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Spinal cord injury (SCI) is a devastating injury that significantly impairs patients' quality of life. To date, there is no effective treatment to mitigate nerve tissue damage and restore neurological function. Neural stem cells (NSCs) derived from human embryonic stem cells (hESCs) are considered an important cell source for reconstructing damaged neural circuits and enabling axonal regeneration. Recent preclinical studies have shown that NSCs are potential therapeutic cell sources for neuroprotection and neuroregeneration in SCI animal models. NSCs can be derived from different sources and the spinal cord‐specific NSCs have a higher potential for the regeneration of SCI. However, the long‐term therapeutic efficacy of spinal cord‐specific NSCs remains unproven. Here, we generated human spinal cord NSCs (hSCNSCs) and investigated the effects of transplanted hSCNSCs on the repair of the SCI model rats for 60 days. The transplanted hSCNSCs improved BBB scores, reduced the lesion area and promoted an increase in the number of Nestin‐positive cells in the spinal cord compared to the model rats. Meanwhile, hSCNSC transplantation promoted the expression of synaptophysin, a synaptic signature protein and MBP, a protein associated with remyelination. Interestingly, BAF45D, a chromatin remodelling factor that contributes to the induction of hSCNSCs with region‐specific spinal cord identity, were increased by the hSCNSC transplantation. In addition, conditioned medium derived from the hSCNSCs also promoted regenerative repair of the injured spinal cord. These results demonstrate that hSCNSCs may play a critical role in the regenerative repair of SCI. [ABSTRACT FROM AUTHOR]

As an essential thrombolytic agent, the tissue plasminogen activator receives increasing attention due to its longer half-life, lower immunogenicity, and easier administration, which are superior to other thrombolytic agents. In this study, the isolated and purified plasminogen activator from the sandworm (Perinereis aibuhitensis) was expressed in E. coli (Escherichia coli) to investigate its potential for simplifying the development process. The sandworm plasminogen activator was previously successfully cloned and expressed in E. coli with low yield and activity in the culture supernatant. This low yield and activity prompted us to optimize its DNA sequence. Furthermore, to raise the efficiency in the separation of the target protein, the protein's solubility was enhanced by fusing it with maltose-binding protein (MBP) tags. Eventually, the fibrinolytic activity was successfully restored after digestion with tobacco etch virus (TEV) protease. This study provides an innovative method of efficiently expressing and purifying plasminogen activators from sandworm in E. coli and broadens its applications in therapeutic treatment of cardiovascular diseases, including thrombosis, stroke, and coronary atherosclerotic heart disease. [ABSTRACT FROM AUTHOR]

Abstract The mung bean peel polysaccharide (MBP) extracted by hot water was chemically modified. By changing the dosage of phosphorylation reagent and acetylation reagent, three kinds of phosphorylated MBP ( P-MBP-1, P-MBP-2, P-MBP-3 ) and acetylated MBP ( AC 0.6-MBP, AC 1-MBP, AC 1.4-MBP ) with different degrees of substitution were prepared. By measuring the sugar content and substitution degree of the modified products, it was found that the amount of reagent had a certain effect on both of them. The modified products were determined by infrared spectrum and nuclear magnetic resonance. The results showed that the chemical modification was successful. The in vitro antioxidant capacity (·OH scavenging ability, O2 −·clearing ability, reducing capacity, resistance to lipid peroxidation) of seven polysaccharide were measured, which manifested that chemical modification could enhance the antioxidant ability of MBP to varying degrees, and the DS also had a certain impact on their antioxidant activity. This promoted the development of mung bean peel polysaccharide functional products and the utilization of mung bean peel resources.

As an essential thrombolytic agent, the tissue plasminogen activator receives increasing attention due to its longer half-life, lower immunogenicity, and easier administration, which are superior to other thrombolytic agents. In this study, the isolated and purified plasminogen activator from the sandworm (Perinereis aibuhitensis) was expressed in E. coli (Escherichia coli) to investigate its potential for simplifying the development process. The sandworm plasminogen activator was previously successfully cloned and expressed in E. coli with low yield and activity in the culture supernatant. This low yield and activity prompted us to optimize its DNA sequence. Furthermore, to raise the efficiency in the separation of the target protein, the protein’s solubility was enhanced by fusing it with maltose-binding protein (MBP) tags. Eventually, the fibrinolytic activity was successfully restored after digestion with tobacco etch virus (TEV) protease. This study provides an innovative method of efficiently expressing and purifying plasminogen activators from sandworm in E. coli and broadens its applications in therapeutic treatment of cardiovascular diseases, including thrombosis, stroke, and coronary atherosclerotic heart disease.

Objective: To explore the relationship between serum C peptide (CP), myelin basic protein (MBP), monocyte chemotactic protein-1 (MCP-1) levels and disease severity and prognosis in patients with acute cerebral infarction (ACI) combine with leukoaraiosis (LA). Methods: 117 patients with ACI combine with LA admitted to Suqian Hospital of Nanjing Gulou Hospital Group from March 2021 to March 2023 were selected as observation group, patients were divided into severe group (39 cases), moderate group (40 cases), and mild group (38 cases) according to the severity of LA. 120 healthy individuals who underwent physical examinations during the same period were selected as control group. Detected serum levels of CP, MBP, and MCP-1. Follow up patients with ACI combine with LA 6 months. The influencing factors of poor prognosis in patients with ACI combined with LA were analyzed by multivariate Logistic regression. The predictive value of serum CP, MBP and MCP-1 in ACI patients with LA was analyzed by receiver operating characteristic(ROC) curve. Results: Compared with control group, observation group had higher levels of MBP and MCP-1, lower levels of CP (P<0.05). Serum CP in severe group was lower than that in mild and moderate groups, and the levels of MBP and MCP-1 were higher than those in mild and moderate groups; Serum CP in moderate group was lower than that in mild group, and the levels of MBP and MCP-1 were higher than those in mild group (all P<0.05). Compared with good prognosis group, poor prognosis group had lower CP and higher MBP and MCP-1 (P<0.05). Multivariate logistic regression analysis showed that elevated NIHSS score, MBP, and MCP-1 were independent risk factors for poor prognosis in patients with ACI combine with LA, and elevated CP was a protective factor (P<0.05). ROC analysis results showed that the area under the curve (AUC) of CP, MBP, and MCP-1 combined predicting poor prognosis in patients with ACI combine with LA was 0.916, significantly higher than CP, MBP and MCP-1 alone. Conclusion: The serum CP of patients with ACI combine with LA is lower than that in healthy group, and the serum MBP and MCP-1 levels are higher than those in healthy group, and there is a close relationship between CP, MBP, and MCP-1 and the severity of the patient's condition. The combined detection of serum CP, MBP, and MCP-1 has high predictive value for the prognosis of patients with ACI combine with LA. [ABSTRACT FROM AUTHOR]

