Awake brain mapping by direct cortical stimulation; technical note to get higher resection rate and low morbidity in low-grade glioma patients.

Introduction: Direct cortical stimulation has been used for brain mapping and localization of eloquent areas in awake patients. This simplified technique is to provide the positive areas, which can be preserved if the tumor or lesions are involved eloquent areas. Objective: The main objective of this study is to determine whether direct cortical stimulation in awake brain mapping for low-grade glioma patients increases the rate of resection or not. Method: The authors present a retrospective study between 2020 to 2022 that includes 35 cases in a single center, to get higher resection rate, and their consequences in awake craniotomy in low-grade glioma patients. Here, two neurosurgeons were involved and the minimum follow-up was 12 months. Results: The authors achieved 80% removal of tumors. To get higher resection rate we emphasized negative mapping with prior anatomical analysis to understand functional realignment. Stimulation-related complications will be thoroughly discussed with a potential future direction to minimize the issues. The authors used PROMIS score to measure patients physical and mental health status and kernofsky score to measure performance status before and after successful surgery. The authors found three cases of transient deficit in repetitive stimulation. Repeated stimulation to identify the eloquent areas with low voltage frequency is a good option. Numbness in the face related to stimulation may continue for 6 weeks. Conclusion: Functional realignment in shifted brain and edema can be seen while doing cortical and subcortical stimulation. Most of the stimulation from low to high for language mapping may vary from patient to patient. For safe removal of low-grade glioma a steep learning curve is needed to find out the negative areas, though the authors emphasize positive mapping of areas to secure the maximum eloquence.

Identification of m6A RNA methylation genes in Oryza sativa and expression profiling in response to different developmental and environmental stimuli.

Eukaryotic messenger RNAs (mRNAs) transcend their predominant function of protein encoding by incorporating auxiliary components that ultimately contribute to their processing, transportation, translation, and decay. In doing so, additional layers of modifications are incorporated in mRNAs at post-transcriptional stage. Among them, N6-methyladenosine (m6A) is the most frequently found mRNA modification that plays crucial roles in plant development and stress response. In the overall mechanism of m6A methylation, key proteins classified based on their functions such as writers, readers, and erasers dynamically add, read, and subtract methyl groups respectively to deliver relevant functions in response to external stimuli. In this study, we identified 30 m6A regulatory genes (9 writers, 5 erasers, and 16 readers) in rice that encode 53 proteins (13 writers, 7 erasers, and 33 readers) where segmental duplication was found in one writer and four reader gene pairs. Reproductive cells such as sperm, anther and panicle showed high levels of expression for most of the m6A regulatory genes. Notably, writers like OsMTA, OsMTD, and OsMTC showed varied responses in different stress and infection contexts, with initial upregulation in response to early exposure followed by downregulation later. OsALKBH9A, a noteworthy eraser, displayed varied expression in response to different stresses at different time intervals, but upregulation in certain infections. Reader genes like OsECT5, OsCPSF30-L3, and OsECT8 showed continuous upregulation in exertion of all kinds of stress relevant here. Conversely, other reader genes along with OsECT11 and OsCPSF30-L2 were observed to be consistently downregulated. The apparent correlation between the expression patterns of m6A regulatory genes and stress modulation pathways in this study underscores the need for additional research to unravel their intricate regulatory mechanisms that could ultimately contribute to the substantial development of enhanced stress tolerance in rice through mRNA modification.

Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared to MNPs, 90% of Ab-MNPs increased in size from 54.7 ± 0.5 to 71.7 ± 2.7 nm. The in vitro and in vivo studies confirmed the therapeutic material as nontoxic and biocompatible. Mice are administered various dosages of Ab-MNPs before receiving concanavalin-A (ConA), an inflammation inducer. Preadministration of Ab-MNPs, as opposed to MNPs or anti-CD3 mAb alone, significantly reduced the serum levels of interferon-γ and interleukin-6 in ConA-treated mice. Additionally, the transdermal stamp patch as an effective delivery system for Ab-MNPs is validated. This study demonstrates the utility of the Ab-MNP complex in pathologies associated with T cell-mediated hyperinflammation, such as organ transplantation and COVID-19.

Application of variation theory in STEM education: A comprehensive guideline for STEM teachers.

