RESUMO
Excessive or inappropriate fear responses can lead to anxiety-related disorders, such as post-traumatic stress disorder (PTSD). Studies have shown that microglial activation occurs after fear conditioning and that microglial inhibition impacts fear memory. However, the role of microglia in fear memory recall remains unclear. In this study, we investigated the activated profiles of microglia after the recall of remote-cued fear memory and the role of activated microglia in the extinction of remote-cued fear in adult male C57BL/6 mice. The results revealed that the expression of the microglia marker Iba1 increased in the medial prefrontal cortex (mPFC) at 10 min and 1 h following remote-cued fear recall, which was accompanied by amoeboid morphology. Inhibiting microglial activation through PLX3397 treatment before remote fear recall did not affect recall, reconsolidation, or regular extinction but facilitated recall-extinction and mitigated spontaneous recovery. Moreover, our results demonstrated reduced co-expression of Iba1 and postsynaptic density protein 95 (PSD95) in the mPFC, along with decreases in the p-PI3K/PI3K ratio, p-Akt/Akt ratio, and KLF4 expression after PLX3397 treatment. Our results suggest that microglial activation after remote fear recall impedes fear extinction through the pruning of synapses in the mPFC, accompanied by alterations in the expression of the PI3K/AKT/KLF4 pathway. This finding can help elucidate the mechanism involved in remote fear extinction, contributing to the theoretical foundation for the intervention and treatment of PTSD.
Assuntos
Extinção Psicológica , Medo , Fator 4 Semelhante a Kruppel , Rememoração Mental , Camundongos Endogâmicos C57BL , Microglia , Córtex Pré-Frontal , Animais , Medo/fisiologia , Medo/psicologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiologia , Masculino , Microglia/metabolismo , Extinção Psicológica/fisiologia , Rememoração Mental/fisiologia , Camundongos , Proteínas dos Microfilamentos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Estimulação Acústica/efeitos adversos , Transdução de SinaisRESUMO
Post-stroke emotional disorders such as post-stroke anxiety and post-stroke depression are typical symptoms in patients with stroke. They are closely associated with poor prognosis and low quality of life. The State Food and Drug Administration of China has approved DL-3-n-butylphthalide (NBP) as a treatment for ischemic stroke (IS). Clinical research has shown that NBP alleviates anxiety and depressive symptoms in patients with IS. Therefore, this study explored the role and molecular mechanisms of NBP in cases of post-stroke emotional disorders using network pharmacology and experimental validation. The results showed that NBP treatment significantly increased the percentage of time spent in the center of the middle cerebral artery occlusion (MCAO) rats in the open field test and the percentage of sucrose consumption in the sucrose preference test. Network pharmacology results suggest that NBP may regulate neuroinflammation and cell death. Further experiments revealed that NBP inhibited the toll-like receptor 4/nuclear factor kappa B signaling pathway, decreased the level of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6, and M1-type microglia markers (CD68, inducible nitric oxide synthase), and reduced the expression of PANoptosis-related molecules including caspase-1, caspase-3, caspase-8, gasdermin D, and mixed lineage kinase domain-like protein in the hippocampus of the MACO rats. These findings demonstrate that the mechanisms through which NBP ameliorates post-stroke emotional disorders in rats are associated with inhibiting neuroinflammation and PANoptosis, providing a new strategy and experimental basis for treating post-stroke emotional disorders.
Assuntos
Benzofuranos , Infarto da Artéria Cerebral Média , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Animais , Benzofuranos/uso terapêutico , Benzofuranos/farmacologia , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Ratos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Farmacologia em Rede , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Citocinas/metabolismo , NF-kappa B/metabolismoRESUMO
To solve the problem of the poor abrasion resistance of concrete pavement surface mortar, this study substituted cement with equal amounts of styrene-butadiene rubber (SBR) latex and silica fume (SF) to investigate the effects of organic/inorganic material composite modification on the fluidity, drying shrinkage, mechanical properties, and abrasion resistance of cement mortar. Also in this study, the microstructure, product, and pore structure characteristics of the composite modified cement mortar were investigated using scanning electron microscope (SEM), X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and the Brunauer-Emmett-Teller (BET) method. This research found that the sole substitution of SF negatively impacted the mortar's fluidity and drying shrinkage yet enhanced its mechanical strength and abrasion resistance; the incorporation of SBR latex improved fluidity, reduced shrinkage, and increased flexural strength but adversely affected the compressive strength of the mortar. Additionally, the enhancement of the mortar's abrasion resistance with SBR latex was significantly greater than that with SF. When SBR latex and SF were used together as substitutes, the latex struggled to offset the negative impact of SF on mortar fluidity but effectively reduced shrinkage; SF compensated for the detrimental effect of the latex on compressive strength. Moreover, the primary role in enhancing the mortar's abrasion resistance was played by the latex. Microscopic tests showed that SBR latex and SF could increase the content of calcium silicate hydrate (C-S-H) gel, inhibit the formation of ettringite (AFt) and reduce carbonation, refine the pore size of cement mortar, and effectively improve the microstructure of mortar.
