Low vitamin D status is considered as a risk factor for breast cancer and has prognostic significance. Furthermore, vitamin D deficiency increases after adjuvant cancer therapy, which alters bone metabolism increasing the risk of osteoporosis. It is now postulated that vitamin D supplementation in breast cancer treatment delays the recurrence of cancer thereby extending survival. We evaluated the impact of calcitriol and its low-calcemic analogs, PRI-2191 and PRI-2205, on the tumor growth, angiogenesis, and metastasis of 4T1 mouse mammary gland cancer. Gene expression analysis related to cancer invasion/metastasis, real-time PCR, ELISA, western blotting, and histochemical studies were performed. In vitro studies were conducted to compare the effects of calcitriol and its analogs on 4T1 and 67NR cell proliferation and expression of selected proteins. Calcitriol and its analogs increased lung metastasis without influencing the growth of primary tumor. The levels of plasma 17β-estradiol and transforming growth factor β (TGFβ) were found to be elevated after treatment. Moreover, the results showed that tumor blood perfusion improved and osteopontin (OPN) levels increased, whereas vascular endothelial growth factor (VEGF) and TGFβ levels decreased in tumors from treated mice. All the studied treatments resulted in increased collagen content in the tumor tissue in the early step of tumor progression, and calcitriol caused an increase in collagen content in lung tissue. In addition, in vitro proliferation of 4T1 tumor cells was not found to be affected by calcitriol or its analogs in contrast to non-metastatic 67NR cells. Calcitriol and its analogs enhanced the metastatic potential of 4T1 mouse mammary gland cancer by inducing the secretion of OPN probably via host cells. In addition, OPN tumor overexpression prevailed over the decreasing tumor TGFβ level and blood vessel normalization via tumor VEGF deprivation induced by calcitriol and its analogs. Moreover, the increased plasma TGFβ and 17β-estradiol levels contributed to the facilitation of metastatic process.

No abstract

No abstract

The results of several experimental and epidemiological studies have shown an inverse correlation between Mg status and the risk of some cancers. However, relationship between magnesium and cancer is complex. The aim of our work was to examine the precise effect of Mg deficiency on transplantable mouse tumor growth and metastasis. The results obtained indicate a significant retardation of primary tumor growth (up to 70%) in mice receiving Mg-deficient diet. However, Mg repletion caused in these mice significant increase of primary tumor burden. Analysis of cell cycle distribution showed a reduced percentage of cells in the S phase and an increase of cells in the G(0)/G(1) phase of the cell cycle in LLC tumors caused by Mg deficiency. This is in agreement with the effect of low Mg level on cell growth observed in vitro. Interestingly, in mice inoculated with LLC cells and receiving low-magnesium diet, a higher metastatic potential was observed as compared to control mice. In conclusion, our results demonstrate a direct role of magnesium in tumor growth and also point at deleterious effect of low magnesium status on tumor metastasis.

No abstract

The objective of this study was to determine the prevalence and types of infections in perinatal mortality (PM) cases from Polish dairy farms and the relevance of the presence of infection to the cause of death. This prospective longitudinal study was carried out on 121 PM and 21 control calves with a gestation of ≥260 days. Six control calves were euthanized and examined using the same protocol as for PM calves. Material was collected over a 20-month period between November 2013 and June 2015. The PM and control calves were collected from 29 to 5 herds, respectively. Blood samples from calves were tested for antibodies to Neospora caninum, glycoprotein B of BoHV-1, BVDV and SBV using ELISAs and Leptospira hardjo and Leptospira pomona with the microscopic agglutination test. Brain and kidney samples from all PM and six euthanized control calves were tested using real time PCR to detect Neospora caninum, pathogenic Leptospira spp., BoHV-1 and SBV; brain was examined histopathologically for detection of N. caninum cysts. Samples from eight inner organs from all PM and six control calves were cultured aerobically, anaerobically and microaerobically. Ear samples from all PM and control calves were tested for BVDV using an antigen ELISA. In total, 21.5% of PM calves were infected (antigen and/or antibody-positive) in utero; none of the control calves were infected. Direct evidence of infection (culture, Ag-ELISA, PCR, histopathology) was detected in 9.1% of PM calves. Gestation length in infected singletons was shorter than in uninfected singletons (274 ± 8 vs. 279 ± 7 days; P < 0.01). The odds ratio for diagnosis of infection in single pregnancies ≤275 days was 3.75 (95% CI:1.2-12.1), (P < 0.05). Infection was the cause of death in 10% of calves. The most common infections detected in these Polish PM calves were parasitic (11.6% of PM cases), viral (7.4%) and bacterial (5%). This study demonstrated that indirect evidence of infection is detected more frequently than direct, coinfection is rare, infection is rarely accompanied by gross lesions and is rarely a cause of death in cases of PM.

Although the disorder of sex development in dogs with female karyotype (XX DSD) is quite common, its molecular basis is still unclear. Among mutations underlying XX DSD in mammals are duplication of a long sequence upstream of the SOX9 gene (RevSex) and duplication of the SOX9 gene (also observed in dogs). We performed a comparative analysis of 16 XX DSD and 30 control female dogs, using FISH and MLPA approaches. Our study was focused on a region harboring SOX9 and a region orthologous to the human RevSex (CanRevSex), which was located by in silico analysis downstream of SOX9. Two highly polymorphic copy number variable regions (CNVRs): CNVR1 upstream of SOX9 and CNVR2 encompassing CanRevSex were identified. Although none of the detected copy number variants were specific to either affected or control animals, we observed that the average number of copies in CNVR1 was higher in XX DSD. No copy variation of SOX9 was observed. Our extensive studies have excluded duplication of SOX9 as the common cause of XX DSD in analyzed samples. However, it remains possible that the causative mutation is hidden in highly polymorphic CNVR1.

Background and Aims. Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods. Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results. Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions. CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.