RNA aptamersare nucleic acids that are obtained using the systematic evolution of ligands by exponential enrichment (SELEX) method. When using conventional selection methods to immobilize target proteins on matrix beads using protein tags, sequences are obtained that bind not only to the target proteins but also to the protein tags and matrix beads. In this study, we performed SELEX using β-1,3-glucan recognition protein (GRP)-tags and curdlan beads to immobilize the acute myeloid leukaemia 1 (AML1) Runt domain (RD) and analysed the enrichment of aptamers using high-throughput sequencing. Comparison of aptamer enrichment using the GRP-tag and His-tag suggested that aptamers were enriched using the GRP-tag as well as using the His-tag. Furthermore, surface plasmon resonance analysis revealed that the aptamer did not bind to the GRP-tag and that the conjugation of the GRP-tag to RD weakened the interaction between the aptamer and RD. The GRP-tag could have acted as a competitor to reduce weakly bound RNAs. Therefore, the affinity system of the GRP-tagged proteins and curdlan beads is suitable for obtaining specific aptamers using SELEX. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship study between serum myelin basic protein (MBP), lactate dehydrogenase (LDH) to albumin (ALB) ratio (LAR), ALB to globulin (GLB) ratio (AGR) and postoperative brain injury and prognosis in patients with glioma. Methods: 90 cases of patients with glioma who received surgical treatment admitted to Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2019 were retrospectively selected, and they were divided into mild brain injury group with 51 cases, moderate brain injury group with 24 cases and severe brain injury group with 15 cases according to the score of the Glasgow Coma Scale (GCS) after surgery. After 3 years of follow-up, they were divided into death group and survival group according to the prognosis. Clinical data were collected, and serum MBP, LAR and AGR before surgery were detected. Spearman correlation was used to analyze the correlation between GCS score and serum MBP, LAR and AGR in patients with glioma, and multivariate logistic regression was used to analyze the influencing factors of death in patients with glioma. Results: Serum MBP and LAR in the mild, moderate and severe brain injury groups were increased successively, while AGR was decreased successively (P< 0.05). Spearman correlation analysis showed that postoperative GCS score in patients with glioma was negatively correlated with serum MBP and LAR, and positively correlated with AGR (all P<0.05). After 3 years of follow-up, the mortality rate of 90 cases of patients with glioma was 35.56% (32/90). Multivariate logistic regression analysis showed that World Health Organization (WHO) grade III, incomplete resection range, decreased postoperative GCS score and elevated MBP and LAR were the independent risk factors for death in patients with glioma, and elevated AGR was the independent protective factor (P<0.05). Conclusion: Serum MBP, LAR and AGR in patients with glioma are closely related to postoperative brain injury and poor prognosis, which may be used as indicators to evaluate postoperative brain injury and prognosis in patients with glioma. [ABSTRACT FROM AUTHOR]

Objectives. To assess electroencephalogram coherence parameters and the levels of peripheral markers of nerve tissue damage in patients with depressive disorders. Materials and methods. The study included 30 patients with diagnoses from the mood disorders cluster: affective disorder as a single depressive episode and recurrent depressive disorder. The control group consisted of 30 healthy subjects of comparable sex and age composition. Brain bioelectrical activity was recorded and analyzed with calculation of mean intra- and interhemisphere coherence coefficients. Serum calcium-binding protein S100b, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) concentrations were determined by enzyme-linked immunosorbent assay. Results. Patients with depressive disorders showed statistically significantly lower coefficients of interhemisphere coherence in the α (p = 0.003), β (p = 0.042), and θ (p = 0.041) rhythms and intrahemisphere coherence of the α rhythm in the left (p = 0.016) and right (p = 0.026) hemispheres and β rhythm in the right hemisphere (p = 0.034), as compared with the healthy group. Higher MBP concentrations were found in the depressive disorders group than the control group (p = 0.008). Statistically significant correlations were identified between EEG coherence coefficients and serum markers in patients with depressive disorders. Conclusions. These data clearly confirm the presence of inflammatory changes in the brain in patients with depression, which is reflected in structural and functional changes. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory neurologic disease characterized by the demyelinating injury of the central nervous system (CNS). It was reported that the mutant peptide came from myelin proteolipid protein (PLP) and myelin basic protein (MBP) might play a critical role in immunotherapy function of MS. However, endogenous peptides in demyelinating brain tissue of MS and their role in the pathologic process of MS have not been revealed. Here, we performed peptidomic analysis of freshly isolated corpus callosum (CC) from the brains of CPZ-treated mice and normal diet controls of male C57BL/6 mice by LC-MS/MS. Identified a total of 217 peptides were expressed at different levels in MS mice model compared with controls. By performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we found that the precursor protein of these differently expressed peptides (DEPs) were associated with myelin sheath and oxidative phosphorylation. Our study is the first brain peptidomic of MS mice model, revealing the distinct features of DEPs in demyelination brain tissue. These DPEs may provide further insight into the pathogenesis and complexity of MS, which would facilitate the discovery of the potential novel and effective strategy for the treatment of MS. [ABSTRACT FROM AUTHOR]

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol. [ABSTRACT FROM AUTHOR]

Objective To estimate the level of myelin basic protein (MBP) and look for its validity in outcome prediction among mild-to-moderate head injury patients. Materials and Methods It was a prospective study done at the Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University from Jan 2018 to July 2019. All patients who presented to us within 48 hours of injury with mild-to-moderate head injury with apparently normal CT brain were include in the study. The serum sample were collected on the day of admission and 48 hours later, and patients were treated with standard protocols and observed 6 months postdischarge. Results Of the 32 patients enrolled, we observed mean MBP level was higher for severity of brain damage, but not associated with age, mode of injury, and radiological diagnosis. Mean MBP levels were not statistically associated with Glasgow coma scale (GCS) score at admission but was correlated to outcome with p < 0.05, with sensitivity of 50% and specificity 72%, that is, patients with good outcome have lower mean MBP levels. Conclusion MBP as per our analysis can be used as a prognostic marker in patients with head injury. It is not the absolute value rather a trend showing rise in serum MBP levels, which carries a significant value in outcome prediction.

