Neuroprotective effects of exosomes derived from bone marrow mesenchymal stem cells treated by Musk Ketone on ischemic stroke.

OBJECTIVES: Ischemic stroke (IS) is a leading cause of morbidity and mortality globally. This study aimed to investigate the role of exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) treated with Musk Ketone (Mus treated-Exo) in the development of IS injury. METHODS: BMSCs were pretreated with 10 µM Mus for 36 h, and Exo derived from these Mus-treated BMSCs (Mus-treated Exo) were extracted. Rats with middle cerebral artery occlusion (MCAO) were administered either 2 mg/kg of control Exo (Ctrl-Exo), 2 mg/kg of Mus treated-Exo, or 10 µM Mus. Neurological deficit and cerebral infarction in the MCAO rats were assessed utilizing neurological scores and TTC staining. Neuronal apoptosis, activation of microglia/macrophages, and inflammation were evaluated through TUNEL staining, immunofluorescence staining, and western blot analysis, respectively. RESULTS: Our findings revealed that Mus-treated Exo possessed a more pronounced neuroprotective effect on MCAO rats when compared to Ctrl-Exo and Mus treatment alone. Specifically, Mus treated-Exo effectively ameliorated neurological function, reduced the volume of cerebral infarction, and diminished hemispheric swelling in MCAO rats. Moreover, it inhibited neuronal apoptosis and activation of microglia/macrophages, promoted the expression of the anti-apoptotic protein Bcl-2 while decreasing the expression of pro-apoptotic protein Bax, Cleaved-caspase 3, and pro-inflammatory factors IL-6 and COX-2. CONCLUSIONS: The findings imply that Mus treated-Exo could confer neuroprotection in rats affected by IS, potentially by attenuating apoptosis and neuroinflammation. The underlying mechanisms, however, warrant further investigation. Mus treated-Exo shows potential as a new therapeutic strategy for IS.

Ostomy Information on the Internet-Is It Good Enough?

PURPOSE: The aim of this study was to determine which internet search engines and keywords patients with ostomies utilize, to identify the common websites using these terms, to determine what aspects of information they wanted, and to perform a quality and readability assessment for these websites. DESIGN: A cross-sectional survey of persons with ostomies to identify search engines and terms, followed by a structured assessment of the quality and readability of the identified web pages. SUBJECT AND SETTINGS: The sample comprised 20 hospitalized patients with ostomies cared for on a colorectal surgical ward of a tertiary care hospital located in Melbourne, Australia. There were 15 (75%) adult males and 5 (25%) adult females; their mean age was 52.2 years. Participants were surveyed between August and December 2020. METHODS: Patients with newly formed ostomies were surveyed about which search engines and keywords they would use to look for information and for which questions regarding ostomies they wanted answers. In addition, 2 researchers then performed independent searches using the search terms identified by patient participants. These searches were conducted in August 2021, with the geographical location set to Australia. The quality of the websites was graded using the DISCERN, Ensuring Quality Information for Patients, and Quality Evaluation Scoring Tool scoring assessments, and their readability was graded using the Flesch Reading Ease Score tool. RESULTS: Participants used Google as their primary search engine. Four keywords/phrases were identified: stoma for bowel surgery, ileostomy, colostomy, and caring for stoma. Multiple web pages were identified, 8 (21%) originated from Australia, 7 (18%) were from the United Kingdom, and 23 (61%) were from the United States. Most web pages lacked recent updates; only 18% had been undated within the last 12 months. The overall quality of the online information on ostomies was moderate with an average level of readability, deemed suitable for patient educational purposes. CONCLUSIONS: Information for persons living with an ostomy can be obtained from multiple web pages, and many sites have reasonable quality and are written at a suitable level. Unfortunately, these websites are rarely up-to-date and may contain advice that may not be applicable to individual patients.

Gene transcriptional expression of cortical thinning during childhood and adolescence.

