Background:Polysaccharides have various biological activities;the complexation of polysaccharides with trace element ions can produce synergistic effects,improving the original biological activities of sugars and trac...Background:Polysaccharides have various biological activities;the complexation of polysaccharides with trace element ions can produce synergistic effects,improving the original biological activities of sugars and trace elements.Methods:The preparation process of chitosan oligosaccharide selenium(COSSe)was optimized by the response surface method,followed by a detailed analysis of the resultant compound’s characteristics.The anti-cancer activity of COSSe was studied using the human ovarian cancer cell line SKOV3 as a cell model.Results:The prepared COSSe response surface was well predicted,indicating successful chitosan oligosaccharide binding with selenium.Response surface method analyses identified the optimal synthesis conditions for COSSe:the reaction time of 5.08 h,the reaction temperature of 71.8°C,and mass ratio(Na2SeO3:chitosan oligosaccharide)of 1.02.Under the optimal conditions,the final product,the selenium content,reached 1.302%.The results of cell experiments showed that COSSe significantly inhibited SKOV3 proliferation in a concentration-dependent manner.RNA-seq results showed that chitosan oligosaccharide and COSSe significantly modulated the expression of genes’DNA metabolic processes and cell cycle in SKOV3 cells.Gene enrichment analysis showed the inhibition of the cell cycle,and the results of flow cytometry showed that SKOV3 cells increased in the S phase and decreased in the G2/M phase,with a noted suppression in the protein expression of cyclin-dependent kinase 2(CDK2)and cyclin A1(CCNA1).Conclusion:COSSe has a stronger effect than chitosan oligosaccharide,leading to the arrest of the cell cycle in the S phase.Thus,COSSe may be an effective candidate for the treatment of ovarian cancer.展开更多
Effects of dietary supplementation of chitosan-oligosaccharides(COS)on the growth performance,immune response,stress resistance,and disease resistance of juvenile rainbow trout Oncorhynchus mykiss were studied.Four ex...Effects of dietary supplementation of chitosan-oligosaccharides(COS)on the growth performance,immune response,stress resistance,and disease resistance of juvenile rainbow trout Oncorhynchus mykiss were studied.Four experimental diets containing 0,20,40,or 60 mg/kg COS(COS0,COS20,COS40,and COS60,respectively)were fed to juvenile rainbow trout(initial weight=5.2±0.3 g)for 8 weeks.By the end of the feeding trial,representative groups of fish from each dietary treatment were challenged with stressor(30 sec air exposure)and pathogen exposure(intraperitoneal injection with Aeromonas hydrophila).Results showed that supplementation of COS in diets did not affect production performance and body composition of rainbow trout.However,fish fed the COS40 diet demonstrated improved phagocytic activities,respiratory burst activities and decreased serum cortisol level.Additionally,survival following A.hydrophila challenge was significant higher among fish fed the COS-supplemented feeds,although there was no difference based on the level of supplementation.The present study suggests that COS can be used as an immuno-stimulant in rainbow trout feeds.展开更多
This study investigated the effect of a chitosan oligosaccharide-Ca complex (COS-Ca) on the depuration of cadmium (Cd) from Chlamys ferrari. After exposure to 0.5 mg L-1 CdCl2 for 3 or 7 d, the scallops were treated b...This study investigated the effect of a chitosan oligosaccharide-Ca complex (COS-Ca) on the depuration of cadmium (Cd) from Chlamys ferrari. After exposure to 0.5 mg L-1 CdCl2 for 3 or 7 d, the scallops were treated by COS-Ca prior to determina-tion of Cd, calcium (Ca) and zinc (Zn) contents, Cd distribution in organs, malondialdehyde (MDA) content and antioxidant variables. Results showed that COS-Ca reduced Cd content in the viscera of the scallops, with highest Cd depuration rate (47%) observed on day 3. The COS-Ca concentration substantially affected Cd depuration, and the exposure to 8.75 mg L-1 COS-Ca led to significantly higher Cd depuration rate compared with those of lower COS-Ca concentrations (1.75, 3.5, 5.25, and 7.00 mg L-1). Distribution analysis of Cd in scallop organs indicated that COS-Ca significantly reduced Cd content in the kidney throughout the 5-d experiment, as well as in the gill during the early stage of Cd depuration. In addition, COS-Ca treatment decreased glutathione peroxidase (GSH-Px) activity and MDA content while increasing superoxide dismutase (SOD) and catalase (CAT) activities on different days. Our work suggested COS-Ca complex treatment as an effective method for acceleration of Cd depuration from Cd-contaminated bivalves.展开更多
