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1.
Neurology ; 102(9): e209299, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38598742

RESUMO

BACKGROUND AND OBJECTIVES: Stroke attributable to nonoptimal temperature needs more attention with dramatic climate change. The aim of this study was to estimate the global burden and distribution characteristics of the burden. METHODS: In this ecological study, we collected data from the Climate Research Unit Gridded Time Series, the World Bank databases, and the Global Burden of Diseases study to estimate the distribution of burden. We used the joinpoint model, decomposition analysis, age-period-cohort model, panel data analysis, and health inequality analysis to assess the different types of stroke burden attributable to different climatic conditions. RESULTS: The burden of stroke attributable to nonoptimal temperature continued to grow, and aging was a key factor in this increase. In 2019, 521,031 (95% uncertainty interval [UI] 402,433-663,996) deaths and 9,423,649 (95% UI 7,207,660-12,055,172) disability-adjusted life years [DALYs] attributable to stroke due to nonoptimal temperature were recorded globally. Globally, men (age-standardized mortality rate [ASMR] 7.70, 95% UI 5.80-9.73; age-standardized DALY rate [ASDR] 139.69, 95% UI 102.96-178.54 in 2019) had a heavier burden than women (ASMR 5.89, 95% UI 4.50-7.60; ASDR 96.02, 95% UI 72.62-123.85 in 2019). Central Asia (ASMR 18.12, 95% UI 13.40-24.53; ASDR 327.35, 95% UI 240.24-440.61 in 2019) had the heaviest burden at the regional level. In the national level, North Macedonia (ASMR 32.97, 95% UI 20.57-47.44 in 2019) and Mongolia (ASDR 568.54, 95% UI 242.03-1,031.14 in 2019) had the highest ASMR/ASDR, respectively. Low temperature currently contributes to the main burden (deaths 474,002, 95% UI 355,077-606,537; DALYs 8,357,198, 95% UI 6,186,217-10,801,911 attributable to low temperature vs deaths 48,030, 95% UI 5,630-104,370; DALYs 1,089,329, 95% UI 112,690-2,375,345 attributable to high temperature in 2019). However, the burden due to high temperature has increased rapidly, especially among people aged older than 10 years, and was disproportionately concentrated in low sociodemographic index (SDI) regions such as Africa. In addition, the rapid increase in the stroke burden due to high temperature in Central Asia also requires special attention. DISCUSSION: This is the first study to assess the global stroke burden attributed to nonoptimal temperature. The dramatic increase in the burden due to high temperature requires special attention, especially in low-SDI countries.


Assuntos
Carga Global da Doença , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Idoso , Temperatura , Disparidades nos Níveis de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Saúde Global , Acidente Vascular Cerebral/epidemiologia
2.
J Environ Manage ; 357: 120766, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38565032

RESUMO

Biofouling presents hazards to a variety of freshwater and marine underwater infrastructures and is one of the direct causes of species invasion. These negative impacts provide a unified goal for both industry practitioners and researchers: the development of novel antifouling materials to prevent the adhesion of biofouling. The prohibition of tributyltin (TBT) by the International Maritime Organization (IMO) in 2001 propelled the research and development of new antifouling materials. However, the evaluation process and framework for these materials remain incomplete and unsystematic. This mini-review starts with the classification and principles of new antifouling materials, discussing and summarizing the methods for assessing their biofouling resistance. The paper also compiles the relevant regulations and environmental requirements from different countries necessary for developing new antifouling materials with commercial potential. It concludes by highlighting the current challenges in antifouling material development and future outlooks. Systematic evaluation of newly developed antifouling materials can lead to the emergence of more genuinely applicable solutions, transitioning from merely laboratory products to materials that can be effectively used in real-world applications.


Assuntos
Incrustação Biológica , Incrustação Biológica/prevenção & controle , Água Doce , Indústrias
3.
Toxicology ; 504: 153799, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608860

RESUMO

Given the widespread production and use of plastics, poor biodegradability, and inadequate recycling, micro/nanoplastics (MNPs) have caused widespread environmental pollution. As a result, humans inevitably ingest MNPs through various pathways. However, there is still no consensus on whether exposure to MNPs has adverse effects on humans. This article aims to provide a comprehensive overview of the knowledge of MNPs and the potential mechanisms of their impact on the central nervous system. Numerous in vivo and in vitro studies have shown that exposure to MNPs may pass through the blood-brain barrier (BBB) and lead to neurotoxicity through impairments in oxidative and inflammatory balance, neurotransmitter alternation, nerve conduction-related key enzymes, and impact through the gut-brain axis. It is worth noting that MNPs may act as carriers and have more severe effects on the body when co-exposed with other substances. MNPs of smaller sizes cause more severe harm. Despite the scarcity of reports directly relevant to humans, this review brings together a growing body of evidence showing that exposure to MNPs disturbs neurons and has even been found to alter the memory and behavior of organisms. This effect may lead to further potential negative influence on the central nervous system and contribute to the development of other diseases such as central nervous system inflammation and Parkinson 's-like neurodegenerative disorders. There is a need further to investigate the threat of MNPs to human health.

