The incidence and mortality rates of gastrointestinal(GI)cancer remain high.Despite constant improvements in diagnostic and therapeutic techniques,the early diagnosis,mid-and late-stage treatment,drug tolerance,and ca...The incidence and mortality rates of gastrointestinal(GI)cancer remain high.Despite constant improvements in diagnostic and therapeutic techniques,the early diagnosis,mid-and late-stage treatment,drug tolerance,and cancer recurrence and metastasis in GI cancer remain challenging.In this review article we summarize the recent research advance in the roles of keratins in GI cancer,with the hope that they will become efficient biomarkers for the prediction,diagnosis,or treatment of these malignancies.展开更多
Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and ...Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.展开更多
Taking a widely contaminated yet abundant waste,such as poultry feathers,and extracting keratin from this struc-ture appears to be a real challenge whenever the preservation of the secondary structure of the protein i...Taking a widely contaminated yet abundant waste,such as poultry feathers,and extracting keratin from this struc-ture appears to be a real challenge whenever the preservation of the secondary structure of the protein is desired.This process would allow exploiting it in ways(e.g.,in the biomedicalfield)that are inspired by a structure that is primarily designed forflight,therefore capable specifically of withstandingflexure and lateral buckling,also with very low thicknesses.The preservation of the structure is based on disulfide crosslinks,and it is offered with pre-ference by some chemical treatments,mainly those based on ionic liquid and on a reduction process.However,the degree of preservation cannot always be precisely assessed;however,beyond chemical characterization,the forma-tion of homogeneous gels can also suggest that the process was successful in this sense.An extraction respectful of nature’s intentions,considering that the secondary structure builds up according to the very function of the feath-ers in the animal,can be deemed to be biomimetic.In particular,biomimetic extractions comply with the very characteristics the protein was designed for to serve in the specific environmental and mechanical situation in which it is inserted.This review tries to elucidate in which cases this aim is achieved and for which specific appli-cations a chicken feather keratin that has preserved its secondary structure can be suited.展开更多
Wearable electronics incorporating proteins for biocompatibility have garnered significant research attention,given their potential applications in biocompatible medical devices,artificial skin,humanoid robots,and oth...Wearable electronics incorporating proteins for biocompatibility have garnered significant research attention,given their potential applications in biocompatible medical devices,artificial skin,humanoid robots,and other fields.However,a notable challenge exists,as many wearable electronics currently lack those essential properties due to issues such as non-biological compatibility,as well as insufficient mechanical and conductive performance.Here,we have developed a hybrid keratin(KE)hydrogel by incorporating a liquid metal(LM,eutectic gallium-indium alloy)to design a wearable electronic device with excellent biocompatibility,enhanced conductivity,and good mechanical properties.The resulting keratin liquid metal(KELM)hydrogel demonstrates favorable mechanical characteristics,including good tensile strength(166 kPa),impressive stretchability(2600%),and long-term stability.Furthermore,it exhibits good conductivity(6.84 S·m^(-1))and sensitivity as a sensing material(gauge factor(GF)=7.03),rendering it suitable for constructing high-performance strain sensors.Notably,the KELM hydrogel-based wearable electronics extend their functionality to monitoring marine inhabitants'health.This innovative application provides new insights for designing the next generation of biomimetic electronic devices,with potential applications in human-machine interfaces,electronic skin,artificial intelligence,and health monitoring.展开更多
The increasing consciousness about the depletion of natural resources and the sustainability agenda are the major driving forces to try to reuse and recycle organic materials such as agri-food and industrial wastes.In...The increasing consciousness about the depletion of natural resources and the sustainability agenda are the major driving forces to try to reuse and recycle organic materials such as agri-food and industrial wastes.In this context,keratin fibers,as a waste from the tannery industry,represent a great opportunity for the development of green functional materials.In this paper,keratin fibers were surface functionalized using the Layer-by-Layer(LbL)deposition technique and then freeze-dried in order to obtain a lightweight,fire-resistant,and sustainable material.The LbL coating,made with chitosan and carboxymethylated cellulose nanofibers,is fundamental in enabling the formation of a self-sustained structure after freeze-drying.The prepared porous fiber networks(density 100 kg m^(-3))display a keratin fiber content greater than 95 wt%and can easily self-extinguish the flame during a flammability test in a vertical configuration.In addition,during forced combustion tests(50 kW m^(-2))the samples exhibited a reduction of 37% in heat release rate and a reduction of 75%in smoke production if compared with a commercial polyurethane foam.The results obtained represent an excellent opportunity for the development of fire-safe sustainable materials based on fiber wastes.展开更多
BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological proce...BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.展开更多
BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progre...BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progression of UC remains to be fully eluci-dated.AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.METHODS A KRT1 antibody concentration gradient test,along with a dextran sulfate sodium(DSS)-induced animal model,was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system(KKS)and the cleavage of bradykinin(BK)/high molecular weight kininogen(HK)in UC.RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation,induced apoptosis,reduced HK expression,and increased BK expression.It further downregulated intestinal barrier proteins,including occludin,zonula occludens-1,and claudin,and negatively impacted the coagulation factor XII.These changes led to enhanced activation of BK and HK cleavage,thereby intensifying KKS-mediated inflammation in UC.In the DSS-induced mouse model,administration of KRT1 antibody mitigated colonic injury,increased colon length,alleviated weight loss,and suppressed inflammatory cytokines such as interleukin(IL)-1,IL-6,tumor necrosis factor-α.It also facilitated repair of the intestinal barrier,reducing DSS-induced injury.CONCLUSION KRT1 inhibits BK expression,suppresses inflammatory cytokines,and enhances markers of intestinal barrier function,thus ameliorating colonic damage and maintaining barrier integrity.KRT1 is a viable therapeutic target for UC.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
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
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
Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromoso...Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromosomal translocations on gene expression through involved breakpoints and structural gene abnormalities detected by array CGH. We believe that the family we present gives further insight to the better understanding of molecular and structural basis of keratin disorders, and to the late onset and genetic basis of PCT through the possible role of C-type lectins and human epithelial membrane protein1 (EMP1). Better understanding of the molecular basis of keratin disorders is the foundation for improved diagnosis, genetic counseling and novel therapeutic approaches to overcome the current treatment limitations related to this disease.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
基金supported by the Wu Jieping Medical Foundation(320.6750.19020).
文摘The incidence and mortality rates of gastrointestinal(GI)cancer remain high.Despite constant improvements in diagnostic and therapeutic techniques,the early diagnosis,mid-and late-stage treatment,drug tolerance,and cancer recurrence and metastasis in GI cancer remain challenging.In this review article we summarize the recent research advance in the roles of keratins in GI cancer,with the hope that they will become efficient biomarkers for the prediction,diagnosis,or treatment of these malignancies.
基金National Natural Science Foundation of China,Grant/Award Numbers:11972099,82202340Venture&Innovation Support Program for Chongqing Overseas Returnees,Grant/Award Number:cx2020079Scientific and Fundamental Research Funds for the Central Universities,Grant/Award Numbers:2023CDJXY-050,2023CDJXY-051。
文摘Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.
文摘Taking a widely contaminated yet abundant waste,such as poultry feathers,and extracting keratin from this struc-ture appears to be a real challenge whenever the preservation of the secondary structure of the protein is desired.This process would allow exploiting it in ways(e.g.,in the biomedicalfield)that are inspired by a structure that is primarily designed forflight,therefore capable specifically of withstandingflexure and lateral buckling,also with very low thicknesses.The preservation of the structure is based on disulfide crosslinks,and it is offered with pre-ference by some chemical treatments,mainly those based on ionic liquid and on a reduction process.However,the degree of preservation cannot always be precisely assessed;however,beyond chemical characterization,the forma-tion of homogeneous gels can also suggest that the process was successful in this sense.An extraction respectful of nature’s intentions,considering that the secondary structure builds up according to the very function of the feath-ers in the animal,can be deemed to be biomimetic.In particular,biomimetic extractions comply with the very characteristics the protein was designed for to serve in the specific environmental and mechanical situation in which it is inserted.This review tries to elucidate in which cases this aim is achieved and for which specific appli-cations a chicken feather keratin that has preserved its secondary structure can be suited.
