Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response.

We developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other and using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex.

Novel Technique for Box-Lesion Ablation of Atrial Fibrillation Combined with Off-Pump Coronary Surgery.

Introduction: We propose a new technique for box-lesion ablation combined with off-pump coronary artery bypass grafting for the treatment of patients with coronary artery disease and paroxysmal or persistent atrial fibrillation.

Methods: Eight male patients with paroxysmal (n=2) or persistent atrial fibrillation (n=6) and coronary artery disease underwent box-lesion ablation combined with off-pump coronary artery bypass grafting. Box-lesion ablation was performed using a bipolar flexible clamping device with irrigated electrodes which was originally designed for thoracoscopic epicardial ablation.

Epigenetic Clock and Circadian Rhythms in Stem Cell Aging and Rejuvenation.

This review summarizes the current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the senescence of all somatic cells and stem cells in particular. Basic mechanisms of regulation for circadian genes CLOCK-BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by the finely tuned regulation of transcription and rely on various epigenetic mechanisms including the activation of enhancers/suppressors, acetylation/deacetylation of histones and other proteins as well as DNA methylation.

Biomechanical Changes in Gait Patterns of Patients with Grade II Medial Gonarthritis.

Deforming osteoarthritis (OA) of the knee is a progressive disease associated with pain and compromised function of the joint. Typical biomechanical modifications in the gait of subjects with medial knee OA are characterized by decreased gait speed and overload on the affected limb. The borderline stage for conservative versus surgical management is Grade II OA.