4.
Biofouling ; 40(2): 130-152, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38450626

RESUMO

The identification and management of biofouling remain pressing challenges in marine and freshwater ecosystems, with significant implications for environmental sustainability and industrial operations. This comprehensive review synthesizes the current state-of-the-art in biofouling identification technologies, examining eight prominent methodologies: Microscopy Examination, Molecular Biology, Remote Sensing, Community Involvement, Ecological Methods, Artificial Intelligence, Chemical Analysis, and Macro Photography. Each method is evaluated for its respective advantages and disadvantages, considering factors such as precision, scalability, cost, and data quality. Furthermore, the review identifies current obstacles that inhibit the optimal utilization of these technologies, ranging from technical limitations and high operational costs to issues of data inconsistency and subjectivity. Finally, the review posits a future outlook, advocating for the development of integrated, standardized systems that amalgamate the strengths of individual approaches. Such advancement will pave the way for more effective and sustainable strategies for biofouling identification and management.


Assuntos
Incrustação Biológica , Incrustação Biológica/prevenção & controle , Biofilmes , Ecossistema , Inteligência Artificial
5.
Sensors (Basel) ; 24(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400469

RESUMO

The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.

6.
Opt Express ; 32(3): 4093-4101, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297617

RESUMO

Antiresonant hollow-core fiber (AR-HCF) exhibits unprecedented optical performance in low transmission attenuation, broad transmission bandwidth, and single spatial mode quality. However, due to its lower numerical aperture, when utilizing the Fiber-Enhanced Raman Spectroscopy (FERS) principle for gas detection, the efficiency of AR-HCF in collecting Raman signals per unit length is significantly lower than that of hollow-core photonic crystal fiber. Nonetheless, AR-HCF effectively suppresses higher-order modes and offers bandwidth in hundreds of nanometers. By increasing the length of AR-HCF, its advantages can be effectively harnessed, leading to a considerable enhancement in the system's ability for low-concentration gas detection. We combine the nodeless antiresonant hollow-core fiber and Raman spectroscopy for enhanced Raman gas sensing in a forward scattering measurement configuration to investigate the attenuation behavior of the silica background signals. The silica background attenuation behavior enables the low baseline of the gas Raman spectroscopy and extends the integration time of the system. In addition, a convenient spatial filtering method is investigated. A multimode fiber with a suitable core diameter was employed to transmit the signal so that the fiber end face plays the role of pinhole, thus filtering the silica signal and reducing the baseline. The natural isotopes 12C16O2, 13C16O2, and 12C18O16O in ambient air can be observed using a 5-meter-long AR-HCF at 1 bar with a laser output power of 1.8 W and an integration time of 300 seconds. Limits of detection have been determined to be 0.5 ppm for 13C16O2 and 1.2 ppm for 12C16O2, which shows that the FERS with AR-HCF has remarkable potential for isotopes and multigas sensing.

8.
Dev Cell ; 59(4): 482-495.e6, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38272027

RESUMO

Mutations or dysregulation of nucleoporins (Nups) are strongly associated with neural developmental diseases, yet the underlying mechanisms remain poorly understood. Here, we show that depletion of Nup Seh1 in radial glial progenitors results in defective neural progenitor proliferation and differentiation that ultimately manifests in impaired neurogenesis and microcephaly. This loss of stem cell proliferation is not associated with defects in the nucleocytoplasmic transport. Rather, transcriptome analysis showed that ablation of Seh1 in neural stem cells derepresses the expression of p21, and knockdown of p21 partially restored self-renewal capacity. Mechanistically, Seh1 cooperates with the NuRD transcription repressor complex at the nuclear periphery to regulate p21 expression. Together, these findings identified that Nups regulate brain development by exerting a chromatin-associated role and affecting neural stem cell proliferation.


