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Purpose: The pathophysiological mechanisms underlying migraine remain elusive, with oxidative stress hypothesized as a potential etiological factor. The Oxidative Balance Score (OBS) is a comprehensive tool for assessing the impact of diet and lifestyle on oxidative stress, thereby gauging an individual's overall antioxidant capacity. In this cross-sectional study, we explored the correlation between OBS and migraine prevalence among a cohort of US adults. Methods: We analyzed data from 6195 participants aged 20 years and above, drawn from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. We employed multiple logistic regression, coupled with sensitivity analyses, to investigate the relationship between OBS and migraine. Subsequent subgroup analyses and interaction tests were performed to assess the consistency of this association across the population. Results: Multiple logistic regression revealed an inverse relationship between OBS and the likelihood of experiencing migraines. Specifically, individuals in the highest OBS quartile exhibited a significantly reduced migraine risk compared to those in the lowest quartile (OR = 0.98, 95% Confidence Interval (CI): 0.97-0.99, P = 0.0001). Furthermore, restricted cubic spline curves indicated a non-linear association between dietary OBS and migraine incidence (non-linear P = 0.0258). Discussion: Our findings suggest that adherence to an antioxidant-rich diet may be an effective strategy for mitigating migraine, potentially by influencing oxidative balance.
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Background: Pain is a common symptom in multiple sclerosis (MS), especially neuropathic pain, which has a significant impact on patients' mental and physical health and quality of life. However, risk factors that related to neuropathic pain, still remain unclear. Objective: The study aimed to explore the risk factors of neuropathic pain among MS patients. Materials and methods: This retrospective study examined the consecutive patients diagnosed with MS in the Department of Neurology of Guangdong Provincial Hospital of Chinese Medicine between August 2011 and October 2022. Neuropathic pain was defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Demographic and clinical features were obtained from the electronic system of the hospital. Results: Our cohort revealed that the prevalence of patients with neuropathic pain in MS was 34.1%. The results indicated that the longer the spinal lesions, the greater the neuropathic pain risks (2-4: OR, 13.3(2.1-82), >5: OR, 15.2(2.7-86.8), p for tread: 0.037). Meanwhile, multivariate regression analysis showed that cervical and thoracic lesions (OR 4.276, 95% CI 1.366-13.382, P = 0.013), upper thoracic lesions (T1-T6) (OR 3.047, 95% CI 1.018-9.124, P = 0.046) were positively correlated with neuropathic pain, while basal ganglia lesions (OR 0.188, 95% CI 0.044-0.809, P = 0.025) were negatively correlated with neuropathic pain among MS patients. Conclusion: Extended spinal lesions (≥3 spinal lesions), cervical and thoracic lesions, upper thoracic lesions were independent risk factors of neuropathic pain among MS patients. Furthermore, our study found that the longer the spinal lesions, the greater the neuropathic pain risks.
Subject(s)
Multiple Sclerosis , Neuralgia , Humans , Retrospective Studies , Multiple Sclerosis/complications , Multiple Sclerosis/epidemiology , Multiple Sclerosis/pathology , Cohort Studies , Quality of Life , Neuralgia/epidemiology , Neuralgia/etiology , Risk FactorsABSTRACT
Objective: To report the case of a patient with refractory neuromyelitis optica spectrum disorder (NMOSD), who, despite showing poor response or intolerance to multiple immunosuppressants, was successfully treated with Ofatumumab. Case presentation: A 42-year-old female was diagnosed with NMOSD in the first episode of the disease. Despite treatment with intravenous methylprednisolone, immunoglobulin, rituximab and immunoadsorption, together with oral steroids, azathioprine, mycophenolate mofetil and tacrolimus, she underwent various adverse events, such as abnormal liver function, repeated infections, fever, rashes, hemorrhagic shock, etc., and experienced five relapses over the ensuing four years. Finally, clinicians decided to initiate Ofatumumab to control the disease. The patient received 9 doses of Ofatumumab over the next 10 months at customized intervals. Her symptoms were stable and there was no recurrence or any adverse events. Conclusion: Ofatumumab might serve as an effective and safe alternative for NMOSD patients who are resistant to other current immunotherapies.
