UV-Vis spectrum and the third-order nonlinear optical properties of the chiral camphor-derived β-diketonate have been studied at the B3LYP/6-31G＊ level. The results showed that the introduction of electron-drawing g...UV-Vis spectrum and the third-order nonlinear optical properties of the chiral camphor-derived β-diketonate have been studied at the B3LYP/6-31G＊ level. The results showed that the introduction of electron-drawing group -CF3 and -C3F7 on β-diketonate made the strongest absorption peak red-shift and the lowest energy absorption blue-shied. Introduction of -OC2H5 on the benzene or pyridine ring made the lowest energy absorption blue-shift. When the -C2H3 was introduced on the benzene or pyridine ring, the lowest energy absorption was red-shifted. Introduction of electron-donating group on β-diketonate can enlarge their nonlinear optical properties. On the contrary, the introduction of electron-drawing group dropped it down.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.Th...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.展开更多
BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an e...BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
基金supported by the National Natural Science Foundation of China(21172161)
文摘UV-Vis spectrum and the third-order nonlinear optical properties of the chiral camphor-derived β-diketonate have been studied at the B3LYP/6-31G＊ level. The results showed that the introduction of electron-drawing group -CF3 and -C3F7 on β-diketonate made the strongest absorption peak red-shift and the lowest energy absorption blue-shied. Introduction of -OC2H5 on the benzene or pyridine ring made the lowest energy absorption blue-shift. When the -C2H3 was introduced on the benzene or pyridine ring, the lowest energy absorption was red-shifted. Introduction of electron-donating group on β-diketonate can enlarge their nonlinear optical properties. On the contrary, the introduction of electron-drawing group dropped it down.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.
文摘BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.
基金the National Natural Science Foundation of China(5117214451372153)+2 种基金Science Technology Foundation of shanghai(12410710300)Leading Academic Discipline Project of Shanghai Municipal Education Commission(J51503)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning
