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Abstract Background MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decitabine (DAC) has made great progress in the treatment of AML in recent years, but DAC resistance is still common phenomenon and the mechanism of resistance is still unclear. We further analyze the influences of miR-29c to leukemic cells treated with DAC. Methods Real-time quantitative PCR (RQ-PCR) was carried out to detect miR-29c transcript level in 102 de novo AML patients and 25 normal controls. miR-29c/shRNA-29c were respectively transfected into K562 cells and HEL cells. Cell viability after transfection was detected by cell counting Kit-8 assays. Flow cytometry was used to detect apoptosis. Results MiR-29c was significantly down-regulated in AML (P

Abstract Background Leukemia stem cell (LSC)-enriched genes have been shown to be highly prognostic in acute myeloid leukemia (AML). However, the prognostic value of tumor suppressor genes (TSGs) that are repressed early in LSC remains largely unknown. Methods We compared the public available expression/methylation profiling data of LSCs with that of hematopoietic stem cells (HSCs), in order to identify potential tumor suppressor genes in LSC. The prognostic relevance of PCDH17 was analyzed on a cohort of 173 AML patients from The Cancer Genome Atlas (TCGA), and further validated in three independent cohorts (n = 339). Results We identified protocadherin17 (PCDH17) and demonstrated that it was significantly down-regulated and hypermethylated in LSCs compared with HSCs. Our analyses of primary AML patient samples also confirmed these deregulations. Clinically, low PCDH17 expression was associated with female sex (P = 0.01), higher WBC (P

Abstract Background Increasing studies showed that miR-200 family (miR-200s) clusters are aberrantly expressed in multiple human cancers, and miR-200s clusters function as tumor suppressor genes by affecting cell proliferation, self-renewal, differentiation, division and apoptosis. Herein, we aimed to investigate the expression and clinical implication of miR-200s clusters in acute myeloid leukemia (AML). Methods RT-qPCR was performed to detect expression of miR-200s clusters in 19 healthy donors, 98 newly diagnosed AML patients, and 35 AML patients achieved complete remission (CR). Results Expression of miR-200a/200b/429 cluster but not miR-200c/141 cluster was decreased in newly diagnosed AML patients as compared to healthy donors and AML patients achieved CR. Although no significant differences were observed between miR-200s clusters and most of the features, low expression of miR-200s clusters seems to be associated with higher white blood cells especially for miR-200a/200b. Of the five members of miR-200s clusters, low expression of miR-200b/429/200c was found to be associated with lower CR rate. Logistic regression analysis further revealed that low expression of miR-429 acted as an independent risk factor for CR in AML. Based on Kaplan–Meier analysis, low expression of miR-200b/429/200c was associated with shorter OS, whereas miR-200a/141 had a trend. Moreover, multivariate analysis of Cox regression models confirmed the independently prognostic value of miR-200b expression for OS in AML. Conclusions Expression of miR-200a/200b/429 cluster was frequently down-regulated in AML, and low expression of miR-429 as an independent risk factor for CR, whereas low expression of miR-200b as an independent prognostic biomarker for OS.

Abstract Background Previous studies have disclosed up‐regulation of MIR‐378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR‐378 was also identified in AML, particularly for FAB‐M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR‐378 has not been illustrated in myelodysplastic syndrome (MDS). Herein we designed to understand the methylation pattern of MIR‐378 involved in MDS and clinical interrelation thereof. Methods Real‐time quantitative methylation‐specific PCR (RQ‐MSP) was performed to evaluate the methylation degree of MIR‐378 5’‐flanking region on bone marrow mononuclear cells collected from 95 de novo MDS patients. Five gene mutations (IDH1, IDH2, DNMT3A, U2AF1, and SF3B1) were detected by high‐resolution melting analysis to further evaluate the clinical relevance of hypomethylation of MIR‐378. Results Unmethylated level of MIR‐378 5’‐flanking region was significantly higher in MDS patients than that in controls (p = .034). Hypomethylated MIR‐378 was identified in 20 of 95 (21%) cases with MDS. Male patients appeared to be more frequent to harbor MIR‐378 hypomethylation compared to female patients (15/55, 27.3% vs. 4/40, 10.0%, p = .04). There was no significant difference in age, white blood cell counts, platelet counts, hemoglobin concentration, and karyotypes between the patients with and without MIR‐378‐hypomethylation. Distinct distribution of five gene mutations was not observed in the two groups as well. However, MIR‐378‐hypomethylated patients had significantly shorter overall survival than those without MIR‐378 hypomethylation (p = .036). Moreover, among patients

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease mainly characterized by B cell hyperactivity. Glucocorticoid (GC) is widely used in SLE for its potent anti-inflammatory and immunosuppressive effects. Despite its important clinical efficacy, high-dose or long-term use of GC can cause severe side effects, such as osteoporosis, osteonecrosis, cataracts, hyperglycemia, coronary heart disease and cognitive impairment. Our early clinical studies have shown that Jieduquyuzishen prescription (JP) can effectively reduce the adverse effects and improve the curative effect of GC in the treatment of SLE. The BAFF/BAFF-R signaling pathway plays an important role in the development of SLE and has been regarded as a potential target for the therapy of SLE. In this study, we attempt to investigate the effect of JP on the BAFF/BAFF-R signaling pathway to explore the mechanism of JP in reducing the toxicity and enhancing the efficacy of GC. YAC-1 cells, isolated rat peripheral blood lymphocytes, polymorphonuclear neutrophils and spleen lymphocytes were treated with drug-containing serum. The results of RT-PCR, Western blot and dual-luciferase reporter gene assays indicate that either JP or GC can inhibit the mBAFF-induced up-regulation of BAFF, BAFF-R, Bcl-2, IL-10 and NF-κB in YAC-1 cells and WEHI-231 cells. Furthermore, MTS, flow cytometry and CFSE results reveal that the proliferation and survival of lymphocytes activated by mBAFF are suppressed by JP, GC and their combination. Contrary to GC, JP can reduce the apoptosis and raise the survival of polymorphonuclear neutrophils and can't increase the apoptosis of the peripheral blood lymphocytes and spleen lymphocytes. Therefore, it is possible that JP can down-regulate the BAFF/BAFF-R signaling pathway as effectively as GC, which may result in the dosage reduction of GC, thus decreasing the toxicity and improving the efficacy of GC-based treatment of SLE.