Subject(s)
Neuromyelitis Optica , Humans , Female , Adult , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/drug therapy , Treatment Outcome , Immunosuppressive Agents/therapeutic use , Azathioprine/adverse effectsABSTRACT
Introduction: In this study, we aimed to investigate the association between gut microbiota and high on-treatment platelet reactivity (HTPR) in patients with acute ischemic stroke (AIS). Methods: We enrolled a total of 48 AIS patients, including 19 HTPR patients and 29 non-high on-treatment platelet reactivity (NHTPR) patients, along with 10 healthy controls. Clinical and laboratory data, as well as stool samples, were collected from all participants. The composition and function of gut microbiota were assessed using 16S rRNA sequencing. Differences in the gut microbiota between the two groups were analyzed, and a diagnostic model based on the gut microbiota was established using random forest model. Results: HTPR patients exhibited a decreased microbial richness compared to NHTPR patients. Additionally, the relative abundance of unidentified_Clostridia and Ralstonia was lower in HTPR patients. Significant differences in biological functions, such as toxoplasmosis, were observed between the two groups. The combination of Ralstonia, unidentified-Clostridia, Mailhella, Anaerofustis, and Aggregatibacter showed excellent predictive ability for HTPR occurrence (AUC=0.896). When comparing AIS patients with healthy controls, alterations in the microbiota structure were observed in AIS patients, with imbalances in short-chain fatty acid-producing bacteria and pathogenic bacteria. Significant differences in biological functions, such as oxidative phosphorylation, were noted between the two groups. The combination of Alloprevotella, Terrisporobacter, Streptococcus, Proteus, and unidentified_Bacteria exhibited strong predictive power for AIS occurrence (AUC=0.994). Conclusions: This study is the first to uncover the microbial characteristics of HTPR in AIS patients and demonstrate the predictive potential of specific bacterial combinations for HTPR occurrence.
Subject(s)
Gastrointestinal Microbiome , Ischemic Stroke , Stroke , Humans , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/therapeutic use , Clopidogrel/therapeutic use , Stroke/pathology , Ischemic Stroke/drug therapy , RNA, Ribosomal, 16S/genetics , Bacteria/geneticsABSTRACT
BACKGROUND: Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. OBJECTIVE: To investigate the risk factors of neuropathic pain in a NMOSD cohort. MATERIALS AND METHODS: Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". RESULTS: One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18-346.05], P = 0.038) and age (OR 1.35 (1-1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97-151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. CONCLUSION: Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.
Subject(s)
Neuralgia , Neuromyelitis Optica , Aquaporin 4 , Autoantibodies , Cohort Studies , Female , Humans , Immunoglobulin G , Male , Neuralgia/epidemiology , Neuromyelitis Optica/complications , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/epidemiology , Quality of Life , Retrospective Studies , Risk FactorsABSTRACT
ABSTRACT BACKGROUND: There have been inconsistent results regarding the association between alcohol intake and susceptibility to multiple sclerosis. OBJECTIVE: To assess the potential role of alcohol intake regarding the risk of multiple sclerosis by using a meta-analytic approach. DESIGN AND SETTING: Observational meta-analysis study conducted in a hospital in China. METHODS: The electronic databases of PubMed, EMBASE and the Cochrane library were systematically searched for eligible studies from their inception up to January 2020. The summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the association between alcohol intake and multiple sclerosis, using a random-effects model. RESULTS: One prospective cohort study and eight case-control studies involving a total of 211,396 subjects and 10,407 cases of multiple sclerosis were selected for the final meta-analysis. From the pooled data, no significant association between alcohol intake and multiple sclerosis risk was found (OR: 0.94; 95% CI: 0.73-1.22; P = 0.668), and this conclusion was judged to be robust. Subgroup analysis found that intake of beer was associated with an increased risk of multiple sclerosis (OR: 1.58; 95% CI: 1.12-2.23; P = 0.010). CONCLUSION: This study found that beer intake could cause an excess risk of multiple sclerosis. Further large-scale prospective studies should be conducted to verify this conclusion.
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A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.
Subject(s)
Curcumin , Emodin , Encephalomyelitis, Autoimmune, Experimental , Animals , Chromatography, High Pressure Liquid , Claudin-5/metabolism , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/genetics , Female , Interleukin-6/genetics , Interleukin-6/metabolism , Janus Kinase 2/genetics , Janus Kinase 2/metabolism , Mice , Mice, Inbred C57BL , Molecular Docking Simulation , Occludin/metabolism , Powders , RNA, Messenger , Reproducibility of Results , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction , Water/metabolismABSTRACT
BACKGROUND: There have been inconsistent results regarding the association between alcohol intake and susceptibility to multiple sclerosis. OBJECTIVE: To assess the potential role of alcohol intake regarding the risk of multiple sclerosis by using a meta-analytic approach. DESIGN AND SETTING: Observational meta-analysis study conducted in a hospital in China. METHODS: The electronic databases of PubMed, EMBASE and the Cochrane library were systematically searched for eligible studies from their inception up to January 2020. The summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the association between alcohol intake and multiple sclerosis, using a random-effects model. RESULTS: One prospective cohort study and eight case-control studies involving a total of 211,396 subjects and 10,407 cases of multiple sclerosis were selected for the final meta-analysis. From the pooled data, no significant association between alcohol intake and multiple sclerosis risk was found (OR: 0.94; 95% CI: 0.73-1.22; P = 0.668), and this conclusion was judged to be robust. Subgroup analysis found that intake of beer was associated with an increased risk of multiple sclerosis (OR: 1.58; 95% CI: 1.12-2.23; P = 0.010). CONCLUSION: This study found that beer intake could cause an excess risk of multiple sclerosis. Further large-scale prospective studies should be conducted to verify this conclusion.