(Macro)autophagy is a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an es-sential mechanism for oligodendrocyte maturation in vitro. Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated atg5, a core gene of the autophagic machinery, specifically in myelinating glial cells in vivo by tamoxifen administration (plp-CreERT2; atg5 f/f) and showed that myelin maintenance is perturbed, leading to PLP accumulation. Significant morphological defects in myelin membrane such as de-compaction accompanied with increased axonal degeneration are observed. As a result, the mice exhibit behavioral deficits. In summary, our data highlight that the maintenance of adult myelin homeostasis in the CNS requires the involvement of a fully functional autophagic machinery.

Multiple sclerosis (MS) is the chronic inflammatory demyelinating disease of the CNS. Relapsing–remitting MS (RRMS) is the most common type of MS. However, the mechanisms of relapse and remission in MS have not been fully understood. While SJL mice immunized with proteolipid protein (PLP) develop relapsing–remitting experimental autoimmune encephalomyelitis (RR-EAE), we have recently observed that some of these mice were resistant to the active induction of relapsing EAE after initial clinical and histological symptoms of EAE with a severity similar to the relapsing EAE mice. To clarify the mechanism of relapsing, we examined myelin morphology during PLP139–151-induced RR-EAE in the SJL mice. While RR-EAE mice showed an increased EAE severity (relapse) with CNS inflammation, demyelination with abnormal myelin morphology in the spinal cord, the resistant mice exhibited a milder EAE phenotype with diminished relapse. Compared with the RR-EAE mice, the resistant mice showed less CNS inflammation, demyelination, and abnormalities of the myelin structure. In addition, scanning electron microscopic (SEM) analysis with the osmium-maceration method displayed ultrastructural abnormalities of the myelin structure in the white matter of the RR-EAE spinal cord, but not in that of the resistant mice. While the intensity of myelin staining was reduced in the relapsing EAE spinal cord, immunohistochemistry and immunoblot analysis revealed that the 21.5 kDa isoform of degenerating myelin basic protein (MBP) was specifically induced in the relapsing EAE spinal cord. Taken together, the neuroinflammation-induced degenerating 21 kDa isoform of MBP sheds light on the development of abnormal myelin on the relapse of MS pathogenesis. [ABSTRACT FROM AUTHOR]

It was previously identified that there may be an active metabolite of bisphenol A (BPA), 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). An in vitro system was developed to detect MBP toxicity to the Michigan Cancer Foundation-7 (MCF-7) cells that had been repeatedly exposed to a low dose of the metabolite. MBP profoundly activated estrogen receptor (ER)-dependent transcription as a ligand, with an EC 50 of 2.8 nM. Women are continuously exposed to numerous estrogenic environmental chemicals; but their susceptibility to these chemicals may be significantly altered after menopause. Long-term estrogen-deprived (LTED) cells, which display ligand-independent ER activation, are a postmenopausal breast cancer model derived from MCF-7 cells. In this study, we investigated the estrogenic effects of MBP on LTED cells in a repeated exposure in vitro model. The results suggest that i) nanomolar levels of MBP reciprocally disrupt the balanced expression of ERα and ERβ proteins, leading to the dominant expression of ERβ, ii) MBP stimulates ERs-mediated transcription without acting as an ERβ ligand, and iii) MBP utilizes mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling to evoke its estrogenic action. Moreover, the repeated exposure strategy was effective for detecting low-dose estrogenic-like effects caused by MBP in LTED cells. ● A bisphenol A metabolite, MBP, activates endocrine-resistant LTED cells. ● Repeated exposure methodology enables us to detect low-dose effects of MBP. ● MBP disrupts the balanced expression of ERα/β proteins, which leads to dominant ERβ. ● MBP stimulates ERs-mediated transcription without acting as a ligand for ERβ. ● MBP utilizes both MAPK and PI3K signaling to elicit ERβ-driven estrogenic action. [ABSTRACT FROM AUTHOR]

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor expressed in epithelial cells from different tissues in which collagen binding activates pleiotropic functions. In the brain, DDR1 is mainly expressed in oligodendrocytes (OLs), the function of which is unclear. Whether collagen can activate DDR1 in OLs has not been studied. Here, we assessed the expression of DDR1 during in vitro OL differentiation, including collagen IV incubation, and the capability of collagen IV to induce DDR1 phosphorylation. Experiments were performed using two in vitro models of OL differentiation: OLs derived from adult rat neural stem cells (NSCs) and the HOG16 human oligodendroglial cell line. Immunocytofluorescence, western blotting, and ELISA were performed to analyze these questions. The differentiation of OLs from NSCs was addressed using oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP). In HOG16 OLs, collagen IV induced DDR1 phosphorylation through slow and sustained kinetics. In NSC-derived OLs, DDR1 was found in a high proportion of differentiating cells (MBP+/Olig2+), but its protein expression was decreased in later stages. The addition of collagen IV did not change the number of DDR1+/MBP+ cells but did accelerate OL branching. Here, we provide the first demonstration that collagen IV mediates the phosphorylation of DDR1 in HOG16 cells and that the in vitro co-expression of DDR1 and MBP is associated with accelerated branching during the differentiation of primary OLs. [ABSTRACT FROM AUTHOR]

