Attention/memory complaint is correlated with motor speech disorder in Parkinson's disease.

BACKGROUND: The mechanisms underlying the online modulation of motor speech in Parkinson's disease (PD) have not been determined. Moreover, medical and rehabilitation interventions for PD-associated motor speech disorder (MSD) have a poor long-term prognosis. METHODS: To compare risk factors in PD patients with MSD to those without MSD (non-MSD) and determine predictive independent risk factors correlated with the MSD phenotype, we enrolled 314 PD patients, including 250 with and 64 without MSD. We compared demographic, characteristic data, as well as PD-associated evaluations between the MSD group and non-MSD group. RESULTS: Univariate analysis showed that demographic characteristics, including occupation, educational level, monthly income and speaking background; clinical characteristics, including lesions in the frontal and temporal lobes, and concurrent dysphagia; and PD-associated evaluations, including the activity of daily living (ADL) score, non-motor symptoms scale (NMSS) domain 4 score (perceptual problem), and NMSS domain 5 score (attention/memory) were all significantly different between the MSD and non-MSD group (all P < 0.05). Multivariate logistic regression analysis showed that educational level, frontal lesions, and NMSS domain 5 score (attention/memory) were independent risk factors for PD-associated MSD (all P < 0.005). CONCLUSIONS: We determined an association between MSD phenotype and cognitive impairment, reflected by low-level education and related clinical profiles. Moreover, attention and memory dysfunction may play key roles in the progression of MSD in PD patients. Further studies are required to detail the mechanism underlying abnormal speech motor modulation in PD patients. Early cognitive intervention may enhance rehabilitation management and motor speech function in patients with PD-associated MSD.

Diagnostic Value and Clinical Significance of Methylated SEPT9 for Colorectal Cancer: A Meta-Analysis.

BACKGROUND This meta-analysis aimed to clarify the diagnostic role of plasma methylated SEPT9 (mSEPT9) in colorectal cancer (CRC) and examined its association with CRC. MATERIAL AND METHODS A systematic review was conducted prior to July 2018. Summary sensitivity, specificity, and positive and negative likelihood ratio (PLR/NLR) were calculated for the diagnostic value of mSEPT9 for CRC. The areas under the receiver operating curves (AUCs) were used to summarize the overall test performance. RESULTS Twenty-two studies with 2271 CRC patients were enrolled. The summary sensitivity, specificity, PLR, NLR, DOR, and AUC of the overall analysis of mSEPT9 were 0.69, 0.92, 8.1, 0.34, 24, and 0.89, respectively. Subgroup and meta-regression analyses demonstrated that the diagnostic value was higher for the Epi proColon 2.0 assay, Asian ethnicity, and mSEPT9 test combined with fecal occult blood test (FOBT) or fecal immunochemical test (FIT) than for other test methods, white ethnicity, and mSEPT9 test alone. The rate of mSEPT9 positivity was higher in advanced CRC cases compared with early-stage CRC cases, and was higher in CRC cases than in adenoma cases. No significant difference in mSEPT9 positivity rate was found between left- and right-sided CRC. CONCLUSIONS Plasma mSEPT9 has a high diagnostic value for CRC, especially on the newly developed Epi proColon test 2.0 method. The diagnostic sensitivity is superior among Asians compared to whites, and the combination of mSEPT9 and FOBT/FIT has a better performance than mSEPT9 alone. Finally, the expression of mSEPT9 is associated with CRC stage but not with location.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning.

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Electroacupuncture-Modulated MiR-106b-5p Expression Enhances Autophagy by Targeting Beclin-1 to Promote Motor Function Recovery After Spinal Cord Injury in Rats.

OBJECTIVE: Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR106b-5p is an autophagy- and apoptosis-related microribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI. METHODS: The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction. In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in vivo, SCI rats were treated with EA for 7 days at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively. RESULTS: The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p. CONCLUSION: EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.