Subject(s)
Multiple Sclerosis , Alcohol Drinking/adverse effects , Case-Control Studies , Humans , Multiple Sclerosis/epidemiology , Multiple Sclerosis/etiology , Observational Studies as Topic , Odds Ratio , Prospective StudiesABSTRACT
BACKGROUND: Previous studies have shown high triglyceride (TG) is associated with platelet hyperactivation in metabolic syndrome patients. However, limited information is available regarding this relationship on dual anti-platelet therapy (DAPT) in ischemic stroke (IS). In this study, we attempted to evaluate the association between TG and high on-treatment platelet reactivity (HTPR) in IS patients. METHODS: Ischemic stroke patients who received maintenance doses of clopidogrel and aspirin were categorized and analyzed retrospectively in this research. The platelet reactivity was assessed by Thromboelastography (TEG). If ADP-induced platelet inhibition rate (ADPi)<30%, it was defined as HTPR, else, it would be defined as normal on-treatment platelet reactivity (NTPR). Patients were divided into high-TG-level and lower-TG-level based on a TG level of 1.7mmol/L, the cutoff point of hypertriglyceridemia. A logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 123 patients were included in this study and 24 (19.51%) patients were identified as HTPR. HTPR was observed in 36.2% of the patients in high-TG-level (TG≥1.7mmol/L) group while only 9.2% of the patients in the low-TG-level group (TG<1.7mmol/L) were HTPR (P<0.001 ). According to multivariate analysis, TG≥1.7mmol/L was independently associated with HTPR (OR=14.715, 2.445-88.549,P=0.003). CONCLUSIONS: High TG is an independent predictor of HTPR in IS patients. For IS patients with high TG level undergoing DAPT, platelet reactivity should be monitored to identify HTPR, which may proactively help to optimize the anti-platelet therapy.
Subject(s)
Ischemic Stroke , Stroke , Blood Platelets/metabolism , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Retrospective Studies , Stroke/chemically induced , Stroke/diagnosis , Stroke/drug therapy , Treatment Outcome , TriglyceridesABSTRACT
Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K-Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.
Subject(s)
Emodin , Encephalomyelitis, Autoimmune, Experimental , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Emodin/metabolism , Emodin/pharmacology , Emodin/therapeutic use , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Inflammation/metabolism , Mice , Mice, Inbred C57BL , Microglia/metabolism , Microglia/pathology , Molecular Docking Simulation , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Spinal Cord/metabolism , Spinal Cord/pathologyABSTRACT
BACKGROUND: The association between matrix metalloproteinase 9 (MMP-9) gene -1562C/T (rs3918242) polymorphism and the susceptibility of ischemic stroke (IS) has been investigated. However, results were ambiguous and inconsistent. Therefore, we performed this study to better assess the potential relationship between rs3918242 polymorphism and susceptibility risk of IS. METHODS: We included case-control studies concerning the relationship between the rs3918242 polymorphism and IS, and odds ratios with corresponding 95% confidence intervals were used to describe the associations. Furthermore, meta-regression analyses, heterogeneity, cumulative analyses, sensitivity analyses, and publication bias were examined. RESULTS: A total of 19 studies were included for analysis. Significant associations with the risk of IS were detected for the rs3918242 polymorphism in overall population, Asians, and whites. When available data were stratified by gender, we found a significant correlation with the risk of IS in both males and females. Further subgroup analysis by the subtypes of IS showed that the rs3918242 polymorphism was significantly correlated with the risk of patients with large artery atherosclerosis. When stratified by age, we found that the rs3918242 polymorphism was significantly correlated with the risk of IS in patients both aged ≥65 years and >65 years. Both the diabetes and the nondiabetes subgroups reached significant results, and in an analysis stratified by smoking status, an increased risk of IS was associated with smoking. CONCLUSIONS: The rs3918242 polymorphism may be a susceptible predictor of susceptibility of IS. Further large-scale studies are needed to verify the results of our findings.