Incorporating appropriate pedagogical strategies has been instrumental in the development of a favorable learning environment for holistic learning, particularly in Science, Technology, Engineering, and Mathematics (STEM) education. However, there is growing evidence of the need to advance the existing methods, through more robust and comprehensive fieldwork grounded in design study. It has been shown that the lack of guidance in lesson planning using variation theory is also thought to require particular attention, as the accuracy of the student learning relies significantly on the planning of the lesson. However, little research has outlined the strategy to be followed for incorporating variation theory. This article proposes a method of preparing lesson plans to systematically implement the variation theory in STEM classrooms. The method seeks to design and implement current techniques as follows:•According to variation theory, teachers must create the necessary conditions for learning for the students to recognize what they are expected to learn.•To create the necessary conditions for learning, teachers define the key aspects of the topic to be covered and use different patterns of variations in teaching those contents, such as contrast, separation, generalization, and fusion.•Finally, teachers focus on the key aspects one by one or simultaneously to grab students' attention.

Factors affecting student readiness towards OBE implementation in engineering education: Evidence from a developing country.

Engineering universities in the South Asian region have been investigating the efficacy of Outcome-Based Education (OBE) in preparing their students to meet the demands of the Fourth Industrial Revolution (4IR). Evaluating students' motivations towards OBE is crucial for its successful implementation into engineering degree programs. This research aims to explore students' readiness towards OBE implementation at one of the prominent engineering universities in Bangladesh. To achieve this aim, an instrument was developed to comprehensively measure students' readiness towards the implementation of OBE. The survey instrument with a 7-point scale, measuring six constructs of the proposed model, such as (a) Students' awareness, (b) Teachers' commitment, (c) Institutional support, (d) Perceived easiness, (e) Students' motivation, and (f) Self-efficacy, was developed and administered to a pilot sample of sixty-eight participants (N = 68) from two engineering domains: Civil and Environmental Engineering (CEE), and Computer Science and Engineering (CSE). The final data was collected from a cohort of Three Hundred and Seventy participants (N = 370), distributed across four engineering domains. A structural equation modeling (SEM) with the help of the Smart-PLS software was conducted to determine the construct validity of the measurement model and to evaluate the model fit. Results from the analysis indicate no significant positive effect of teachers' commitment (TC) on students' readiness (SR). However, the results reveal a significant positive effect of students' awareness (SA) and perceived easiness (PE) on students' readiness (SR). Results also reveal no significant moderating role of institutional support (IS) on the relation between the exogenous variables (IS, SA, PE) and the endogenous variable (SR). The research recommends Institutional Support as essential for instructors and students to implement outcome-based education (OBE) in engineering education.

Risk perception of sun exposure and knowledge of vitamin D among the healthcare providers in a high-risk country: a cross-sectional study.

BACKGROUND: High levels of vitamin D deficiency are commonly reported even in regions with abundant sunshine. This necessitates a comprehensive understanding of the determinants that influence sun exposure practices. As the primary source of health-related knowledge for the general public, the attitude of the healthcare professionals towards sunlight and their awareness related to vitamin D deficiency can be critical in this regard. METHODS: A cross-sectional survey was conducted among 2,242 physicians, intern doctors, and senior medical students in Bangladesh from October 2019 to February 2020. A pre-tested structured questionnaire (containing twelve close-ended questions) was used. The perceptions of health risks due to sun exposure, and basic knowledge of the physiological and epidemiological aspects of vitamin D deficiency were tested. RESULTS: An overall negative attitude towards sunlight in the context of Bangladesh was highlighted - 68% participants thought regular sun exposure would be harmful or very harmful; 26% thought the level of UV radiation was very high; 44% recommended using sunscreen always; skin burns, heat stroke, and cancer were selected as potential consequences of regular sun exposure by 45%, 21%, and 30% respondents respectively. Overall knowledge regarding vitamin D deficiency appeared to be biased towards bone health; other symptoms and associated illnesses not having obvious link to Calcium-metabolism were identified much lesser frequently. Furthermore, 'sunrise to 10 am' was identified as the best time to get vitamin D by 69% participants; 60% believed < 30 min of weekly sun exposure would be sufficient for the Bangladeshi population; an only 33% identified that prevalence of vitamin D insufficiency in Bangladesh would be 50% or more. Taking vitamin D-rich food was suggested by more respondents over regular sun exposure (43% vs. 33%) as more effective remedial strategy to curb vitamin D deficiency in Bangladesh. CONCLUSION: In addition to highlighting some crucial knowledge gaps, results from this study provides a comprehensive baseline dataset for knowledge and attitude regarding the public health aspects of vitamin D deficiency among the healthcare providers in Bangladesh, which would be generalizable to other countries with similar socio-demographic context, and will facilitate taking more effective policies worldwide.

