Stroke subtype-dependent synapse elimination by reactive gliosis in mice

AbstractThe pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.

Download Full-text

The Role of Nanomaterials in Stroke Treatment: Targeting Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/8857486 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Guini Song ◽

Min Zhao ◽

Hanmin Chen ◽

Cameron Lenahan ◽

Xiangyue Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Hemorrhagic Stroke ◽

Neural Regeneration ◽

High Rate ◽

Protective Effects ◽

Ischemic Brain ◽

Stroke Treatment ◽

The Brain ◽

Target Effects

Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage to the brain tissue. Therefore, treatment for oxidative stress is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but the clinical studies have not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used to deliver drugs and have demonstrated excellent performance in treating various diseases. Additionally, some nanomaterials have shown potential in scavenging reactive oxygen species (ROS) in stroke according to the nature of nanomaterials. The drugs’ delivery ability of nanomaterials has great significance for the clinical translation and application of antioxidants. It increases drug blood concentration and half-life and targets the ischemic brain to protect cells from oxidative stress-induced death. This review summarizes the characteristics and progress of nanomaterials in the application of antioxidant therapy in stroke, including ischemic stroke, hemorrhagic stroke, and neural regeneration. We also discuss the prospect of nanomaterials for the treatment of oxidative stress in stroke and the challenges in their application, such as the toxicity and the off-target effects of nanomaterials.

Download Full-text

From Preclinical Stroke Models to Humans: Polyphenols in the Prevention and Treatment of Stroke

Nutrients ◽

10.3390/nu13010085 ◽

2020 ◽

Vol 13 (1) ◽

pp. 85

Author(s):

Edoardo Parrella ◽

Cristina Gussago ◽

Vanessa Porrini ◽

Marina Benarese ◽

Marina Pizzi

Keyword(s):

Hemorrhagic Stroke ◽

Protective Role ◽

Polyphenolic Compounds ◽

Preclinical Studies ◽

Preclinical Models ◽

Human Diet ◽

In Vivo Models ◽

Stroke Models

Polyphenols are an important family of molecules of vegetal origin present in many medicinal and edible plants, which represent important alimentary sources in the human diet. Polyphenols are known for their beneficial health effects and have been investigated for their potential protective role against various pathologies, including cancer, brain dysfunctions, cardiovascular diseases and stroke. The prevention of stroke promoted by polyphenols relies mainly on their effect on cardio- and cerebrovascular systems. However, a growing body of evidence from preclinical models of stroke points out a neuroprotective role of these molecules. Notably, in many preclinical studies, the polyphenolic compounds were effective also when administered after the stroke onset, suggesting their possible use in promoting recovery of patients suffering from stroke. Here, we review the effects of the major polyphenols in cellular and in vivo models of both ischemic and hemorrhagic stroke in immature and adult brains. The results from human studies are also reported.

Download Full-text

Faculty Opinions recommendation of Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5896957.5887055 ◽

2010 ◽

Author(s):

Lorenz Hirt

Keyword(s):

Brain Injury ◽

Pivotal Role ◽

Interleukin 17 ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Delayed Phase

Download Full-text

Feeding behaviour and bioerosion: the ecological role of the rock-boring urchin, Echinometra mathaei (de Blainville, 1825), in Okinawa reef flat

AQUATIC SCIENCE & MANAGEMENT ◽

10.35800/jasm.1.1.2013.1976 ◽

2013 ◽

Vol 1 (1) ◽

pp. 10

Author(s):

Noar Muda Satyawan ◽

Shelly Tutupoho ◽

Yusli Wardiatno ◽

Makoto Tsuchiya

Keyword(s):