Bioinformatics analysis of genomic and immune infiltration patterns in autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a specific type of pervasive developmental disorder, and most studies suggest that the onset of autism may be related to genetic and immune factors. The etiology of autism and the underlying molecular events need to be further addressed. Methods: The ASD-related dataset GSE18123 was downloaded from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to screen for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that may be associated with autism. The top 5,000 genes with an absolute median difference were obtained, and a co-expression network was constructed using weighted correlation network analysis (WGCNA). In addition, GO and KEGG enrichment analyses were performed for genes in the modules most closely related to ASD. Hub genes were found in the significant modules, and the expression values and receiver operating characteristic (ROC) curves of the hub genes were analyzed and validated. Immune cell infiltration in ASD was calculated using the CIBERSORT algorithm, and the relationship between hub genes and immune cells was analyzed. Finally, GSEA was used to explore the potential pathways of hub genes affecting ASD. Results: The 5,000 DEGs were divided into eight significant modules by WGCNA. The green module was most significantly associated with ASD, and two hub genes [fatty acid-binding protein 2 (FABP2) and Janus kinase 2 (JAK2)] were found. Immune cell infiltration showed that resting dendritic cells and monocytes differed significantly in ASD and healthy individuals. FABP2 was significantly associated with memory B cells and CD8 T cells. JAK2 was significantly associated with monocytes, CD4 activated memory T cells, CD4 resting memory T cells, activated dendritic cells, gamma delta T cells, regulatory T cells (Tregs), CD8 T cells, and naïve CD4 T cells. FABP2 and JAK2 were found to affect multiple pathways of immunity. Conclusions: FABP2 and JAK2 may influence the immune microenvironment of ASD by regulating immune cells and immune-related pathways and are candidate molecular markers for the development of ASD.

miR-28-5p inhibits carcinogenesis in colon cancer cells and is necessary for erastin-induced ferroptosis.

BACKGROUND: Ferroptosis is a newly discovered type of regulated cell death, the underlying mechanisms of which need to be further illuminated. The regulatory activity of miR-28-5p in ferroptosis in colon cancer cells is currently unclear. This study set out to investigate the effect of miR-28-5p on ferroptosis in colon cancer cells and determine its underlying mechanism. METHODS: Biochemical Kits were used to measure iron concentration, malondialdehyde (MDA) concentration, glutathione (GSH) concentration and glutathione peroxidase (GPX) vitality. Cell counting kit 8 (CCK8) assays were conducted to evaluate cell viability. Flow cytometry was conducted to assess apoptosis. Transwell™ assays were used to measure the migratory and invasive abilities of HCT116 cells. Western blotting was used to measure the protein relative expression of NEDD4 binding protein 1 (N4BP1). Quantitative real-time polymerase chain reaction (RT-PCR) was used to measure the RNA relative expression of N4BP1 and miR-28-5p. RESULTS: Ferroptosis was induced in HCT116 cells by erastin in a dose- and time-dependent manner, which caused significant inhibition of proliferation, migration, and invasion in HCT116 cells; however, there was no obvious effect on apoptosis. miR-28-5p expression was decreased in colon cancer cells compared with the normal colon cells but was upregulated in erastin-treated HTC116 cells. Additionally, when overexpressed via the transfection of miR-28-5p mimics, miR-28-5p had an inhibitive effect on proliferation, migration, and invasion, while promoting apoptosis, in HCT116 cells. erastin-induced ferroptosis was also increased by miR-28-5p overexpression. Compared with normal colon cells, following erastin treatment, NEDD4 binding protein 1 (N4BP1) expression was increased in colon cancer cells and further decreased in HTC116 cells. miR-28-5p overexpression also inhibited N4BP1 mRNA and protein expression in HTC116 cells. CONCLUSIONS: miR-28-5p plays an important role in ferroptosis by targeting N4BP1 and could serve as a potential therapeutic approach for colon cancer.

Analyzing the prognostic value of DKK1 expression in human cancers based on bioinformatics.

