scholarly journals Network Structure Analysis Identifying Key Genes of Autism and Its Mechanism

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yanhui Wang ◽  
Yanming Kou ◽  
Dazhi Meng

Identifying the key genes of autism is of great significance for understanding its pathogenesis and improving the clinical level of medicine. In this paper, we use the structural parameters (average degree) of gene correlation networks to identify genes related to autism and study its pathogenesis. Based on the gene expression profiles of 82 autistic patients (the experimental group, E) and 64 healthy persons (the control group, C) in NCBI database, spearman correlation networks are established, and their average degrees under different thresholds are analyzed. It is found that average degrees of C and E are basically separable at the full thresholds. This indicates that there is a clear difference between the network structures of C and E, and it also suggests that this difference is related to the mechanism of disease. By annotating and enrichment analysis of the first 20 genes (MD-Gs) with significant difference in the average degree, we find that they are significantly related to gland development, cardiovascular development, and embryogenesis of nervous system, which support the results in Alter et al.’s original research. In addition, FIGF and CSF3 may play an important role in the mechanism of autism.

Author(s):  
Xitong Yang ◽  
Pengyu Wang ◽  
Shanquan Yan ◽  
Guangming Wang

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.


2020 ◽  
Author(s):  
Desmond Onyeka Agwunobi ◽  
Tingwei Pei ◽  
Xiaoshuang Wang ◽  
Zhijun Yu ◽  
Jing-Ze Liu

Abstract Background: The tick Haemaphysalis longicornis is well known as vector of several zoonotic pathogens responsible for various clinical conditions, increasingly threatens the veterinary and public health. It is mainly distributed in East Asia, New Zealand, Australia, and several Pacific islands, and has been expanded rapidly in United States since its first founding on a nonimported domestic sheep in New Jersey. Glutathione S-transferases (GSTs) are phase II detoxification enzymes, which function via combining with pesticidal molecules and catalyzing the conjugation of molecules by thiol of glutathione, so as to protect tissues from oxidative stress damage. In the tick H. longicornis, glutathione S-transferases (HlGST and HlGST2) have been previously identified. However, the relationship between the expression of glutathione S-transferases and the essential oil treatment in ticks remains unexplored. Hence, in the present study, the expression profiles of HlGST and HlGST2 mRNAs were evaluated in H. longicornis after exposure to Cymbopogon citratus essential oil. Results: At 24 h post-exposure of H. longicornis to different sublethal concentrations of C. citratus essential oil, ANOVA results revealed significant difference (F2,6 = 55.94, P = 0.0001) in the expression of HlGST. Tukey’s test showed that HlGST was significantly induced after treatment with 1% C. citratus essential oil (P = 0.0002); whereas no significant difference (P = 0.3551) was detected after treated by 2% C. citratus essential oil. No significant difference (F2,6 = 0.8990, P = 0.4555) in the expression of HlGST2 between the treatment and the control group of 50% ethanol. Nevertheless, the under-expression of HlGST2 in the treatment groups versus the untreated control group was not significant (F3,8 = 2.643, P = 0.1208). Conclusion: The results implied that GST mRNA is a potential molecular target for C. citratus essential oil in H. longicornis. Further understanding of the underlying mechanisms of the GST at the molecular level could contribute to develop effective control measures for ticks and tick-borne diseases.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chenlei Zheng ◽  
Cheng Wang ◽  
Tan Zhang ◽  
Ding Li ◽  
Xiao-feng Ni ◽  
...  

Objective. Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods. We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results. Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions. This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.


2020 ◽  
Vol 25 (5) ◽  
pp. 918-930
Author(s):  
Desmond O. Agwunobi ◽  
Tingwei Pei ◽  
Jia Yang ◽  
Xiaoshuang Wang ◽  
Lihong Lv ◽  
...  

