CHEN Xiru, an expert in mathematical statistics. He graduated from the Department of Mathematics, Wuhan University in 1956. Now Chen is a professor at the Beijing-based Graduate School of University of Science and Tec...CHEN Xiru, an expert in mathematical statistics. He graduated from the Department of Mathematics, Wuhan University in 1956. Now Chen is a professor at the Beijing-based Graduate School of University of Science and Technology of China. Prof. Chen has展开更多
Background: Mutations in COL17A1, coding for type XVII collagen, cause juncti onal epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. Objectiv...Background: Mutations in COL17A1, coding for type XVII collagen, cause juncti onal epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. Objectives: To identify the C OL17A1mutations in a child with reduced type XVII collagen expression and intrae pidermal blister formation. Patient and methods: Protein expression and level of tissue separationwere studied by immunofluorescence and electron microscopy. Th e mutations were identified by analysing the patient’s DNA and mRNA. Results: Immunofluorescence microscopy performed on nonlesional skin demonstrated absence of the type XVII collagen endodomain and presence, although reduced, of the she d ectodomain. Electron microscopy showed that the plane of cleavage was through the basal cells, not through the lamina lucida. Two heterozygous mutations were identified in COL17A1: a new 3- acceptor splice-site mutation in intron 21 (1 877- 2A→ C), and a deletion in exon 48 (3432delT). The splice-sitemutation in intron 21 results in alternative transcripts of which two are in-frame,with deletions of the first nine codons of exon 22 and the entire exon 22, respectiv ely. By Western blot analysis, a type XVII collagen molecule was detected that w as slightly smaller than normal. Conclusions: Occasionally mutations in the COL1 7A1 gene may result in split levels suggesting epidermolysis bullosa simplex rat her than junctional epidermolysis bullosa.展开更多
Collagen XVII(COL17)is a transmembrane protein that mediates skin homeostasis.Due to expression of full length collagen was hard to achieve in microorganisms,arising the needs for selection of collagen fragments with ...Collagen XVII(COL17)is a transmembrane protein that mediates skin homeostasis.Due to expression of full length collagen was hard to achieve in microorganisms,arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis.Here,COL17 fragments(27-33 amino acids)were extracted and replicated 16 times for recombinant expression in Escherichia coli.Five variants were soluble expressed,with the highest yield of 223 mg/L.The fusion tag was removed for biochemical and biophysical characterization.Circular dichroism results suggested one variant(sample-1707)with a triple-helix structure at>37℃.Sample-1707 can assemble into nanofiber(width,5.6 nm)and form hydrogel at 3 mg/mL.Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation.Furthermore,sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration,demonstrating a high capacity to induce skin cell regeneration and promote wound healing.A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of>30%higher than simply using chitosan.Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L.These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.展开更多
A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)syn...A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)synthesis,along with other active ingredients targeting scalp health and follicular regeneration.In vitro assays confirmed that ALRE significantly enhanced COL17A1 expression.A 28-day clinical trial involving Chinese participants demonstrated that the tonic reduced hair loss by 37.61%and increased local hair density by 26.63%,with no reported adverse effects.These findings validate the product’s effectiveness in a distinct consumer population and highlight the importance of integrating mechanistic insights with clinical validation.Further research should explore long-term efficacy and demographic-specific responses to optimize its application.展开更多
Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obst...Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.展开更多
文摘CHEN Xiru, an expert in mathematical statistics. He graduated from the Department of Mathematics, Wuhan University in 1956. Now Chen is a professor at the Beijing-based Graduate School of University of Science and Technology of China. Prof. Chen has
文摘Background: Mutations in COL17A1, coding for type XVII collagen, cause juncti onal epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. Objectives: To identify the C OL17A1mutations in a child with reduced type XVII collagen expression and intrae pidermal blister formation. Patient and methods: Protein expression and level of tissue separationwere studied by immunofluorescence and electron microscopy. Th e mutations were identified by analysing the patient’s DNA and mRNA. Results: Immunofluorescence microscopy performed on nonlesional skin demonstrated absence of the type XVII collagen endodomain and presence, although reduced, of the she d ectodomain. Electron microscopy showed that the plane of cleavage was through the basal cells, not through the lamina lucida. Two heterozygous mutations were identified in COL17A1: a new 3- acceptor splice-site mutation in intron 21 (1 877- 2A→ C), and a deletion in exon 48 (3432delT). The splice-sitemutation in intron 21 results in alternative transcripts of which two are in-frame,with deletions of the first nine codons of exon 22 and the entire exon 22, respectiv ely. By Western blot analysis, a type XVII collagen molecule was detected that w as slightly smaller than normal. Conclusions: Occasionally mutations in the COL1 7A1 gene may result in split levels suggesting epidermolysis bullosa simplex rat her than junctional epidermolysis bullosa.
基金funded by the Natural Science Foundation of Jiangsu Province(BK20202002)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(Grant No.SN-ZJU-SIAS-0013)+2 种基金China Postdoctoral Science Foundation(2023M741403)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB037)the National First-class Discipline Program of Light Industry Technology and Engineering(QGJC20230102).
文摘Collagen XVII(COL17)is a transmembrane protein that mediates skin homeostasis.Due to expression of full length collagen was hard to achieve in microorganisms,arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis.Here,COL17 fragments(27-33 amino acids)were extracted and replicated 16 times for recombinant expression in Escherichia coli.Five variants were soluble expressed,with the highest yield of 223 mg/L.The fusion tag was removed for biochemical and biophysical characterization.Circular dichroism results suggested one variant(sample-1707)with a triple-helix structure at>37℃.Sample-1707 can assemble into nanofiber(width,5.6 nm)and form hydrogel at 3 mg/mL.Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation.Furthermore,sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration,demonstrating a high capacity to induce skin cell regeneration and promote wound healing.A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of>30%higher than simply using chitosan.Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L.These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.
文摘A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)synthesis,along with other active ingredients targeting scalp health and follicular regeneration.In vitro assays confirmed that ALRE significantly enhanced COL17A1 expression.A 28-day clinical trial involving Chinese participants demonstrated that the tonic reduced hair loss by 37.61%and increased local hair density by 26.63%,with no reported adverse effects.These findings validate the product’s effectiveness in a distinct consumer population and highlight the importance of integrating mechanistic insights with clinical validation.Further research should explore long-term efficacy and demographic-specific responses to optimize its application.
基金supported by National Natural Science Foundation of China(Nos.82073780 and 82273868,China)Shanghai Municipal Natural Science Foundation(No.19ZR1406200,China)。
文摘Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.
