In Brief There have been 22 reported cases of Behçet disease associated with myelodysplastic syndrome. The majority of cases belong to incomplete types of Behçet disease and the refractory anemia subtype of myelodysplastic syndrome. We describe a case of a 49-year-old woman with Behçet disease who developed myelodysplastic syndrome with abnormal karyotype-trisomy 8. This change was not due to immunosuppressive agents because her Behçet disease was not treated with these drugs before the onset of myelodysplastic syndrome. This is the first report of a case of Behçet disease with pathologic evidence associated with the chronic myelomonocytic leukemia subtype of myelodysplastic syndrome. After reviewing the past case studies, we suggest that patients with myelodysplastic syndrome and trisomy 8 might be prone to have Behçet disease. Furthermore, more intestinal ulcers but with less eye lesions and arthritis have been noted in patients of Behçet disease with myelodysplastic syndrome than in those without myelodysplastic syndrome. These states seem to occur together more often than expected by chance. Chromosome analysis of this and other cases often shows trisomy 8 which leads to interesting speculation about pathogenesis of the two diseases.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P) + -dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD + /NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na 2 EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na 2 EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.
Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.
An ultrafiltration method employing a Centrifree filter for determining the unbound fraction of estradiol was studied. Centrifugation was performed under conditions similar to those in vivo. Good correlation was recognized between this method and the equilibrium dialysis. This method was employed to determine the unbound fraction of estradiol in the serum and the peritoneal fluid of 26 infertility patients classified according to their menstrual dates. The total estradiol and progesterone contents in the peritoneal fluid were high after ovulation. There was no significant difference in the percentage of unbound estradiol in the serum among various groups. In the peritoneal fluid, however, the percentage of unbound estradiol for the day 12-14 patients was 4.5 +/- 0.2% in contrast with 3.8 +/- 0.4% for the day 15-18 group (p less than 0.05) and 3.5 +/- 0.1% (p less than 0.05) for the day 19-28 group. Moreover, the fraction (4.5%) of unbound estradiol in the peritoneal fluid of a patient with luteinized unruptured follicle (LUF) syndrome was comparable with that of patients in the follicular phase. The difference between the percentage of unbound estradiol in the peritoneal fluid before and after ovulation is considered to be due to the transudation of follicular estradiol in the follicular phase and the exudation of estradiol from the corpus luteum into the peritoneal cavity in the luteal phase.
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