The cognitive and behavioral development of children and adolescents is closely related to the maturation of brain morphology. Although the trajectory of brain development has been depicted in detail, the underlying biological mechanism of normal cortical morphological development in childhood and adolescence remains unclear. By combining the Allen Human Brain Atlas dataset with two single-site magnetic resonance imaging data including 427 and 733 subjects from China and the United States, respectively, we performed partial least squares regression and enrichment analysis to explore the relationship between the gene transcriptional expression and the development of cortical thickness in childhood and adolescence. We found that the spatial model of normal cortical thinning during childhood and adolescence is associated with genes expressed predominantly in astrocytes, microglia, excitatory and inhibitory neurons. Top cortical development-related genes are enriched for energy-related and DNA-related terms and are associated with psychological and cognitive disorders. Interestingly, there is a great deal of similarity between the findings derived from the two single-site datasets. This fills the gap between early cortical development and transcriptomes, which promotes an integrative understanding of the potential biological neural mechanisms.

Effects of a low glycemic index or low glycemic load diet on pregnant women at high risk of gestational diabetes: A meta-analysis of randomized controlled trials.

AIMS: To evaluate the effect of low glycemic index or low glycemic load diets on maternal and neonatal outcomes at high risk of gestational diabetes mellitus (GDM). DATA SYNTHESIS: Several databases (PubMed, Cochrane Library, Web of Science, Embase, OVID, Clinical Trials. gov, China National Knowledge Infrastructure, China Biomedical Database, and Wanfang Database) were searched from January 1990 to January 2022 (updated to November 2022). Randomized controlled trials of low glycemic index diets interventions for women at high risk of GDM were included. From 2131 articles initially were screened, after eliminating duplicates, 1749 titles and abstracts were analyzed. 71 documents that met the inclusion criteria were selected and 3 documents were obtained through searching the reference lists. After reading the full text, 10 studies were retained. Two authors evaluated the studies, extracted data and conducted quality assessment independently. A total of 10 studies with 2304 patients met the inclusion criteria. Compared with the control group, a low glycemic index diet could control the range of weight gain (WMD -1.01, 95% CI -1.41 to -0.61), decrease the incidence of excessive weight gain (OR 0.69, 95% CI 0.54-0.87), lessen the incidence of large-for-gestational-age infants (OR 0.32, 95% CI 0.16-0.62) and reduce the incidence of preterm infants (OR 0.45, 95% CI 0.29-0.71). CONCLUSION: A low glycemic index or low glycemic load diet could control maternal weight gain, reduce the incidence of excessive weight gain, and decrease the incidence of large-for-gestational-age infants and preterm infants in group with high risk of GDM. PROSPERO: CRD42022322697.

Cortical thickness distinguishes between major depression and schizophrenia in adolescents.

BACKGROUND: Early diagnosis of adolescent psychiatric disorder is crucial for early intervention. However, there is extensive comorbidity between affective and psychotic disorders, which increases the difficulty of precise diagnoses among adolescents. METHODS: We obtained structural magnetic resonance imaging scans from 150 adolescents, including 67 and 47 patients with major depressive disorder (MDD) and schizophrenia (SCZ), as well as 34 healthy controls (HC) to explore whether psychiatric disorders could be identified using a machine learning technique. Specifically, we used the support vector machine and the leave-one-out cross-validation method to distinguish among adolescents with MDD and SCZ and healthy controls. RESULTS: We found that cortical thickness was a classification feature of a) MDD and HC with 79.21% accuracy where the temporal pole had the highest weight; b) SCZ and HC with 69.88% accuracy where the left superior temporal sulcus had the highest weight. Notably, adolescents with MDD and SCZ could be classified with 62.93% accuracy where the right pars triangularis had the highest weight. CONCLUSIONS: Our findings suggest that cortical thickness may be a critical biological feature in the diagnosis of adolescent psychiatric disorders. These findings might be helpful to establish an early prediction model for adolescents to better diagnose psychiatric disorders.

Silencing of PTGS2 exerts promoting effects on angiogenesis endothelial progenitor cells in mice with ischemic stroke via repression of the NF-κB signaling pathway.

