AIM： To reveal the characteristics of CD133^＋ cells in the liver, METHODS： This study examined the histological characteristics of CD133^＋ cells in non-neoplastic and neoplastic liver tissues by immunostaining, an...AIM： To reveal the characteristics of CD133^＋ cells in the liver, METHODS： This study examined the histological characteristics of CD133^＋ cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133^＋ cells derived from human hepatocellular carcinoma （HCC） or cholangiocarcinoma cell lines. RESULTS： Immunostaining reveated constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133^＋/CK19^＋/HepPar-1. A small number of CD133^＋/CK19/HepPar-1^＋ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC （HUH7, PLC5 and HepG2） and two cholangiocarcinoma cell lines （HuCCT1 and CCKS1）. Fluorescence-activated cell sorting （FACS） revealed that CD133^＋ and CD133 cells derived from HuH7 and HuCCT1 cells similarly produced CD133^＋ and CD133 cells during subculture. To examine the relationship between CD133^＋ cells and the side population （SP） phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133^＋/CD133 cells were almost identical in the SP and non-SP in HUH7. In addition, four different cellular populations （SP/CD133^＋, SP/CD133, nonP/CD133^＋, and non- SP/CD133） could similarly produce CD133^＋ and CD133- cells during subculture. CONCLUSION： This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.展开更多
AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, a...AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.展开更多
Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral ...Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC（10 mg/kg/day,intraperitoneally）for 14 consecutive days.Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta（Aβ）immunoreactivity in the hippocampus of the model rats.Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal6A after GC treatment compared with model rats that had received saline.Western blot assay confirmed these findings.Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.展开更多
Monilethrix, a congenital disease of hair, is usually associated with mutations in keratin genes, like KRT81, KRT83 and KRT86. We conducted this study to investigate the mutation of type Ⅱ human basic hair keratin hH...Monilethrix, a congenital disease of hair, is usually associated with mutations in keratin genes, like KRT81, KRT83 and KRT86. We conducted this study to investigate the mutation of type Ⅱ human basic hair keratin hHb/ KRT gene in a Han family with monilethrix and obtain information for potential pathogenic mechanism study of monilethrix. Peripheral blood samples were drawn for genomic DNA detection. Exon 1 and exon 7 of the KRT81, KRT83 and KRT86 genes were amplified by PCR. All PCR products were sequenced directly using an ABI 310 DNA sequencer. These sequences were aligned with the standard sequences in GenBank using the BLAST software. PCR products were digested with restriction endonuclease and restriction fragment length polymorphism （RFLP） analysis was performed. In this study, we identified one novel mutation, which is a heterozygous transitional mutation of G→A at position 1,289 in exon 7 of the KRT86 gene [R430Q （KRT86）]. RFLP assays for the novel mutation excluded the possibility of polymorphism. The R430Q mutation of the KRT86 gene may be pathogenic for monilethrix. Meanwhile, we did not find any novel mutation or recurrent mutation in exons 1 and 7 of KRT81 and KRT83 and exon 1 of KRT86. There is a potential pathogenic gene in the subjects and our results expand the spectrum of mutations in the hHb6 gene.展开更多
文摘Pathogenic mutations in 3-keto-dihydrosphingosine reductase(KDSR)gene are associated with keratinization disorders and impaired platelet function.However,no case with both homozygotic mutation of KDSR and hepatic hemangioendothelioma has ever been reported due to its low prevalence.Here we report a seven months old Chinese boy with a homozygotic missense mutation in KDSR and both of his parents carry a same heterozygous mutation.He was born with thick plate-like scales overlying erythrodermic skin,but the skin symptoms were resolved spontaneously over the first month of his birth.He was also diagnosed with hepatic hemangioendothelioma at birth and accepted a resection surgery at 2 months old.At birth,his platelet count was severely low(10-20×10~9/L)with recurrent skin and gingival bleeding.Meanwhile,he suffered a mild normocytic,normochromic anemia with normal iron and hematinic levels.The anemia spontaneously recovered over the first 6 months,while the platelet count keeped at a low level(4-20×10~9/L).Treatment with corticosteroids,immunoglobulin or thrombopoietin was all suboptimal.
