CRMP2 modulates mossy fiber sprouting in dentate gyrus of pilocarpine induced rat model of epilepsy.

As a hallmark of epilepsy, mossy fiber sprouting was regarded as an ideal mode to study neural rewiring upon injury. The process of mossy fiber sprouting constitutes key steps for neural circuit formation, including axon collateral formation and outgrowth, reversed pathfinding and synapse connection. The canonical function of CRMP2 is to promote neurite/axon outgrowth via binding to tubulin heterodimers, which is mainly regulated by its phosphorylation state. CRMP2 expression and phosphorylation were reported to change in medial temporal epilepsy patients and animal modes of epilepsy. As a novel anti-epilepsy drug, Lacosamide is able to impair CRMP2 mediated tubulin polymerization. Previous studies suggested possible roles of CRMP2 in mossy fiber sprouting. Here, we provide direct evidence to support the role of CRMP2 in the process of mossy fiber sprouting in an animal model of epilepsy. We found that CRMP2 phosphorylation was downregulated specifically in the hippocampus during latent phase of epileptic rats. In addition, with the reduction of CRMP2 expression levels in dentate gyrus by CRMP2 shRNA, we observed decreased mossy fiber sprouting in these CRMP2 knockdown rats. Our results demonstrated that CRMP2 modulates mossy fiber sprouting in dentate gyrus of pilocarpine induced rat model of epilepsy.

Gold-Nanobipyramid-Based Nanotheranostics for Dual-Modality Imaging-Guided Phototherapy.

Multimodality imaging-guided therapy can improve the diagnostics and therapeutics efficiency of cancer. Herein, we developed a light-responsive nanotheranostic agent based on the indocyanine green (ICG) conjugated mesoporous silica coated gold nanobipyramid (GNB@SiO2) (denoted as GNB@SiO2-ICG) for simultaneous fluorescence (FL)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). The GNB@SiO2 with excellent photostability was used for PA imaging as well as PTT. The loaded ICG promised FL imaging and PTT. The feasibility of the cancer theranostic capability of GNB@SiO2-ICG was evaluated from cancer cells to mice. Under the guidance of FL/PA imaging, GNB@SiO2-ICG exhibited remarkably enhanced therapeutic efficacy, which could eliminate the tumor tissues completely without tumor recurrence. This well-defined nanotheranostic nanoplatform that intelligently integrates dual-modality imaging and phototherapy provides an efficient nanoplatform for cancer nanotheranostics.

Beneficial effect of atorvastatin-modified dendritic cells pulsed with myelin oligodendrocyte glycoprotein autoantigen on experimental autoimmune encephalomyelitis.

It is well known that dendritic cells play a key role in producing antigen-specific responses. Inversely, tolerogenic dendritic cells (TolDCs), a specialized subset, induce immune tolerance and negatively regulate autoimmune responses. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the mevalonate pathway for cholesterol biosynthesis, might be a promising inductive agent for inducing TolDCs. This study aimed to investigate the effectiveness of TolDCs induced by atorvastatin pulsed with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) in experimental autoimmune encephalomyelitis mice established by MOG35-55 immunization and to investigate the potential effects on Th17/Treg balance in the murine model of multiple sclerosis. Our results showed that atorvastatin-treated dendritic cells maintained a steady semimature phenotype with a low level of costimulatory molecules and proinflammatory cytokines. Upon an intraperitoneal injection into experimental autoimmune encephalomyelitis mice, TolDCs pulsed with MOG (TolDCs-MOG) significantly alleviated disease activity and regulated Th17/Treg balance with a marked decrease in Th17 cells and an obvious increase in regulatory T cells. Taken together, TolDCs-MOG modified by atorvastatin showed a characteristic tolerogenic phenotype and the antigen-specific TolDCs might represent a new promising strategy for the future treatments for multiple sclerosis.

Low serum levels of uric acid and albumin in patients with Guillain-Barre syndrome.

Free radical toxicity due to poorly maintained cellular redox levels is crucial events that have been associated with the pathogenesis of Guillain-Barre syndrome (GBS) patients. Uric acid (UA) and albumin correlate with oxidative stress in some degree. We aimed to evaluate the relationship between GBS and serum levels of UA and albumin in the present study.The serum levels of UA and albumin were determined in 203 individuals including 88 patients with GBS and 153 healthy controls (HC).We found that serum levels of UA and albumin in patients with GBS were significantly lower than those in HC group. Besides, similar phenomenon was observed when the male and female subgroups were estimated, respectively. Additionally, we found that there is no statistic difference among subgroups of GBS regarding UA and albumin. The univariate analysis revealed that both the high UA and high albumin were protective factors for patients with GBS (odds ratio [OR] 0.140; 95% confidence interval [CI]: 0.074-0.264; P < .001 and OR 0.016; 95% CI: 0.006-0.038; P < .001, respectively). It was further confirmed by the multivariable logistic regression analysis after adjusting for other potential confounding factors (OR 0.168; 95% CI: 0.055-0.514; P = .002 and OR 0.027; 95% CI: 0.011-0.071; P < .001, respectively).In conclusion, we found that patients with GBS had significantly low serum UA and albumin levels. Moreover, we demonstrated that both the high UA and high albumin were protective factors for patients with GBS.

Therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) mice.