The objective of the current study is to investigate the effect of PTGS2 on proliferation, migration, angiogenesis and apoptosis of endothelial progenitor cells (EPCs) in mice with ischemic stroke through the NF-κB signaling pathway. Middle cerebral artery occlusion (MCAO) model was established in mice. EPCs were identified, in which ectopic expression and depletion experiments were conducted. The mRNA and protein expression of related factors in tissues and cells were measured. Besides, proliferation, migration, angiogenesis, and apoptosis, as well as cell cycle distribution, of cells were determined. MCAO mice showed overexpression of interleukin-6 (IL-6), IL-17, and IL-23, and increased positive protein expression of PTGS2, as well as expression of PTGS2, nuclear factor-κB (NF-κB), tumor suppressor region 1 (TSP-1) and Bcl-2-associated X protein (Bax), but underexpression of vascular endothelial growth factor (VEGF), S-phase kinase associated protein 2 (Skp2), and B-cell lymphoma 2 (Bcl-2). Moreover, ectopic expression of tumor necrosis factor-α significantly elevated the expression of PTGS2, NF-κB, TSP-1, and Bax, as well as cell apoptosis and cell cycle arrest, but decreased the expression of VEGF, Skp2, and Bcl-2, as well as proliferation, migration and angiogenesis of EPCs, and the PTGS2-siRNA group showed an opposite trend. Taken together, we conclude that the specific knockdown of PTGS2 expression could repress the NF-κB signaling pathway, thereby inhibits apoptosis and promotes proliferation, migration and angiogenesis of EPCs, providing protective effect on mice with ischemic stroke.

Interleukin-6 is correlated with amygdala volume and depression severity in adolescents and young adults with first-episode major depressive disorder.

Inflammatory mechanisms may play crucial roles in the pathophysiology of major depressive disorder (MDD), and cytokine concentrations are correlated with brain alterations. Adolescents and young adults with MDD have higher recurrence and suicide rates than adults, but there has been limited research on the underlying mechanisms. In this study, we aimed to investigate the potential correlations among cytokines, depression severity, and the volumes of the amygdala, hippocampus, and nucleus accumbens in Han Chinese adolescents and young adults with first-episode MDD. Nineteen patients with MDD aged 10-21 years were enrolled from the Psychiatry Department of the First Affiliated Hospital of Chongqing Medical University, along with 18 age-matched healthy controls from a local school. We measured the concentrations of interleukin (IL)-4, IL-6, IL-8, and IL-10 in the peripheral blood, along with the volumes of the amygdala, hippocampus, and nucleus accumbens, as determined by magnetic resonance imaging. We observed that patients with MDD had higher concentrations of IL-6 and a trend towards reduced left amygdala and bilateral hippocampus volumes than healthy controls. Additionally, the concentration of IL-6 was correlated with the left amygdala volume and depression severity, while the left hippocampus volume was correlated with depression severity. This study suggests that inflammation is an underlying neurobiological change and implies that IL-6 could serve as a potential biomarker for identifying early stage MDD in adolescents and young adults.

Development and acceptability of a gestational diabetes mellitus prevention system (Better pregnancy) based on a user-centered approach: A clinical feasibility study.

Background: Gestational diabetes mellitus (GDM) can increase the risk of adverse outcomes for both mothers and infants. Preventive interventions can effectively assist pregnant women suffering from GDM. At present, pregnant women are unaware of the importance of preventing GDM, and they possess a low level of self-management ability. Recently, mHealth technology has been used worldwide. Therefore, developing a mobile health app for GDM prevention could potentially help pregnant women reduce the risk of GDM. Objective: To design and develop a mobile application, evaluate its acceptance, and understand the users'using experience and suggestions, thus providing a valid tool to assist pregnant women at risk of GDM in enhancing their self-management ability and preventing GDM. Methods: An evidence-based GDM prevent app (Better pregnancy) was developed using user-centered design methods, following the health belief model, and incorporating GDM risk prediction. A convenient sampling method was employed from June to August 2022 to select 102 pregnant women at risk of GDM for the pilot study. After a week, the app's acceptability was evaluated using an application acceptance questionnaire, and we updated the app based on the feedback from the women. We used SPSS 26.0 for data analysis. Results: The application offers various functionalities, including GDM risk prediction, health management plan, behavior management, health information, personalized guidance and consultation, peer support, family support, and other functions. In total, 102 pregnant women consented to participate in the study, achieving a retention rate of 98%; however, 2% (n = 2) withdrew. The Better pregnancy app's average acceptability score is 4.07 out of 5. Additionally, participants offered several suggestions aimed at enhancing the application. Conclusions: The Better pregnancy app developed in this study can serve as an auxiliary management tool for the prevention of GDM, providing a foundation for subsequent randomized controlled trials.