Approximately 15% of multiple sclerosis (MS) patients develop a progressive form of disease from onset; this condition (primary progressive-PP) MS is difficult to diagnose and treat, and is associated with a poor prognosis. Extracellular vesicles (EVs) of brain origin isolated from blood and their protein cargoes could function as a biomarker of pathological conditions. We verified whether MBP and MOG content in oligodendrocytes-derived EVs (ODEVs) could be biomarkers of MS and could help in the differential diagnosis of clinical MS phenotypes. A total of 136 individuals (7 clinically isolated syndrome (CIS), 18 PPMS, 49 relapsing remitting (RRMS)) and 70 matched healthy controls (HC) were enrolled. ODEVs were enriched from serum by immune-capture with anti-MOG antibody; MBP and MOG protein cargoes were measured by ELISA. MBP concentration in ODEVs was significantly increased in CIS (p < 0.001), RRMS (p < 0.001) and PPMS (p < 0.001) compared to HC and was correlated with disease severity measured by EDSS and MSSS. Notably, MBP concentration in ODEVs was also significantly augmented in PPMS compared to RRMS (p = 0.004) and CIS (p = 0.03). Logistic regression and ROC analyses confirmed these results. A minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis. [ABSTRACT FROM AUTHOR]

Monobutyl phthalate (MBP) is the primary active metabolite of dibutyl phthalate (DBP), the key plasticizer component. A substantial body of evidence from studies conducted on both animals and humans indicates that MBP exposure could result in harmful impacts on toxicity pathways. In addition, it can seriously affect human and animal reproductive health. In our present study, we showed that exposure to MBP causes abnormal epigenetic modifications in porcine oocytes and failure of early embryonic development. However, glycine (Gly) can protect oocytes and early embryos from damage caused by MBP. Our study indicated a significant decrease in the percentage of porcine oocytes that reached the metaphase II (MII) phase when exposed to MBP. SET-domain-containing 2(SETD2)-mediated H3K36me3 histone methylation was detected, and the results showed that MBP significantly decreased the protein expression of H3K36me3 and SETD2. Moreover, the expression of the DNA break markers γH2AX and the mRNA expression of Asf1a, and Asf1b increased in the MBP group. The detection of DNA methylation marker proteins showed that MBP significantly increased the fluorescence intensity of 5-methylcytosine (5mC). The results from our RT-qPCR analysis demonstrated a significant decrease in the mRNA expression of the DNA methylation-related genes Dnmt1 and Dnmt3a , as well as the embryonic developmental potential-related genes Oct4 and Nanog , in porcine oocytes following exposure to MBP. Additionally, the mRNA expression of p53 significantly increased. Subsequently, the effects of MBP on early embryonic development were examined via parthenogenesis activation (PA) and in vitro fertilization (IVF). Exposure to MBP significantly impacted the development of embryos in both PA and IVF processes. The TUNEL staining data showed that MBP significantly increased embryonic apoptosis. However, Gly can ameliorate MBP-induced defects in oocyte epigenetic modifications and early embryonic development. • MBP exposure significantly compromised early embryonic evelopment in porcine. • Glycine rescues epigenetic modifications altered in porcine oocytesby MBP exposure. • Glycine mitigates the accumulation of DNA damage induced by MBPexposure in porcine oocytes. [ABSTRACT FROM AUTHOR]

In this paper, we propose and analyze an efficient maximum bound principle (MBP) preserving and mass conservative projection method for the conservative Allen–Cahn equation. The proposed projection operator can be proven contractive in the discrete L 2 norm. Discrete MBP and mass conservation are rigorously presented for a second-order exponential time differencing scheme with a central difference discretization in space. Various numerical examples are performed to verify these theoretical results and demonstrate the accuracy and robustness of the proposed scheme. [ABSTRACT FROM AUTHOR]

Background: Prenatal stress (PS) can induce depression in offspring, but the underlying mechanisms are still unknown. Objective: The aim of this work was to investigate the mechanism that underlies PS-induced depressive-like behavior in offspring. Methods: A prenatal restraint stress procedure was developed in which pregnant rats at GD14 to GD20 were placed head-first into a well-ventilated bottle three times each day and for 45 min each time. Depressive-like behavior in the male offspring was examined using the sucrose preference test (SPT) and the forced swim test (FST). The level of glutamate and the expression levels of GluN2A, p-CaMKII and myelin basic protein (MBP) in the hippocampus of PS-susceptible (PS-S) offspring were also evaluated. To clarify the mechanism by which PS leads to depression in offspring, the effects of excessive corticosterone were also investigated using an in vitro “injured neuronal” model. Results: The glutamate level in the hippocampus of PS-S male offspring was significantly elevated compared to controls. The expression levels of GluN2A and p-CaMKII were also altered. In addition, the optical density of MBP staining and the expression levels of MBP mRNA and MBP protein were decreased, demonstrating impaired myelinization in the hippocampus. Treatment of PS-S offspring with the GluN2A receptor antagonist NVP-AAM077 resulted in antidepressant-like effects in the FST, as well as rescue of the MBP and p-CaMKII abnormalities. Conclusions: These findings indicate that GluN2A is a promising target in the development of pharmacotherapies for PS-induced depression.

This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex. Moreover, Gram-negative bacterial LPS was found in aging control and AD brains, though LPS levels were much higher in AD brains. In addition, LPS co-localized with amyloid plaques, peri-vascular amyloid, neurons, and oligodendrocytes in AD brains. Based upon the postulate LPS caused oligodendrocyte injury, degraded Myelin Basic Protein (dMBP) levels were found to be much higher in AD compared to control brains. Immunofluorescence showed that the dMBP co-localized with β amyloid (Aβ) and LPS in amyloid plaques in AD brain, and dMBP and other myelin molecules were found in the walls of vesicles in periventricular White Matter (WM). These data led to the hypothesis that LPS acts on leukocyte and microglial TLR4-CD14/TLR2 receptors to produce NFkB mediated increases of cytokines which increase Aβ levels, damage oligodendrocytes and produce myelin injury found in AD brain. Since Aβ1-42 is also an agonist for TLR4 receptors, this could produce a vicious cycle that accounts for the relentless progression of AD. Thus, LPS, the TLR4 receptor complex, and Gram-negative bacteria might be treatment or prevention targets for sporadic AD.