Glutathione S-transferases (GSTs) are phase II detoxification enzymes, which function via combining with pesticidal molecules and catalyzing the conjugation of molecules by thiol of glutathione, so as to protect tissues from oxidative stress damage. In the tick Haemaphysalis longicornis, glutathione S-transferases (HlGST and HlGST2) have been previously identified. However, the relationship between the transcription of glutathione S-transferases and the essential oil treatment in ticks remains unexplored. Hence, in the present study, the transcription profiles of HlGST and HlGST2 mRNAs were evaluated in H. longicornis after exposure to Cymbopogon citratus essential oil. At 24 h post-exposure of H. longicornis to different sublethal concentrations of C. citratus essential oil, there was significant difference (P = 0.0001) in the transcription of HlGST. Tukey’s test showed that HlGST was significantly induced after treatment with 1% C. citratus essential oil (P = 0.0002); whereas no significant difference (P = 0.3551) was detected after treated by 2% C. citratus essential oil. No significant difference (P = 0.4555) in the transcription of HlGST2 between the treatment and the control group of 50% ethanol. Nevertheless, the down-regulation of HlGST2 in the treatment groups versus the untreated control group was not significant (P = 0.1208). The above results imply that the essential oil can modulate the expression of GST mRNA, therefore, further understanding of the underlying mechanisms of the GST at the molecular level could contribute to the development of effective control measures for ticks and tick-borne diseases.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2068-2068
Author(s):  
Xi Huang ◽  
Enfan Zhang ◽  
Xing Guo ◽  
Jing Chen ◽  
Xuanru Lin ◽  
...  

Abstract Background: Multiple myeloma (MM) is among the most common hematologic malignancies. Proteasome inhibitor bortezomib (Bor) is one of the most effective drugs for treatment of MM. However, during long-term Bor treatment, MM cells may eventually develop acquired-resistance to Bor which results in recurrence and a poor prognosis of MM. Several researches show that E3 ubiquitin ligases (E3s) primarily determine the substrate specificity of ubiquitin proteasome system and play an essential role in Bor resistance of MM. NEDD4-1 E3s, a founding member of the Neural precursor cell-Expressed Developmentally Downregulated gene 4 (NEDD4) family, was proved to involve in the proliferation, migration, invasion of cancer cells and the sensitivity of anticancer therapies. Our current study aims to explore the role and underlying mechanism of NEDD4-1 in acquired resistance of Bor in MM. Methods: The mRNA and protein levels of NEDD4-1 and its substrates in MM cell lines (H929, LP-1, RPMI8226, OPM-2 and ARP-1) and MM patients were detected by Quantitative Realtime PCR and Western Blotting. Lentiviral plasmids containing shRNA against NEDD4-1 were transfected into MM cells. Cell viability, proliferation and apoptosis of MM cells were measured by Cell Counting kit8 (CCK8) and flow cytometry. Gene array was used to compare the gene expression profiles of a panel of Bor treated MM cells vs vehicle-treated MM cells. Results: Gene array showed NEDD4-1 was significantly increased in MM cells treated with Bor. MM cells (CD138+ plasma cells of the bone marrow) from refractory/recurrence patients expressed lower NEDD4-1 than primary patient myeloma cells. Also, MM cell lines H929, ARP-1, LP-1 highly expressed NEDD4-1 at mRNA and protein levels. RPMI8226 and OPM-2 were relatively low expressed. Cell growth assay displayed no significant difference in proliferation between the NEDD4-1 knockdown (KD) and the control group (P>0.05). After suppression of NEDD4-1 using shRNAs, the killing effect of Bor in MM was significantly weaker than the control group (P<0.05). We also found that PTEN was decreased in the NEDD4-1 KD H929 cell line. Otherwise, phospho-STAT3 (ser727) and oncoprotein c-Myc and Bcl-2 were upregulated. Conclusion: Collectively, our study reveals that inhibition of NEDD4-1 can reduce MM sensitivity to Bor via regulating PTEN, c-Myc and Bcl-2, may be related to JAK/STAT signaling pathway, which suggests that NEDD4-1 probably acts as a novel drug target and therapeutic paradigm in the battle against multiple myeloma. Disclosures No relevant conflicts of interest to declare.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18530-18530
Author(s):  
V. B. Reddy ◽  
D. K. Oelschlager ◽  
J. S. Nolan ◽  
K. L. Taylor ◽  
J. Post ◽  
...  