The effects of five chito-oligomers, from dimer to hexamer (chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose) separated from chitosan oligosaccharides, on nuclear factor -kappaB (NF-rd3) signali...The effects of five chito-oligomers, from dimer to hexamer (chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose) separated from chitosan oligosaccharides, on nuclear factor -kappaB (NF-rd3) signaling pathway were investigated by using luciferase assay and laser scanning microscopy. The expression of NF-rd3 downstream genes (cyclin DI, TNFa and IL-6) were tested by real time PCR. We found that all five chitosan oligosaccharides increased NF-KB-dependent luciferase gene expression and NF-KB downstream genes transcription, and the most significant were chitotetraose and chitohexaose. In addition, laser scanning microscopy experiments showed that chitotetraose and chitohexaose also activated the p65 subunite of NF-kB translocating from cytoplasm to nucleus, which suggested that they were the most potent activators of NF-kB signaling pathway.展开更多
Atherosclerosis(AS)is a primary cause of morbidity and mortality all over the world.Molecular imaging techniques can enable early localization and diagnosis of atherosclerosis plaques.Recent newly developed chitooligo...Atherosclerosis(AS)is a primary cause of morbidity and mortality all over the world.Molecular imaging techniques can enable early localization and diagnosis of atherosclerosis plaques.Recent newly developed chitooligosaccharides(CSO)is considered to be capable of target mannose receptors on the surface of macrophages and to inhibit foam cell formation.Here we present a targeting magnetic resonance imaging(MRI)nanoprobe,which was successfully constructed with polyacrylic acid(PAA)modified nanometer iron oxide(Fe_(3)O_(4))as the core,and coating with CSO molecules,possessing the abilities of targeted MRI and specifically inhibition of the formation of foamy macrophages in the atherosclerotic process.The experimental results showed that the distributions of PAA-Fe_(3)O_(4) and CSO-PAA-Fe_(3)O_(4) were uniform and the corresponding sizes were about 5.93 nm and 8.15 nm,respectively.The Fourier transform infrared spectra(FTIR)testified the CSO was coupled with PAA-Fe_(3)O_(4) successfully.After coupled with CSO,the r1 of PAA-Fe_(3)O_(4) was increased from 5.317 mM s-1 to 6.147 mM s-1,indicating their potential as MRI contrast agent.Oil Red O staining and total cholesterols(TC)determination showed that CSO-PAA-Fe_(3)O_(4) could significantly inhibit the foaming process of RAW264.7 cells induced by oxidatively modified low density lipoprotein(ox-LDL).In vitro cellular MRI displayed that,compared with PAA-Fe_(3)O_(4),CSO-PAA-Fe_(3)O_(4) could lower the T1 relaxation time of RAW264.7 cells better.In summary,construction of CSO-PAA-Fe_(3)O_(4) nanoprobe in this study could realize the targeted MRI of macrophages and inhibition of ox-LDL induced macrophage foaming process.This will provide a new avenue in the diagnosis and treatment of AS.展开更多
Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein express...Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein expression profiles in sciatic nerves after injury using proteomics.A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides(COS),implying that exosomes are involved in COS-induced peripheral nerve regeneration.In fact,exosomes derived from fibroblasts(f-EXOs)treated with COS significantly promoted axon extension and regeneration.Exosomal protein identification and functional studies,revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs.Furthermore,we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons.Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension.In rats,miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury.Our data reveal the mechanism for COS in axon regeneration,that is COS induce fibroblasts to produce TFAP2C-enriched EXOs,which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1.Moreover,these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.展开更多
Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated...Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.展开更多
基金supported by Localization of oxygen radicals and enzymes in bivalve haemocytes to Jing Liu(20230058,6602423063).