Objective To estimate the level of myelin basic protein (MBP) and look for its validity in outcome prediction among mild-to-moderate head injury patients. Materials and Methods It was a prospective study done at the Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University from Jan 2018 to July 2019. All patients who presented to us within 48 hours of injury with mild-to-moderate head injury with apparently normal CT brain were include in the study. The serum sample were collected on the day of admission and 48 hours later, and patients were treated with standard protocols and observed 6 months postdischarge. Results Of the 32 patients enrolled, we observed mean MBP level was higher for severity of brain damage, but not associated with age, mode of injury, and radiological diagnosis. Mean MBP levels were not statistically associated with Glasgow coma scale (GCS) score at admission but was correlated to outcome with p < 0.05, with sensitivity of 50% and specificity 72%, that is, patients with good outcome have lower mean MBP levels. Conclusion MBP as per our analysis can be used as a prognostic marker in patients with head injury. It is not the absolute value rather a trend showing rise in serum MBP levels, which carries a significant value in outcome prediction. [ABSTRACT FROM AUTHOR]

Parmi les cellules immunitaires participant à la réaction allergique, les mastocytes et les éosinophiles occupent une place majeure. Cependant, ces cellules jouent aussi un rôle de premier plan dans l'immunité innée. Ici, nous proposons une courte revue des connaissances actuelles sur l'ontogénie, la physiologie et la physiopathologie de ces deux types cellulaires. Mast cells and eosinophils are prominent players of allergic reactions. However, these cells also make significant contributions to the innate immune defense. Here, we provide a concise update on the ontogeny, physiology and pathophysiology of mast cells and eosinophils. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE.

Cryptococcus gattii and its medical implications have been extensively studied. There is, however, a significant knowledge gap regarding cryptococcal survival in its environmental niche, namely woody material, which is glaring given that infection is linked to environmental populations. A gene from C. gattii (WM276), the predominant global molecular type (VGI), has been sequenced and annotated as a putative cellulase. It is therefore, of both medical and industrial intertest to delineate the structure and function of this enzyme. A homology model of the enzyme was constructed as a fusion protein to a maltose binding protein (MBP). The CGB_E4160W gene was overexpressed as an MBP fusion enzyme in Escherichia coli T7 cells and purified to homogeneity using amylose affinity chromatography. The structural and functional character of the enzyme was investigated using fluorescence spectroscopy and enzyme activity assays, respectively. The optimal enzyme pH and temperature were found to be 6.0 and 50 °C, respectively, with an optimal salt concentration of 500 mM. Secondary structure analysis using Far-UV CD reveals that the MBP fusion protein is primarily α-helical with some β-sheets. Intrinsic tryptophan fluorescence illustrates that the MBP-cellulase undergoes a conformational change in the presence of its substrate, CMC-Na+. The thermotolerant and halotolerant nature of this particular cellulase, makes it useful for industrial applications, and adds to our understanding of the pathogen's environmental physiology. • The yeast Cryptococcus gattii produces a functional cellulase. • The optimal recombinant cellulase pH and temperature were found to be 6.0 and 50 °C, respectively. • The recombinant cellulase possesses a (α/β)8 triose phosphate isomerase (TIM) barrel fold typical of other GH5 cellulases. • This recombinant cellulase provides insight into the environmental physiology of Cryptococcus gattii. [ABSTRACT FROM AUTHOR]

Myelin basic protein (MBP) is an auto-antigen able to induce intractable pain from innocuous mechanical stimulation (mechanical allodynia). The mechanisms provoking this algesic MBP activity remain obscure. Our present study demonstrates that membrane type 1 matrix metalloproteinase (MT1-MMP/MMP-14) releases the algesic MBP peptides from the damaged myelin, which then reciprocally enhance the expression of MT1-MMP in nerve to sustain a state of allodynia. Specifically, MT1-MMP expression and activity in rat sciatic nerve gradually increased starting at day 3 after chronic constriction injury (CCI). Inhibition of the MT1-MMP activity by intraneural injection of the function-blocking human DX2400 monoclonal antibody at day 3 post-CCI reduced mechanical allodynia and neuropathological signs of Wallerian degeneration, including axon demyelination, degeneration, edema and formation of myelin ovoids. Consistent with its role in allodynia, the MT1-MMP proteolysis of MBP generated the MBP69-86-containing epitope sequences in vitro. In agreement, the DX2400 therapy reduced the release of the MBP69-86 epitope in CCI nerve. Finally, intraneural injection of the algesic MBP69-86 and control MBP2-18 peptides differentially induced MT1-MMP and MMP-2 expression in the nerve. With these data we offer a novel, self-sustaining mechanism of persistent allodynia via the positive feedback loop between MT1-MMP and the algesic MBP peptides. Accordingly, short-term inhibition of MT1-MMP activity presents a feasible pharmacological approach to intervene in this molecular circuit and the development of neuropathic pain.

Prenatal alcohol exposure (PAE) is a major cause of nongenetic mental retardation and can lead to fetal alcohol syndrome (FAS), the most severe manifestation of fetal alcohol spectrum disorder (FASD). FASD infants present behavioral disabilities resulting from neurodevelopmental defects. Both grey and white matter lesions have been characterized and are associated with apoptotic death and/or ectopic migration profiles. In the last decade, it was shown that PAE impairs brain angiogenesis, and the radial organization of cortical microvessels is lost. Concurrently, several studies have reported that tangential migration of oligodendrocyte precursors (OPCs) originating from ganglionic eminences is vascular associated. Because numerous migrating oligodendrocytes enter the developing neocortex, the present study aimed to determine whether migrating OPCs interacted with radial cortical microvessels and whether alcohol-induced vascular impairments were associated with altered positioning and differentiation of cortical oligodendrocytes. Using a 3D morphometric analysis, the results revealed that in both human and mouse cortices, 15 to 40% of Olig2-positive cells were in close association with radial cortical microvessels, respectively. Despite perinatal vascular disorganization, PAE did not modify the vessel association of Olig2-positive cells but impaired their positioning between deep and superficial cortical layers. At the molecular level, PAE markedly but transiently reduced the expression of CNPase and MBP, two differentiation markers of immature and mature oligodendrocytes. In particular, PAE inverted their distribution profiles in cortical layers V and VI and reduced the thickness of the myelin sheath of efferent axons. These perinatal oligo-vascular defects were associated with motor disabilities that persisted in adults. Altogether, the present study provides the first evidence that Olig2-positive cells entering the neocortex are associated with radial microvessels. PAE disorganized the cortical microvasculature and delayed the positioning and differentiation of oligodendrocytes. Although most of these oligovascular defects occurred in perinatal life, the offspring developed long-term motor troubles. Altogether, these data suggest that alcohol-induced oligo-vascular impairments contribute to the neurodevelopmental issues described in FASD.

