Towards Multitargeted Ligands as Pain Therapeutics: Dual Ligands of the Caα2δ-1 Subunit of Voltage-Gated Calcium Channel and the μ-Opioid Receptor.

The synthesis and pharmacological activity of a new series of dual ligands combining activities towards the α2δ-1 subunit of voltage-gated calcium channels (Caα2δ-1) and the μ-opioid receptor (MOR) as novel pain therapeutics are reported. A careful exploration of the pharmacophores related to both targets, which in principle had few common characteristics, led to the design of novel compounds exhibiting both activities. The construction of the dual ligands started from published Caα2δ-1 ligands, onto which MOR ligand pharmacophoric elements were added.

Nuclear expression of histone deacetylases and their histone modifications predicts clinical outcome in colorectal cancer.

Aims: Epigenetic changes are of crucial importance in cancer development and are potentially reversible; they are therefore targets of interest for anti-cancer therapy. The aim of this study was to investigate the clinical prognostic value of the histone deacetylases SIRT1, HDAC1 and HDAC2 and the histone modifications H4K16Ac and H3K56Ac in colorectal cancer.

Methods And Results: The epigenetic markers were immunohistochemically stained on tissue microarrays containing colorectal tumours (n = 254) and normal colorectal tissues (n = 50).

Histone trimethylation at H3K4, H3K9 and H4K20 correlates with patient survival and tumor recurrence in early-stage colon cancer.

Background: Post-translational modification of histone tails by methylation plays an important role in tumorigenesis. In this study, we investigated the nuclear expression of H3K4me3, H3K9me3 and H4K20me3 in early-stage colon cancer in relation to clinical outcome.

Methods: Tumor tissue cores of 254 TNM stage I-III colorectal cancer patients were immunohistochemically stained for H3K4me3, H3K9me3 and H4K20me3 and scored using the semi-automated Ariol system.

Toll-like receptor ligation for the induction of regulatory B cells.

Toll-like receptors (TLRs) are key components for the recognition of microorganisms, for the initiation of innate immunity, and for promoting adaptive immune responses. TLR signaling in B cells, in addition to B cell receptor or CD40 ligation, plays an important role in B cell differentiation and activation. In contrast, various infectious agents and/or TLR ligands can also prime B cells to induce tolerance and downregulate inflammatory reactions; those B cells are called regulatory B (Breg) cells and are characterized by a dominant IL-10 production.

The presence of family members during cardiopulmonary resuscitation: European federation of Critical Care Nursing associations, European Society of Paediatric and Neonatal Intensive Care and European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions Joint Position Statement.

This paper presents the European federation of Critical Care Nursing associations, the European Society of Paediatric and Neonatal Intensive Care, and the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions Joint Position Statement on The Presence of Family Members During Cardiopulmonary Resuscitation.