Novel NMR-Based Approach to Reveal the 'Metabolic Fingerprint' of Cytotoxic Gold Drugs in Cancer Cells.

A combination of pathway enrichment and metabolite clustering analysis is used to interpret untargeted H NMR metabolomics data, enabling a biochemically informative comparison of the effects induced by a panel of known cytotoxic gold(I) and gold(III) compounds in A2780 ovarian cancer cells. The identification of the most dysregulated pathways for the major classes of compounds highlights specific chemical features that lead to common biological effects. The proposed approach may have broader applicability to the screening of metal-based drug candidate libraries, which is always complicated by their multitarget nature, and support the comprehensive interpretation of their metabolic actions.

Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera.

Exposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response.

Gastrointestinal Conditions Affect Chronic Pain and Quality of Life in Women.

Pain is a chronic condition in many women; drugs used for its treatment are often accompanied by detrimental effects on many organs, including the gut. Once inflamed, the gut can affect pain processes. The aim of this study was to evaluate the general health of women suffering chronic pain, with particular attention to gastrointestinal (GI) conditions.

Design of a Glycoconjugate Vaccine Against Paratyphi A.

Background/objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against Paratyphi A. Here we describe the design of a Paratyphi A conjugate.

Deciphering the role of neutral diruthenium complexes in protein binding.

The charge of paddlewheel diruthenium complexes has a major role in defining their interaction with proteins: negatively charged complexes bind proteins non-covalently, while cationic complexes form adducts where the Ru core binds to Asp side chains at the equatorial sites, or to the main chain carbonyl groups or the side chains of His, Arg or Lys residues at the axial sites. Here we study the interactions of the neutral compound [Ru(D-p-FPhF)(OCCH)(OCO)]·3HO (D-p-FPhF = N,N'-bis(4-fluorophenyl)formamidinate), a very rare example of a paddlewheel diruthenium compound with three different equatorial ligands, with the model protein bovine pancreatic ribonuclease (RNase A) by means of UV-visible absorption spectroscopy, circular dichroism (CD), electrospray ionization mass spectrometry (ESI-MS) and X-ray crystallography. It is the first attempt to investigate the binding of a neutral diruthenium compound to a protein.