Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative str...Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS展开更多
Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later tr...Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.展开更多
Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes aff...Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy(DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsingremitting MS(RRMS) and healthy controls(HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase(CMS) compared with those in the acute phase(AMS). A distinctive combination of two elevated genera(Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites(four increased: GPCho(22:5/20:3),PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z));one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera(three decreased: Lysinibacillus, Parabacteroides,UBA1819;one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites(one increased: PE(P-16:0/22:6);one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.展开更多
Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multip...Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis(RRMS)and healthy controls attending the Second Hospital of Lanzhou University from January 2023to October 2024 were collected and analyzed by singlecell RNA sequencing(scRNA-seq)and flow cytometry,and T and NK cell characteristics were summarized and compared in the two groups.展开更多
Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.Th...Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.The goal of this project was to determine the birefringence of the pRNFL by measuring the fiber birefringence using polarization sensitive optical coherence tomography(PS-OCT).Methods:Sixty-six MS patients without history of optic neuritis(age:39.9±11.0 yrs.old,53 females and 13 males)and 66 age-and gender-matched normal controls(age:40.7±11.4 yrs.old)were recruited.Custom built PS-OCT was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)and pRNFL thickness in each quadrant of the pRNFL.In addition,clinical manifestation was used to correlate with the pRNFL birefringence.Results:The pRNFL was thinner in the temporal and inferior quadrants in MS patients compared with normal controls(P<0.05).The PR/UD of the pRNFL was significantly decreased in MS patients(P<0.05)in all quadrants except for the nasal quadrant.In both groups,the PR/UD from all four quadrants was not related to the averaged pRNFL thickness(P>0.05).In MS patients,the PR/UD was not related to the expanded disability status scale(EDSS)nor disease duration(r ranged from−0.17 to 0.02,P>0.05).Conclusion:This is the first study using PS-OCT to study the pRNFL birefringence in MS patients.Decreased birefringence of the pRNFL may indicate microtubule abnormality,and could be a potential biomarker for detecting early neurodegeneration in MS.展开更多
文摘Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS
文摘Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.
基金supported by the National Science Foundation of China (81701191, 82301720)Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0973, CSTB2023NSCQMSX0183, CSTB2023NSCQ-BHX0214)+5 种基金China Postdoctoral Science Foundation (2022M722384, 2023MD734128)the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2020FYYX104)Chongqing Postdoctoral Special Support Foundation (2023CQBSHTB2010)Chongqing Postdoctoral Science Foundation (CSTB2023NSCQ-BHX0214)the First Affiliated Hospital of Chongqing Medical University Postdoctoral Science Foundation (CYYY-BSHPYXM-202310)CQMU Program for Youth Innovation in Future Medicine (W0168)。
文摘Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy(DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsingremitting MS(RRMS) and healthy controls(HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase(CMS) compared with those in the acute phase(AMS). A distinctive combination of two elevated genera(Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites(four increased: GPCho(22:5/20:3),PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z));one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera(three decreased: Lysinibacillus, Parabacteroides,UBA1819;one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites(one increased: PE(P-16:0/22:6);one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.
文摘Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis(RRMS)and healthy controls attending the Second Hospital of Lanzhou University from January 2023to October 2024 were collected and analyzed by singlecell RNA sequencing(scRNA-seq)and flow cytometry,and T and NK cell characteristics were summarized and compared in the two groups.
基金Supported by the National Multiple Sclerosis Society,NIH Center Grant P30 EY014801a grant from Research to Prevent Blindness(RPB).
文摘Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.The goal of this project was to determine the birefringence of the pRNFL by measuring the fiber birefringence using polarization sensitive optical coherence tomography(PS-OCT).Methods:Sixty-six MS patients without history of optic neuritis(age:39.9±11.0 yrs.old,53 females and 13 males)and 66 age-and gender-matched normal controls(age:40.7±11.4 yrs.old)were recruited.Custom built PS-OCT was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)and pRNFL thickness in each quadrant of the pRNFL.In addition,clinical manifestation was used to correlate with the pRNFL birefringence.Results:The pRNFL was thinner in the temporal and inferior quadrants in MS patients compared with normal controls(P<0.05).The PR/UD of the pRNFL was significantly decreased in MS patients(P<0.05)in all quadrants except for the nasal quadrant.In both groups,the PR/UD from all four quadrants was not related to the averaged pRNFL thickness(P>0.05).In MS patients,the PR/UD was not related to the expanded disability status scale(EDSS)nor disease duration(r ranged from−0.17 to 0.02,P>0.05).Conclusion:This is the first study using PS-OCT to study the pRNFL birefringence in MS patients.Decreased birefringence of the pRNFL may indicate microtubule abnormality,and could be a potential biomarker for detecting early neurodegeneration in MS.
