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1.
Neurochem Int ; 168: 105564, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37286109

RESUMO

Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log2(Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-ß, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-ß and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-ß and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments.


Assuntos
Medula Cervical , Compressão da Medula Espinal , Doenças da Medula Espinal , Traumatismos da Medula Espinal , Ratos , Animais , Interleucina-17/metabolismo , Interleucina-17/uso terapêutico , Medula Cervical/patologia , Gliose/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doenças Neuroinflamatórias , Transcriptoma , Fosfatidilinositol 3-Quinases/metabolismo , Compressão da Medula Espinal/patologia , Doenças da Medula Espinal/complicações , Medula Espinal/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Traumatismos da Medula Espinal/metabolismo
2.
J Colloid Interface Sci ; 633: 1033-1041, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36516679

RESUMO

Photocatalytic evolution of hydrogen is becoming a research hotspot because it can help to produce clean energy and reduce environmental pollution. Titanium dioxide (TiO2) and its composites are photocatalysts that are widely used in hydrogen evolution because of their high abundance in nature, low price, and high photo/chemical stability. However, their catalytic performances still need to be further improved, particularly in the visible light spectrum. Herein, visible light-driven photocatalytic evolution of hydrogen on Au/TiO2 nanocomposite is enhanced âˆ¼ 10 folds by selectively functionalizing the nanocomposite with cysteamine molecules. It is revealed that the amine group (-NH2) in cysteamine favors the transfer and separation of photo-generated hot carriers. The rate of hydrogen produced can be further tuned by varying the ionization of the functionalized molecules at different pH values. This work provides a simple, convenient, and effective method that can be used to improve the photocatalytic evolution of hydrogen. This method can also be used for many other nanocatalysts (e.g., Au-MoS2, Au-BiVO4) and catalytic reactions (e.g., carbon dioxide reduction, nitrogen reduction).


Assuntos
Cisteamina , Hidrogênio , Adsorção , Hidrogênio/química , Luz
3.
Neural Regen Res ; 18(3): 634-642, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018188

RESUMO

Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

4.
Medicine (Baltimore) ; 101(39): e30760, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181109

RESUMO

BACKGROUND: Chloride intracellular channel 1 (CLIC1) plays an important role in the process of cell epithelial transport, and is also involved in tumor invasion and metastasis. Due to its aberrant expression in cancer, the mechanism of action of CLIC1 in cancer has been carefully studied. In this study, we tried to investigate the relationship between CLIC1 and lung adenocarcinoma (LUAD). METHODS: The RNA-sequencing data and clinical information of CLIC1 in lung adenocarcinoma were collected from the the cancer genome altas (TCGA) database and analyzed with R software. Paired t test and Mann-Whitney U test were used to detect differences between LUAD tissue and adjacent normal tissue, and the pROC software package performed reactive oxygen species (ROC) curves to detect cutoff values for CLIC1. The expression of CLIC1 in normal human tissues was extracted from the human protein altas (HPA) database, and analyzed clinical proteomic tumor analysis consortium by using UALCAN programme. The relationship between CLIC1 and LUAD was explored by enrichment analysis using gene oncology and Kyoto encyclopedia of genes and genomes. The tumor immunity estimation resource (TIMER) and integrated repository portal for tumor-immune system interactions (TISIDB) databases were used to analyze the correlation between CLIC1 and LUAD immune cell infiltration. Survival analysis of CLIC1 in LUAD was assessed by the PrognoScan database. RESULTS: Compared with normal tissues, both mRNA (messenger Ribose Nucleic Acid) and protein of CLIC1 were overexpressed in LUAD, which was associated with shorter overall survial (OS). In addition, CLIC1 expression was in connection with some clinical-pathological characteristics like tumor node metatasis stages and lymph node metastases. What's more, CLIC1 may play a role in the immune infiltration of LUAD. CONCLUSION: In summary, CLIC1 is up-regulated in LUAD and is associated with tumor metastasis, tumor staging, and OS. It may be regarded as a novel marker for prognostic judgement in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Canais de Cloreto/genética , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Proteômica , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Ribose
5.
Neurochem Int ; 157: 105340, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35398187

