Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyel...Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.展开更多
The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory ...The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.展开更多
Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blaza...Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.展开更多
Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 20...Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested展开更多
AIM: To determine if triptolide influences the contractility and fibronectin production in human Tenon fibroblasts(HTFs). METHODS: HTFs were cultured in type I collagen gels with or without transforming growth fac...AIM: To determine if triptolide influences the contractility and fibronectin production in human Tenon fibroblasts(HTFs). METHODS: HTFs were cultured in type I collagen gels with or without transforming growth factor beta(TGF-β) and/or triptolide. The diameter of the collagen gel was used to measure contraction. Immunoblot analysis was used to quantify myosin light chain(MLC) phosphorylation and integrin expression. Laser confocal fluorescence microscopy was used to monitor the formation of actin stress fibers. Fibronectin production was measured with an enzyme immunoassay. RESULTS: Triptolide inhibition of contraction in TGF-β-induced collagen gel mediated by HTFs was dosedependent and statistically significant at 3 nmol/L(P〈0.05) and maximal at 30 nmol/L and significantly time dependent at 2 d(P〈0.05). Triptolide reduced TGF-β-induced expression of integrins α5 and β1, phosphorylation of MLC, and formation of stress fibers in HTFs. Furthermore, the inhibition of triptolide on the attenuated TGF-β-induced production of fibronectin by HTFs was concentration-dependent and significant at 1 nmol/L(P〈0.05) and maximal at 30 nmol/L. CONCLUSION: Triptolide suppress the contractility of HTFs induced by TGF-β and the production of fibronectin by these cells. It is promising that triptolide treatment may possibly inhibit scar formation after glaucoma filtration surgery.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82001282(to PW)and 81960232(to PW)Overseas Students’Innovation and Entrepreneurship Individual Project of Ningxia(2021)(to PW)+1 种基金Youth Talents Supporting Program of Ningxia Medical University and Ningxia,Nos.XT2019018(to PW),TJGC2019081(to PW)College Students’Innovation and En trepreneurship Training Program,No.X202210752038(to FYY)。
文摘Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.
基金supported by the National Nature Science Foundation of China,Nos.81371338(to HF)and 82071369(PPY)。
文摘The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.
文摘Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.
文摘Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested
基金Supported by the National Natural Science Foundation of China(No.81770889)the Natural Science Foundation of Guangdong Province(No.2017A030313774)the International Cooperation Item from Research Fund of Jilin Provincial Science and Technology Department(No.20160414055GH)
文摘AIM: To determine if triptolide influences the contractility and fibronectin production in human Tenon fibroblasts(HTFs). METHODS: HTFs were cultured in type I collagen gels with or without transforming growth factor beta(TGF-β) and/or triptolide. The diameter of the collagen gel was used to measure contraction. Immunoblot analysis was used to quantify myosin light chain(MLC) phosphorylation and integrin expression. Laser confocal fluorescence microscopy was used to monitor the formation of actin stress fibers. Fibronectin production was measured with an enzyme immunoassay. RESULTS: Triptolide inhibition of contraction in TGF-β-induced collagen gel mediated by HTFs was dosedependent and statistically significant at 3 nmol/L(P〈0.05) and maximal at 30 nmol/L and significantly time dependent at 2 d(P〈0.05). Triptolide reduced TGF-β-induced expression of integrins α5 and β1, phosphorylation of MLC, and formation of stress fibers in HTFs. Furthermore, the inhibition of triptolide on the attenuated TGF-β-induced production of fibronectin by HTFs was concentration-dependent and significant at 1 nmol/L(P〈0.05) and maximal at 30 nmol/L. CONCLUSION: Triptolide suppress the contractility of HTFs induced by TGF-β and the production of fibronectin by these cells. It is promising that triptolide treatment may possibly inhibit scar formation after glaucoma filtration surgery.