Minor red blood cell antigen phenotyping of athletes sampled in international competitions.

Blood transfusion is performed by cheating athletes to rapidly increase oxygen delivery to exercise muscles and enhance their performance. This method is banned by the World Anti-doping Agency (WADA). Heterologous or allogenic blood transfusion happens when blood from a different person is transfused. The method used to detect this type of doping is based on flow cytometry, by identifying variations in blood group minor antigens present on the red blood cells' surface. Transfusion practices have regained interest since the introduction of human recombinant erythropoietin detection method. It has been reported that the number of occurrences of two athletes sharing an identical phenotype in the same sport was five times higher than the theoretical populational probability. The present work describes the prevalence of 10 erythrocytes surface antigens in a population of 261 athletes from all five continents. The matching phenotype per sport is also described.

Flow Characteristics of the Conjugate of Anti-CD3 Monoclonal Antibodies and Magnetic Nanoparticle in PBS and Blood Vessels.

Previously, anti-CD3 antibodies delivered intravenously have been known for their negative side effects. The experimental conditions for optimal liquid production are derived from the Fc-directed conjugation of anti-CD3 foralumab antibodies and magnetic nanoparticles (Ab-MNPs). The anti-CD3 antibodies are prepared for conjugation with MNPs using SiteClick antibody labelling kits. The successful conjugation of the Ab-MNPs is confirmed using a transmission electron microscopy (TEM) image and an energy dispersive spectroscopy (EDS) analysis. The average values ​​of the moving speed of MNPs and Ab-MNPs in phosphate buffer saline (PBS) were + 3.16 pix/frame and + 6.70 pix/frame in the x-axis, respectively. This implies that MNPs with CD3 antibodies attached to the surface through biocompatible ligand functional groups has better fluidity in PBS. Afterwards, a non-clinical animal testing for the flow characteristics of Ab-MNPs inside a blood vessel is carried out to observe the effects of Ab-MNP delivery through intravenous injection.

Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice.

The experimental autoimmune encephalomyelitis mouse model is the most commonly used animal model, and it best represents multiple sclerosis. Grancalcin (GCA) was discovered to be upregulated in EAE mice. GCA comprises 220 amino acids that have been assigned the UniprotKB ID Q8VC88. It is a calcium-binding protein that helps neutrophils adhere to fibronectin and the formation of focal adhesions. However, the protein data bank does not contain the crystal structure of mouse GCA. The current study aims to analyze the structural and physicochemical properties of GCA. Mouse GCA showed a high percentage identity (87%) with the crystal structure of des (1-52) grancalcin with bound calcium (chain A) from Homo sapiens identified by its PDB id 1k94_A. Using the SWISS-MODEL server, we used 1k94_A as a template protein to model the mouse GCA protein. Compared to the template structure 1K94, three potential binding sites for calcium-binding have been proposed, ranging from 13 to 20, 80 to 91, and 109 to 120 amino acids. On an i5 personal computer with 8GB of RAM, GROMACS 2020.1 was utilized to run a 100 ns molecular dynamics (MD) simulation. RMSD, Rg, and RMSF analysis of an MD simulation trajectory indicate a stable and compact state throughout the simulation period of modeled proteins. We found that GCA is primarily alpha helical (Class 1), with eight alpha helices. The essential dynamics analysis captures PCA and SASA, culminating in the biological motions that correspond to the last 1000 frames. These findings will aid the development of potential inhibitors as well as the determination of binding pockets and residues for drug-like molecules.

Current Development and Future Perspective on Natural Jute Fibers and Their Biocomposites.