RESUMO

INTRODUCTION: Cervical spondylotic myelopathy (CSM) is the most prevalent type of non-traumatic spinal cord injury. The pathological process of CSM is relatively complicated. Most of the chronic cervical cord compression animal models established using hydrophilic expanding polymer are single-segment compression, which was deviated from clinical practice with double-segment or multi-segment compression. This study aims to better mimic the actual clinical compression by using a new type of hydrophilic expanding polymer to establish an animal model of double-level cervical cord compression. MATERIALS AND METHODS: Progressive cord compression was done with implantation of polyvinyl alcohol-polyacrylamide hydrogel in the spinal canal at the C3-4 and C5-6 levels. Sprague-Dawley rats (n = 32) were divided into three groups: sham (no compression, n = 12) and screw compression group (n = 8), and hydrogel compression group (n = 12). Functional deficits were characterized using motor function scores, forelimb grip strength, hindlimb pain threshold, and gait analysis, while compression was imaged with magnetic resonance imaging. The apoptosis, inflammation, and demyelination were assessed by hematoxylin and eosin staining, Luxol fast blue staining, TUNEL assay, immunofluorescence staining, and Western blot analysis. RESULTS: Motor function scores for rats with cervical cord hydrogel compression were significantly decline in motor function scores, an increase in allodynia, neurons and oligodendrocytes apoptosis related to B cell lymphoma-2 (Bcl-2)/Bcl-2 associated X (Bax)/cleaved caspase-3, and impaired axonal conduction, as well as neuroinflammation zone related to microglia or macrophages aggregation related to the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome activation, and activation of astrocytes, as well as oxidative stress were observed. CONCLUSION: We believe that this model utilizing compression on double-level cervical cord will allow researchers to investigate of translationally relevant therapeutic methods for CSM.


Assuntos
Medula Cervical , Compressão da Medula Espinal , Doenças da Medula Espinal , Animais , Apoptose/fisiologia , Medula Cervical/patologia , Hidrogéis/farmacologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Polímeros , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/cirurgia
6.
Front Immunol ; 13: 857308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345673

RESUMO

Background: Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction. Methods: By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes. Results: The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers. Conclusion: Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.


Assuntos
Adenocarcinoma , Glipicanas/análise , Neoplasias Pancreáticas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glipicanas/genética , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Prognóstico
7.
Ann Transl Med ; 9(22): 1662, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34988171

RESUMO

BACKGROUND: Artificial intelligence (AI) is used to solve the problem of missed diagnosis of polyps in colonoscopy, which has been proved to improve the detection rate of adenomas. The aim of this review was to evaluate the diagnostic performance of AI-assisted detection and classification of polyps in colonoscopy. METHODS: The literature search was undertaken on 4 electronic databases (PubMed, Web of Science, Embase, and Cochrane Library). The inclusion criteria were as follows: studies reporting AI-assisted detection and classification of polyps; studies containing patients, images, or videos receiving AI-assisted diagnosis; studies which included AI-assisted diagnosis and reported classification based on histopathology; and studies providing accurate diagnostic data. Non-English language studies, case-reports, reviews, meeting abstracts and so on were excluded. The Quality Assessment of Diagnostic Accuracy Studies-2 scale was used to evaluate the quality of literature and the Stata 13.0 software was used to perform meta-analysis. RESULTS: Twenty-six articles were included with all of medium quality. Meta-analysis showed none of literature had any obvious publication bias. The application of AI in detection of colorectal polyps achieved a sensitivity of 0.95 [95% confidence interval (CI): 0.89-0.98] and an area under the curve (AUC) of 0.79 (95% CI: 0.79-0.82). In the AI-assisted classification, the sensitivity was 0.92 (95% CI: 0.88-0.95) with a specificity of 0.82 (95% CI: 0.71-0.89) and an AUC of 0.94 (95% CI: 0.92-0.96). For the classification of diminutive polyps, the AI-assisted technique yielded a sensitivity of 0.95 (95% CI: 0.94-0.97), a specificity of 0.88 (95% CI: 0.74-0.95), and an AUC of 0.97 (95% CI: 0.95-0.98). For AI-assisted classification under magnifying endoscopy, the sensitivity was 0.954 (95% CI: 0.92-0.96) with a specificity of 0.95 (95% CI: 0.80-0.99) and an AUC of 0.97 (95% CI: 0.95-0.98). DISCUSSION: The AI-assisted technique demonstrates impressive accuracy for the detection and characterization of colorectal polyps and can be expected to be a novel auxiliary diagnosis method. Our study has inevitable limitations including heterogeneity due to different AI systems and the inability to further analyze the specificity and sensitivity of AI for different types of endoscopes.

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