Assuntos
Neocórtex , Células-Tronco Neurais , Animais , Camundongos , Diferenciação Celular , Expressão Gênica , Neocórtex/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
9.
J Affect Disord ; 350: 582-589, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38246286

RESUMO

BACKGROUND: Psychiatric disorders are emerging as a serious public health hazard, influencing an increasing number of individuals worldwide. However, the effect of modifiable lifestyle factors on psychiatric disorders remains unclear. METHODS: Genome-wide association studies (GWAS) summary statistics were obtained mainly from Psychiatric Genomics Consortium and UK Biobank, with sample sizes varying between 10,000 and 1,200,000. The two-sample Mendelian randomization (MR) method was applied to investigate the causal associations between 45 lifestyle factors and 13 psychiatric disorders, and screen potential mediator proteins from 2992 candidate plasma proteins. We implemented a four-step framework with step-by-step screening incorporating two-step, univariable, and multivariable MR. RESULTS: We found causal effects of strenuous sports or other exercise on Tourette's syndrome (OR [95%CI]: 0.0047 [5.24E-04-0.042]); lifelong smoking index on attention-deficit hyperactivity disorder (10.53 [6.96-15.93]), anxiety disorders (3.44 [1.95-6.05]), bipolar disorder (BD) (2.25 [1.64-3.09]), BD II (2.89 [1.81-4.62]), and major depressive disorder (MDD) (2.47 [1.90-3.20]); and educational years on anorexia nervosa (AN) (1.47 [1.22-1.76]), and MDD (0.74 [0.66-0.83]). Five proteins were found to have causal associations with psychiatric disorders, namely ADH1B, GHDC, STOM, CD226, and TP63. STOM, a membrane protein deficient in the erythrocytes of hereditary stomatocytosis patients, may mediate the effect of educational attainment on AN. LIMITATIONS: The mechanisms underlying the effects of lifestyle factors on psychiatric disorders require further investigation. CONCLUSIONS: These findings could help assess the risk of psychiatric disorders based on lifestyle factors and also support lifestyle interventions as a prevention strategy for mental illness.


Assuntos
Anorexia Nervosa , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Proteínas Sanguíneas/genética , Estilo de Vida
10.
Clin Immunol ; 258: 109802, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37866784

RESUMO

Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Macrófagos , Terapia de Imunossupressão , Estresse Oxidativo , Microambiente Tumoral
12.
Dev Cell ; 58(21): 2275-2291.e6, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37865085

RESUMO

Dysregulation of factors in nucleocytoplasmic transport is closely linked to neural developmental diseases. Mutation in Hikeshi, encoding a nonconventional nuclear import carrier of heat shock protein 70 family (HSP70s), leads to inherited leukodystrophy; however, the pathological mechanisms remain elusive. Here, we showed that Hikeshi is essential for central nervous system (CNS) myelination. Deficiency of Hikeshi, which is observed in inherited leukodystrophy patients, resulted in murine oligodendrocyte maturation arrest. Hikeshi is required for nuclear translocation of HSP70s upon differentiation. Nuclear-localized HSP70 promotes murine oligodendrocyte differentiation and remyelination after white matter injury. Mechanistically, HSP70s interacted with SOX10 in the nucleus and protected it from E3 ligase FBXW7-mediated ubiquitination degradation. Importantly, we discovered that Hikeshi-dependent hyperthermia therapy, which induces nuclear import of HSP70s, promoted oligodendrocyte differentiation and remyelination following in vivo demyelinating injury. Overall, these findings demonstrate that Hikeshi-mediated nuclear translocation of HSP70s is essential for myelinogenesis and provide insights into pathological mechanisms of Hikeshi-related leukodystrophy.


Assuntos
Proteínas de Transporte , Resposta ao Choque Térmico , Animais , Humanos , Camundongos , Transporte Ativo do Núcleo Celular/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo
13.
Stem Cells ; 41(12): 1101-1112, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37724396

RESUMO

Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.