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

Objective: To observe the effects of core stability training combined with hyperbaric oxygen on hemorheology, brain energy metabolism, serum nerve growth factor (NGF), neuron specific enolase (NSE) and myelin basic protein (MBP) in convalescent patients with cerebral infarction. Methods: 103 convalescent patients with cerebral infarction who were treated in our hospital from March 2018 to March 2021 were selected. The patients were divided into control group and observation group by random number table method, with 51 cases and 52 cases respectively. The patients in the control group received core stability training, and the patients in the observation group received core stability training combined with hyperbaric oxygen. The curative effect, hemorheology, brain energy metabolism indexes, serum NGF, NSE, MBP levels and related scales were compared between the two groups. Results: The total clinical effective rate in the observation group was higher than that in the control group (P<0.05). After treatment, Lovett muscle strength score of upper / lower limbs increased, and National Institutes of Health Stroke Scale (NIHSS) score decreased in the two groups, and the degree of change in the observation group was greater than that in the control group(P<0.05). After treatment, the whole blood high shear viscosity, hematocrit, whole blood low shear viscosity and plasma viscosity decreased in the two groups, and the degree of change in the observation group was greater than that in the control group (P<0.05). After treatment, blood oxygen saturation increased, and fasting blood glucose and lactate levels decreased in the two groups, and the degree of change in the observation group was greater than that in the control group (P<0.05). After treatment, NGF level increased, and NSE, MBP levels decreased in the two groups, and the degree of change in the observation group was greater than that in the control group (P<0.05). Conclusion: Core stability training combined with hyperbaric oxygen in convalescent patients with cerebral infarction can promote the improvement of hemorheology and brain energy metabolism, and effectively regulate the levels of serum NGF, NSE and MBP, the curative effect is clear. [ABSTRACT FROM AUTHOR]

Mechanosensory fibers are enveloped by myelin, a unique multilamellar membrane permitting saltatory neuronal conduction. Damage to myelin is thought to contribute to severe pain evoked by innocuous tactile stimulation (i.e., mechanical allodynia). Our earlier (Liu et al., 2012) and present data demonstrate that a single injection of a myelin basic protein-derived peptide (MBP84-104) into an intact sciatic nerve produces a robust and long-lasting (>30days) mechanical allodynia in female rats. The MBP84-104 peptide represents the immunodominant epitope and requires T cells to maintain allodynia. Surprisingly, only systemic gabapentin (a ligand of voltage-gated calcium channel α2δ1), but not ketorolac (COX inhibitor), lidocaine (sodium channel blocker) or MK801 (NMDA antagonist) reverse allodynia induced by the intrasciatic MBP84-104. The genome-wide transcriptional profiling of the sciatic nerve followed by the bioinformatics analyses of the expression changes identified interleukin (IL)-6 as the major cytokine induced by MBP84-104 in both the control and athymic T cell-deficient nude rats. The intrasciatic MBP84-104 injection resulted in both unilateral allodynia and unilateral IL-6 increase the segmental spinal cord (neurons and astrocytes). An intrathecal delivery of a function-blocking IL-6 antibody reduced the allodynia in part by the transcriptional effects in large-diameter primary afferents in DRG. Our data suggest that MBP regulates IL-6 expression in the nervous system and that the spinal IL-6 activity mediates nociceptive processing stimulated by the MBP epitopes released after damage or disease of the somatosensory nervous system.

Current pharmacological therapies against demyelinating diseases are not quite satisfactory to promote remyelination. Epidermal growth factor (EGF) can expand the population of oligodendrocyte precursor cells (OPCs) that may help with the remyelination process, but its delivery into the injured tissue is still a biomedical challenge. Gold nanoparticles (GNPs) may be a useful tool for drug delivery into the brain. To evaluate remyelination in the septal nucleus, we administered intracerebral GNPs coupled with EGF (EGF–GNPs). C57BL6/J mice were demyelinated with 0.4% cuprizone (CPZ) and divided into several groups: Sham, Ctrl, GNPs, EGF, and EGF–GNPs. We evaluated the remyelination process at two time-points: 2 weeks and 3 weeks post-injection (WPI) of each treatment. We used the rotarod for evaluating motor coordination. Then, we did a Western blot analysis myelin-associated proteins: CNPase, MAG, MOG, and MBP. EGF–GNPs increase the expression of CNPase, MAG, and MOG at 2 WPI. At 3 WPI, we found that the EGF–GNPs treatment improves motor coordination and increases MAG, MOG, and MBP. EGF–GNPs enhance the expression of myelin-associated proteins and improve the motor coordination in mice. Thus, EGF-associated GNPs may be a promising pharmacological vehicle for delivering long-lasting drugs into the brain. [ABSTRACT FROM AUTHOR]