RESUMO
Background: LINC00518 acts as an oncogene in several cancers, but its function in head and neck squamous cell carcinoma (HNSCC) remains unclear. Materials & methods: The expression and methylation status of LINC00518 were analyzed by reviewing public databases. The ceRNA network and the relationship with tumor immunity of LINC00518 were analyzed using online tools and in vitro studies. Results: Upregulated LINC00518 was associated with poor clinicopathological characteristics of HNSCC. Silencing LINC00518 significantly inhibited the migration of HNSCC cells. LINC00518 might positively regulate HMGA2 via the ceRNA mechanism. Additionally, LINC00518 was negatively correlated with various immune cells and immunotherapy markers. Moreover, the upregulation of LINC00518 in HNSCC may be due to DNA hypomethylation. Conclusion: LINC00518 may be a potential biomarker and therapeutic target for HNSCC.
Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , DNA , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , RNA Longo não CodificanteRESUMO
Currently, the recovery of cognitive function has become an essential part of stroke rehabilitation. DL-3-n-butylphthalide (NBP) is a neuroprotective reagent and has been used in stroke treatment. Clinical studies have confirmed that NBP can achieve better cognitive outcomes in ischemic stroke patients than in healthy controls. In this study, we aimed to investigate the influences of NBP on cognitive function in an ischemic reperfusion (I/R) rat model. Our results showed that NBP profoundly decreased neurological scores, reduced cerebral infarct areas and enhanced cerebral blood flow (CBF). NBP potently alleviated poststroke cognitive impairment (PSCI) including depression-like behavior and learning, memory and social cognition impairments, in I/R rats. NBP distinctly suppressed the activation of microglia and astrocytes and improved neuron viability in the ischemic brain. NBP inhibited the expression of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), by targeting the nuclear factor kappa B/inducible nitric oxide synthase (NF-κB/iNOS) pathway and decreased cerebral oxidative stress factors, including reactive oxygen species (ROS) and malondialdehyde (MDA), by targeting the kelch like ECH associated protein 1/nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) pathway in the ischemic brain. The current study revealed that NBP treatment improved neurological function and ameliorated cognitive impairment in I/R rats, possibly by synergistically suppressing inflammation and oxidative stress.
RESUMO
Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear. Here, using an unpredictable chronic mild stress (UCMS) paradigm, we found that the mRNA and protein levels of LASP1 were decreased in the hippocampus of stressed mice and that UCMS-induced down-regulation of LASP1 was abolished by chronic administration of fluoxetine. Adenosine-associated virus-mediated hippocampal LASP1 overexpression alleviated the UCMS-induced behavioral results of forced swimming test and sucrose preference test in stressed mice. It also restored the dendritic spine density, elevated the levels of AKT (a serine/threonine protein kinase), phosphorylated-AKT, insulin-like growth factor 2, and postsynaptic density protein 95. These findings suggest that LASP1 alleviates UCMS-provoked behavioral defects, which may be mediated by an enhanced dendritic spine density and more activated AKT-dependent LASP1 signaling, pointing to the antidepressant role of LASP1.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas com Domínio LIM/metabolismo , Estresse Psicológico/metabolismo , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Doença Crônica , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/patologiaRESUMO
Strain 011410T, isolated from air at the foot of Xiangshan Mountain, Beijing, China, was Gram-reaction-negative, facultatively anaerobic, oval-shaped, motile with two flagella and catalase- and oxidase-positive. Growth of strain 011410T was observed at 4-41 °C (optimum, 30 °C), at pH 4.5-10.0 (optimum, pH 8.0) and at salinities of 0-10â% (w/v) NaCl (optimum, 0-2â%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 011410T was a member of the genus Paracoccus and was related most closely to Paracoccus aestuarii B7T (96.62â% similarity) and Paracoccus sediminis CMB17T (96.48â% similarity). The major fatty acid was identified as C18â:â1ω7c, with smaller amounts of C18â:â0, C10â:â0 3-OH and summed feature 2 (C14â:â0 3-OH and/or iso-C16â:â1 I). The predominant respiratory quinone was ubiquinone-10 (Q-10), with Q-9 as a minor component. Polar lipid analysis indicated the presence of diphosphatidylglycerol, phosphatidylglycerol, one unknown phosphoglycolipid, five unknown phospholipids, one unknown aminolipid, one unknown glycolipid and two unknown polar lipids. The DNA G+C content of the strain was 63.5 mol%. On the basis of the data from this polyphasic characterization, strain 011410T represents a novel species, for which the name Paracoccus aerius sp. nov. is proposed. The type strain is 011410T (=CFCC 14285T=KCTC 42845T).