The increasing trend of the use of synthetic products may result in an increased level of pollution affecting both the environment and living organisms. Therefore, from the sustainability point of view, natural, renewable and biodegradable materials are urgently needed to replace environmentally harmful synthetic materials. Jute, one of the natural fibers, plays a vital role in developing composite materials that showed potential in a variety of applications such as household, automotive and medical appliances. This paper first reviews the characterization and performance of jute fibers. Subsequently, the main focus is shifted towards research advancements in enhancing physical, mechanical, thermal and tribological properties of the polymeric materials (i.e., synthetic or biobased and thermoplastic or thermoset plastic) reinforced with jute fibers in a variety of forms such as particle, short fiber or woven fabric. It is understood that the physio-mechanical properties of jute-polymer composites largely vary based on the fiber processing and treatment, fiber shape and/or size, fabrication processes, fiber volume fraction, layering sequence within the matrix, interaction of the fiber with the matrix and the matrix materials used. Furthermore, the emerging research on jute fiber, such as nanomaterials from jute, bioplastic packaging, heavy metal absorption, electronics, energy device or medical applications and development of jute fiber composites with 3D printing, is explored. Finally, the key challenges for jute and its derivative products in gaining commercial successes have been highlighted and potential future directions are discussed.

Natural Product-Based Potential Therapeutic Interventions of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a disease-refractive lung condition with an increased rate of mortality. The potential factors causing PF include viral infections, radiation exposure, and toxic airborne chemicals. Idiopathic PF (IPF) is related to pneumonia affecting the elderly and is characterized by recurring scar formation in the lungs. An impaired wound healing process, defined by the dysregulated aggregation of extracellular matrix components, triggers fibrotic scar formation in the lungs. The potential pathogenesis includes oxidative stress, altered cell signaling, inflammation, etc. Nintedanib and pirfenidone have been approved with a conditional endorsement for the management of IPF. In addition, natural product-based treatment strategies have shown promising results in treating PF. In this study, we reviewed the recently published literature and discussed the potential uses of natural products, classified into three types-isolated active compounds, crude extracts of plants, and traditional medicine, consisting of mixtures of different plant products-in treating PF. These natural products are promising in the treatment of PF via inhibiting inflammation, oxidative stress, and endothelial mesenchymal transition, as well as affecting TGF-ß-mediated cell signaling, etc. Based on the current review, we have revealed the signaling mechanisms of PF pathogenesis and the potential opportunities offered by natural product-based medicine in treating PF.

Effect of Rot-, Fire-, and Water-Retardant Treatments on Jute Fiber and Their Associated Thermoplastic Composites: A Study by FTIR.

Natural renewable materials can play a big role in reducing the consumption of synthetic materials for environmental sustainability. Natural fiber-reinforced composites have attracted significant research and commercial importance due to their versatile characteristics and multi-dimensional applications. As the natural materials are easily rotten, flammable, and moisture absorbent, they require additional chemical modification for use in sustainable product development. In the present research, jute fibers were treated with rot-, fire-, and water-retardant chemicals and their corresponding polymer composites were fabricated using a compression molding technique. To identify the effects of the chemical treatments on the jute fiber and their polymeric composites, a Fourier transformed infrared radiation (FTIR) study was conducted and the results were analyzed. The presence of various chemicals in the post-treated fibers and the associated composites were identified through the FTIR analysis. The varying weight percentage of the chemicals used for treating the fibers affected the physio-mechanical properties of the fiber as well as their composites. From the FTIR analysis, it was concluded that crystallinity increased with the chemical concentration of the treatment which could be contributed to the improvement in their mechanical performance. This study provides valuable information for both academia and industry on the effect of various chemical treatments of the jute fiber for improved product development.

Cold storage-mediated rearing of Trichogramma evanescens Westwood on eggs of Plodia interpunctella (Hübner) and Galleria mellonella L.

The egg parasitoid Trichogramma evanescens Westwood is considered as an efficient biological control agent for managing several lepidopteran pests and it is widely distributed throughout the world. Mass rearing protocols of parasitoids that are currently in use in biocontrol programs require a meticulous quality control plan, in order to optimize their efficacy, but also their progeny production capacity. In this paper, the effect of different factors on the quality control in mass rearing of T. evenescens, using Plodia interpunctella (Hübner) and Galleria mellonella L. as host species, were investigated. The impact of egg agewas significant in the rates of parasitism, for both host species tested. Significantly highest percent of parasitoid emergence was noticed in two day-old eggs for both host species, while one day-old eggs day exhibited the maximum emergence when both species were used togetherin the same trials. Age-dependent storage egg preservation at either 4 or 9°C significantly influenced the parasitism percentages on both species. The highest parasitism percentage was recorded in two day-old G. mellonella eggs that are kept for 15 days at 9°C while the lower in one day-old P. interpunctella eggs for 60 d storage. Moreover, the highest parasitoid mortality was recorded in T. evanescens reared either on P. interpunctella or G. mellonella at 20°C. Rearing of the parasitoid on a mixture of eggs of both host species resulted in higher parasitism, but not always in higher rates of parasitoid emergence. The results of the present work provide useful information that can be further utilized in rearing protocols of T. evanescens.

