Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons(MNs).Previously,studies on the involvement of glial cells in the pat...Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons(MNs).Previously,studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia.And oligodendrocytes(OLs)have only recently been highlighted.Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells(OPCs)was observed in ALS patients.The selective ablation of mutant SOD1(the dysfunctional superoxide dismutase)from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model(SOD1G37R).In this study,we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS.Particularly,we examined the insufficient local energy supply from OLs to axons,impaired differentiation from OPCs into OLs mediated by oxidative stress damage,and inflammatory injury to the OLs.Since increasing evidence depicted that ALS is not a disease limited to MNs damage,exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets.展开更多
Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospect...Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit （EICU） of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin （ALB）, prealbumin （PAB）, transferrin （TRF）, and C-reactive protein （CRP） levels were also analyzed Results： Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control （P〈0.001 for all time points）, and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score （ISS） of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill （APACHE III） at all time points. When comparing the receiver operating characteristic （ROC） curves for predicting prognosis, the area under the curve （AUC） in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score （TRISS）. Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions： There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein （APP） and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.展开更多
Recently, cognitive impairments(CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis(ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current s...Recently, cognitive impairments(CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis(ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted(bile acids) metabolite mapping between patients with CI and patients with normal cognition(CN). We found altered gut microbial communities and a lower ratio of Firmicutes/Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.展开更多
基金The current study was supported by the innovative population project of Hubei Province(Grant No.2019CFA030)the clinical research project of Bethune Charitable Foundation,China.
文摘Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons(MNs).Previously,studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia.And oligodendrocytes(OLs)have only recently been highlighted.Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells(OPCs)was observed in ALS patients.The selective ablation of mutant SOD1(the dysfunctional superoxide dismutase)from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model(SOD1G37R).In this study,we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS.Particularly,we examined the insufficient local energy supply from OLs to axons,impaired differentiation from OPCs into OLs mediated by oxidative stress damage,and inflammatory injury to the OLs.Since increasing evidence depicted that ALS is not a disease limited to MNs damage,exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets.
基金Project supported by the Zhejiang Medical and Health Research Project(No.2012KYB092)the Education Department of Zhejiang Province(No.Y201018337)the Science and Technology Department of Zhejiang Province(No.2012C33124),China
文摘Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit （EICU） of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin （ALB）, prealbumin （PAB）, transferrin （TRF）, and C-reactive protein （CRP） levels were also analyzed Results： Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control （P〈0.001 for all time points）, and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score （ISS） of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill （APACHE III） at all time points. When comparing the receiver operating characteristic （ROC） curves for predicting prognosis, the area under the curve （AUC） in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score （TRISS）. Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions： There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein （APP） and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.
基金supported by the National Key Research and Development Program of China(Grants No.2018YFE0118900 and 2021YFC2502200)the clinical research project of the Bethune Charitable Foundation。
文摘Recently, cognitive impairments(CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis(ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted(bile acids) metabolite mapping between patients with CI and patients with normal cognition(CN). We found altered gut microbial communities and a lower ratio of Firmicutes/Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.
