Reinforced erythroid differentiation inhibits leukemogenic potential of t(8;21) leukemia.

Oncoprotein AML1-ETO (AE) derived from t(8;21)(q22;q22) translocation is typically present in a portion of French-American-British-M2 subtype of acute myeloid leukemia (AML). Although these patients have relatively favorable prognoses, substantial numbers of them would relapse after conventional therapy. Here, we explored whether reinforcing the endogenous differentiation potential of t(8;21) AML cells would diminish the associated malignancy. In doing so, we noticed an expansion of immature erythroid blasts featured in both AML1-ETO9a (AE9a) and AE plus c-KIT (N822K) (AK) murine leukemic models. Interestingly, in the AE9a murine model, a spontaneous step-wise erythroid differentiation path, as characterized by the differential expression of CD43/c-Kit and the upregulation of several key erythroid transcription factors (TFs), accompanied the decline or loss of leukemia-initiating potential. Notably, overexpression of one of the key erythroid TFs, Ldb1, potently disrupted the repopulation of AE9a leukemic cells in vivo, suggesting a new promising intervention strategy of t(8;21) AML through enforcing their erythroid differentiation.

Pd(II)-Catalyzed Azine-Assisted Enantioselective Oxidative C-H/C-H Cross-Coupling of Ferrocenes with Various Heteroarenes.

A palladium(II)-catalyzed enantioselective oxidative cross-coupling of ferrocenes with heteroarenes is described. Mono-N-protected amino acids can be used as sources of chirality. With azine as an efficient directing group, various substituted planar chiral ferrocenes were obtained via a dual C-H bond activation pathway in medium yields (up to 72%) with good enantioselectivity (up to 89.4:10.6 er) under mild conditions.

Do state insurance mandates alter ICSI utilization?

BACKGROUND: Assisted reproductive technology (ART) insurance mandates resulted in improved access to infertility treatments like intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ART insurance mandates demonstrate an increased association with ICSI use. METHODS: In this retrospective cohort study, clinic-specific data for 2000-2016 from the Centers for Disease Control (CDC) were grouped by state and subgrouped by the presence and extent of ART state insurance mandates. Mandated (n = 8) and non-mandated (n = 22) states were compared for ICSI use and male factor (MF) infertility in fresh non-donor ART cycles with a transfer in women < 35 years. Clinical pregnancy (CPR), live birth (LBR) rates, preimplantation genetic testing (PGT), elective single-embryo transfer (eSET) and twin birth rates per clinic were evaluated utilizing Welch's t-test. Pearson correlation was used to measure the strength of association between MF and ICSI; ICSI and CPR, and ICSI and LBR over time. Results were considered statistically significant at a p-value of < 0.05, with Bonferroni correction used for multiple comparisons. RESULTS: From 2000 to 2016, ICSI use per clinic increased in both mandated and non-mandated states. ICSI use per clinic in non-mandated states was significantly greater from 2011 to 2016 (p < 0.05, all years) than in mandated states. Clinics in mandated states had less MF (30.5 ± 15% vs 36.7 ± 15%; p < 0.001), lower CPR (39.8 ± 4% vs 43.4 ± 4%; p = 0.02) and lower LBR (33.9 ± 3.5% vs 37.9 ± 3.5%; p < 0.05). PGT rates were not significantly different. ICSI use in non-mandated states correlated with MF rates (r = 0.524, p = 0.03). A significant correlation between ICSI and CPR (r = 0.8, p < 0.001) and LBR (r = 0.7, p < 0.001) was noted in mandated states only. eSET rates were greater and twin rates were lower in mandated compared with non-mandated states. CONCLUSIONS: There was greater use of ICSI per clinic in non-mandated states, which correlated with an increased frequency of MF. In mandated states, lower ICSI rates per clinic were accompanied by a positive correlation with CPR and LBR, as well as a trend for greater eSET rates and lower twin rates, suggesting that state mandates for ART coverage may encourage more selective utilization of laboratory resources.

Leukemic IL-17RB signaling regulates leukemic survival and chemoresistance.

Secreted proteins provide crucial signals that have been implicated in the development of acute myeloid leukemia (AML) in the bone marrow microenvironment. Here we identify aberrant expressions of inflammatory IL-17B and its receptor (IL-17RB) in human and mouse mixed lineage leukemia-rearranged AML cells, which were further increased after exposure to chemotherapy. Interestingly, silencing of IL-17B or IL-17RB led to significant suppression of leukemic cell survival and disease progression in vivo. Moreover, the IL-17B-IL-17RB axis protected leukemic cells from chemotherapeutic agent-induced apoptotic effects. Mechanistic studies revealed that IL-17B promoted AML cell survival by enhancing ERK, NF-κB phosphorylation, and the expression of antiapoptotic protein B-cell lymphoma 2, which were reversed by small-molecule inhibitors. Thus, the inhibition of the IL-17B-IL-17RB axis may be a valid strategy to enhance sensitivity and therapeutic benefit of AML chemotherapy.-Guo, H.-Z., Niu, L.-T., Qiang, W.-T., Chen, J., Wang, J., Yang, H., Zhang, W., Zhu, J., Yu, S.-H. Leukemic IL-17RB signaling regulates leukemic survival and chemoresistance.

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice.

CONTEXT: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). MATERIALS AND METHODS: Male BALB/c mice were treated with standardized myrtol for 1.5 h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively. RESULTS: In LPS-challenged mice, standardized myrtol at a dose of 1200 mg/kg significantly inhibited the neutrophile counts (from 820.97 ± 142.44 to 280.42 ± 65.45, 103/mL), protein concentration (from 0.331 ± 0.02 to 0.183 ± 0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70 ± 748.40 to 2317.70 ± 500.14, ng/mL; IL-6: from 1184.85 ± 143.58 to 509.57 ± 133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82 ± 0.04 to 0.48 ± 0.06, U/g) and pathological changes (lung injury score: from 11.67 ± 0.33 to 7.83 ± 0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues. DISCUSSION AND CONCLUSION: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.

SNP in pre-miR-1666 decreases mature miRNA expression and is associated with chicken performance.

Polymorphisms in miRNA genes could potentially alter various biological processes by influencing the processing and (or) target selection of miRNAs. The rs14120863 (C > G) mutation, which we characterized in a Gushi-Anka F2 resource population, resides in the precursor region of miR-1666. Association analysis with chicken carcass and growth traits showed that the SNP was significantly associated with carcass weight, evisceration weight, breast muscle weight, leg muscle weight, and body weight at 8 weeks of age, as well as some body size indexes including shank girth, chest breadth, breast bone length, and body slanting length, in the Gushi-Anka F2 resource population. Quantitative RT-PCR results showed that miR-1666 expression levels in muscle tissues differed within various genotypes. Experiment in DF1 cells further confirmed that the SNP in miR-1666 could significantly alter mature miRNA production. Subsequently, using dual-luciferase report assay, we verified that miR-1666 could perform its function through targeting of the CBFB gene. In conclusion, the SNP in the precursor of miR-1666 could significantly reduce mature miR-1666 production. It may further affect the function of miR-1666 through the target gene CBFB, hence it is associated with chicken growth traits.

Inhibition of spontaneous canine benign prostatic hyperplasia by an Urtica fissa polysaccharide fraction.

In this study, we investigated the inhibition of spontaneous canine benign prostatic hyperplasia by a crude polysaccharide fraction extracted from Urtica fissa roots and stems. After oral administration of U. fissa polysaccharide fraction for 3 months, the dog prostatic volume reduced significantly when compared to that before treatment using CT examination. The high-dosage U. fissa polysaccharide fraction (120 mg/kg body weight/day) and finasteride (0.5 mg/kg body weight/day) treatments showed both almost 30 % reduction of the initial prostatic volume. At the end of the administration of U. fissa polysaccharide fraction, the prostates were excised, and the volumes were measured by water displacement. The prostatic volume showed significant decrease by 11 %, 15 %, and 21 % for the 30, 60, and 120 mg/kg/day U. fissa polysaccharide fraction treatment groups, respectively, compared to the control group. Histological observation found that U. fissa polysaccharide fraction inhibited the dog prostatic epithelial cells proliferation and enlarged glandular lumen diameter. The crude polysaccharide fraction of U. fissa is a possible new candidate for the treatment of benign prostatic hyperplasia.