18530 Background: To determine the cytokine expression profiles of patients with AML and NHL using a sensitive bead-based Luminex multiplex assay in a routine clinical diagnostic setting. Methods: Blood (plasma/serum) samples were collected from ten AML and five NHL patients. Six control samples from patients diagnosed as non-neoplastic/non-autoimmune/non-inflammatory were also analyzed for comparison. All samples were frozen prior to analysis. Using a bead-based Luminex assay (Human Cytokine 8-Plex Assay, Bio- Rad, Hercules, CA) we analyzed these samples for a panel of cytokines (IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha). This assay uses polystyrene microspheres, which provides simultaneous quantitation of these cytokines in a single sample. The expression levels were presented in picograms/mL. Average values for each of these markers were obtained for each group of patients (AML versus NHL versus Controls), and their expression levels were compared using χ2 analysis. Results: Overall, there was a significant difference in the expression profiles of all these cytokines among three patients groups (χ2, P < 0.001). All cytokines were consistently expressed at low levels in NHL patients as compared to control group. However, the levels of IL-6 and IL-8 were increased by 2.7 and 5.8 times, respectively in AML patients as compared to controls. Conclusions: The low levels of cytokines in NHL and AML patients suggest suppressed immune system in these two disease conditions; however, these findings warrant further studies to explore the underlying mechanisms for the increased levels of IL-6 and IL-8 in AML patients. Currently, studies are in progress to compare the levels of cytokines measured by Luminiex assay in different stages of leukemias and lymphomas (initial, post treatment and recovery phase etc.). These studies are partially funded by grants from the National Institute of Health/National Cancer Institute (RO1-CA98932–01 and U24-CA086359). No significant financial relationships to disclose.


2019 ◽  
Vol 24 (1) ◽  
pp. 16 ◽  
Author(s):  
Tianrong Xin ◽  
Xiaoyue Li ◽  
Jiadong Yin ◽  
Xianyan Ye ◽  
Ji Wang ◽  
...  

In almost all aerobic organisms, the superoxide dismutase (SOD) is considered as an important antioxidant enzyme regulating oxidative stress. Tetranychus cinnabarinus is an economically important polyphagous pest mite, which harms a variety of economic crops and ornamental plants. In the present study, the full-length cDNA sequences of cytoplasmic Cu/ZnSOD (TcSOD1), extracellular Cu/ZnSOD (TcSOD2) and mitochondrial MnSOD (TcSOD3) from T. cinnabarinus were cloned by combining RT-PCR and rapid amplification of cDNA ends (RACE). The corresponding open reading frames (ORFs) encode three putative polypeptides of 152, 232, 225 amino acid residues, respectively. These sequences share the conserved SOD functional domains, signature motifs and metal binding sites. Multiple alignment analysis revealed that cytosolic Cu/ZnSOD and mitochondrial MnSOD sequences are relatively conserved, while extracellular Cu/ZnSODs are more diverse. Phylogenetic analysis showed that SODs are organized into two major clades, corresponding to Cu/ZnSODs, and MnSODs. Cu/ZnSODs are subdivided into two branches, one being composed of cytoplasmic Cu/ZnSODs, and the other corresponding to extracellular Cu/ZnSODs. Expression profiles of the three genes were determined at different temperatures (4°C, 25°C, and 40°C) for 2 hours. The relative expression of TcSOD1, TcSOD2, and TcSOD3 were significantly down-regulated (0.344-, 0.287-, and 0.358-fold, respectively) at 4°C compared to 25°C (P<0.05). The relative expression levels of TcSOD1 and TcSOD2 genes were significantly down-regulated at 40°C (0.481- and 0.291-fold less than in the control group, respectively) (P<0.05), while there was no significant difference in the relative expression level of TcSOD3(P>0.05). Moreover, expression levels were altered after exposition to different acaricides. TcSOD1, TcSOD2, and TcSOD3 were significantly down-regulated (0.450-, 0.147- and 0.663-fold decreases, respectively) in the abamectin-treated group (P<0.05). TcSOD1 and TcSOD2 were down-regulated, in the fenpropathrin-treated group with 0.794- and 0.201-fold decreases, respectively. On the other hand, the expression of TcSOD3 was significantly increased (P<0.05), being 2.774-fold higher than in the control group. The expression of TcSOD2 was significantly down-regulated both the propargite- and cyflumetofen-treated groups (0.655- and 0.397-fold, respectively) (P<0.05). The data reported here indicate that SODs from T. cinnabarinus may play different and vital roles in anticipating the effects of oxidative damage at extreme temperatures and under different acaricides stress.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Thaís Tibery Espir ◽  
Luanda de Paula Figueira ◽  
Maricleide de Farias Naiff ◽  
Allyson Guimarães da Costa ◽  
Marcelo Ramalho-Ortigão ◽  
...  