基金Supported by Technology Major Projects for Cultivation of New Varieties of National Genetically Modified Organism(2008ZX08005-002)~~
文摘[Objective] The paper was to provide new germplasm sources for efficient and economical degradation and utilization of animal keratin.[Method] The keratin-degrading fungus was isolated,screened and primarily identified by using the combination method of traditional isolation and screening,solid culture-medium degradation and animal test.[Result] A strain of non-pathogenic filamentous fungi with high degradation efficiency was obtained,which was preliminarily identified to be a species in Mucoraceae.[Conclusion] The discovery of the strain enriched the family members of keratin-degrading fungus,and provided new germplasm resources for degradation and utilization of animal keratin.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA26040301-02)National Natural Science Foundation of China(31970392,32172752,32122083)+2 种基金Research Funds for Interdisciplinary Subject of NWPU(19SH030408)Funds Awarded by the 1000 Talent Project of Shaanxi Province,Project for Top Young Talents Program of College of Animal Science and Technology of Nanjing Agricultural University(DKQB201904)Talents Team Construction Fund of Jilin Agricultural University.
文摘As an important evolutionary innovation and unique organ,the rumen has played a crucial role in ruminant adaptation to complex ecological environments.However,the cellular basis of its complex morphology and function remains largely unknown.In this study,we identified eight major cell types from seven representative prenatal and postnatal rumen samples using~56600 single-cell transcriptomes.We captured the dynamic changes and high heterogeneity in cellular and molecular profiles before,during,and after the appearance of keratinized stratified squamous epithelium with neatly arranged papillae and functional maturity.Basal cells,keratinocytes,differentiating keratinocytes,terminally differentiated keratinocytes,and special spinous cells provided the cellular basis for rumen epithelium formation.Notably,we obtained clear evidence of two keratinization processes involved in early papillogenesis and papillae keratinization and identified TBX3 as a potential marker gene.Importantly,enriched stratum spinosum cells played crucial roles in volatile fatty acid(VFA)metabolism and immune response.Our results provide a comprehensive transcriptional landscape of rumen development at single-cell resolution,as well as valuable insight into the interactions between dietary metabolism and the rumen.
文摘2016年10月Nature Genetics在线发表了北京大学第一医院皮肤性病科杨勇、林志淼课题组与清华大学谭旭课题组合作的研究成果,题为＂Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility＂。该研究在国际上确定了遗传性大疱性表皮松解症（epidermolysis bullosa,EB）的一种新致病基因KLHL24及其全新发病机制，同时，研究还发现，KLHL24是皮肤结构分化形成及蛋白代谢稳态的重要调节基因，揭示了皮肤角蛋白泛素化的信号传导通路，为角蛋白异常性疾病治疗提供了新途径。
基金Project (No.3057130) supported by the National Natural Science Foundation of China
文摘A new feather-degrading bacterium was isolated from a local feather waste site and identified as Bacillus subtilis based on morphological, physiochemical, and phylogenetic characteristics. Screening for mutants with elevated keratinolytic activity using N-methyl-N＇-nitro-N-nitrosoguanidine mutagenesis resulted in a mutant strain KD-N2 producing keratinolytic activity about 2.5 times that of the wild-type strain. The mutant strain produced inducible keratinase in different substrates of feathers, hair, wool and silk under submerged cultivation. Scanning electron microscopy studies showed the degradation of feathers, hair and silk by the keratinase. The optimal conditions for keratinase production include initial pH of 7.5, inoculum size of 2% （v/v）, age of inoculum of 16 h, and cultivation at 23 ℃. The maximum keratinolytic activity of KD-N2 was achieved after 30 h. Essential amino acids like threonine, valine, methionine as well as ammonia were produced when feathers were used as substrates. Strain KD-N2, therefore, shows great promise of finding potential applications in keratin hydrolysis and keratinase production.
文摘The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.