Employing metabolomic approaches to determine the influence of age on experimental autoimmune encephalomyelitis (EAE).

The immune system plays a critical role not only in homeostasis of the body but also in pathogenesis. Autoimmunity and dysregulation of the immune balance are closely related to age. To examine the influence of age on autoimmunity, the pathophysiological features of experimental autoimmune encephalomyelitis (EAE) induced at different ages were elucidated on the basis of plasma-level metabolic changes. In the present study, female 6 week-old (6 W) and 15 month-old (15 M) C57BL/6 mice were immunized for EAE induction. The plasma and tissue samples were collected to determine the phenotypic characteristics. The activity of NADPH oxidase in plasma and the IL-6 concentrations in the brain and spinal cord were higher in both EAE groups compared to those in the control groups as well as in the 15 M EAE (15 M-E) group compared to those in the 6 W EAE (6 W-E) group. The metabolomic profiles related to characteristics of EAE were characterized by the biosynthesis of unsaturated fatty acids and the metabolism of tryptophan, tyrosine and sphingolipid. The reduced availability of unsaturated fatty acids and perturbations in tryptophan metabolism were high risk factors for EAE development regardless of age. The changes in tyrosine metabolism and sphingolipid metabolites were more dramatic in the 15 M-E group. From these findings, it can be concluded that changes in unsaturated fatty acid and tryptophan metabolism contributed to the development of EAE, whereas changes in sphingolipid and tyrosine metabolism, which corresponded to age, were additional risk factors that influenced the incidence and severity of EAE.

Mating Attributes Relating to Parasitization and Productivity in Habrobracon hebetor (Hymenoptera: Braconidae) Rearing on Host Indian Meal Moth (Lepidoptera: Pyralidae).

The mating attributes in relating to parasitism and progeny production capacity of the parasitoid Habrobracon hebetor Say, using Plodia interpunctella (Hübner) as a host, were investigated in laboratory studies. The results indicated that 100% of the host larvae were parasitized by different individuals of H. hebetor females that were mated by the same male. Mating duration did not differ significantly among different successive matings with different females and had no effect on the rate of parasitism. In general, pairs that had their copulation early after emergence exhibited the maximum rate of parasitism as compared to delayed intervals. Moreover, the age of the H. hebetor females had no effect on the percentage of parasitism. The maximum parasitism percentage was recorded for the H. hebetor individuals that had been developed from the age group of the 6-d-old adults. The male: female ratios did not differ significantly among the female age groups. The percentage of parasitism clearly indicated a decrease with the increase of the male: female ratio. Overall, the results of the present work can be further utilized in mass rearing and release of H. hebetor in biological control programs in stored product protection.

Identification of Altered Metabolic Pathways during Disease Progression in EAE Mice via Metabolomics and Lipidomics.

Multiple sclerosis (MS) is a demyelination disease that causes gradual damage to neurons. Despite the necessity of appropriate treatments at each disease stage to prevent the worsening of the damage, it is still difficult to cure MS. In this study, metabolomics and lipidomics studies were performed with time-course plasma samples (early, peak, chronic phase for MS) to elucidate the mechanism during MS progression after induction of experimental autoimmune encephalomyelitis (EAE), which is the animal model for multiple sclerosis (MS). Plasma samples were analyzed using ultra-high performance liquid chromatography-orbitrap-mass spectrometry (UHPLC-Orbitrap-MS) and metabolic changes were observed using multivariate analysis. We also measured the activity of NADPH and MMP-9 to evaluate the degree of the inflammation during the disease progression. As a result, 49 metabolites, which had significant differences either at each time point or with time-course changes between control (CTL) and EAE groups, were identified. Among them, glycerophospholipids and fatty acyls were downregulated during disease progression compared with the CTL group. However, glycerolipids, taurine-conjugated bile acids (BAs), and sphingolipids exhibited the reverse pattern. These metabolic changes were accompanied by increases in oxidative stress and immune response upon observing the changes in the activities of NADPH oxidase and MMP-9. In particular, 26 metabolites showed significant differences at specific stages. The metabolite level of the plasma was significantly altered in response to the EAE pathogenesis, and these changes were related to inflammation status at each disease stage. This study can provide crucial information for reducing damage by differentiating treatment strategies according to disease progression.