文摘Background:Polysaccharides have various biological activities;the complexation of polysaccharides with trace element ions can produce synergistic effects,improving the original biological activities of sugars and trace elements.Methods:The preparation process of chitosan oligosaccharide selenium(COSSe)was optimized by the response surface method,followed by a detailed analysis of the resultant compound’s characteristics.The anti-cancer activity of COSSe was studied using the human ovarian cancer cell line SKOV3 as a cell model.Results:The prepared COSSe response surface was well predicted,indicating successful chitosan oligosaccharide binding with selenium.Response surface method analyses identified the optimal synthesis conditions for COSSe:the reaction time of 5.08 h,the reaction temperature of 71.8°C,and mass ratio(Na2SeO3:chitosan oligosaccharide)of 1.02.Under the optimal conditions,the final product,the selenium content,reached 1.302%.The results of cell experiments showed that COSSe significantly inhibited SKOV3 proliferation in a concentration-dependent manner.RNA-seq results showed that chitosan oligosaccharide and COSSe significantly modulated the expression of genes’DNA metabolic processes and cell cycle in SKOV3 cells.Gene enrichment analysis showed the inhibition of the cell cycle,and the results of flow cytometry showed that SKOV3 cells increased in the S phase and decreased in the G2/M phase,with a noted suppression in the protein expression of cyclin-dependent kinase 2(CDK2)and cyclin A1(CCNA1).Conclusion:COSSe has a stronger effect than chitosan oligosaccharide,leading to the arrest of the cell cycle in the S phase.Thus,COSSe may be an effective candidate for the treatment of ovarian cancer.
基金Financial support was provided by 11th 5-year National Key Technologies R & D Program Project No.2006BAD12B06,2006BAD12B08
文摘Effects of dietary supplementation of chitosan-oligosaccharides(COS)on the growth performance,immune response,stress resistance,and disease resistance of juvenile rainbow trout Oncorhynchus mykiss were studied.Four experimental diets containing 0,20,40,or 60 mg/kg COS(COS0,COS20,COS40,and COS60,respectively)were fed to juvenile rainbow trout(initial weight=5.2±0.3 g)for 8 weeks.By the end of the feeding trial,representative groups of fish from each dietary treatment were challenged with stressor(30 sec air exposure)and pathogen exposure(intraperitoneal injection with Aeromonas hydrophila).Results showed that supplementation of COS in diets did not affect production performance and body composition of rainbow trout.However,fish fed the COS40 diet demonstrated improved phagocytic activities,respiratory burst activities and decreased serum cortisol level.Additionally,survival following A.hydrophila challenge was significant higher among fish fed the COS-supplemented feeds,although there was no difference based on the level of supplementation.The present study suggests that COS can be used as an immuno-stimulant in rainbow trout feeds.
基金supported by grants of the National Key Technology Research and Development Program in the 11th Five-Year Plan of China (2008BAD94B\09)the National Natural Science Foundation of China (Grant No. 30972289)
文摘This study investigated the effect of a chitosan oligosaccharide-Ca complex (COS-Ca) on the depuration of cadmium (Cd) from Chlamys ferrari. After exposure to 0.5 mg L-1 CdCl2 for 3 or 7 d, the scallops were treated by COS-Ca prior to determina-tion of Cd, calcium (Ca) and zinc (Zn) contents, Cd distribution in organs, malondialdehyde (MDA) content and antioxidant variables. Results showed that COS-Ca reduced Cd content in the viscera of the scallops, with highest Cd depuration rate (47%) observed on day 3. The COS-Ca concentration substantially affected Cd depuration, and the exposure to 8.75 mg L-1 COS-Ca led to significantly higher Cd depuration rate compared with those of lower COS-Ca concentrations (1.75, 3.5, 5.25, and 7.00 mg L-1). Distribution analysis of Cd in scallop organs indicated that COS-Ca significantly reduced Cd content in the kidney throughout the 5-d experiment, as well as in the gill during the early stage of Cd depuration. In addition, COS-Ca treatment decreased glutathione peroxidase (GSH-Px) activity and MDA content while increasing superoxide dismutase (SOD) and catalase (CAT) activities on different days. Our work suggested COS-Ca complex treatment as an effective method for acceleration of Cd depuration from Cd-contaminated bivalves.