基金National Natural Science Foundation of China (No.30872808No.81100637)
文摘AIM:To reconstruct the lamellar cornea using human amniotic epithelial(HAE) cells and rabbit cornea stroma in vitro using tissue engineering technology.·METHODS:Human amnia taken from uncomplicated caesarean sections were digested by collagenase to obtain HAE cells,and the cells were cultured to proliferate.Rabbit corneal epithelial cells were removed by n-heptanol to make lamellar matrix sheets.The second passage of HAE cells were cultured on the corneal stroma sheets for 1 or 2 days,then transferred to an air-liquid interface environment to culture for 2weeks.Tissue engineered lamellar cornea(TELC)morphology was observed by Hematoxylin-eosin(HE)staining;its ultrastructure was observed by transmission electron microscopy(TEM) and scanning electron microscopy(SEM);corneal epithelial cell-specific keratin3 and keratin 12 were detected with immunofluorescence microscopy.·RESULTS:HAE cells grew on the rabbit corneal stroma,forming a monolayer after 1-2 days.About 4-5 layers of epithelial cells developed after 2 weeks of air-liquid interface cultivation,a result similar to normal corneal epithelium.Rabbit corneal stromal cells were significantly reduced after one week,then almost completely disappeared after 2 weeks.TEM showed desmosomes between the epithelial cells;hemidesmosomes formed between the epithelial cells and the basement membrane.SEM revealed that the HAE cells which grew on the lamellar cornea had abundant microvilli.The tissue-engineered cornea expressed keratin 3 and keratin 12,as detected by immunofluorescence assay.·CONCLUSION:Functional tissue-engineered lamellar corneal grafts can be constructed in vitro using HAE cells and rabbit corneal stroma.
文摘AIM： To reveal the characteristics of CD133^＋ cells in the liver, METHODS： This study examined the histological characteristics of CD133^＋ cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133^＋ cells derived from human hepatocellular carcinoma （HCC） or cholangiocarcinoma cell lines. RESULTS： Immunostaining reveated constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133^＋/CK19^＋/HepPar-1. A small number of CD133^＋/CK19/HepPar-1^＋ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC （HUH7, PLC5 and HepG2） and two cholangiocarcinoma cell lines （HuCCT1 and CCKS1）. Fluorescence-activated cell sorting （FACS） revealed that CD133^＋ and CD133 cells derived from HuH7 and HuCCT1 cells similarly produced CD133^＋ and CD133 cells during subculture. To examine the relationship between CD133^＋ cells and the side population （SP） phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133^＋/CD133 cells were almost identical in the SP and non-SP in HUH7. In addition, four different cellular populations （SP/CD133^＋, SP/CD133, nonP/CD133^＋, and non- SP/CD133） could similarly produce CD133^＋ and CD133- cells during subculture. CONCLUSION： This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.
基金Supportod ty the State Key Basic Research Program Grant G1998051211 the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Public Health.
文摘AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.
基金supported by the National Natural Science Foundation of China,No.30960520the Natural Science Foundation of Inner Mongolia Autonomous Region of China,No.2016MS0837
文摘Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC（10 mg/kg/day,intraperitoneally）for 14 consecutive days.Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta（Aβ）immunoreactivity in the hippocampus of the model rats.Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal6A after GC treatment compared with model rats that had received saline.Western blot assay confirmed these findings.Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.
基金supported by the National Natural Science Foundation of China (No. 30771947)Provincal Natural Science Foundation of Jiangsu (No. BK2007248)
文摘Monilethrix, a congenital disease of hair, is usually associated with mutations in keratin genes, like KRT81, KRT83 and KRT86. We conducted this study to investigate the mutation of type Ⅱ human basic hair keratin hHb/ KRT gene in a Han family with monilethrix and obtain information for potential pathogenic mechanism study of monilethrix. Peripheral blood samples were drawn for genomic DNA detection. Exon 1 and exon 7 of the KRT81, KRT83 and KRT86 genes were amplified by PCR. All PCR products were sequenced directly using an ABI 310 DNA sequencer. These sequences were aligned with the standard sequences in GenBank using the BLAST software. PCR products were digested with restriction endonuclease and restriction fragment length polymorphism （RFLP） analysis was performed. In this study, we identified one novel mutation, which is a heterozygous transitional mutation of G→A at position 1,289 in exon 7 of the KRT86 gene [R430Q （KRT86）]. RFLP assays for the novel mutation excluded the possibility of polymorphism. The R430Q mutation of the KRT86 gene may be pathogenic for monilethrix. Meanwhile, we did not find any novel mutation or recurrent mutation in exons 1 and 7 of KRT81 and KRT83 and exon 1 of KRT86. There is a potential pathogenic gene in the subjects and our results expand the spectrum of mutations in the hHb6 gene.