Medical staff's perception of factors contributing to accelerated rehabilitation in patients with cervical spinal cord injury: A qualitative research.

AIM: To explore the factors affecting the quality of accelerated rehabilitation for patients with cervical spinal cord injury, therefore, to propose targeted improvement strategies and provide reference for promoting the quality of nursing care for accelerated rehabilitation. DESIGN: This descriptive qualitative inquiry followed the COREQ guidelines. METHODS: From December 2020 to April 2021, 16 subjects including orthopaedic nurses, nursing management experts, orthopaedic surgeons, anaesthesiologists and physical therapists experienced in accelerated rehabilitation were selected by objective sampling method to conduct semi-structured interviews. Thematic analysis was used to analyse the interview content. RESULTS: Through analysis and summary of the interview data, the following two themes and nine sub-themes were finally extracted. Factors related to the quality of accelerated rehabilitation structure include: construction of multidisciplinary teams, thorough system guarantee and adequate staffing. Factors related to the quality of accelerated rehabilitation process include: inadequate training and assessment, lack of medical staff's awareness, incapability of the accelerated rehabilitation team members, poor multidisciplinary communication and collaboration, lack of patient's awareness, and ineffective health education. CONCLUSION: Quality of implementation of accelerated rehabilitation can be improved by maximizing the role of multidisciplinary team, establishing a flawless accelerated rehabilitation system, increasing allocation of nursing resources, enhancing knowledge of medical staff, improving their awareness of accelerated rehabilitation, establishing personalized clinical pathways of accelerated rehabilitation, increasing communication and collaboration among multidisciplinary disciplines, and improving health education of patients.

In vivo analyses reveal hippocampal subfield volume reductions in adolescents with schizophrenia, but not with major depressive disorder.

BACKGROUND: Adult studies have reported atypicalities in the hippocampus and subfields in patients with schizophrenia (SCZ) and major depressive disorder (MDD). Both affective and psychotic disorders typically onset in adolescence, when human brain develops rapidly and shows increased susceptibility to adverse environments. However, few in vivo studies have investigated whether hippocampus subfield abnormalities occur in adolescence and whether they differ between SCZ and MDD cases. METHODS: We recruited 150 adolescents (49 SCZ patients, 67 MDD patients, and 34 healthy controls) and obtained their structural images. We used FreeSurfer to automatically segment hippocampus into 12 subfields and analyzed subfield volumetric differences between groups by analysis of covariance, covarying for age, sex, and intracranial volume. Composite measures by summing subfield volumes were further compared across groups and analyzed in relation to clinical characteristic. RESULTS: SCZ adolescents showed significant volume reductions in subfields of CA1, molecular layer, subiculum, parasubiculum, dentate gyrus and CA4 than healthy controls, and almost significant reductions, as compared to the MDD group, in left molecular layer, dentate gyrus, CA2/3 and CA4. Composite analyses showed smaller volumes in SCZ group than in healthy controls in all bilateral composite measures, and reduced volumes in comparison to MDD group in all left composite measures only. CONCLUSIONS: SCZ adolescents exhibited both hippocampal subfield and composite volumes reduction, and also showed greater magnitude of deviance than those diagnosed with MDD, particularly in core CA regions. These results indicate a hippocampal disease process, suggesting a potential intervention marker of early psychotic patients and risk youths.

Differential effects of generalized anxiety and separation anxiety on brain structural development during adolescence.

Excessive anxiety is highly prevalent during childhood and adolescence, with detrimental effects on somatic and mental health, and quality of life. Although structural abnormalities in the brain have been found in people with anxiety disorders, whether anxiety affects the brain development of children and adolescents remains unknown. Here, we applied a multivariate approach to two single-site MRI datasets consisting of 733 and 775 participants aged 5-18 years. Using linear support vector regression and cross-validation, brain age is estimated by predicting the chronological age from the features that combine cortical thickness and surface area of 68 brain regions. We found that gray matter can predict the chronological age of children and adolescents with a low mean absolute error. Compared to specific brain network, the whole structural brain measures predicted brain age better. Importantly, adolescents with higher generalized anxiety and those with lower separation anxiety showed lower brain age, indicating a slow development of brain structures. The relationship between anxiety and brain age of youths could also be found in parent-reported separation anxiety. The findings highlight differential effects of different anxiety types on brain structural development and suggest that different types of anxiety during childhood and adolescence should be treated differently.