This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels. Transplantation of hADSCs significantly alleviated the body weight loss and neurological function impairment of EAE mice. Inflammatory cell infiltration and demyelination were significantly increased, which were relieved by hADSC transplantation. Moreover, the Th17 cells and the ROR-γt mRNA level were significantly elevated, while the Treg cells and the Foxp3 mRNA level were significantly declined, resulting in significantly increased Th17/Treg ratio. This was reversed by the transplantation of hADSCs. Furthermore, serum levels of IL-17A, IL-6, IL-23, and TGF-ß, were significantly increased, which could be influenced by the hADSC transplantation. Transplantation of hADSCs alleviates the neurological function impairment and histological changes, and reduces the inflammatory cell infiltration and demyelination in EAE mice, which might be associated with the regulation of Th17/Treg balance.

Thyroid hormone level is associated with the frequency and severity of acute transverse myelitis.

Acute transverse myelitis (ATM) is a progressive and autoimmune disease with inflammatory cell infiltrates into the spinal cord, and thyroid hormone (TH) level is associated with the oxidative and antioxidant status. Variations in oxidative stress and antioxidant levels are related to the pathogenesis of autoimmune and inflammatory diseases. Our study aimed to investigate the possible correlation between ATM and TH levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and FT4/FT3. We measured serum concentrations of TSH, FT4, and FT3 in 205 individuals, including 42 ATM patients, 49 multiple sclerosis patients, and 114 healthy controls. Our findings show that ATM patients had lower levels of TSH and FT3 and higher levels of FT4 and FT4/FT3 compared with healthy controls, whether male or female. Moreover, levels of TSH and FT3 in patients with ATM were inversely correlated with disease severity measured by the Expanded Disability Status Scale. Variations in TH level may represent the oxidative status and are surrogate biomarkers of the incidence and severity of ATM.

Thyroid hormone level is associated with the frequency and severity of Guillain-Barré syndrome.

OBJECTIVE: Guillain-Barré syndrome (GBS) is a neurodegenerative and inflammatory demyelination disorder, and oxidative stress is concerned with the pathogenesis of the disease. Also, we found that thyroid hormone level is correlated to the oxidative and antioxidant status in previous studies. Our study was aimed to find the possible relationship between the frequency and severity of GBS and thyroid hormone levels. MATERIALS AND METHODS: We measured serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in 238 individuals, including 90 GBS, 44 multiple sclerosis and 104 healthy controls. RESULTS: Our findings demonstrate that the patients with GBS had lower TSH and higher FT4, FT4/FT3 than healthy controls in the normal range. Furthermore, it was also shown in our study that TSH levels in patients with GBS were correlated with disease severity measured by the Hughes Functional Grading Scale. CONCLUSION: Lower TSH, higher FT4 and FT4/FT3 stand for the oxidative status and are associated with the incidence and severity of GBS.

Antioxidant status of serum bilirubin and uric acid in patients with polymyositis and dermatomyositis.

OBJECTIVE: Oxidative stress and variations in antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells infiltrating into skeletal muscles, and the antioxidant status is still controversial. The aim of our study was to investigate the correlation between PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and uric acid (UA). MATERIALS AND METHODS: We measured serum concentrations of bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110 PM/DM patients and 274 healthy controls. RESULTS: We found that PM/DM patients had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and uric acid than healthy controls, whether male or female. Also, after separately adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all relevant factors for PM/DM. Moreover, there were no significant differences in serum antioxidant molecule levels between PM and DM subgroups. CONCLUSION: Our study demonstrated the low serum levels of bilirubin and uric acid in patients with PM/DM. This suggested low antioxidant status in PM/DM patients with excessive oxidative stress.

Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for 90-Day Outcomes in Ischemic Stroke Patients with Intravenous Thrombolysis.

BACKGROUND: This study is aimed to investigate the relationship between platelet-to-white blood cell ratio (PWR) and 90-day outcomes in acute stroke patients with intravenous thrombolysis (IVT). MATERIALS AND METHODS: A retrospective analysis was performed on 168 patients receiving IVT for acute ischemic stroke. Complete blood count evaluation was conducted at admission before IVT. A modified Rankin Scale (mRS) score of 3-6 at 90 days was considered an unfavorable outcome. RESULTS: A total of 168 patients were included from 2013 to 2015. The mean age of the sample was 64.6 (±12.3) years, and 23.2% were women. The median baseline National Institutes of Health Stroke Scale score was 7.5 (interquartile range [IQR] 8.0) and the 90-day mRS score was 2 (IQR 2). In our multivariate logistic regression model, a PWR greater than 23.52 (odds ratio .454, 95% confidence interval: .212-.973, P < .050) was a predictor of 90-day outcomes. In addition, there was a significant difference in the PWR values of patients between favorable outcome and unfavorable outcome in the large-artery atherosclerosis subtype (28.241 ± 11.581 and 21.899 ± 9.107, respectively; P = .005). CONCLUSIONS: The PWR at admission predicts 90-day outcomes in ischemic stroke patients with IVT. With the easy and routine use of hemogram analysis, the PWR should be investigated in further prospective randomized controlled trials of acute stroke.

Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis.

OBJECTIVE: Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine. MATERIALS AND METHODS: We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls. RESULTS: We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America. CONCLUSION: Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.