Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from osteoarthritic cartilage through up-regulation of extracellular signal-regulated kinase 1/2 and suppression of FASL,FAS, and Caspase 3

Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti-inflammatory and analgesic effect. However, Dex also has many side effects following repeated use over prolonged periods mainly through increasing apoptosis and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic effect on many cells and little is known about its effect on OA chondrocytes. Therefore, the aim of this study is to investigate whether LF can inhibit Dex-induced OA chondrocytes apoptosis and explore its possible molecular mechanism involved in. MTT assay was used to determine the optimal concentration of Dex and recombinant human LF (rhLF) on chondrocytes at different time and dose points. Chondrocytes were then stimulated with Dex in the absence or presence of optimal concentration of rhLF. Cell proliferation and viability were evaluated using MTT and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi-parameter apoptosis assay kit using both confocal microscopy and flow cytometry, respectively. The expression of extracellular signal-regulated kinase (ERK), FAS, FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The optimal concentration of Dex (25 μg/ml) and rhLF (200 μg/ml) were chosen for the following experiments. rhLF significantly reversed the detrimental effect of Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF significantly prevented Dex-induced down-regulation of ERK and up-regulation of FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as an anabolic effect on chondrocytes through significantly reversing Dex-induced chondrocytes apoptosis. This study may contribute to further investigating the clinical application of LF on OA.     

Synthesis and antioxidant activity of 4-[2-(3,5-dimethoxyphenyl)ethenyl]-1,2-benzenediol, a metabolite of Sphaerophysa salsula

4-[2-(3,5-Dimethoxyphenyl)ethenyl]-1,2-benzenediol (7), a stilbene isolated from Sphaerophysa salsula, was synthesized from 3,4-dihydroxybenzaldehyde (1) in five steps in an overall yield of 33%. The spectral data for synthetic 7 are in good agreement with those of the natural product. Hydroxystilbene 7 showed potent antioxidative activity.     

Influence ofParthenium hysterophorus L. on native soil algal flora

Soil was amended with powder from air-dried leaves, inflorescences or roots ofParthenium hysterophorus L. at 1, 2 and 5 per cent (w/w) levels, and inhibitory effect towards indigenous algal population was assessed. The inhibition of algae was more pronounced in the soil amended with leaf material followed by treatments with inflorescence and least with root powder. Higher levels (2 and 5%) of leaf and inflorescence amendment resulted in a greater inhibition of the algae.     

Measurement of γ-H2AX foci,miRNA-101, and gene expression as a means to quantify radiation-absorbed dose in cancer patients who had undergone radiotherapy

Radiation and Environmental Biophysics - Radiological accidents and nuclear terrorism pose an increased threat to members of the public who, following such an event, would need to be assessed for...     

Structural properties of DNA:RNA duplexes containing 2'-O-methyl and 2'-S-methyl substitutions: a molecular dynamics investigation

The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)*(CCAACGUUGG) with modifications at the C2'-positions of the DNA strand by 2'-O-methyl (OMe) and 2'-S-methyl (SMe) groups are studied using computational techniques. Molecular dynamics simu-lations of SMe_DNA:RNA, OMe_DNA:RNA and standard DNA:RNA hybrids in explicit water indicate that the nature of the C2'-substituent has a significant influence on the macromolecular conformation. While the RNA strand in all duplexes maintains a strong preference for C3'-endo sugar puckering, the DNA strand shows considerable variation in this parameter depending on the nature of the C2'-substituent. In general, the preference for C3'-endo puckering follows the following trend: OMe_DNA>DNA>SMe_DNA. These results are further corroborated using ab initio methods. Both gas phase and implicit solvation calculations show the C2'-OMe group stabilizes the C3'-endo conformation while the less electronegative SMe group stabilizes the C2'-endo conformation when compared to the standard nucleoside. The macromolecular conformation of these nucleic acids also follows an analogous trend with the degree of A-form character decreasing as OMe_DNA:RNA>DNA:RNA>SMe_DNA:RNA. A structural analysis of these complexes is performed and compared with experimental melting point temper-atures to explain the structural basis to improved binding affinity across this series. Finally, a possible correlation between RNase H activity and conformational changes within the minor groove of these complexes is hypothesized.     

HIV/AIDS,Food Supplementation and Livelihood Programs in Uganda: A Way Forward?

Background

Over the last decade, health, nutrition and policy experts have become increasingly aware of the many ways in which food insecurity and HIV infection negatively impact and reinforce one another. In response, many organizations providing HIV care began supplying food aid to clients in need. Food supplementation, however, was quickly recognized as an unsustainable and incomplete intervention. Many HIV care organizations therefore developed integrated HIV and livelihood programs (IHLPs) to target the root causes of food insecurity.

Methods and Findings

We conducted a qualitative study using in-depth interviews with 21 key informants who worked at seven organizations providing HIV care, food aid, or IHLPs in Kampala, Uganda in 2007-2008 to better understand the impact of IHLPs on the well-being of people living with HIV and AIDS (PLWHAs) and the challenges in transitioning clients from food aid to IHLPs. There was strong consensus among those interviewed that IHLPs are an important intervention in addressing food insecurity and its adverse health consequences among PLWHAs. Key informants identified three main challenges in transitioning PLWHAs from food supplementation programs to IHLPs: (1) lack of resources (2) timing of the transition and (3) logistical considerations including geography and weather. Factors seen as contributing to the success of programs included: (1) close involvement of community leaders (2) close ties with local and national government (3) diversification of IHLP activities and (4) close integration with food supplementation programs, all linked through a central program of HIV care.

Conclusion

Health, policy and development experts should continue to strengthen IHLPs for participants in need. Further research is needed to determine when and how participants should be transitioned from food supplementation to IHLPs, and to determine how to better correlate measures of food insecurity with objective clinical outcomes so as to better evaluate program results.     

Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists

A novel class of azetidinone acid-derived dual PPARalpha/gamma agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARalpha and PPARgamma receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.