Dataset Information

Rapid Discovery of Potential Drugs for Osteonecrosis of Femoral Head Based on Gene Expression Omnibus Database and Connectivity Map.

ABSTRACT: OBJECTIVE:To use Gene Expression Omnibus (GEO) database coupled with Connectivity Map (CMap) databases to screen potential therapeutic drugs for osteonecrosis of femoral head (ONFH) rapidly. METHODS:Raw genetic data with accession number GSE74089 that contained eight hip articular cartilage specimens from four ONFH patients and four healthy controls were obtained from the Gene Expression Omnibus (GEO) database and were then integrated using R to identify differentially expressed genes (DEGs). Subsequently, to identify several potential small molecular compounds that were most strongly negatively correlated with ONFH, a search query of DEGs was explored by using CMap. RESULTS:Filtering revealed 1937 DEGs with log (fold-change) ?1 and adjust P value < 0.001. Finally, a network of candidate targets for ONFH with 135 nodes and 660 edges was constructed through network topology analysis, including 96 up-regulated genes and 39 down-regulated genes. Several significant gene functions and signaling pathways associated with pathological processes of ONFH were identified via gene enrichment analysis. Based on the CMap database, some potential small molecular components that may be possible to counteract the effects of molecular signal imbalance for ONFH were identified. Neostigmine bromide with low CMap score and P value and specificity score was predicted to be the most candidate compound, involved in the "positive regulation of stem cell proliferation," "regulation of protein autophosphorylation," "VEGF signaling pathway," and "ECM-receptor interaction." CONCLUSIONS:The GEO and CMap databases can be effectively used in understanding the molecular changes in ONFH and provide a systematic manner to identify potential drugs for ONFH prevention and treatment. However, additional clinical and experimental research of the candidate compound is warranted.

SUBMITTER: Luo D

PROVIDER: S-EPMC6904644 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Rapid Discovery of Potential Drugs for Osteonecrosis of Femoral Head Based on Gene Expression Omnibus Database and Connectivity Map.

Luo Di D Liang Xue-Zhen XZ Xu Bo B Liu Jin-Bao JB Wei Chuan-Fu CF Li Gang G

Orthopaedic surgery 20191106 6

<h4>Objective</h4>To use Gene Expression Omnibus (GEO) database coupled with Connectivity Map (CMap) databases to screen potential therapeutic drugs for osteonecrosis of femoral head (ONFH) rapidly.<h4>Methods</h4>Raw genetic data with accession number GSE74089 that contained eight hip articular cartilage specimens from four ONFH patients and four healthy controls were obtained from the Gene Expression Omnibus (GEO) database and were then integrated using R to identify differentially expressed g ...[more]

PMID: 31692295

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Project description:BackgroundGlucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH.PurposesTo investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH.MethodsFrom September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels.ResultsIn the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH.ConclusionsGONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Project description:BackgroundThe coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19.MethodBased on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2.Results and conclusionThe up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir.

Project description:Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

Dataset Information

Rapid Discovery of Potential Drugs for Osteonecrosis of Femoral Head Based on Gene Expression Omnibus Database and Connectivity Map.

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Rapid Discovery of Potential Drugs for Osteonecrosis of Femoral Head Based on Gene Expression Omnibus Database and Connectivity Map.

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