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species ofLeishmaniain Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified asLeishmania guyanensis,L. naiffi, andL. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to theLeishmaniaspecies. Infection caused byL. guyanensisaccounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection byL. amazonensis. Patients with infection caused byL. naiffishowed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jia-qi Wu ◽  
Lin-bo Mao ◽  
Ling-feng Liu ◽  
Yong-mei Li ◽  
Jian Wu ◽  
...  

Abstract Background The purpose of present study was to identify the differentially expressed genes (DEGs) associated with BMP-9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by using bioinformatics methods. Methods Gene expression profiles of BMP-9-induced MSCs were compared between with GFP-induced MSCs and BMP-9-induced MSCs. GSE48882 containing two groups of gene expression profiles, 3 GFP-induced MSC samples and 3 from BMP-9-induced MSCs, was downloaded from the Gene Expression Omnibus (GEO) database. Then, DEGs were clustered based on functions and signaling pathways with significant enrichment analysis. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in cytoplasm, nucleus, and extracellular exosome signaling pathway. Results A total of 1967 DEGs (1029 upregulated and 938 downregulated) were identified from GSE48882 datasets. R/Bioconductor package limma was used to identify the DEGs. Further analysis revealed that there were 35 common DEGs observed between the samples. GO function and KEGG pathway enrichment analysis, among which endoplasmic reticulum, protein export, RNA transport, and apoptosis was the most significant dysregulated pathway. The result of protein-protein interaction (PPI) network modules demonstrated that the Hspa5, P4hb, Sec61a1, Smarca2, Pdia3, Dnajc3, Hyou1, Smad7, Derl1, and Surf4 were the high-degree hub nodes. Conclusion Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in BMP-9 induced MSCs, which could improve our understanding of the key genes and pathways for BMP-9-induced osteogenic of MSCs.


Author(s):  
M.I. Lesiv ◽  
V.A. Hryb

This article presents the investigation of structural parameters of the brain in 67 patients aged 47.23 ± 2.64 years, whose duration of the disease was 13.27 ± 0.75 (from 2 to 19) years. The control group included 18 healthy individuals of the same age (47.84 ± 0.36 years), whose selection was carried out based on the anamnesis and the absence of hypothyroidism and hypertension. According to the data we discussed in our previous publications, during neuropsychological testing we registered memory deterioration in patients with hypertension assessed by the test for learning 10 words according to the method proposed by A.R. Luria (p <0.05), as well as serial counting by the Matisse scale (p <0.05). The patients with hypothyroidism were found as demonstrating attention deficiency (p <0.05) by applying the method of "Selectivity of attention" (G. Munsterberg test). For more detailed assessment, we used Schulte tables, the result of which demonstrates the state of the domain of the patient's executive functions and proves the instability of attention. The analysis of the results showed that taking into account the interaction between hypertension and hypothyroidism, the most affected cognitive domains were memory and attention, respectively (p <0.05). To diagnose cognitive and mnestic disorders of all groups, we used MR imaging, measured the transverse dimensions of the medial, lateral (temporal horn) and vertical perihippocampal spaces, and evaluated the volume of gray matter (cortex) of the frontal lobe of the brain in 3 zones. The measurements were performed in the right and left hemispheres. There was a significant increase in the indices of the medial and upper perihippocampal right and left in the patients in group III compared with the groups I and II. The lateral perihypocampal index did not differ significantly in the three groups (p> 0.05). Thus, taking into account the interaction of factors (hypertension and hypothyroidism), the patients were found to have an increase in perihippocampal indices (p> 0.05). Based on the data in table 2, in the patients of group I the average value of the frontal lobe was 634.06 ± 10.92. In the patients of group II, the average value of the frontal lobe was 638.6 ± 7.82, and in the patients of group III, the average value of the frontal lobe was 601.3 ± 3,325. There was no statistically significant difference between groups I and II (p = 0.05). But groups I and III demonstrated statistically significant difference between the indicators (p <0.05). We also found a statistically significant difference between groups II and III (p <0.05). Thus, in patients with hypertension, hypothyroidism and hypertension with concomitant hypothyroidism, an increase in perihippocampal indices, a decrease in the volume of gray matter (cortex) of the frontal lobe of the brain (right and left), significantly exceeded possible (involutional or otherwise). Thus, the results of the study indicate that in cases of isolated hypertension, hypothyroidism, and in the comorbidity of hypertension and hypothyroidism, there has been detected a significant acceleration of atrophic processes.


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