Quantitative Proteome Analysis of Brain Subregions and Spinal Cord from Experimental Autoimmune Encephalomyelitis Mice by TMT-Based Mass Spectrometry.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, the aim is to build a proteome map of the biological changes that occur during MS at the major onset sites-the brain and the spinal cord. Quantitative proteome profiling is performed in five specific brain regions and the spinal cord of EAE and healthy mice with high-resolution mass spectrometry based on tandem mass tags. On average, 7400 proteins per region are quantified, with the most differentially expressed proteins in the spinal cord (1691), hippocampus (104), frontal cortex (83), cerebellum (63), brainstem (50), and caudate nucleus (41). Moreover, region-specific and commonly expressed proteins in each region are identified and bioinformatics analysis is performed. Pathway analysis reveals that protein clusters resemble their functions in disease pathogenesis (i.e., by inducing inflammatory responses, immune activation, and cell-cell adhesion). In conclusion, the study provides an understanding of the pathogenesis of MS in the EAE animal model. It is expected that the comprehensive proteome map of the brain and spinal cord can be used to identify biomarkers for the pathogenesis of MS.

Novel genes in brain tissues of EAE-induced normal and obese mice: Upregulation of metal ion-binding protein genes in obese-EAE mice.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system resulting from degeneration of the myelin sheath. This study is aimed to identify differentially expressed genes (DEGs) in the brain of EAE-induced normal diet (ND) mice and high-fat diet (HFD)-induced obese mice, and to identify novel genes responsible for elucidating the mechanism of the disease. Purified mRNA samples from the brain tissue were analyzed for gene microarray and validated by real-time RT-PCR. DEGs were identified if significant changes greater than 1.5-fold or less than 0.66-fold were observed (p<0.05). Pathway construction and functional categorization were performed using the Kyoto encyclopedia of genes and genomes pathways and gene ontology (GO) analysis. HFD-EAE mice showed more severe disease symptoms than ND-EAE mice. From GO study, fold changes of HFD-EAE to ND-EAE genes indicated that the genes were significantly associated to the pathways related with the immune response, antigen presentation, and complement activation. The genes related with metal ion-binding proteins were upregulated in HFD-EAE and ND-EAE mice. Upregulation of Cul9, Mast2, and C4b expression is significantly higher in HFD-EAE mice than ND-EAE mice. Cul9, Mast2, C4b, Psmb8, Ly86, and Ms4a6d were significantly upregulated in both ND- and HFD-EAE mice. Fcgr4, S3-12, Gca, and Zdhhc4 were upregulated only in ND-EAE, and Xlr4b was upregulated only in HFD-EAE mice. And significant upregulated genes of metal ion-binding proteins (Cul9 and Mast2) were observed in HFD-EAE mice.

A leading role for NADPH oxidase in an in-vitro study of experimental autoimmune encephalomyelitis.

Myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG35-55) is a major autoantigen inducing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis that is characterized by blood-brain barrier (BBB) disruption. Various experimental approaches have employed MOG35-55 in vivo; however, in vitro BBB models using MOG35-55 are rarely reported. We investigated MOG35-55 exposure effects with complete Freund's adjuvant (CFA) and pertussis toxin (PTX) on brain endothelial cells and elucidated the relationships among NADPH oxidase, MMP-9, ICAM-1, and VCAM-1. These 4 factors significantly increased in MOG35-55+CFA+PTX-exposed endothelial cells compared with the control cells. NADPH oxidase inhibition using apocynin reduced MMP-9 activity, ICAM-1, and VCAM-1. MMP-9 inhibitor I decreased expression of ICAM-1 and VCAM-1, and both anti-ICAM-1 and anti-VCAM-1 inhibited MMP-9 activity. Inhibitions of MMP-9, ICAM-1, and VCAM-1 did not change NADPH oxidase activity. Although inhibition of these 4 factors decreased BBB permeability in cells, inhibition of NADPH oxidase exhibited the highest decrease among these. NADPH oxidase directly influenced MMP-9, ICAM-1, and VCAM-1, but not vice versa. MMP-9 and the cell adhesion molecules reversibly affected each other. In conclusion, NADPH oxidase-derived superoxide elevated expression of MMP-9, ICAM-1, and VCAM-1, and these interactions can finally result in increases of BBB permeability in MOG35-55+CFA+PTX-exposed endothelial cells.