基金Funded by the State High-Technology R&D Project of China (863 Program) ( 2007AA091603)
文摘The effects of five chito-oligomers, from dimer to hexamer (chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose) separated from chitosan oligosaccharides, on nuclear factor -kappaB (NF-rd3) signaling pathway were investigated by using luciferase assay and laser scanning microscopy. The expression of NF-rd3 downstream genes (cyclin DI, TNFa and IL-6) were tested by real time PCR. We found that all five chitosan oligosaccharides increased NF-KB-dependent luciferase gene expression and NF-KB downstream genes transcription, and the most significant were chitotetraose and chitohexaose. In addition, laser scanning microscopy experiments showed that chitotetraose and chitohexaose also activated the p65 subunite of NF-kB translocating from cytoplasm to nucleus, which suggested that they were the most potent activators of NF-kB signaling pathway.
基金funded by Innovation and Entrepreneurship Training Program of College Students(201910313120H)financially supported by Outstanding Youth Project of Natural Science Foundation of Jiangsu Province(BK20170054)National Demonstration Center for Experimental Basic Medical Science Education(Xuzhou Medical University).
文摘Atherosclerosis(AS)is a primary cause of morbidity and mortality all over the world.Molecular imaging techniques can enable early localization and diagnosis of atherosclerosis plaques.Recent newly developed chitooligosaccharides(CSO)is considered to be capable of target mannose receptors on the surface of macrophages and to inhibit foam cell formation.Here we present a targeting magnetic resonance imaging(MRI)nanoprobe,which was successfully constructed with polyacrylic acid(PAA)modified nanometer iron oxide(Fe_(3)O_(4))as the core,and coating with CSO molecules,possessing the abilities of targeted MRI and specifically inhibition of the formation of foamy macrophages in the atherosclerotic process.The experimental results showed that the distributions of PAA-Fe_(3)O_(4) and CSO-PAA-Fe_(3)O_(4) were uniform and the corresponding sizes were about 5.93 nm and 8.15 nm,respectively.The Fourier transform infrared spectra(FTIR)testified the CSO was coupled with PAA-Fe_(3)O_(4) successfully.After coupled with CSO,the r1 of PAA-Fe_(3)O_(4) was increased from 5.317 mM s-1 to 6.147 mM s-1,indicating their potential as MRI contrast agent.Oil Red O staining and total cholesterols(TC)determination showed that CSO-PAA-Fe_(3)O_(4) could significantly inhibit the foaming process of RAW264.7 cells induced by oxidatively modified low density lipoprotein(ox-LDL).In vitro cellular MRI displayed that,compared with PAA-Fe_(3)O_(4),CSO-PAA-Fe_(3)O_(4) could lower the T1 relaxation time of RAW264.7 cells better.In summary,construction of CSO-PAA-Fe_(3)O_(4) nanoprobe in this study could realize the targeted MRI of macrophages and inhibition of ox-LDL induced macrophage foaming process.This will provide a new avenue in the diagnosis and treatment of AS.
基金supported by the National Natural Science Foundation of China(Nos.32230057,81970747,32271193)the National Key Research and Development Program of China(No.2017YFA0701304)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein expression profiles in sciatic nerves after injury using proteomics.A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides(COS),implying that exosomes are involved in COS-induced peripheral nerve regeneration.In fact,exosomes derived from fibroblasts(f-EXOs)treated with COS significantly promoted axon extension and regeneration.Exosomal protein identification and functional studies,revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs.Furthermore,we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons.Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension.In rats,miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury.Our data reveal the mechanism for COS in axon regeneration,that is COS induce fibroblasts to produce TFAP2C-enriched EXOs,which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1.Moreover,these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.
基金This work was supported by National Natural Science Foundation of China(31500646,81874320,and 81672585)Shandong Major Science and Technology Project(2021ZDSYS22)+2 种基金the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province(BS2015YY040)Qingdao Science and Technology Development project(15-9-1-67-JCH)Youth Research Fund of Afliated Hospital of Qingdao University(QDFYQN202101003).
文摘Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.