Assuntos
Organoides , Medicina Regenerativa , Humanos , Reprodutibilidade dos Testes , Engenharia Tecidual , Células-Tronco
14.
Cancer Lett ; 577: 216368, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37652287

RESUMO

INTRODUCTION: SEM1, a 26 S proteasome complex subunit, is an essential regulator of tumor growth. However, the underlying mechanism of SEM1 mediated glioma progression remains to be elucidated. METHODS: Data from bulk-tumor, single-cell, and spatial sequencing were analyzed to reveal correlations between SEM1 and clinical traits, cell types, and functional enrichment in gliomas. Immunohistochemistry was used to assess SEM1 expression. MTT, flow cytometry, apoptosis signature, epithelial-mesenchymal transition signature, Transwell, and organoid assays were used to study SEM1's effect on the malignant behavior of glioma (U251 and LN229) cells. Weighted gene co-expression network analysis (WGCNA) was conducted to construct an SEM1-mediated malignant regulatory network. Accordingly, survival analysis, therapeutic response, drug prediction, and molecular docking analyses were performed. RESULTS: High SEM1 expression was observed in gliomas and correlated with worse clinical features and prognosis. Moreover, SEM1 is mainly localized in malignant cells (glioma cells). SEM1 knockout inhibited the proliferation, invasion, and migration of glioma cells and promoted their apoptosis. We also constructed an SEM1 malignant regulatory network that was bridged by the PI3K-Akt pathway. The network had a high prognostic value. Finally, drugs potentially targeting SEM1 were screened and docked to SEM1. CONCLUSIONS: SEM1 is critically involved in the proliferation, apoptosis, invasion, and migration of glioma cells. The SEM1 malignant regulatory network shows high significance for the prognosis and treatment of gliomas.


Assuntos
Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Proliferação de Células , Linhagem Celular Tumoral , Transdução de Sinais , Glioma/patologia , Apoptose , Movimento Celular
15.
Ultramicroscopy ; 254: 113776, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37544853

RESUMO

In this article the analytical expressions of the fifth-order asymptotic geometric aberrations of electron lenses are derived by Mathematica. The process of the derivation is analogous to the method described in "Principles of Electron Optics" by P.W. Hawkes and E. Kasper. All the analytical formulae for asymptotic aberration coefficients in polynomials in the reciprocal magnification are numerically cross-validated with the differential algebraic (DA) method. The results indicate that the derived formulae are doubtless correct.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 303: 123232, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37562209

RESUMO

In this study, a novel ratiometric fluorescence probe based on dual-emission carbon dots (CDs) for the sensitive detection of salicylic acid (SA) was constructed for the first time. The dual-emission CDs were synthesized by simple hydrothermal method using tartaric acid (TA) and m-phenylenediamine (mPD) as raw materials. In the presence of SA, the fluorescence intensity of CDs was enhanced at 499 nm, but remained basically unchanged at 439 nm. This phenomenon is caused by the intermolecular hydrogen bond interactions. The concentrations of SA had an excellent linear relationship with CDs' fluorescence intensity ratio (F499/F439) in a range of 1 âˆ¼ 120 and 120 âˆ¼ 240 µM with low detection limits of 0.68 and 1.05 µM. The established ratiometric fluorescent probe is economical, simple and green, and can be used for the effective detection of SA. In addition, the proposed ratiometric fluorescent probe was successfully used to monitor SA in facial mask and toning lotion samples with a satisfactory recovery of 99.7-106.7 %. The results show that the constructed fluorescent probe based on dual-emission CDs has a great potential for the rapid and sensitive analysis of SA in actual samples.


Assuntos
Pontos Quânticos , Pontos Quânticos/química , Corantes Fluorescentes/química , Carbono/química , Ácido Salicílico
17.
Front Bioeng Biotechnol ; 11: 1191240, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37425359

RESUMO

Crop rotation and other tillage systems can affect soil microbial communities and functions. Few studies have reported the response of soil spatial microbial communities to rotation under drought stress. Therefore, the purpose of our study was to explore the dynamic changes of the soil space microbial community under different drought stress-rotation patterns. In this study, two water treatments were set up, control W1 (mass water content 25%-28%), and drought W2 (mass water content 9%-12%). Four crop rotation patterns were set in each water content, spring wheat continuous (R1), spring wheat-potato (R2), spring wheat-potato-rape (R3) and spring wheat-rape (R4), for a total of eight treatments (W1R1, W1R2, W1R3, W1R4, W2R1, W2R2, W2R3, W2R4). Endosphere, rhizosphere and bulk soil of spring wheat in each treatment were collected, and root space microbial community data were generated. The soil microbial community changed under different treatments and their relationship with soil factors were analyzed using a co-occurrence network, mantel test, and other methods. The results revealed that the alpha diversity of microorganisms in the rhizosphere and bulk soil did not differ significantly, but it was significantly greater than in the endosphere. The bacteria community structure was more stable, fungi alpha-diversity significant changes (p < 0.05), that were more sensitive to the response of various treatments than bacteria. The co-occurrence network between fungal species was stable under rotation patterns (R2, R3, R4), while the community stability was poor under continuous cropping pattern (R1), and interactions were strengthened. Soil organic matter (SOM), microbial biomass carbon (MBC), and pH value were the most important factors dominating the bacteria community structural changed in the endosphere, rhizosphere, and bulk soil. The dominant factor that affected the fungal community structural changed in the endosphere, rhizosphere, and bulk soil was SOM. Therefore, we conclude that soil microbial community changes under the drought stress-rotation patterns are mainly influenced by soil SOM and microbial biomass content.

