Assessment of a 50:50 mixture of two Bacillus subtilis strains as growth promoters for finishing pigs: productivity improvement and noxious gas reduction.

In this study, we aimed to assess the potential of a 50:50 mixture of two Bacillus subtilis strains in improving the productivity and health of finishing pigs and reducing noxious gases in their feces. These strains were found to abundantly secrete surfactin which has been shown to alleviate the effects of lipopolysaccharides in vitro. For the 10-wk experiment, 200 finishing pigs ([Landrace × Yorkshire] × Duroc) with an average body weight of 54.

Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression.

Development of resistance to TNF-related apoptosis-inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF-induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL-induced apoptosis in HeLa cells. CCAAT/enhancer-binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER-stress) signaling and sensitize the cells to TRAIL.

Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation.

Patulin is a fungal mycotoxin of Aspergilus and Penicillium that is commonly found in rotting fruits and exerts its potential toxic effect mainly by reactive oxygen species (ROS) generation. However, the effect of patulin on cancer cells as well as its intracellular mechanism has been controversial and not clearly defined yet. In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116.

Proteasome inhibitor-I enhances tunicamycin-induced chemosensitization of prostate cancer cells through regulation of NF-κB and CHOP expression.

Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed a differential mechanism of proteasome inhibitor-I (Pro-I)-induced cell death.

Modulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b.

E-cadherin, as a tumor suppressor, plays an important role for intercellular adhesion involved in metastasis. Although K-Ras is highly expressed in a variety of cancers, the regulation of E-cadherin expression by K-Ras in association with DNA methylation and cell metastasis has not been completely clarified. In this study, E-cadherin expression was repressed in 267B1/K-Ras human epithelial prostate cancer cells stably overexpressing K-Ras, resulting from hypermethylation of E-cadherin promoter as evidenced by methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, real-time reverse transcription-PCR and western blot analysis.

ATM blocks tunicamycin-induced endoplasmic reticulum stress.

Endoplasmic reticulum stress (ER-stress) is associated with ataxia telangiectasia mutated (ATM) gene. We present here conclusive data showing that ATM blocks ER-stress induced by tunicamycin or ionizing radiation (IR). X-box protein-1 (XBP-1) splicing, GRP78 expression and caspase-12 activation were increased by tunicamycin or IR in Atm-deficient AT5BIVA fibroblasts.

Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-kappaB.

Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus was found to interact with both Ki-Ras and Akt1, suggesting the nuclear translocation of Akt1:Ki-Ras complex for NF- kappaB activation. In support of this, compared with wild type Akt1, the dominant negative Akt1 mutant was decreased in its nuclear expression, reducing the Ki-Ras-induced NF-kappaB transcriptional activation.

p53 activation in response to mitotic spindle damage requires signaling via BubR1-mediated phosphorylation.

The mitotic spindle checkpoint plays a crucial role in regulating accurate chromosome segregation and preventing the adaptation of multiploid progeny cells. Recent reports have indicated that the induction of p53 by mitotic checkpoint activation is essential for protecting cells from abnormal chromosome ploidization caused by mitotic failure. However, although studies have shown that p53 deficiencies arrest mitosis, compromise apoptosis, and may cause profound aneuploidy, the molecular mechanisms leading to p53 induction following mitotic checkpoint activation remain unknown.

Differential promoter methylation may be a key molecular mechanism in regulating BubR1 expression in cancer cells.

The BubR1 mitotic-checkpoint protein monitors proper attachment of microtubules to kinetochores, and links regulation of chromosome-spindle attachment to mitotic-checkpoint signaling. Thus, disruption of BubR1 activity results in a loss of checkpoint control, chromosomal instability caused by a premature anaphase, and/or the early onset of tumorigenesis. The mechanisms by which deregulation and/or abnormalities of BubR1 expression operate, however, remain to be elucidated.

Overexpression of hepatitis C virus NS5A protein induces chromosome instability via mitotic cell cycle dysregulation.

Hepatocellular carcinoma (HCC) is a common primary cancer associated with high incidences of genetic variations including chromosome instability. Moreover, it has been demonstrated that hepatitis C virus (HCV) is one of the major causes of HCC. However, no previous work has assessed whether HCV proteins are associated with the induction of chromosome instability.

STAT4 expression in human T cells is regulated by DNA methylation but not by promoter polymorphism.

STAT4, which plays a pivotal role in Th1 immune responses, enhances IFN-gamma transcription in response to the interaction of IL-12 with the IL-12R. Mice deficient in STAT4 lack IL-12-induced IFN-gamma production and Th1 differentiation and display a predominantly Th2 phenotype. Although these findings indicate that STAT4 expression levels are important for the development of cytokine-producing Th1 cells, the transcriptional and posttranscriptional mechanisms regulating STAT4 expression are unknown.

Caspases-dependent cleavage of mitotic checkpoint proteins in response to microtubule inhibitor.

The mitotic checkpoint ensures the fidelity of chromosomal segregation by delaying the onset of anaphase until all chromosomes are aligned on the metaphase plate. After sustained mitotic arrest, however, cells eventually exit mitosis without the mitotic checkpoint being silenced. These cells then undergo apoptosis, an event that is important for prevention of the chromosomal instability observed in human cancers.

Transcriptional abnormality of the hsMAD2 mitotic checkpoint gene is a potential link to hepatocellular carcinogenesis.

MAD2 is localized to kinetochores of unaligned chromosomes, where it inactivates the anaphase-promoting complex/cyclosome, thus contributing to the production of a diffusible anaphase inhibitory signal. Disruption of MAD2 expression leads to defects in the mitotic checkpoint, chromosome missegregation, and tumorigenesis. However, the mechanism by which deregulation and/or abnormality of hsMAD2 expression remains to be elucidated.

WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase.

WD repeats are implicated in protein-protein interactions and regulate a wide variety of cellular functions, including chromatin remodeling and transcription. The WD repeats of the Bub3 and Cdc20 kinetochore proteins are important for the physical interactions of these proteins with Mad2 and BubR1 to yield a kinetochore protein complex capable of delaying anaphase by inhibiting ubiquitin ligation via the anaphase-promoting complex/cyclosome. Here, we show that Bub3 and Cdc20 form a complex with histone deacetylases; this interaction appears to confer transcriptional repressor activity in a heterologous DNA-binding context.

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells.

DLC-1 (deleted in liver cancer) gene is frequently deleted in hepatocellular carcinoma. However, little is known about the genetic status and the expression of this gene in gastric cancer. In this study, Northern and Southern analysis showed that seven of nine human gastric cancer cell lines did not express DLC-1 mRNA, but contained the DLC-1 gene.