Tongqiao Huoxue decoction alleviates neurological impairment following ischemic stroke via the PTGS2/NF-kappa B axis.

Traditional Chinese medicine has emerged as promising targets for ischemic stroke (IS) therapy, yet the mechanism remains elusive. The current study was performed with an aim to investigate the action and mechanism of Tongqiao Huoxue decoction (TQHXD) affecting the neurological impairment secondary to IS based on network pharmacology. Based on network pharmacology and bioinformatics analysis, target genes and pathways involved in the treatment of TQHXD against IS were predicted. Serum containing TQHXD was prepared through blood collection from C57BL/6 mice after intragastric administration of TQHXD. The main results exhibited that Prostaglandin-endoperoxide synthase 2 (PTGS2) exhibited an abundance in IS and enrichment in the NF-kappa B signaling pathway, holding the potential as targets related to TQHXD treatment for IS. TQHXD was found to rescue cell viability, inhibit apoptosis, and alleviate inflammation under oxygen and glucose deprivation and reoxygenation (OGD/R) exposure. Furthermore, our in vivo experiment validated the protective function of TQHXD in ischemic brain damage stimulated by middle cerebral artery occlusion (MCAO). This protective action of TQHXD could be attenuated by overexpressing nuclear factor (NF)-kappa B, which was dependent on PTGS2. Collectively, TQHXD was demonstrated to ameliorate IS-induced neurological impairment by blocking the NF-kappa B signaling pathway and down-regulating PTGS2.

IRAK-M suppresses the activation of microglial NLRP3 inflammasome and GSDMD-mediated pyroptosis through inhibiting IRAK1 phosphorylation during experimental autoimmune encephalomyelitis.

The activation of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers pyroptosis proinflammatory cell death in experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanisms of the inflammatory processes of microglia in EAE remain unclear. Our previous studies suggested that interleukin-1 receptor-associated kinase (IRAK)-M down-regulates the toll-like receptor 4/interleukin-1 receptor signaling pathway. Here, we used IRAK-M knockout (IRAK-M-/-) mice and their microglia to dissect the role of IRAK-M in EAE. We found that deletion of IRAK-M increased the incidence rate and exacerbated the clinical symptoms in EAE mice. We then found that IRAK-M deficiency promoted the activation of microglia, activated NLRP3 inflammasomes, and enhanced GSDMD-mediated pyroptosis in the microglia of EAE. In contrast, over-expression of IRAK-M exerted inhibitory effects on neuroinflammation, NLRP3 activation, and pyroptosis. Moreover, IRAK-M deficiency enhanced the phosphorylation of IRAK1, while IRAK-M over-expression downregulated the level of phosphorylated IRAK1. Finally, we found upregulated binding of IRAK1 and TNF receptor-associated factor 6 (TRAF6) in IRAK-M-/- EAE mice compared to WT mice, which was blocked in AAVIRAK-M EAE mice. Our study reveals a complex signaling network of IRAK-M, which negatively regulates microglial NLRP3 inflammasomes and pyroptosis by inhibiting IRAK1 phosphorylation during EAE. These findings suggest a potential target for the novel therapeutic approaches of multiple sclerosis (MS)/EAE and NLRP3-related inflammatory diseases.

Brain development mediates the relationship between self-reported poor parental monitoring and adolescent anxiety.

Adolescence is the peak period for the onset of generalized anxiety disorder (GAD). Brain networks of cognitive and affective control in adolescents are not well developed when their exposure to external stimuli suddenly increases.Reasonable parental monitoring is especially important during this period.To examine the role of parental monitoring in the development of functional brain networks of GAD, we conducted a cross-validation-based predictive study based on the functional brain networks of 192 participants. We found that a set of functional brain networks, especially the default mode network and its connectivity with the frontoparietal network, could predict the ages of adolescents, which was replicated in three independent samples.Importantly, the difference between predicted age and chronological age significantly mediated the relationship between parental monitoring and anxiety levels. These findings suggest that inadequate parental monitoring plays a crucial role in the delayed development of specific brain networks associated with GAD in adolescents. Our work highlights the important role of parental monitoring in adolescent development.

Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma.

epatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide. Currently, the prevention and treatment of HCC remains a major challenge. As a traditional Chinese medicine (TCM) formula, Ruangan Lidan decoction (RGLD) has been proved to own the effect of relieving HCC symptoms. However, due to its biological effects and complex compositions, its underlying mechanism of actions (MOAs) have not been fully clarified yet. In this study, we proposed a pharmacological framework to systematically explore the MOAs of RGLD against HCC. We firstly integrated the active ingredients and potential targets of RGLD. We next highlighted 25 key targets that played vital roles in both RGLD and HCC disease via a protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, an ingredient-target network of RGLD consisting of 216 ingredients with 306 targets was constructed, and multilevel systems pharmacology analyses indicated that RGLD could act on multiple biological processes related to the pathogenesis of HCC, such as cellular response to hypoxia and cell proliferation. Additionally, integrated pathway analysis of RGLD uncovered that RGLD might treat HCC through regulating various pathways, including MAPK signaling pathway, PI3K/Akt signaling pathway, TNF signaling pathway, and ERBB signaling pathway. Survival analysis results showed that HCC patients with low expression of VEGFA, HIF1A, CASP8, and TOP2A were related with a higher survival rate than those with high expression, indicating the potential clinical significance for HCC. Finally, molecular docking results of core ingredients and targets further proved the feasibility of RGLD in the treatment of HCC. Overall, this study indicates that RGLD may treat HCC through multiple mechanisms, which also provides a potential paradigm to investigate the MOAs of TCM prescription.

The neuroprotective effect of YaoYi-moxibustion on ischemic stroke by attenuating NK-κB expression in rats.

Background: Traditional Chinese medicine (TCM) has become a crucial direction for ischemic stroke treatment. This study sought to explore the underlying roles of YaoYi-moxibustion (YY-moxi) in ischemic stroke. Methods: A total of 75 Sprague-Dawley rats were randomly divided into the following 5 groups: (I) the sham-operated group; (II) the middle cerebral artery occlusion model (MCAO) group; (III) the YY-moxi group; (IV) the antioxidant (N-acetylcysteine, NAC) group; and (V) the NAC + YY-moxi group. After the model had been established, the NAC group received intracerebroventricular injections of NAC, the YY-moxi group received YY-moxi, and the NAC + YY-moxi group received a combination of these 2 interventions. The neurological deficit score was confirmed, and the cerebral infarction was examined by triphenyl tetrazolium chloride (TTC) staining. In the ischemia site of stroke, terminal deoxynucleotidyl transferase-mediated Dutp nick end labeling staining was applied to examine the apoptotic cells. Additionally, the apoptosis-associated genes and protein expressions in the ischemic brains were investigated by the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry, and western blot analysis. Results: YY-moxi alone and YY-moxi combined with NAC significantly reduced the neurological scores and cerebral infarction area of the MCAO rats. Additionally, YY-moxi alone and the combined application of YY-moxi and NAC improved the pathological status of ischemic brain tissues. Further, we found that YY-moxi alone and YY-moxi in combination with NAC could enhanced the antioxidation ability and reduced the inflammatory response of the MCAO model rats. We also proved that YY-moxi alone and YY-moxi combined with NAC significantly suppressed apoptosis-related proteins in the MCAO model rats. Conclusions: These findings indicate that YY-moxi exerts a protective effect on cerebral ischemic injury by reducing apoptosis. The study suggests that the mechanism may be related to its downregulating the expression of nuclear factor kappa B (NK-κB).

High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica.

Background: Neuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood. Purpose: To detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value. Methods: We obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA. Results: Serum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores. Conclusions: Our results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.

Rostral middle frontal gyrus thickness mediates the relationship between genetic risk and neuroticism trait.