Background: Quickly changing technologies and dramatic world-wide increase in the uses of radiofrequency electromagnetic radiations (RF-EMRs) emitting cell phones represents a challenge to public health. So, the interest of studying its hazards that could affect human health has been increased. Recently, omega-3 and saffron had attracted a great attention as an antioxidant. Aim of Work: This study focused on estimation of the neuroprotective effects of omega-3 and saffron against the histological and immunohistochemical changes within the cerebellum of adult male albino rats exposed to the cell phone electromagnetic radiations. Materials and Methods: Sixty adults male albino rats were used. They were divided into six groups, group I (control group), group II (omega-3 group), group III (saffron group), group IV (cell phone-exposed group), group V (cell phone and omega-3 group) and group VI (cell phone and saffron group). The cerebellum from each animal was cut off and processed for biochemical, histological studies by hematoxylin and eosin (Hx. & E.), toluidine blue (T.B) and electron microscope examination, immunohistochemical studies by glial fibrillary acidic protein (GFAP), caspase-3, myelin basic protein (MBP) and morphometric studies were also, done. Results: Cell phone exposed group revealed disturbed cerebellar architecture. The molecular layer displayed pyknotic nuclei, perineuronal vacuolation and disruption of myelin sheath around nerve fibers. The Purkinje cells appeared with irregular heterochromatic nuclei, shrunken, and surrounded with empty neuropil. The granular layer appeared with some small, degenerated granule cells. Significant increase in GFAP, caspase-3 and significant decrease in MBP immunoreactivity were also observed. Omega-3 and saffron administrations decreased these adverse effects. Saffron showed higher protection against the histological alterations on the cerebellar cortex exposed to cell phone electromagnetic radiations (EMRs). Conclusion: Cell phone emitted EMRs induces histological and immunohistochemical changes within the cerebellar tissues of male albino rats and saffron has a better neuroprotective effect than omega 3. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major neurological disorder without FDA-approved therapies. In this study, we have examined the concept that TBI might trigger global brain proteolysis in the acute post-injury phase. Thus, we conducted a systemic proteolytic peptidomics analysis using acute cerebrospinal fluid (CSF) samples from TBI patients and normal control samples. We employed ultrafiltration-based low molecular weight (LMW; < 10 kDa) peptide enrichment, coupled with nano-reversed-phase liquid chromatography/tandem mass spectrometry analysis, followed with orthogonal quantitative immunoblotting-based protein degradation analysis. We indeed identified novel patterns of injury-dependent proteolytic peptides derived from neuronal components (pre- and post-synaptic terminal, dendrites, axons), extracellular matrix, oligodendrocytes, microglial cells, and astrocytes. Among these, post-synaptic protein neurogranin was identified for the first time converted to neurogranin peptides including neurogranin peptide (aa 16–64) that is phosphorylated at Ser-36/48 (P-NG-fragment) in acute human TBI CSF samples vs. normal control with a receiver operating characteristic area under the curve of 0.957. We also identified detailed processing of astroglia protein (vimentin) and oligodendrocyte protein (MBP and Golli-MBP) to protein breakdown products (BDPs) and/or LMW proteolytic peptides after TBI. In addition, using MS/MS selected reaction monitoring method, two C-terminally released MBP peptides TQDENPVVHFF and TQDENPVVHF were found to be elevated in acute and subacute TBI CSF samples as compared to their normal control counterparts. These findings imply that future therapeutic strategies might be placed on the suppression of brain proteolysis as a target. The endogenous proteolytic peptides discovered in human TBI biofluid could represent useful diagnostic and monitoring tools for TBI. [ABSTRACT FROM AUTHOR]

Introduction:Multiple sclerosis (MS) is the most common, chronic, inflammatory, demyelinating disease of the central nervous system. We aimed to evaluate the levels of some neurobiochemical markers in order to evaluate their predictive role in MS.Methods:Fifty-one patients with a diagnosis of MS and 37 healthy subjects were included in the study. The patients with MS were diagnosed by a skilled neurologist based on the medical history and physical examination according to revised McDonald criteria. Neuron-specific enolase (NSE) and S100B levels were measured by electrochemiluminescence immunoassay. Glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were measured by quantitive sandwich enzyme immunoassay technique with a commercially available ELISA kit.Results:There was a significant difference in NSE levels between the patient and the control groups. No significant difference was determined between the patient and the control groups in terms of S100B, MBP, and GFAP levels. S100B levels were positively correlated with Expanded Disability Status scale scores.Conclusion:Our findings indicated that NSE levels are significantly lower in MS patients. However, NSE levels should not be used alone at discriminating the disease. Multifactorial evaluation should be done during the diagnosis and follow-up of MS.

[Display omitted] • Non-peptide-guided secretion of anti-HER2 scFv was attempted in E. coli. • The MBP-fused scFv was effective for the chemical-aided extracellular secretion. • The MBP-scFv was simply purified and retained the target-binding affinity. • Enzymatic cleavage of the MBP-scFv by TEV protease yielded the isolated scFv. • Specific binding of the final scFv product to HER2 showed a Kd value of 0.2 nM. The overexpression of human epidermal growth factor receptor 2 (HER2) is recognized as a hallmark of several solid tumors, and the anti-HER2 monoclonal antibody and its engineered variants have been developed as therapeutic or diagnostic tools for HER2-overexpressing cancers. Here, we demonstrate the first example of extracellular production of an anti-HER2 single-chain variable fragment (scFv) in Escherichia coli via a non-peptide-guided secretion. The initial construct expressing an engineered green fluorescent protein-fused scFv was successful in extracellular secretion, but the expressed protein appeared to be readily truncated before the final purification. Alternatively, by adding Triton X-100 to the culture media, maltose-binding protein (MBP)-fused scFv could be secreted without significant truncation, and homogeneous purification of the intact protein was enabled. The affinity of the MBP-fused scFv to the extracellular domain of HER2 was confirmed by enzyme-linked immunosorbent assay, and the dissociation constant of the finally isolated scFv estimated by surface plasmon resonance was approximately 0.2 nM, which was superior to the other known anti-HER2 scFvs. Given that anti-HER2 scFv is an invaluable asset for developing various therapeutic or diagnostic agents for cancers, we expect that our method for the extracellular production will enable a better manufacturing process for its industrial application. [ABSTRACT FROM AUTHOR]

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats. [ABSTRACT FROM AUTHOR]

Purpose: Spinal cord injury is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss and severe functional deficits. Neurotrophic factors are potential treatment for reducing secondary damage, promoting axon growth, and are responsible for inducing myelination after injury. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In the present study, we investigated the neuroprotective effects of combined treatment with minocycline and OECs on the spinal cord injury in relation with brain-derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF) expressions after SCI. Methods: Adult female rats were used to experimental SCI by weight compression method. Rats received intraperitoneal injection of minocycline (90 mg/kg) immediately after SCI and then 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and electromyography (EMG). After five weeks, the segment of the spinal cord centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF and myelin basic protein (MBP). Results: SCI induced loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline +OECs increased the score of BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results showed NeuN expression significantly increased in minocycline + OECs group than other groups. Also electromyography amplitude in treated rats was increased compared to control group. BDNF, GDNF and MBP expressions and the number of ventral motor neurons increased further by minocycline + OECs in SCI rats. Conclusion: The present study provides the evidence that minocycline may facilitate recovery of locomotor function by OECs through increasing of BDNF and GDNF expressions following SCI. [ABSTRACT FROM AUTHOR]