基金supported by the National Natural Science Foundation of China(22176221 and 22273045)the Central Public-interest Scientific Institution Basal Research Fund,Chinese Academy of Fishery Sciences(2024XT09)+1 种基金the Tsinghua University Independent Scientific Research Plan for Young Investigatorthe Tsinghua University Initiative Scientific Research Program。
文摘Wearable electronics incorporating proteins for biocompatibility have garnered significant research attention,given their potential applications in biocompatible medical devices,artificial skin,humanoid robots,and other fields.However,a notable challenge exists,as many wearable electronics currently lack those essential properties due to issues such as non-biological compatibility,as well as insufficient mechanical and conductive performance.Here,we have developed a hybrid keratin(KE)hydrogel by incorporating a liquid metal(LM,eutectic gallium-indium alloy)to design a wearable electronic device with excellent biocompatibility,enhanced conductivity,and good mechanical properties.The resulting keratin liquid metal(KELM)hydrogel demonstrates favorable mechanical characteristics,including good tensile strength(166 kPa),impressive stretchability(2600%),and long-term stability.Furthermore,it exhibits good conductivity(6.84 S·m^(-1))and sensitivity as a sensing material(gauge factor(GF)=7.03),rendering it suitable for constructing high-performance strain sensors.Notably,the KELM hydrogel-based wearable electronics extend their functionality to monitoring marine inhabitants'health.This innovative application provides new insights for designing the next generation of biomimetic electronic devices,with potential applications in human-machine interfaces,electronic skin,artificial intelligence,and health monitoring.
基金supported by the Italian Ministry of University(MIUR)call PRIN 2017 with the project“PANACEA:A technology Platform for the sustainable recovery and advanced use of NAnostructured CEllulose from Agro-food residues”(grant No.2017LEPH3M).
文摘The increasing consciousness about the depletion of natural resources and the sustainability agenda are the major driving forces to try to reuse and recycle organic materials such as agri-food and industrial wastes.In this context,keratin fibers,as a waste from the tannery industry,represent a great opportunity for the development of green functional materials.In this paper,keratin fibers were surface functionalized using the Layer-by-Layer(LbL)deposition technique and then freeze-dried in order to obtain a lightweight,fire-resistant,and sustainable material.The LbL coating,made with chitosan and carboxymethylated cellulose nanofibers,is fundamental in enabling the formation of a self-sustained structure after freeze-drying.The prepared porous fiber networks(density 100 kg m^(-3))display a keratin fiber content greater than 95 wt%and can easily self-extinguish the flame during a flammability test in a vertical configuration.In addition,during forced combustion tests(50 kW m^(-2))the samples exhibited a reduction of 37% in heat release rate and a reduction of 75%in smoke production if compared with a commercial polyurethane foam.The results obtained represent an excellent opportunity for the development of fire-safe sustainable materials based on fiber wastes.
基金Supported by National Natural Science Foundation of China,No.874063.
文摘BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.
基金Supported by the National Natural Science Foundation of China,No.82160113the“Xingdian Talents”Support Project of Yunnan Province,No.RLMY20220007+1 种基金the Yunnan Province Clinical Research Center for Digestive Diseases,No.202102AA100062the Applied Basic Research Projects of Yunnan Province,No.2019FE001-039.
文摘BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progression of UC remains to be fully eluci-dated.AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.METHODS A KRT1 antibody concentration gradient test,along with a dextran sulfate sodium(DSS)-induced animal model,was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system(KKS)and the cleavage of bradykinin(BK)/high molecular weight kininogen(HK)in UC.RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation,induced apoptosis,reduced HK expression,and increased BK expression.It further downregulated intestinal barrier proteins,including occludin,zonula occludens-1,and claudin,and negatively impacted the coagulation factor XII.These changes led to enhanced activation of BK and HK cleavage,thereby intensifying KKS-mediated inflammation in UC.In the DSS-induced mouse model,administration of KRT1 antibody mitigated colonic injury,increased colon length,alleviated weight loss,and suppressed inflammatory cytokines such as interleukin(IL)-1,IL-6,tumor necrosis factor-α.It also facilitated repair of the intestinal barrier,reducing DSS-induced injury.CONCLUSION KRT1 inhibits BK expression,suppresses inflammatory cytokines,and enhances markers of intestinal barrier function,thus ameliorating colonic damage and maintaining barrier integrity.KRT1 is a viable therapeutic target for UC.
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.
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.
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。
文摘Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromosomal translocations on gene expression through involved breakpoints and structural gene abnormalities detected by array CGH. We believe that the family we present gives further insight to the better understanding of molecular and structural basis of keratin disorders, and to the late onset and genetic basis of PCT through the possible role of C-type lectins and human epithelial membrane protein1 (EMP1). Better understanding of the molecular basis of keratin disorders is the foundation for improved diagnosis, genetic counseling and novel therapeutic approaches to overcome the current treatment limitations related to this disease.
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.
