Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.

Type A spermatogonia, including spermatogonial stem cells, are primary cells that maintain spermatogenesis and produce spermatozoa. Many spermatogonial markers have been reported in rodents. However, few markers have been identified in pig spermatogonia. Despite the lack of information, it is necessary to separate pure spermatogonial cells from whole testicular cells to understand the mechanism of spermatogenic meiosis and to establish spermatogonial stem cells for further biotechnological studies. The purpose of this study was to identify glial cell-derived neurotrophic factor receptor alpha-1 (GFRα-1) as a surface marker for early spermatogonia in neonatal pig testes. Histological analysis of 3-day-old pig testes revealed that type A spermatogonia, which lack heterochromatin, could be distinguished in neonatal pig testes. Immunohistochemistry of neonatal pig testes with GFRα-1 antibody identified that some of the spermatogonial cells expressed GFRα-1 on the cell membrane. Co-immunostaining with both GFRα-1 and protein gene product 9.5 (PGP 9.5) detected PGP 9.5 in all spermatogonia of neonatal pig testes, whereas GFRα-1 was not detected on the surface of some PGP 9.5-positive cells, indicating that some of the spermatogonial cells were PGP 9.5 positive and GFRα-1 negative. After immunomagnetic cell sorting using a GFRα-1 antibody, both GFRα-1-positive and GFRα-1-negative cells expressed PGP 9.5. Identifying the differential mRNA expression of both GFRα-1-positive and GFRα-1-negative cells using reverse transcription-polymerase chain reaction analysis revealed the expression of promyelocytic leukaemia zinc finger, octamer-binding protein 4 and homeobox transcription factor in both cell types. These results suggest that GFRα-1-positive and GFRα-1-negative spermatogonia exist in PGP 9.5-positive spermatogonia during the early stage of pig testes spermatogenesis, and that GFRα-1 can be used for sorting PGP 9.5-expressing spermatogonia.

The average total cost of illness was estimated to be KRW 9.82 million (US $ 8993) per year, of which 41.6% was accounted for by direct costs and 58.4% by indirect costs. In multivariate regression, patients with renal involvement and those with depression incurred an average increment in annual total costs of 37.6% (p = 0.050) and 49.1% (p = 0.024), respectively, and an average increment in annual direct costs of 26.4% (p = 0.050) and 43.3% (p = 0.002), respectively, compared with patients without renal involvement and depression, respectively. In addition, disease damage was positively associated with an average increment in annual total and direct costs (55.3%, p = 0.006; 33.3%, p = 0.013, respectively), and the occurrence of indirect costs (OR 2.21, 1.09-4.88). There was no significant difference in HRQOL between patients with and without renal involvement (0.655 vs. 0.693, p = 0.203) CONCLUSION: Renal involvement, depression, and disease damage were major factors associated with higher total and medical costs for patients with SLE in South Korea. Effective treatment of renal disorders and depression may reduce the high economic burden of SLE.

Putative markers for each specific germ cell stage can be a useful tool to study the fate and functions of these cells. Undifferentiated embryonic cell transcription factor 1 (UTF1) is a putative marker for undifferentiated spermatogonia in humans, rats and horses. The deleted in azoospermia-like (DAZL) protein is also expressed by differentiated spermatogonia and primary spermatocytes in several species. However, whether the expression patterns of these molecular markers are identical and applicable to donkeys remains to be elucidated. The objective of this study was to investigate the expression patterns of UTF1 and DAZL in donkey testicular tissue, using immunohistochemistry (IHC). Testicular samples were collected from routine field castration of donkeys in Korea. The reproductive stages (pre- or post-puberty) of the testes were determined from the morphological characteristics of cross-sections of the seminiferous tubules. For IHC, the UTF1 and DAZL primary antibodies were diluted at 1:100 and 1:200, respectively. The immunolabelling revealed that UTF1 was expressed in approximately 50% of spermatogonia in the pre-pubertal stage, whereas its expression was limited to an early subset of spermatogonia in the post-pubertal stage. DAZL was expressed in some, but not all, spermatogonia in the pre-pubertal spermatogonia, and interestingly, its expression was also observed in spermatogonia and primary spermatocytes in the post-pubertal stage. Co-immunolabelling of the germ cells with both UTF1 and DAZL revealed three types of protein expression patterns at both reproductive stages, namely UTF1 only, DAZL only and both UTF1 and DAZL. These protein molecules were not expressed in Sertoli and Leydig cells. In conclusion, a co-immunolabelling system with UTF1 and DAZL antibodies may be used to identify undifferentiated (UTF1 only), differentiating (UTF1 and DAZL), and differentiated spermatogonia (DAZL only) in donkey testes.

No abstract