Reversal of multidrug resistance in leukemia cells using a transferrin-modified nanomicelle encapsulating both doxorubicin and psoralen.

To ameliorate multidrug resistance (MDR) observed in leukemia cells, nanomicelles modified by transferrin (Tf-M-DOX/PSO), coencapsulating doxorubicin (DOX) and psoralen (PSO), were designed, synthesized and tested in K562 and doxorubicin-resistant K562 (K562/DOX) cells. In vitro drug release kinetics for constructed nanomicelles were measured using high-performance liquid chromatography. Characterization of the produced nanomicelles was completed using transmission electron microscopy and dynamic light scattering. Uptake of the nanomicelles in K562 cells was investigated using both confocal microscopy and flow cytometry. Apoptosis levels as well as the expression of glycoprotein (P-gp) were analyzing by western blotting and flow cytometry. Cellular cytotoxicity resulting from the exposure of nanomicelles was evaluated using MTT assays. The nanomicelles all showed mild release of DOX in PBS solution. In K562/DOX cells, Tf-M-Dox/PSO exhibited higher uptake compared to the other nanomicelles observed. Furthermore, cellular cytotoxicity when exposed to Tf-M-Dox/PSO was 2.8 and 1.6-fold greater than observed in the unmodified DOX and Tf-nanomicelles loaded with DOX alone, respectively. Tf-M-Dox/PSO strongly increased apoptosis of K562/DOX cells. Finally, the reversal of the drug resistance when cells are exposed to Tf-M-DOX/PSO was associated with P-gp expression inhibition. The Tf-M-Dox/PSO nanomicelle showed a reversal of MDR, with enhanced cellular uptake and delivery release.

Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

3-(4-Amino-3-methyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4-triazol-1-yl)-3-(2-fur-yl)-1-phenyl-propan-1-one.

In the title mol-ecule, C(16)H(16)N(4)O(2)S, the plane of the 1,2,4-triazole ring forms dihedral angles of 77.9 (2) and 30.0 (2)° with the planes of the furyl and phenyl rings, respectively. Weak inter-molecular N-H⋯S and C-H⋯O hydrogen bonds consolidate the crystal packing.

3-(4-Amino-3-phenyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4-triazol-1-yl)-3-(2-chloro-phen-yl)-1-phenyl-propan-1-one.

In the title mol-ecule, C(23)H(19)ClN(4)OS, the 1,2,4-triazole ring forms dihedral angles of 46.5 (2), 87.4 (2) and 80.9 (2) Šwith the three six-membered rings. Weak inter-molecular N-H⋯S and C-H⋯O hydrogen bonds consolidate the crystal packing.

4-Amino-1-(2-benzoyl-1-phenyl-eth-yl)-3-phenyl-1H-1,2,4-triazol-5(4H)-thione.

In the title compound, C(23)H(20)N(4)OS, the two phenyl rings of the diphenyl-propanone fragment form a dihedral angle of 86.8 (1)°, and the third phenyl ring attached to the triazole ring is twisted from the latter at 40.1 (1)°. In the crystal, mol-ecules are paired into centrosymmetric dimers via pairs of inter-molecular N-H⋯O and N-H⋯S hydrogen bonds.

Bis[(5-phenyl-1,3,4-thia-diazol-2-yl)sulfan-yl]methane.

The asymmetric unit of the title compound, C(17)H(12)N(4)S(4), contains one half-mol-ecule situated on a twofold rotational axis. In the mol-ecule, the thia-diazole and attached phenyl rings are twisted by 5.8 (3)°.