18.
Plants (Basel) ; 12(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37514354

RESUMO

Arabidopsis AGAMOUS (AG) play roles in determining stamens' and carpels' identities, floral meristem determinacy, and repression of the A-function. Gynostemium fused by stamens and carpels is a characteristic reproductive structure in orchid flowers, which shows a considerable difference from the reproductive organs of eudicots and other monocot species. The molecular basis of orchid gynostemium development remains largely unknown. Here, we report the identification and functional characterization of two AG-like genes, CyfaAG1 and CyfaAG2, and their promoters from C. faberi. Both CyfaAG1 and CyfaAG2 are highly expressed in the anther cap, gynostemium, and ovary. Ectopic expression of CyfaAG1 and CyfaAG2 promotes early flowering of wild-type Arabidopsis. Moreover, ectopic expression of CyfaAG1 completely rescues floral defects in the Arabidopsis ag-1 mutant, while ectopic expression of CyfaAG2 only completes filament and carpel development. Our findings suggest that CyfaAG1 acts as an evolutionarily conserved C-function gene in determining reproductive organ identity and mediating floral meristem determinacy. CyfaAG2 redundantly mediates the C-function in floral meristem determinacy and gynostemium development. Our results provided more details to understand how the C-class function has been partitioned in orchids, and the roles of two AG orthologs in regulating gynostemium development in C. faberi.

19.
Mol Neurobiol ; 60(11): 6676-6688, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37474884

RESUMO

Status epilepticus (SE) is a severe manifestation of epilepsy which can cause neurologic injury and death. This study aimed to identify key proteins involved in the pathogenesis of epilepsy and find a potential drug target for SE treatment. Tandem mass tag (TMT)-based quantitative proteomic analysis was applied to screen differentially expressed proteins (DEPs) in epilepsy. The adeno-associated virus was employed to overexpress candidate DEP in mice, and kainic acid (KA) was used to generate a mouse model of epilepsy. Then histopathological examination of the hippocampal tissue was performed, and the inflammatory factors levels in serum and hippocampus were measured. The IP-MS analysis was carried out to identify the interacting protein of nuclear cap-binding protein 1 (NCBP1). The results were that NCBP1 was downregulated in the epileptic hippocampus. NCBP1 overexpression alleviated KA-induced cognitive impairment in mice and reduced the apoptosis and damage of hippocampal neurons. Additionally, overexpressed NCBP1 increased the expression of NeuN and reduced the expression of GFAP and IBA-1 in the hippocampus of the mice. Further study indicated that NCBP1 overexpression inhibited the expression of IL-6, IL-1ß, and IFN-γ in serum and hippocampus as well as MDA and LDH in the hippocampus, whereas it increased the SOD levels, suggesting that overexpression of NCBP1 could diminish KA-induced inflammatory responses and oxidative stress. The IP-MS analysis identified that ELAVL4 was the NCBP1-interacting protein. In conclusion, this finding suggests that NCBP1 may potentially serve as a drug target for the treatment of epilepsy.

20.
Cell Rep ; 42(7): 112802, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37453065

RESUMO

Schwann cells play critical roles in peripheral neuropathies; however, the regulatory mechanisms of their homeostasis remain largely unknown. Here, we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis. Expression of Seh1 decreases as mice age. Loss of Seh1 leads to activated immune responses and cell necroptosis. Mice with depletion of Seh1 in Schwann cell lineage develop progressive reduction of Schwann cells in sciatic nerves, predominantly non-myelinating Schwann cells, followed by neural fiber degeneration and malfunction of the sensory and motor system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in Schwann cells. Collectively, our results demonstrate that Seh1 is required for Schwann cell homeostasis by maintaining genome integrity and suggest that decrease of nucleoporins may participate in the pathogenesis of periphery neuropathies.


Assuntos
Complexo de Proteínas Formadoras de Poros Nucleares , Doenças do Sistema Nervoso Periférico , Animais , Camundongos , Instabilidade Genômica , Bainha de Mielina/metabolismo , Necroptose , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo
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