In the title molecular salt, (C10H16N)2[CuBr4], the CuII ion adopts a squashed tetrahedral geometry with Br—Cu—Br angles varying between 99.29 (3) and 132.53 (3)°. In the crystal, the components are linked by C—H...Br interactions, thereby generating a three-dimensional network.

The asymmetric unit of the title compound, C8H12N+·ClO4−.C12H24O6, contains one half of the cationic [(C2H5—C6H4—NH3)(18-crown-6)]+ moiety and one half of the ClO4− anion. Two O atoms of the crown ether, four C atoms and the N atom of the ethylanilinium unit and the Cl and two O atoms of the anion lie on a mirror plane. In the crystal structure, the –NH3+ group lies in the 18-crown-6 ring, forming a supramolecular rotator–stator-like structure linked by intramolecular N—H...O hydrogen bonds. The six O atoms of the crown ether lie approximately in a plane, the mean deviation being 0.1771 (3) Å; the N atom lies approximately 0.855 (3) Å from the centroid of the crown ether ring.

In the crystal structure of the title compound, C8H12N+·C3H3O4−, the hydrogen malonate anions are linked into infinite chains parallel to the b axis by intermolecular O—H...O hydrogen bonds of the type COO−...HO2C in a head-to-tail fashion. The 4-ethylanilinium cations link adjacent anion chains by intermolecular N—H...O hydrogen bonds into a two-dimensional network parallel to the b and c axes.

In the crystal structure of the title molecular salt, C8H12N+·C7H7O3S−, the 4-ethylanilinium cations and 4-methylbenzenesulfonate anions are linked into chains parallel to the b axis by intermolecular N—H...O hydrogen bonds.

In the crystal structure of the title compound, NH4+·PF6−·C12H24O6, the cation is situated in the 18-crown-6 ring, forming a supramolecular rotator-stator-like structure held by N—H...O hydrogen bonds. The six O atoms of the crown ether lie approximately in a plane [mean deviation 0.2129 (3) Å]; the N atom is displaced by 0.864 (3)Å from the centroid of the 18-crown-6 ring. The slightly distorted tetrahedral cations further interact with the slightly distorted octahedral anions via intermolecular N—H...F hydrogen bonds.

The asymmetric unit of the title compound, C15H15N3O2S, contains two independent molecules corresponding to the R and S enantiomers. The dihydropyrimidinone rings adopt a flattened boat conformation. One of the ethyl groups is disordered over two orientations with occupancy factors of 0.700 (7) and 0.300 (7). In the crystal structure, molecules are linked by intermolecular N—H...O hydrogen-bonding interactions into one-dimensional chains along the c-axis direction. The chains are further connected by N—H...S hydrogen bonds, forming a three-dimensional network.

The title molecule, C14H19NO6, was synthesized by the reaction of glyoxylic acid, ethyl acetoacetate and NH4HCO3. In the crystal structure, the dihydropyridine ring adopts an asymmetric boat-type conformation with the C atom bearing the carboxyl group showing a signficantly larger deviation [0.325 (2) Å] from the base plane then the N atom [0.137 (2) Å]. One of the ethyl groups is disordered over two positions with occupancies of 0.741 (10) and 0.259 (10). The crystal is stabilized by strong intermolecular hydrogen bonds. N—H...O interactions form infinite chains in the a direction. O—H...O hydrogen bonds form typical carboxylic acid dimers, which link the N—H...O chains into a ladder-type double chain.

The molecule of the title compound, C17H10N4O, has crystallographically imposed C2 symmetry. The urea group and the benzene ring are nearly coplanar, the dihedral angle between them being 4.15 (7)°. The crystal packing is stabilized by aromatic π–π stacking interactions, with a centroid-to-centroid separation of 3.833 (4) Å.

The molecule of the title compound, C8H8N4O2S, adopts an E configuration about both the C—N bonds. In the crystal structure, adjacent molecules are linked by intermolecular N—H...S hydrogen-bonding interactions, forming chains running parallel to the b axis.

The molecule of the title compound, C9H8N4S, adopts an E configuration about both the C=N and C—NH bonds. In the crystal structure, adjacent molecules are linked by intermolecular N—H...S hydrogen-bonding interactions, forming chains running parallel to the b axis.

The title compound, C17H12N2O, was synthesized by an ether synthesis from quinolin-6-ol and 4-(bromomethyl)benzonitrile. The phenyl ring of the benzonitrile group makes a dihedral angle of 47.52 (6)° with the plane of the quinoline fragment. The crystal structure is stabilized by intermolecular C—H...π interactions between a benzene H atom of the benzonitrile group and the benzene ring of the quinoline fragment. In addition, the crystal structure also exhibits a weak intermolecular C—H...N hydrogen bond.

In the title compound, C25H18O2S·C4H8O2, there are intermolecular O—H...O hydrogen bonds between the main molecule and the solvent molecule. The thiophene ring is oriented at dihedral angles of 70.87 (7) and 75.36 (4)° with respect to the mean planes of the two naphthyl ring systems.