Neuroticism is a robust personality trait associated with multiple mental disorders. Heretofore, research on the relationship among genes, brain, and behavior to explore individual differences in neuroticism is scarce. Hence, in this study (N = 630), genetic data, self-reported neuroticism, and brain structural data were combined to explore whether the cortical thickness (CT) of brain regions mediated the relationship between the polygenic risk score (PRS) of neuroticism and NEO neuroticism (NEO-N), and the enrichment analysis was performed to reveal the underlying mechanism of their relationship. Results showed that the PRSs were significantly associated with NEO-N scores (p < .05). The CT of left rostral middle frontal gyrus was negatively related to the best PRS in PRSice (PRSbest ) or the PRS at 0.05 threshold (PRS0.05 ) (corrected p < .05), which was also found to mediate the association between the PRS and NEO-N (PRSbest : ab = .012, p < .05; PRS0.05 : ab = .012, p < .05). Enrichment analysis revealed that these genes were mainly involved in biological adhesion, cell adhesion, neuron part, and synapse part, which were associated with the abnormal thickness of frontal cortex. By integrating genetic, brain imaging, and behavioral data, our research initially revealed the neurogenetic underpinnings of neuroticism, which is helpful for understanding individual differences in neuroticism.

Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway.

Traditional Chinese medicine has been reported to influence the proliferation and differentiation of neural stem cells (NSCs) that may be protective against nervous system diseases. Recent evidence indicates the importance of musk ketone in nerve recovery and preventing secondary damage after cerebral ischemic injury. A middle cerebral artery occlusion (MCAO) rat model was established by a transient filament model, and rats were treated with musk ketone (0.9 or 1.8 µM). Next, an in vitro oxygen-glucose deprivation (OGD) cell model was established to study the effect of musk ketone on the proliferation and differentiation of NSCs. To determine the potential mechanisms of musk ketone involved in activities of NSCs, the effect of musk ketone on the PI3K/Akt signaling pathway activation was assessed. Furthermore, NSCs were treated with musk ketone in the presence of PI3K/Akt inhibitor Akti-1/2 to examine their roles on NSC proliferation and differentiation. Musk ketone reduced cerebral ischemic injury in a dose-dependent manner in rats. In addition, NSCs treated with musk ketone showed enhanced proliferation and differentiation along with increased PI3K/Akt signaling pathway activation. The effects of muck ketone were reversed by Akti-1/2. Altogether, musk ketone promoted NSC proliferation and differentiation and protected against cerebral ischemia by activating the PI3K/Akt signaling pathway, highlighting the potential of musk ketone as a physiologically validated approach for the treatment of cerebral ischemia.

Suppression of lncRNA RMRP ameliorates oxygen-glucose deprivation/re-oxygenation-induced neural cells injury by inhibiting autophagy and PI3K/Akt/mTOR-mediated apoptosis.

The aberrant expression of lncRNAs has been inferred to be closely related with the progression of neural ischemia/reperfusion (I/R) injury. RMRP is an lncRNA associated with I/R injury. In order to determine the role of RMRP in I/R injury, the effects of RMRP knockdown on oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced injury in SH-SY5Y cells were evaluated. The effect of OGD/R administration on the expression of RMRP and apoptosis in SH-SY5Y cells, and the effect of RMRP suppression by siRNA on the impairments of cells proliferation and mobility potential due to OGD/R administration were assessed in the current study. At the molecular level, the current study detected the expressions of indicators involved in autophagy and PI3K/Akt/mTOR-mediated apoptosis pathways. The OGD/R administration induced the expression of RMRP and apoptosis in SH-SY5Y cells. After RMRP knockdown, the proliferation potential of SH-SY5Y cells was restored, and apoptosis and cell cycle arrest were inhibited. Moreover, RMRP inhibition also increased the invasion and migration of SH-SY5Y cells which were treated with OGD/R. The effects of RMRP suppression on the phenotypes of SH-SY5Y were associated with the inhibition of LC3II, p-PI3K, p-Akt, and p-mTOR as well as the induction of P62 and Bcl-2. Inhibition of RMRP contributed to the improvement of OGD/R-induced neuronal injury, which might be mediated through the inhibition of autophagy and apoptosis pathways.