Global trends in COVID-19 Alzheimer's related research: a bibliometric analysis.

Background: The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. Methods: The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. Results: During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. Conclusion: The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.

Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate.

Extracellular vesicles (EVs) play a crucial role in regulating cell behavior by delivering their cargo to target cells. However, the mechanisms underlying EV-cell interactions are not well understood. Previous studies have shown that heparan sulfate (HS) on target cell surfaces can act as receptors for exosomes uptake, but the ligand for HS on EVs has not been identified. In this study, we isolated EVs from glioma cell lines and glioma patients and identified Annexin A2 (AnxA2) on EVs as a key HS-binding ligand and mediator of EV-cell interactions. Our findings suggest that HS plays a dual role in EV-cell interactions, where HS on EVs captures AnxA2, and on target cells, it acts as a receptor for AnxA2. Removal of HS from the EV surface inhibits EV-target cell interaction by releasing AnxA2. Furthermore, we found that AnxA2-mediated binding of EVs to vascular endothelial cells promotes angiogenesis, and that antibody against AnxA2 inhibited the ability of glioma-derived EVs to stimulate angiogenesis by reducing the uptake of EVs. Our study also suggests that the AnxA2-HS interaction may accelerate the glioma-derived EVs-mediated angiogenesis and that combining AnxA2 on glioma cells with HS on endothelial cells may effectively improve the prognosis evaluation of glioma patients.

Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma.

In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential "combination biomarker" for predicting prognosis of glioma patients.

Hsa_circ_0002468 Regulates the Neuronal Differentiation of SH-SY5Y Cells by Modulating the MiR-561/E2F8 Axis.

BACKGROUND It has been shown that circular RNAs (circRNAs) play a vital role in the regulation of neuronal differentiation; however, the precise role of circRNAs in human neuronal differentiation remains largely unexplored. MATERIAL AND METHODS A dual-luciferase reporter assay was carried out to confirm the targets of hsa_circ_0002468, miR-561, E2F8 (E2F transcription factor 8, a protein coding gene), and miR-561. We detected the expression of hsa_circ_0002468, miR-561, and E2F8 by using quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, we performed the functional experiments by using a BrdU (5-bromo-2'-deoxyuridine) assay and qRT-PCR analyses. RESULTS In this study, we showed that hsa_circ_0002468 can act as a sponge of miR-561 to regulate SH-SY5Y proliferation and differentiation. A bioinformatics analysis showed that hsa_circ_0002468 had a binding site that corresponded to miR-561, which was verified by dual-luciferase reporter assay. The expression of hsa_circ_0002468 was increased during SH-SY5Y differentiation and was inversely correlated with miR-561 expression. Using qRT-PCR analysis, we showed that hsa_circ_0002468 negatively regulated miR-561 in SH-SY5Y cells. Intriguingly, the overexpression of hsa_circ_0002468 increased SH-SY5Y differentiation and reduced SH-SY5Y proliferation; the suppression of hsa_circ_0002468 led to decreased SH-SY5Y differentiation levels and increased SH-SY5Y proliferation levels. Additionally, overexpression of miR-561 rescued the SH-SY5Y proliferation deficiency induced by hsa_circ_0002468 overexpression and abolished the SH-SY5Y differentiation promoted by hsa_circ_0002468. Furthermore, E2F8 was validated as a direct target of miR-561. CONCLUSIONS Our data suggested that hsa_circ_0002468 was a novel circRNA that regulated SH-SY5Y cell proliferation and differentiation via targeting the miR-561/E2F8 axis. Therefore, manipulating hsa_circ_0002468 in SH-SY5Y cells could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders.

Effect of Clozapine on Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Psychiatric Symptoms: A Series of Three Cases.

The main clinical manifestations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are acute or subacute seizures, cognition impairment, and psychiatric symptoms. Nowadays, the scheme of antipsychotic therapy for this disease has not been established. This study reports three cases of anti-NMDAR encephalitis with psychiatric symptoms. The anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum were positive. The psychiatric symptoms still existed after intravenous immunoglobulin (IVIG) treatment; thus, clozapine was used for antipsychotic therapy. Case 1 was a 37-year-old man who suffered from bad mood and suicide behaviors for 1 month. Hallucination and delusion still existed after IVIG treatment and hormone therapy, and the symptoms were relieved when given clozapine for 12 months. Case 2 was a 28-year-old man who was admitted to our hospital due to injuring other people and destructive behaviors for 2 days. He showed irritability, bad temper, declined cognition, and severe delusion of persecution after IVIG treatment and hormone therapy, but the psychiatric symptoms disappeared when given clozapine for 3 months. Case 3 was a 23-year-old man who suffered from headache and babbing for 7 days. Symptoms such as irritability, bad temper, babbing, and injuring other people still existed after IVIG treatment and hormone therapy, but they disappeared when given clozapine for 2 months. Therefore, we suggest that during the treatment of anti-NMDAR encephalitis with psychiatric symptoms, if the anti-NMDAR antibodies in CSF and serum were positive, and psychiatric symptoms could not be controlled after IVIG and hormone therapy, clozapine may work.