New and Notable This Week

This week’s selection of recently published papers from MDPI journals.

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Adjuvants in the Driver’s Seat: How Magnitude, Type, Fine Specificity and Longevity of Immune Responses Are Driven by Distinct Classes of Immune Potentiators

Abstract: The mechanism by which vaccine adjuvants enhance immune responses has historically been considered to be the creation of an antigen depot. From here, the antigen is slowly released and provided to immune cells over an extended period of time. This “depot” was formed by associating the antigen with substances able to persist at the injection site, such as aluminum salts or emulsions. The identification of Pathogen-Associated Molecular Patterns (PAMPs) has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants. This review focuses on the mode of action of different adjuvant classes in regards to the stimulation of specific immune cell subsets, the biasing of immune responses towards cellular or humoral immune response, the ability to mediate epitope spreading and the induction of persistent immunological memory. A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

For open-access article, see: Bergmann-Leitner, E.S.; Leitner, W.W. Adjuvants in the Driver’s Seat: How Magnitude, Type, Fine Specificity and Longevity of Immune Responses Are Driven by Distinct Classes of Immune PotentiatorsVaccines 20142, 252-296.

 

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Critical Role of Aberrant Angiogenesis in the Development of Tumor Hypoxia and Associated Radioresistance

Abstract: Newly formed microvessels in most solid tumors show an abnormal morphology and thus do not fulfil the metabolic demands of the growing tumor mass. Due to the chaotic and heterogeneous tumor microcirculation, a hostile tumor microenvironment develops, that is characterized inter alia by local hypoxia, which in turn can stimulate the HIF-system. The latter can lead to tumor progression and may be involved in hypoxia-mediated radioresistance of tumor cells. Herein, cellular and molecular mechanisms in tumor angiogenesis are discussed that, among others, might impact hypoxia-related radioresistance.

For open-access article, see: Multhoff, G.; Radons, J.; Vaupel, P. Critical Role of Aberrant Angiogenesis in the Development of Tumor Hypoxia and Associated RadioresistanceCancers 20146, 813-828.

 

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Effects of Neuropeptides and Mechanical Loading on Bone Cell Resorption in Vitro

Abstract: Neuropeptides such as vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are present in nerve fibers of bone tissues and have been suggested to potentially regulate bone remodeling. Oscillatory fluid flow (OFF)-induced shear stress is a potent signal in mechanotransduction that is capable of regulating both anabolic and catabolic bone remodeling. However, the interaction between neuropeptides and mechanical induction in bone remodeling is poorly understood. In this study, we attempted to quantify the effects of combined neuropeptides and mechanical stimuli on mRNA and protein expression related to bone resorption. Neuropeptides (VIP or CGRP) and/or OFF-induced shear stress were applied to MC3T3-E1 pre-osteoblastic cells and changes in receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and osteoprotegerin (OPG) mRNA and protein levels were quantified. Neuropeptides and OFF-induced shear stress similarly decreased RANKL and increased OPG levels compared to control. Changes were not further enhanced with combined neuropeptides and OFF-induced shear stress. These results suggest that neuropeptides CGRP and VIP have an important role in suppressing bone resorptive activities through RANKL/OPG pathway, similar to mechanical loading.

For open-access article, see: Yoo, Y.-M.; Kwag, J.H.; Kim, K.H.; Kim, C.H. Effects of Neuropeptides and Mechanical Loading on Bone Cell Resorption in VitroInt. J. Mol. Sci.201415, 5874-5883.

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