Feeding Behaviour ◽

Reef Flat ◽

Type A ◽

Gut Contents ◽

Biological Processes ◽

Type B ◽

Night Time ◽

Echinometra Mathaei ◽

Benthic Ecosystems

Erosion rate on corals due to activities of other biota is called bioerosion. The rock-boring urchin, Echinometra mathaei, when it is abundant, plays a significant role in benthic ecosystems, including biological processes like coral erosion. During feeding, E. mathaei erodes calcium carbonate besides grazing on algae living on coral, so it plays an important role in both organic and inorganic carbons in coral reefs. The urchin E. mathaei actively feeds during the night time (nocturnal grazer). Although in Okinawa four types (A-D) of the urchin exist, the research only focused on the types A and B. Type A of E. mathaei produced 0.44951 g feces per day on average while type B produced 0.38030 g feces per day. CaCO3 analysis in feces and gut contents showed bioerosion rate of E. mathaei type A was 0.64492 g/individu/day, and 0.54436 g/individu/day in type B. There were no significant differences in bioerosion impact of E. mathaei type A and B© Laju erosi pada karang yang disebabkan oleh biota, dikenal dengan bioerosi. Bulu babi jenis Echinometra mathaei, ketika melimpah, menjadi sangat berpengaruh terhadap ekosistem bentik termasuk proses biologi seperti erosi karang. Selama aktivitas makan, E. mathaei menggerus kalsium karbonat dalam proporsi yang besar di samping alga yang tumbuh menempel pada karang sehingga memiliki peran penting dalam siklus karbon organik dan anorganik di ekosistem terumbu karang. Bulu babi E. mathaei aktif mencari makan pada malam hari (nocturnal grazer). Meskipun di Okinanawa ada 4 tipe (A-D), pada eksperimen kali ini memfokuskan pada tipe A dan B saja. Tipe A E. mathaei rata-rata memproduksi 0,44951 g feses/hari dan tipe B memproduksi 0,38030 g feses/hari. Berdasarkan analisis CaCO3 yang dilakukan pada feses dan isi lambung, laju bioerosi yang disebabkan oleh E. mathaei tipe A sebesar 0,64492 g/individu/hari sedangkan tipe B sebesar 0,54436 g/individu/hari. Tidak terdapat perbedaan dampak bioerosi yang signifikan antara E. mathaei tipe A dan B©

Download Full-text

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200902144348 ◽

2020 ◽

Vol 23 ◽

Author(s):

Xiao Zhou ◽

Xiao-Fei Zhang ◽

Dong-Yan Guo ◽

Yan-Jun Yang ◽

Lin Liu ◽

...

Keyword(s):

Febrile Seizures ◽

Network Pharmacology ◽

Biological Processes ◽

Active Compounds ◽

Potential Core ◽

R Language ◽

The Core ◽

Multiple Factors ◽

Therapeutic Mechanism

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Download Full-text

The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

Download Full-text

Emerging multifaceted roles of BAP1 complexes in biological processes

Cell Death Discovery ◽

10.1038/s41420-021-00406-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Aileen Patricia Szczepanski ◽

Lu Wang

Keyword(s):

Transcriptional Repression ◽

Target Genes ◽

Regulatory Mechanisms ◽

Biological Processes ◽

Multiprotein Complex ◽

Downstream Target ◽

Evolutionarily Conserved ◽

Complex Forms ◽

Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

Download Full-text

MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽

10.3390/cells9010113 ◽

2020 ◽

Vol 9 (1) ◽

pp. 113 ◽

Cited By ~ 3

Author(s):

Stephanie Maia Acuña ◽

Lucile Maria Floeter-Winter ◽

Sandra Marcia Muxel

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Small Rnas ◽

Immune Cell ◽

Fine Tuning ◽

Biological Processes ◽

Host Interactions ◽

The Past ◽

Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

Download Full-text

Streptococcus suis Induces Expression of Cyclooxygenase-2 in Porcine Lung Tissue

Microorganisms ◽

10.3390/microorganisms9020366 ◽

2021 ◽

Vol 9 (2) ◽

pp. 366

Author(s):

Muriel Dresen ◽

Josephine Schenk ◽

Yenehiwot Berhanu Weldearegay ◽

Désirée Vötsch ◽

Wolfgang Baumgärtner ◽

...

Keyword(s):

Lung Tissue ◽

Streptococcus Suis ◽

Cyclooxygenase 2 ◽

Economic Losses ◽

Biological Processes ◽

Alveolar Tissue ◽

Cox 2 ◽

Ciliated Epithelial Cells ◽

Immunohistological Analysis

Streptococcus suis is a common pathogen colonising the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like inflammation modulation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E2 (PGE2) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE2 levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE2 production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infections with S. suis.

Download Full-text