Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.

The apolipoprotein E ɛ4 allele (APOE4) is universally acknowledged as the most potent genetic risk factor for Alzheimer's disease (AD). APOE4 promotes the initiation and progression of AD. Although the underlying mechanisms are unclearly understood, differences in lipid-bound affinity among the three APOE isoforms may constitute the basis. The protein APOE4 isoform has a high affinity with triglycerides and cholesterol. A distinction in lipid metabolism extensively impacts neurons, microglia, and astrocytes. APOE4 carriers exhibit phenotypic differences from non-carriers in clinical examinations and respond differently to multiple treatments. Therefore, we hypothesized that phenotypic classification of AD patients according to the status of APOE4 carrier will help specify research and promote its use in diagnosing and treating AD. Recent reviews have mainly evaluated the differences between APOE4 allele carriers and non-carriers from gene to protein structures, clinical features, neuroimaging, pathology, the neural network, and the response to various treatments, and have provided the feasibility of phenotypic group classification based on APOE4 carrier status. This review will facilitate the application of APOE phenomics concept in clinical practice and promote further medical research on AD.

Aurora retrieval in all-sky images based on hash vision transformer.

Auroras are bright occurrences when high-energy particles from the magnetosphere and solar wind enter Earth's atmosphere through the magnetic field and collide with atoms in the upper atmosphere. The morphological and temporal characteristics of auroras are essential for studying large-scale magnetospheric processes. While auroras are visible to the naked eye from the ground, scientists use deep learning algorithms to analyze all-sky images to understand this phenomenon better. However, the current algorithms face challenges due to inefficient utilization of global features and neglect the excellent fusion of local and global feature representations extracted from aurora images. Hence, this paper introduces a Hash-Transformer model based on Vision Transformer for aurora retrieval from all-sky images. Experimental results based on real-world data demonstrate that the proposed method effectively improves aurora image retrieval performance. It provides a new avenue to study aurora phenomena and facilitates the development of related fields.

CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis.

Meningioma is one of the most common primary neoplasms in the central nervous system, whereas there is still no specific molecularly targeted therapy that has been approved for the clinical treatment of aggressive meningiomas. There is therefore an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up of 445 meningioma patients, we uncovered that CBX7 is progressively decreased with malignancy grade and neoplasia stage in meningioma and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC proteins by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, which attenuates c-MYC-mediated transactivation of LDHA transcripts and further inhibits glycolysis and subsequent cellular proliferation. More importantly, the functional role of CBX7 was further confirmed in both subcutaneous and orthotopic meningioma xenografts mouse models and human meningioma patients. Together, our results shed light on the critical role of CBX7 during meningioma malignancy progression and identified the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression.

Endogenous Neural Stem Cell-induced Neurogenesis after Ischemic Stroke: Processes for Brain Repair and Perspectives.

Ischemic stroke is a very common cerebrovascular accident that occurred in adults and causes higher risk of neural deficits. After ischemic stroke, patients are often left with severe neurological deficits. Therapeutic strategies for ischemic stroke might mitigate neuronal loss due to delayed neural cell death in the penumbra or seek to replace dead neural cells in the ischemic core. Currently, stem cell therapy is the most promising approach for inducing neurogenesis for neural repair after ischemic stroke. Stem cell treatments include transplantation of exogenous stem cells but also stimulating endogenous neural stem cells (NSCs) proliferation and differentiation into neural cells. In this review, we will discuss endogenous NSCs-induced neurogenesis after ischemic stroke and provide perspectives for the therapeutic effects of endogenous NSCs in ischemic stroke. Our review would inform future therapeutic development not only for patients with ischemic stroke but also with other neurological deficits.

Learning from magnetotactic bacteria: mms6 protects stem cells from oxidative damage.

Oxidative damage generally exists in stroke and impairs stem cells' survival; however, the problem is difficult to treat. In order to help stem cells to resist this damage, we inserted a magnetotactic bacteria (MB) gene, mms6, into the neural stem cell genome by lentiviral transfection. It was found that the transfection of mms6 significantly improved the survival rate of stem cells in the condition of iron overload but not hypoxia. The bioenergetic profile also revealed that iron overloading weakened the mitochondrial respiration and spare respiration capacity of stem cells, but that these were enhanced after the expression of mms6. Additionally, Western blotting (WB) data revealed that mms6 upregulated the expression of glutathione peroxidase (GPX4), which protected stem cells from oxidative damage and ferroptosis. In order to determine the possible mechanisms, we analyzed the interactions between the MMS6 protein, Fe2+, and GPX4 via analog computation. The predicted models found that the MMS6 protein had a direct chelating site in the region of M6A with divalent iron; it also had weak binding with GPX4. Taken together, the magnetotactic bacterial gene mms6 protected stem cells from oxidative damage via binding with Fe2+, which could help them adapt to the microenvironment of stroke.

PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and Mitochondrial Dysfunction.

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood-brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases.

Meningioma Related Epilepsy- Pathophysiology, Pre/postoperative Seizures Predicators and Treatment.

Meningiomas are the most common primary brain tumors accounting for about 30% of all brain tumors. The vast majority of meningiomas are slow-growing and of benign histopathology rendering them curable by surgery alone. Symptomatic lesions depend on the location with signs of mass effect or neurological deficits. Seizures are the presenting symptoms in approximately 30% of cases, which negatively affect quality of life, limit independence, impair cognitive functioning, as well as increase the risk for psychiatric comorbidities including depression. Although surgical resection may offer seizure freedom in 60-90% of meningiomas, seizures persist after surgical resection in approximately 12-19% of patients. Anti-seizure medications (ASMs) are employed in management, however, are limited by adverse neurocognitive side-effects and inefficacy in some patients. The potential predictors of pre- and post-operative seizures in meningioma patients have been identified in the literature. Understanding various factors associated with seizure likelihood in meningioma patients can help guide more effective seizure control and allow for better determination of risk before and after surgery.

Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges.

Ischemic stroke, with its high morbidity and mortality, is the most common cerebrovascular accident and results in severe neurological deficits. Despite advances in medical and surgical intervention, post-stroke therapies remain scarce, which seriously affects the quality of life of patients. Over the past decades, stem cell transplantation has been recognized as very promising therapy for neurological diseases. Neural stem cell (NSC) transplantation is the optimal choice for ischemic stroke as NSCs inherently reside in the brain and can potentially differentiate into a variety of cell types within the central nervous system. Recent research has demonstrated that NSC transplantation can facilitate neural recovery after ischemic stroke, but the mechanisms still remain unclear, and basic/clinical studies of NSC transplantation for ischemic stroke have not yet been thoroughly elucidated. We thus, in this review, provide a futher understanding of the therapeutic role of NSCs for ischemic stroke, and evaluate their prospects for future application in clinical patients of ischemic stroke.

Increase of ALCAM and VCAM-1 in the plasma predicts the Alzheimer's disease.

Cell adhesion molecules (CAM) are crucial in several pathological inflammation processes in Alzheimer's disease (AD). However, their potential for clinical diagnostics remains unknown. The present investigation evaluated the clinical significance of ALCAM, VCAM-1, NCAM, and ICAM-1 levels in the plasma of participants with cognitive impairment (44 patients with mild cognitive impairment, 71 patients with Alzheimer's dementia, and 18 patients with other dementia) and 28 controls with normal cognitive ability. We also detected plasma levels of multiple inflammatory factors (IFN-gamma, IL-18, IL-1beta, IL-13, IL-8, IL-7, CCL11, MCP-1, TSLP, IL-10, BDNF, IL-17, IL-5, TREM-1) using Multiplex liquid chip and plasma levels of Abeta1-42 and Abeta1-40 using liquid-phase flow cytometry (FCM). Our findings demonstrated a correlation of ALCAM and VCAM-1 with age, the severity of cognitive decline, and MTA, but no significant difference between groups for NCAM and ICAM-1. ALCAM and VCAM-1 both demonstrated a positive correlation with the degree of atrophy in the medial temporal lobe structure. Further analysis revealed no significant correlation in plasma between VCAM-1, ALCAM and Abeta1-40, Abeta1-42. Nevertheless, there was a significant correlation between VCAM-1, ALCAM and many inflammatory factors. Furthermore, the predictive value of ALCAM and VCAM-1 for AD was assessed using a multi-parameter regression model. ALCAM and VCAM-1 in combination with ApoE4, education, age, and MMSE could predict AD with high precision (AUC=0.891; AIC=146.9) without imaging diagnosis. ALCAM and VCAM-1 combination improved the predictive accuracy significantly. In a nutshell, these findings revealed ALCAM and VCAM-1 as reliable indicators of Alzheimer's disease.

Pathogenesis Study of Glioma: From Glioma Stem Cells, Genomic Tags, to Rodent Models.

Glioma remains the toughest brain tumor among all primary central nervous system (CNS) tumors [...].

Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation.

Neural stem cell (NSC) therapy is a promising therapeutic strategy for stroke. Researchers have frequently carried out genetic modification or gene editing of stem cells to improve survival or therapeutic function. However, NSC transplantation carries the risk of immune rejection, and genetic modification or gene-editing might further increase this risk. For instance, recent studies have reported on manipulating the stem cell genome and transplantation via the insertion of an exogenous gene derived from magnetotactic bacteria. However, whether transgene-modified stem cells are capable of inducing immunological reactions has not been explored. Although NSCs rarely express the major histocompatibility complex (MHC), they can still cause some immunological issues. To investigate whether transgene-modified NSCs aggravate immunological responses, we detected the changes in peripheral immune organs and intracerebral astrocytes, glial cells, and MHC-I and MHC-II molecules after the injection of GFP-labeled or mms6-GFP-labeled NSCs in a rat model. Xenogeneic human embryonic kidney (HEK-293T) cells were grafted as a positive control group. Our results indicated that xenogeneic cell transplantation resulted in a strong peripheral splenic response, increased astrocytes, enhanced microglial responses, and upregulation of MHC-I and MHC-II expression on the third day of transplantation. But they decreased obviously except Iba-1 positive cells and MHC-II expression. When injection of both mms6-GFP-labeled NSCs and GFP-labeled NSCs also induced similar responses as HEK-293T cells on the third days, but MHC-I and MHC-II expression decreased 3 weeks after transplantation. In addition, mms6 transgene-modified NSCs did not produce peripheral splenic response responses as well as astrocytes, microglial cells, MHC-I and MHC-II positive cells responses when compared with non-modified NSCs. The present study provides preliminary evidence that transgenic modification does not aggravate immunological responses in NSC transplantation.

A Review of Hematoma Components Clearance Mechanism After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a complicated clinical syndrome, which is caused by several kinds of cerebrovascular disorders, with high morbidity, disability and mortality rate. In recent years, several studies have shown that early brain injury (EBI) is an important factor leading to the poor prognosis of SAH. A major cause of EBI has been attributed that hematoma components invade into the brain parenchyma, resulting in neuronal cell death. Therefore, the clearance of hematoma components is essential in the clinical outcome of patients after SAH. Here, in the review, we provide a summary of the current known hematoma components clearance mechanisms and simultaneously propose a new hypothesis for hematoma components clearance.

The Activation of Phosphatidylserine/CD36/TGF-ß1 Pathway prior to Surgical Brain Injury Attenuates Neuroinflammation in Rats.

Neuroinflammation plays an important pathological role in experimental surgical brain injury (SBI). Apoptotic associated with phosphatidylserine (PS) externalization promotes anti-inflammatory mediator TGF-ß1 release. In the present study, we investigated the anti-neuroinflammation effect of PS liposome or isoflurane pretreatment via PS/CD36/TGF-ß1 signaling in a rat model of SBI. A total of 120 male Sprague-Dawley rats (weighing 280-330 gms) were used. SBI was induced by partial right frontal lobe corticotomy. Intranasal PS liposome or isoflurane inhalation was administered prior to SBI induction. CD36 small interfering RNA (siRNA) was administered intracerebroventricularly. Recombinant Annexin V protein (rAnnexin V) was delivered intranasally. Post-SBI assessments included neurological tests, brain water content, Western blot, and immunohistochemistry. Endogenous CD36 protein levels but not TGF-ß1 was significantly increased within peri-resection brain tissues over 72 h after SBI. SBI rats were associated with increased brain water content surrounding corticotomy and neurological deficits. PS liposome pretreatment significantly reduced brain water content and improved some neurological deficits at 24 hours and 72 hours after SBI. PS liposome increased CD36 and TGF-ß1 protein levels, but decreased IL-1ß and TNFα protein levels in peri-resection brain tissues at 24 hours after SBI. CD36 siRNA or rAnnexin V partially countered the protective effect of PS liposome. Isoflurane pretreatment produced similar antineuroinflammation and neurological benefits in SBI rats partially by upregulating CD36/Lyn/TGF-ß1 signaling. Collectively, our findings suggest that the activation of PS/CD36/TGF-ß1 pathway by PS liposome or isoflurane prior to SBI could attenuate neuroinflammation and improve neurological outcomes in rats. PS liposome or isoflurane pretreatment may serve as an effective preventive strategy to minimize the brain injury caused by neurosurgical procedures in patients.