26 research outputs found
Factors regulating the synthesis and secretion of corticosteroid-binding globulin (CBG) in the young pig
This study examined the in vitro production of corticosteroid-binding globulin (CBG) by liver collected from pigs at various ages following birth, the effects of various hormone treatments on the in vitro hepatic release of CBG, and the relationship between the hormone effects and postnatal development. Liver was collected from pigs (n=20) immediately following euthanasia on 3, 10, 20, 30 or 40 days of age. Liver slices (200 mg) were incubated for 12 and 24 hours with either cortisol (10-7 M), estradiol (10-8 M), progesterone (10-7 M), or thyroxine (10-7 M) prepared in 0.5% ethanol. A single blood sample was collected upon euthanasia for determination of plasma CBG levels. The amount of CBG released per unit weight of liver slices and in circulation was measured using an enzyme-linked immunosorbent assay (ELISA) procedure. The percentage of cell\u27s dying and the amount of total protein released were measured to compare with CBG concentration. Cell death was higher (P\u3c0.05) on days 3, 10, and 20 than on days 30 and 40. Addition of 0.5% ethanol to the media did not affect the release of total protein or CBG. The release of total protein did not change (P\u3e0.10) with age. Plasma CBG levels increased (P\u3c0.05) on day 30 and CBG levels measured in media from liver slices decreased (P\u3c0.01) on day 20. Hormone treatment had no apparent effect on the release of CBG by the cultured liver. Consequently, the release of CBG per unit weight of liver decreased (P\u3c0.01) on day 20. CBG release from hepatic tissue may be regulated in a different manner from that of other proteins. The absence of a hormone treatment effect on the release of CBG from liver slices may indicate that regulation of CBG release from the liver may be primarily related to age
Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression
Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells
Application of comparative functional genomics to identify best-fit mouse models to study human cancer
Genetically modified mice have been extensively used for
analyzing the molecular events that occur during tumor
development. In many, if not all, cases, however, it is uncertain
to what extent the mouse models reproduce features observed
in the corresponding human conditions1–3. This is due largely
to lack of precise methods for direct and comprehensive
comparison at the molecular level of the mouse and human
tumors. Here we use global gene expression patterns of 68
hepatocellular carcinomas (HCCs) from seven different mouse
models and 91 human HCCs from predefined subclasses4 to
obtain direct comparison of the molecular features of mouse
and human HCCs. Gene expression patterns in HCCs from
Myc, E2f1 and Myc E2f1 transgenic mice were most similar to
those of the better survival group of human HCCs, whereas the
expression patterns in HCCs from Myc Tgfa transgenic mice
and in diethylnitrosamine-induced mouse HCCs were most
similar to those of the poorer survival group of human HCCs.
Gene expression patterns in HCCs from Acox1 ̸ mice and
in ciprofibrate-induced HCCs were least similar to those
observed in human HCCs. We conclude that our approach
can effectively identify appropriate mouse models to study
human cancers
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Review of Suicide Prevention Programs: Massachusetts, United States, in Comparison with Seoul
Suicide is a tragedy that has massive impact on society. In order to prevent suicide, active government intervention is necessary. The suicide rate in Seoul is rapidly increasing and is more than five times higher than that in the state of Massachusetts (MA) during the last decade, especially in the elderly. The suicide prevention program of MA is one of the most effective suicide prevention programs in the United States. The program views suicide as a preventable public health problem, and emphasizes treatment of depression and de-stigmatization of mental health illnesses to prevent suicide. Also, through active collaboration with mental health professionals, they try to identify at-risk populations and help them to get medical interventions. The program also actively collaborates with the regional coalition program and the Samaritans in taking care of the elderly, and supports the elderly in feeling worthwhile after retirement by helping them to work for communities as volunteers. For its part, the Seoul suicide prevention program puts more emphasis on "life respect culture" and "emotional support to high risk individuals by regular visiting". The annual budget of the Seoul suicide prevention program is one-quarter and that for mental health is about one-twentieth that of MA. Considering the high suicide rate and lower mental health service usage in Seoul, it is crucial to raise awareness of depression and decrease the stigma on mental illnesses. Furthermore, educational efforts with long-term investment in research on suicide are necessary
Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns
Abstract Corneal chemical burns can lead to blindness following serious complications. As most of these complications are caused by failure of reepithelization during the acute phase, treatment at this stage is critical. Although there have been some studies on corneal injury recovery using adipose tissue-derived stem cells (ADSCs), none has reported the effect of topical cell-free conditioned culture media (CM) derived from ADSCs on corneal epithelial regeneration. Here, the best conditions for CM were selected and used for in vitro and in vivo experiments. Corneal burn in rats was induced using 100% alcohol. The chosen CM was administered to corneal burn rats (CM-treated [CT] group) four times a day for three days and this group was compared with the normal control and corneal burn (CB) groups. Biomicroscopic fluorescence images and the actual physical corneas were taken over time and used for analysis. mRNA levels of hepatocyte growth factor and epidermal growth factor (EGF) were significantly increased, whereas those of vascular endothelial growth factor, interleukin (IL)-1β, IL-6, IL-10, and matrix metalloproteinase-9 were significantly decreased in the CT group compared with those in the CB group. The numbers of proliferating cell nuclear antigen- and zonular occludens-1-positive cells in the CT group were significantly higher than those in the CB group. The macrophage-infiltrating corneas in the CT group expressed significantly more of the M2 marker arginase than corneas in the CB group. Optimal CM (× 0.5 concentration) treatment significantly accelerated the migration of corneal epithelial cells and induced upregulation of the expression of IL-6, EGF, and C-X-C chemokine receptor type 4 mRNAs. Overall, in this study, topical administration of cell-free CM promoted regeneration of the corneal epithelium after induction of chemical burns
Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
Tristetraprolin (TTP), a well-characterized AU-rich element (ARE) binding protein, functions as a tumor suppressor gene. The purpose of this study was to investigate whether a bioactive substance derived from a natural medicinal plant affects the induction of TTP and to elucidate its mechanism. We examined the effects of natural bioactive materials including Resveratrol (RSV), thymoquinone (TQ) and curcumin on the expression of TTP in cancer cell. TQ derived from a natural plant Nigella sativa increased the expression levels of TTP mRNA and proteins in a dose-dependent manner in gastric and breast cancer cells. TQ-induced TTP increased the instability of MUC4 mRNA by direct binding of TTP to ARE in the 3′UTR of MUC4 mRNA. The induction of TTP by TQ also reduced the proliferation, migration and invasion of cancer cells. The expression of the epithelial-mesenchymal (EMT)-related genes, which were target genes of TTP, was also decreased by the TQ treatment. In the in vivo experiments using mouse melanoma cells, TQ-induced TTP inhibited metastasis of tumor cells. We have found that TQ-induced TTP might inhibit metastasis by reducing tumor cell migration and invasion through destabilization of MUC4 mRNA, which suggest the MUC4 as a novel target to TTP