Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation.

We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1-3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC50 ~0.6-7.9 µM and 0.7-10.9 µM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors.

Pattern recognition receptors in annelids.

The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.

Tomentomimulol and mimulone B: two new C-geranylated flavonoids from Paulownia tomentosa fruits.

Two new discovered C-geranylated flavonoids tomentomimulol (1) and mimulone B (2) were isolated from the methanol extract of Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits by exhaustive chromatographic separation together with one known compound tanariflavanone D (3). The identification of compounds and structure elucidation was carried out using 1D and 2D NMR experiments, as well as mass spectroscopy, ultra-violet, infra red and CD experiments.

[Bezalip in the treatment of hyperlipoproteinemia]. / Bezalip v lécbe hyperlipoproteinémií.

In a specialized clinic for hyperlipoproteinaemias 15 patients with different types of hyperlipoproteinaemias were treated with bezafibrate (Bezalip R tablets a 200 mg of Boehringer Co.) for a period of four weeks 3 X 1 tablet per day. The administration of Bezalip led to a significant drop of cholesterol (-20%), triglycerides by 40% and LDL-cholesterol (-17%), while the HDL cholesterol level did not change significantly. During treatment a drop of the apolipoprotein B level by 17% occurred, the concentration of apolipoprotein A-I increased by 12%. The drug was well tolerated by the patients, there were no undesirable effects calling for discontinuation of treatment. The results are discussed along with those of other authors who had the opportunity to administer the drug for a prolonged period. The authors mention also briefly the results obtained during treatment of patients with hyperlipoproteinaemias, using other hypolipidaemic drugs.