Search

AbstractBackground:Studies have shown that many patients with type 2 diabetes do not achieve optimal glycemic control, and progression of diabetes over time requires more than one pharmacotherapy to achieve glycemic goal.Objective:To examine the efficacy and safety of the fixed-dose combination (FDC) of pioglitazone 15 mg and metformin 850 mg versus its individual components in a twice-daily regimen over 24 weeks of treatment in type 2 diabetes patients who were currently not receiving antidiabetes therapy.Methods:This was a double-blind, randomized, parallel-group, controlled study. The primary endpoint was change from baseline in hemoglobin A1c (HbA1c) of pioglitazone/metformin FDC therapy compared with pioglitazone and metformin monotherapy. Secondary endpoints included change from baseline in fasting plasma glucose (FPG), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerability of pioglitazone/metformin FDC therapy and its individual components were also evaluated. Study limitations to be noted include the early stage of diabetes in these patients, which may be more responsive to treatment, and the 6 month treatment period, which does not provide durability data.Clinical trial registration:ClinicalTrials.gov, NCT00727857.Results:From a baseline HbA1c >8.6, mean HbA1c decreased the most with pioglitazone/metformin FDC (−1.83) (P < 0.0001), compared with pioglitazone (−0.96) and metformin (−0.99) monotherapy, with 63.8 of FDC patients achieving HbA1c ≤ 7 versus 46.9 of pioglitazone- and 38.9 of metformin-treated patients. The decrease from baseline to final visit in FPG was significantly larger in the pioglitazone/metformin FDC group (−39.9 mg/dL) (P < 0.01) compared with either monotherapy; the decrease in mean HOMA-IR was greatest with pioglitazone/metformin FDC. The pioglitazone/metformin FDC was well tolerated with no unexpected findings in adverse events of special interest, including hypoglycemia, bone fractures, peripheral edema, and cardiac failure.Conclusions:Overall, treatment with pioglitazone/metformin FDC demonstrated greater efficacy than its individual components. The FDC therapy was well tolerated, with reduced or similar adverse event rates compared with each individual monotherapy. [ABSTRACT FROM AUTHOR]

Low-molecular-weight (LMW) organic acids exist widely in soils and have been implicated in many soil processes. In the present paper, the effect of the anions of four LMW organic acids on the adsorption of potassium (K) by two variable charge soils was investigated. The results showed that the presence of organic anions led to an increase in K adsorption. The ability of organic anions to induce K adsorption followed the order: citrate>malate>malonate˜oxalate>acetate. The adsorption of K induced by organic anions increased with the increases in pH and the concentration of the anions. Both Langmuir and Freundlish equations can be used to describe the adsorption of K by variable charge soils in the presence of organic anions. Adsorption of ions is a direct consequence of carrying of surface charge for soils. Recent works have shown that the presence of organic anions led to an increase in negative surface charge and a decrease in positive surface charge of variable charge soils. The results indicated that the extents of the effect of different organic anions on adsorption of K and surface charge were generally of the same order. Therefore, it can be considered that the main reason for the adsorption of K induced by organic anions is the increase in net negative surface charge caused by the adsorption of the anions on the soils. [ABSTRACT FROM AUTHOR]

The regeneration of the articular cartilage defects is characterized by the improvement in the quality of the repaired tissue and the reduction in the potential development of perifocal osteoarthritis (OA). Usually, the injection of dexamethasone (Dex) in the OA joints slows down the progression of inflammation and relieves pain. However, the anti-inflammatory Dex injected in the joint cavity is rapidly cleared, leading to a poor therapeutic effect. Multifunctional hydrogels with simultaneous chondrogenic differentiation, antioxidative, and anti-inflammatory capacities may represent a promising solution. Therefore, in this work, a novel injectable hydrogel based on double cross-linking of Schiff base bonds and coordination of catechol-Fe was developed. The obtained hydrogel (Gel-DA/DOHA/DMON@Dex@Fe) possessed molding performance in situ, excellent mechanical strength, controllable biodegradability, the on-demand release of the drug, and biocompatibility. The hydrogel system stimulated the HIF-1α signaling pathway and suppressed inflammation thanks to the introduction of DMON@Fe, consequently facilitating chondrogenic differentiation. The synergistic antiinflammatory effect together with the induction of chondrogenesis by Dex-loaded Gel-DA /DOHA/DMON@Fe hydrogel allowed the promotion of cartilage repair, as demonstrated by in vivo experiments. Hence, the proposed multifunctional scaffold provides a promising advancement in articular cartilage tissue engineering and may have great prospects in the prevention of OA. [ABSTRACT FROM AUTHOR]

Context: Formononetin, an isoflavone, can inhibit the proliferation of cancer cells, including those of the prostate. However, its antitumor mechanism remains unclear. Aim: To investigate whether the insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF-1 R) signaling pathway mediates the formononetin antitumor effect on prostate cancer cells. Materials and methods: The viability of PC-3 cells was measured by MTT assay 48 h after formononetin treatment (25, 50 and 100 μM). Formononetin-induced cell apoptosis was measured by Hoechst 33258 staining and flow cytometry. Expression of Bax mRNA was detected by real-time PCR, and the expression levels of Bax and IGF-1 R proteins were detected by western blots. Results: At concentrations >12.5 μM, formononetin significantly inhibited the proliferation of human prostate cancer cells. Formononetin increased Bax mRNA and protein expression levels and decreased the expression levels of pIGF-1 R protein in a dose-dependent manner. Conclusion: High concentrations of formononetin-induced apoptosis in androgen-independent prostate cancer cells through inhibition of the IGF-1/IGF-1 R pathway. [ABSTRACT FROM AUTHOR]

A series of four novel azobenzene liquid crystals (LCs) with high birefringence were synthesized by coupling of intermediate molecules with a phenylacetylene fragment. The chemical structures of synthetic intermediates and compounds were confirmed by FT-IR and ¹H-NMR. The LC behavior including transition temperatures and phase sequences were investigated by differential scanning calorimetry (DSC) and polarizing optical microscope (POM). as a very important parameter, the birefringence was also measured using polarizing light interferometry method. Moreover, the characteristics of selective reflection which was associated with the birefringence of the N*-LC dropped with azobenzene LCs and the effect of trans-cis photoisomerization of these compounds on selective reflection were studied in detail. [ABSTRACT FROM AUTHOR]