Diabetes mellitus (DM) is one of the most common diseases worldwide. Uncontrolled and prolonged hyperglycemia can cause diabetic complications, which reduce the quality of life of patients. Diabetic ...complications are common in DM patients. Because it is impossible to completely recover from diabetic complications, it is important for early detection. In this study, we suggest a novel method of determining blood flow characteristics based on fluorescence image analysis with indocyanine green and report that diabetic complications have unique blood flow characteristics.
We analyzed time-series fluorescence images obtained from controls, DM patients, and DM patients with complications. The images were segmented into the digits and the dorsum of the feet and hands, and each part has been considered as arterial and capillary flow. We compared the blood flow parameters in each region among the three groups.
The DM patients with complications showed similar blood flow parameters to the controls, except the area under the curve and the maximum intensity, which indicate the blood flow volume. These parameters were significantly decreased in DM patients with complications. Although some blood flow parameters in the feet of DM patients with complications were close to normal blood flow, the vascular response of the macrovessels and microvessels to stimulation of the hands was significantly reduced, which indicates less reactivity in DM patients with complications.
Our results suggest that DM patients, and DM patients with complications, have unique peripheral blood flow characteristics.
Glioblastoma (GBM) is a representative malignant brain tumor characterized by a dismal prognosis, with survival rates of less than 2 years and high recurrence rates. Despite surgical resection and ...several alternative treatments, GBM remains a refractory disease due to its aggressive invasiveness and resistance to anticancer therapy. In this report, we explore the role of fibronectin type III domain containing 3B (FNDC3B) and its potential as a prognostic and therapeutic biomarker in GBM. GBM exhibited a significantly higher cancer-to-normal ratio compared to other organs, and patients with high FNDC3B expression had a poor prognosis (
< 0.01). In vitro studies revealed that silencing FNDC3B significantly reduced the expression of Survivin, an apoptosis inhibitor, and also reduced cell migration, invasion, extracellular matrix adhesion ability, and stem cell properties in GBM cells. Furthermore, we identified that FNDC3B regulates PTEN/PI3K/Akt signaling in GBM cells using MetaCore integrated pathway bioinformatics analysis and a proteome profiler phospho-kinase array with sequential western blot analysis. Collectively, our findings suggest FNDC3B as a potential biomarker for predicting GBM patient survival and for the development of treatment strategies for GBM.
Abstract Analysis using the public microarray database Gene Expression Omnibus indicates significantly higher mRNA expression of VEGF and VEGFRs in colorectal cancer and high grade astrocytoma but ...not in hepatocellular carcinoma compared to normal tissue. Human malignant astrocytoma cell lines (U251-MG and U373-MG) and HT-1080 fibrosarcoma cells expressed relatively higher levels of VEGF and VEGFRs compared to hepatocellular and colorectal cancer cell lines. Administration of exogenous VEGF-A induced cell growth in a dose-dependent fashion in astrocytoma and fibrosarcoma cells but not in colorectal and hepatocellular cancer cells. The blockade of VEGF inhibited cell survival only in U251-MG, U373-MG and HT-1080 cells. These results collectively suggest the role of autocrine VEGF signaling in various cancer cells and provide a basis for the variable clinical responses to antiangiogenic therapy observed in different types of malignancies.
Expression profile of normal tissue is primary source to find genes showing aberrant expression pattern specific in matched cancer tissue, but sample number of normal control in public gene ...expression repositories is disproportionally small compared to cancer and scattered in several datasets.
We built oncopression by integrating several datasets into one large dataset for comprehensive analysis about 25 types of human cancers including 20 640 cancer samples and 6801 normal control profiles. Expression profiles in cancers can be directly compared to normal tissue counterparts. Validity of the integration was tested using immunohistochemical staining results and principal component analysis. We have utilized the pre-release version of oncopression to identify cancer-specific genes in several studies.
Free access at http://www.oncopression.com and all expression data are available for download at the site.
cchoi@kaist.ac.kr or jungsullee@gmail.com.
Supplementary data are available at Bioinformatics online.
Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep ...into tissue, significant attention has been given to intravital NIR fluorescence imaging.
We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1.
We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.
A frameshift mutation of ubiquitin called ubiquitin(+1) (UBB(+1)) was found in the aging and Alzheimer's disease brains and thought to be associated with neuronal dysfuction and degeneration. Even ...though ubiquitylation has been known to regulate vital cellular functions mainly through proteasome-dependent degradation of polyubiquitinated substrates, proteolysis-independent roles of ubiquitylation have emerged as key mechanisms in various signaling cascades. In this study, we have investigated the effect of UBB(+1) on proinflammatory signaling such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in human astrocytes. Treatment with TNF-α and IL-1β induced expression of CCL2 and CXCL8 by human astrocytic cells; while ectopic expression of UBB(+1) significantly abrogated the proinflammatory cytokine-induced expression of chemokines. Ectopic expression of UBB(+1) suppressed TNF-α- and IL-1β-induced activation of NF-κB and JNK signaling pathway. Furthermore, we have demonstrated that polyubiquitylation of TRAFs and subsequent phosphorylation of TAK1 were significantly inhibited by stable expression of UBB(+1). Collectively, these results suggest that UBB(+1) may affect proinflammatory signaling in the central nervous system via inhibitory mechanisms of ubiquitin-dependent signaling in human astrocytes.
Diacylglycerol acyltransferase‐1 (DGAT1), a key enzyme in triglyceride (TG) biogenesis, is highly associated with metabolic abnormalities, such as obesity and type 2 diabetes. However, the effects of ...DGAT1 silencing in the human liver have not been elucidated. To investigate the effects of DGAT1 silencing in human liver cells, we compared the cellular behaviours of DGAT1‐deficient Huh‐7.5 cell lines with those of control Huh‐7.5 cells. DGAT1‐deficient cells acquired dedifferentiated and stem cell‐like characteristics, such as formation of aggregates in the presence of high levels of growth factors, high proliferation rates and loss of albumin secretion. In relation to aggregate formation, the expression level of various adhesion molecules was significantly altered in DGAT1‐deficient cells. Microarray data analysis and immunostaining of patient tissue samples clearly showed decreased expression levels of DGAT1 and integrin β1 in patients who have nodular cirrhosis without fatty degeneration.
Adrenomedullin (ADM), a secretory peptide with multiple functions in physiological to pathological conditions, is upregulated in several human cancers, including brain, breast, colon, prostate, and ...lung cancer. However, the molecular mechanisms underlying the regulation of ADM expression in cancerous cells are not fully understood. Here, we report that oncostatin M (OSM), a cytokine belonging to the interleukin-6 family, induces ADM expression in astroglioma cells through induction of signal transducer and activator of transcription-3 (STAT-3) phosphorylation, nuclear translocation, and subsequent DNA binding to the ADM promoter. STAT-3 knockdown decreased OSM-mediated expression of ADM, indicating that ADM expression is regulated by STAT-3 in astroglioma cells. Lastly, scratch wound healing assay showed that astroglioma cell migration was significantly enhanced by ADM peptides. These data suggest that aberrant activation of STAT-3, which is observed in malignant brain tumors, may function as one of the key regulators for ADM expression and glioma invasion.
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