The study aimed to assess the level of inflammatory biomarkers related to eosinophilia: interleukins 5 (IL-5) and 13 (IL-13), eotaxin 3, major basic protein (MBP) and transforming growth factor β1 (TGF-β1) in patients with dysphagia and Schatzki ring (SR), as well as the characteristics of this group of patients in terms of the features differentiating gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). We analyzed 42 patients with dysphagia, each of whom underwent panendoscopy with an assessment of the occurrence of SR, retrospectively assessed EoE Endoscopic Reference Score (EREFS) total, inflammatory and fibrostenotic and serum concentrations of IL-5 and 13, TGF-β1, eotaxin 3 and MBP. All of them completed a symptom and comorbid questionnaire. Patients diagnosed with SR constituted the SR group (n ​= ​8), the rest – the non-SR group. The quantification of the biomarkers was performed by enzyme immunoassay (ELISA). In the data analysis, p ​≤ ​0.05 was considered statistically significant. We demonstrated a significant increase in terms of exceeding the reference values of TGF-β1 (37.5% vs 8.8%) and MBP (75% vs 35.3%) in patients with SR compared to the non-SR group (qualitative analysis). There was also a statistically significant increase in the concentration of each of the determined biomarkers (quantitative analysis) in the SR group. The increase in TGF-β1 and MBP concentrations indicates the inflammatory and probably fibrostenotic pathogenesis of SR. Obtained results do not allow for an unequivocal classification of SR as a complication typical only for GERD or EoE. [ABSTRACT FROM AUTHOR]

Objectives: Spirituality has historically been a neglected aspect of people's lives within a healthcare context. Previous meta-analyses of the effect of Mindfulness-Based Programs (MBPs) on spirituality have been limited by the small number of includable studies that were available at the time, by not comparing MBPs to active controls, and by not investigating whether effects continue to be observed at follow-up. Therefore, the current systematic review and meta-analysis aimed to more comprehensively examine whether, and to what extent, secular MBPs increase spirituality, and to identify moderators of any observed effects. Methods: Random effects meta-analyses were conducted on 13 controlled trials of MBPs measuring spirituality that were identified by a systematic search of PsycInfo and Medline. Results: At post-intervention, MBPs increased spirituality compared to both passive and active controls (passive: g = 0.52, 95% C.I.: 0.35 to 0.68; active: g = 0.34, 95% C.I.: 0.14 to 0.54), and effects continued to be observed at follow-up (passive: g = 0.32, 95% C.I.: 0.09 to 0.55; active: g = 0.44, 95% C.I.: 0.18 to 0.71). For passive controls at post-intervention, cancer samples showed a significantly larger pooled effect than the non-cancer ones (cancer: g = 0.75, 95% C.I.: 0.52 to 0.98; non-cancer: g = 0.38, 95% C.I.: 0.20 to 0.56; χ2(1) = 6.14, p = 0.01), but moderation analysis was not possible at follow-up or for active controls. Study quality was not significantly associated with effect size. Conclusions: Secular MBPs appear to increase spirituality; these effects endure beyond the end of the MBP and they cannot wholly be attributed to non-specific therapeutic factors. Limitations are discussed. [ABSTRACT FROM AUTHOR]

Remyelination in patients with multiple sclerosis frequently fails, especially in the chronic phase of the disease promoting axonal and neuronal degeneration and progressive disease disability. Drug-based therapies able to promote endogenous remyelination capability of oligodendrocytes are thus emerging as primary approaches to multiple sclerosis. We have recently reported that the co-ultramicronized composite of palmitoylethanolamide and the flavonoid luteolin (PEALut) promotes oligodendrocyte precursor cell (OPC) maturation without affecting proliferation. Since TAM receptor signaling has been reported to be important modulator of oligodendrocyte survival, we here evaluated the eventual involvement of TAM receptors in PEALut-induced OPC maturation. The mRNAs related to TAM receptors -Tyro3, Axl, and Mertk- were all present at day 2 in vitro. However, while Tyro3 gene expression significantly increased upon cell differentiation, Axl and Mertk did not change during the first week in vitro. Tyro3 gene expression developmental pattern resembled that of MBP myelin protein. In OPCs treated with PEALut the developmental increase of Tyro3 mRNA was significantly higher as compared to vehicle while was reduced gene expression related to Axl and Mertk. Rapamycin, an inhibitor of mTOR, prevented oligodendrocyte growth differentiation and myelination. PEALut, administered to the cultures 30 min after rapamycin, prevented the alteration of mRNA basal expression of the TAM receptors as well as the expression of myelin proteins MBP and CNPase. Altogether, data obtained confirm that PEALut promotes oligodendrocyte differentiation as shown by the increase of MBP and CNPase and Tyro3 mRNAs as well as CNPase and Tyro3 immunostainings. The finding that these effects are reduced when OPCs are exposed to rapamycin suggests an involvement of mTOR signaling in PEALut effects.

The velocity of nerve conduction along vertebrate axons depends on their ensheathment with myelin. Myelin membranes comprise specialized proteins well characterized in mice. Much less is known about the protein composition of myelin in non-mammalian species. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish (Danio rerio), considering its increasing popularity as model organism for myelin biology. Combining gel-based and gel-free proteomic approaches, we identified > 1,000 proteins in purified zebrafish myelin, including all known constituents. By mass spectrometric quantification, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP), and the short-chain dehydrogenase 36K constitute 12%, 8%, and 6% of the total myelin protein, respectively. Comparison with previously established mRNA-abundance profiles shows that expression of many myelin-related transcripts coincides with the maturation of zebrafish oligodendrocytes. Zebrafish myelin comprises several proteins that are not present in mice, including 36K, CLDNK, and ZWI. However, a surprisingly large number of ortholog proteins is present in myelin of both species, indicating partial evolutionary preservation of its constituents. Yet, the relative abundance of CNS myelin proteins can differ markedly as exemplified by the complement inhibitor CD59 that constitutes 5% of the total zebrafish myelin protein but is a low-abundant myelin component in mice. Using novel transgenic reporter constructs and cryo-immuno electron microscopy, we confirm the incorporation of CD59 into myelin sheaths. These data provide the first proteome resource of zebrafish CNS myelin and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents.