Colorectal cancer (CRC) is the second leading cause of cancer-related death in males and females in the world. It is of immediate importance to develop novel therapeutics. Human ribonucleotide reductase (RRM1/RRM2) has an essential role in converting ribonucleoside diphosphate to 2′-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools. RRM2 is a prognostic biomarker and predicts poor survival of CRC. In addition, increased RRM2 activity is associated with malignant transformation and tumor cell growth. Bioinformatics analyses show that RRM2 was overexpressed in CRC and might be an attractive target for treating CRC. Therefore, we attempted to search novel RRM2 inhibitors by using a gene expression signature-based approach, connectivity MAP (CMAP). The result predicted GW8510, a cyclin-dependent kinase inhibitor, as a potential RRM2 inhibitor. Western blot analysis indicated that GW8510 inhibited RRM2 expression through promoting its proteasomal degradation. In addition, GW8510 induced autophagic cell death. In addition, the sensitivities of CRC cells to GW8510 were associated with the levels of RRM2 and endogenous autophagic flux. Taken together, our study indicates that GW8510 could be a potential anti-CRC agent through targeting RRM2.

Contents Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti‐inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein‐Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein‐Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast‐like morphology. They were positive for β‐integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10–15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility.

We used a more accurate pair distribution function -the nearest -available-neighbor one -to reanalyze previous work on the relative luminescence transition probabilities of donors in ZnSe.Earlier work with the nearest-neighbor distribution had shown that these relative transition probabilities differed by orders of magnitude between interstitial (alkali-metal) donors and substitutional (group-III) donors. At low concentration the results are practically unchanged. For high concentration, the relative results now show even larger differences. We conclude again that the interstitial (alkali-metal) donors have a substantially lower transition probability than the group-III donors in ZnSe.Recent results have shown a striking difference in properties of donors in ZnSe, depending on lattice site.First, the interstitial alkali-metal donors exhibited a substantially lower transition probability in the donor-acceptor -pair luminescence than the group-III substitutional donors. Secondly, these interstitial donors also gave an appreciably more shallow energy level. Moreover, these phenomena cannot be understood within the effective-mass approximation.In view of these factors, the reliability of these conclusions' is of high interest. These results were based on analyses of donoracceptor -pair (DAP) spectra using a widely accepted model for the pair distribution i.e. , one where it is assumed that the donor-acceptor pairs are described by the nearest-neighbor (NN) distribution. ' ' lt has, however, been pointed out by Dunstan ' and Eggert' '" that the decay of excited donor-acceptor pairs is more accurately described by the nearest -available-neighbor (NAN) distribution. This distribution differs from the NN distribution in that each particle in a NAN pair is the nearest neighbor of the other. The NAN relation is therefore commutative. In the NN distribution, however, the relation is not commutative: if 3 is the nearest neighbor of B, then B is not necessarily the nearest neighbor of A. It is this noncommutative relation that makes the NN distribution inappropriate for the description of a commutative process, such as the luminescence transition. In the present paper we therefore carry out an analysis analogous to the previous one, but utilizing the NAN distribution. Specifically, we use the analytic approximation to this distribution.As in the earlier work, we analyze the Coulomb shift of the distant pair peak. Since the analysis on the zerophonon peak is sufhcient, we discuss the zero-phonon transitions only. We now summarize the required equations. As a good approximation in the analysis of the distant pair peak in DAP spectra, the energy (E) of emission and the separation (R) of the donor-acceptor pair are related by' E =E +e /eR, where e is the electron charge, e the dielectric constant, and E =E (ED+E~-), (2) with E the band gap and ED and E~the energies of donor and acceptor, respectively. At large separation, the intensity I(E) is given ' by I(E)=ND(e/e )R W(R)f (R)P(R),where ND is the concentration of the minority d...

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.