BACKGROUND: The Dickkopf1 (DKK1) gene encodes a protein that belongs to the Dickkopf family. The protein can inhibit the Wnt signaling pathway which plays a key role in the carcinogenesis and progression of various types of cancers. Based on this, we hypothesized that the differential expression of DKK1 may figure significantly in cancers by regulating Wnt signaling pathway transduction. In this study, we conducted bioinformatics analysis to evaluate the prognostic and therapeutic value of DKK1 expression level in human cancers. METHODS: The expression level was analyzed by using the Oncomine database and Gene Expression Profiling Interactive Analysis tool. The analysis of prognosis was conducted by using the UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), and DriverDBv3 databases. We also investigated using DKK1 promoter methylation to define cancer types through the UALCAN database. Meanwhile, the related functional networks of DKK1 were analyzed by using the GeneMANIA interactive tool and Cytoscape software. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted using the Metascape online website, and we used the cBioPotartal database to explored DKK1 expression, aberrant information, and the co-expression genes in the subgroups of lung cancer. Finally, we performed the overall survival (OS) meta-analysis of the DKK1 expression in lung squamous cell carcinoma (LUSC) via the Lung Cancer Explorer (LCE). RESULTS: DKK1 was differentially expressed in different types of human cancers. DKK1 was overexpressed in human cancers including head and neck squamous cell carcinoma (HNSC), LUSC, and pancreatic adenocarcinoma (PAAD). Overexpression of DKK1 indicated adverse OS in bladder urothelial carcinoma (BLCA), HNSC, and PADD, but no difference in OS was found between the LUSC and healthy groups. The high expression of DKK1 was also associated with shorter disease-free survival (DFS) in HNSC, LUSC, and PAAD. Gene regulation network analysis indicated that DKK1 was mainly involved in Wnt signaling pathways and several other signaling pathways. CONCLUSIONS: Our findings showed that DKK1 is significantly expressed in various cancers and could be a biomarker for targeted therapy and a predictor for prognosis of these specific cancers. The bioinformatics analysis revealed a significant overexpression of DKK1 in HNSC, LUSC, and PAAD, with DKK1 overexpression being associated with adverse outcome in these patients, but how DKK1 expression levels relate to hematological malignancies and prognosis is still unclear. These new insights into the function of DKK1 may provide a basis for new targeted drug therapy and an avenue for further investigation into the mechanisms underlying carcinogenesis of DKK1 in different cancer types.

Expression and prognostic potential of GPX1 in human cancers based on data mining.

BACKGROUND: Glutathione peroxidase-1 (GPX1) is a member of the GPX family, which considered an enzyme that interacts with oxidative stress. GPX1 differential expression is closely correlated with carcinogenesis and disease progression. In this study, we used bioinformatics analysis to investigate GPX1 expression level and explore the prognostic information in different human cancers. METHODS: Expression was analyzed via the Oncomine database and Gene Expression Profiling Interactive Analysis tool, and potential prognostic analysis was evaluated using the UALCAN, GEPIA, and DriverDBv3 databases. Then, the UALCAN database was used to find the promoter methylation of GPX1 in defied cancer types. While GPX1 related functional networks were found within the GeneMANIA interactive tool and Cytoscape software. Moreover, Metascape online website was used to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. RESULTS: We found that GPX1 was commonly overexpressed in most human cancers. High expression of GPX1 could lead to poor outcomes in Brain Lower Grade Glioma, while GPX1 over expression was correlated with better prognosis in Kidney renal papillary cell carcinoma (KIPP). High GPX1 expression was marginally associated with poor prognosis in acute myeloid leukemia (AML). Gene regulation network suggested that GPX1 mainly involved in pathways including the glutathione metabolism, ferroptosis, TP53 regulates metabolic genes, reactive oxygen species (ROS) metabolic process, and several other signaling pathways. CONCLUSIONS: Our findings revealed that GPX1 showed significant expression differences among cancers and served as a prognostic biomarker for defined cancer types. The data mining effectively revealed useful information about GPX1 expression, prognostic values, and potential functional networks in cancers, thus providing researchers with an available way to further explore the mechanism underlying carcinogenesis of genes of interest in different cancers.

Genome-wide analysis to identify a novel distant metastasis-related gene signature predicting survival in patients with gastric cancer.

This study designed to identify a potential novel distant metastasis-related gene (DMGs) signature that predicting prognosis in patients with gastric cancer. DMGs was screened by overlapping the differentially expressed genes between M0 and M1 stage, and between tumor and adjacent normal tissue of gastric cancer by analyzing The Cancer Genome Atlas (TCGA) dataset. There were 83 DMGs were identified, the integrative analysis revealed these DMGs were involved in several biological process and pathway. A six-DMGs prognostic signature was developed based on the risk score obtained from Cox analysis. Patients with low risk score presented significantly shorter survival time. This prognostic signature has a moderate predictive value for the overall survival in gastric cancer patients, with an area under curve of 0.604. The DMGs prognostic signature also significantly associated with the overall survival of gastric cancer patients, and showed a better performance for predicting prognosis than traditional clinical indicators. The joint effect of risk score with clinical features could remarkably increased the predictive value as compared with single variable. The results from 60 gastric cancer tissues verified the prognostic value of the six-DMGs prognostic signature. In conclusions, the present study identified a novel six-DMGs prognostic signature that could serve as a biomarker for the prognosis prediction of patients with gastric cancer.