Assuntos
Microbiologia do Ar , Paracoccus/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Pequim , DNA Bacteriano/genética , Ácidos Graxos/química , Paracoccus/genética , Paracoccus/isolamento & purificação , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
A Gram-stain-negative, yellow-pigmented, ovoid to rod-shaped, strictly aerobic bacterial strain, designated 100921-2T, was isolated from air at the foot of Xiangshan Mountain. Phylogenetic and phenotypic analysis of the organism revealed that the isolate belongs to the genus Altererythrobacter. Strain 100921-2T showed high 16S rRNA gene sequence similarity (96.01-94.70 %) to other type strains of the genus Altererythrobacter, with the highest similarity to Altererythrobactermarensis MSW-14T. Growth of strain 100921-2T was observed at 4-50 °C (optimum, 30 °C), at pH 4.5-10.0 (optimum, pH 7.0) and at salinities of 0-10 % (w/v) NaCl (optimum 0-0.5 %). The major fatty acids were C18 : 1ω7c (27.8 %), C17 : 1ω6c (23.1 %), 11-methyl C18 : 1ω7c(11.9 %), summed feature 3 (9.1 %) and C15 : 0 2-OH (7.9 %). The predominant respiratory quinone was ubiquinone-10 (Q-10). Polar lipid analysis indicated the presence of diphosphatidylglycerol, sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unknown phospholipids, five unknown polar lipids and two unknown glycolipids. The DNA G+C content of the type strain was 67.5 mol%. On the basis of the data from the polyphasic characterization, strain 100921-2T represents a novel species, for which the name Altererythrobacter aerius sp. nov. is proposed. The type strain is 100921-2T (=CFCC 14287T=KCTC 42844T).
Assuntos
Microbiologia do Ar , Alphaproteobacteria/classificação , Filogenia , Alphaproteobacteria/genética , Alphaproteobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
Three novel endophytic strains, designated 17B10-2-12T, 26C10-4-4 and D13-10-4-9, were isolated from the bark of Populus euramericana in Heze, Shandong Province, China. They were Gram-reaction-negative, aerobic, non-motile, short-rod-shaped, oxidase-positive and catalase-negative. A phylogenetic analysis of the 16S rRNA gene showed that the three novel strains clustered with members of the family Comamonadaceae and formed a distinct branch. The isolates shared 100 % similarities among themselves and had the highest sequence similarity with Xenophilus azovorans DSM 13620T (95.2 %) and Xenophilus arseniciresistens YW8T (95.0 %), and less than 95.0 % sequence similarities with members of other species. Their major fatty acids were C16 : 0, C17 : 0 cyclo, C18 : 1ω7c and C16 : 1ω7c/C16 : 1ω6c. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unknown aminophospholipids. The predominant quinone was ubiquinone-8 (Q-8). The DNA G+C content was 69.570.0âmol%. Based on data from a polyphasic taxonomy study, the three strains represent a novel species of a novel genus of the family Comamonadaceae, for which the name Corticibacter populi gen. nov., sp. nov. is proposed. The type strain is 17B10-2-12T ( = CFCC 12099T = KCTC 42091T).