Identification of co-expression modules and pathways correlated with osteosarcoma and its metastasis.

BACKGROUND: Osteosarcoma is the most common bone tumor that occurs in children. METHODS: To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules. RESULTS: A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset. CONCLUSIONS: Our analysis might provide insight for molecular mechanisms of osteosarcoma.

Investigating age­induced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis.

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age­induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age­induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA­mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan­Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in 'ubiquitin protein ligase binding', 'response to growth factor', 'regulation of type I interferon production', 'response to decreased oxygen levels', 'voltage­gated potassium channel complex', 'synapse part', 'regulation of stem cell proliferation'. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.

Galectin-3 deficiency protects lipopolysaccharide-induced chondrocytes injury via regulation of TLR4 and PPAR-γ-mediated NF-κB signaling pathway.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis.

Tele-ICU: the way forward in geriatric care?

Aging population is set to increase in the near future, and will need specialized care when admitted to ICUs. The elderly are beset with chronic conditions, such as cardiovascular, COPD, diabetes, renal complications and depression. Specialist opinions can now be made available through telemedicine facilities. Tele-ICU is a specialized hub consisting of highly skilled staff trained in critical care able to deliver timely, quality care service to patients admitted to ICUs in remote areas using highly advanced information technology services. These specialists in the tele-ICU hub are able to analyze and gather data arriving at timely interventional management decisions and provide this vital feedback to the nursing staff and doctors manning remote ICU locations where specialized intensivist may not be available. Known clinical benefits of such a system include better patient outcomes, reduced medical errors, mortality and reduced hospital length of stay. The main disadvantage in implementation could be the upfront high cost involved, for which low-cost models are being explored. In the face of delivering such remote care, it is up to the local health policy to make legislative changes to include associated legal and ethical issues. Considering the burgeoning aging population, tele-ICU could become the way forward in delivering geriatric critical care.