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This review proposes an optimized plan for guiding the design of future clinical research to identify therapeutic options for this complex disease.The inappropriate accumulation and activation of leukocytes is a shared pathological feature of immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Cellular accumulation is therefore an attractive target for therapeutic intervention. However, attempts to modulate leukocyte entry and exit from the joint have proven unsuccessful to date, indicating that gaps in our knowledge remain. Technological advancements are now allowing real-time tracking of leukocyte movement through arthritic joints or in vitro joint constructs. Coupling this technology with improvements in analyzing the cellular composition, location and interactions of leukocytes with neighboring cells has increased our understanding of the temporal dynamics and molecular mechanisms underpinning pathological accumulation of leukocytes in arthritic joints. In this review, we explore our current understanding of the mechanisms leading to inappropriate leukocyte trafficking in inflammatory arthritis, and how these evolve with disease progression. Moreover, we highlight the advances in imaging of human and murine joints, along with multi-cellular ex vivo joint constructs that have led to our current knowledge base.The insulin-like growth factors (IGFs) are polypeptides with similar sequences with insulin. These factors regulate cell growth, development, maturation, and aging via different processes including the interplay with MAPK, Akt, and PI3K. IGF signaling participates in the pathogenesis of neoplasia, insulin resistance, diabetes mellitus, polycystic ovarian syndrome, cerebral ischemic injury, fatty liver disease, and several other conditions. Recent investigations have demonstrated the interplay between non-coding RNAs and IGF signaling. This interplay has fundamental roles in the development of the mentioned disorders. We designed the current study to search the available data about the role of IGF-associated non-coding RNAs in the evolution of neoplasia and other conditions. As novel therapeutic strategies have been designed for modification of IGF signaling, identification of the impact of non-coding RNAs in this pathway is necessary for the prediction of response to these modalities.Calcification of various tissues is a significant health issue associated with aging, cancer and autoimmune diseases. There are both environmental and genetic factors behind this phenomenon and understanding them is essential for the development of efficient therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease, a prototype for calcification disorders, resulting from the dysfunction of ABCC6, a transport protein found in the membranes of cells. It is identified by excess calcification in a variety of tissues (e.g., eyes, skin, arteries) and currently it has no cure, known treatments target the symptoms only. Preclinical studies of PXE have been successful in mice, proving the usefulness of animal models for the study of the disease. Here, we present a new zebrafish (Danio rerio) model for PXE. By resolving some ambiguous assemblies in the zebrafish genome, we show that there are two functional and one non-functional paralogs for ABCC6 in zebrafish (abcc6a, abcc6b.1, and abcc6b.2, respectively). We created single and double mutants for the functional paralogs and characterized their calcification defects with a combination of techniques. Zebrafish deficient in abcc6a show defects in their vertebral calcification and also display ectopic calcification foci in their soft tissues. BAY-218 chemical structure Our results also suggest that the impairment of abcc6b.1 does not affect this biological process.It has been known for decades or even centuries that arteries calcify as they age. Vascular calcification probably affects all adults, since virtually all have atherosclerotic plaques an accumulation of lipids, inflammatory cells, necrotic debris, and calcium phosphate crystals. A high vascular calcium score is associated with a high cardiovascular mortality risk, and relatively recent data suggest that even microcalcifications that form in early plaques may destabilize plaques and trigger a cardiovascular event. If the cellular and molecular mechanisms of plaque calcification have been relatively well characterized in mice, human plaques appear to calcify through different mechanisms that remain obscure. In this context, we will first review articles reporting the location and features of early calcifications in human plaques and then review the articles that explored the mechanisms though which human and mouse plaques calcify.Chronic wounds in diabetic patients represent an escalating health problem, leading to significant morbidity and mortality. Our group previously reported that whole body low-intensity vibration (LIV) can improve angiogenesis and wound healing in diabetic mice. The purpose of the current study was to determine whether effects of LIV on wound healing are frequency and/or amplitude dependent. Wound healing was assessed in diabetic (db/db) mice exposed to one of four LIV protocols with different combinations of two acceleration magnitudes (0.3 and 0.6 g) and two frequencies (45 and 90 Hz) or in non-vibration sham controls. The low acceleration, low frequency protocol (0.3 g and 45 Hz) was the only one that improved wound healing, increasing angiogenesis and granulation tissue formation, leading to accelerated re-epithelialization and wound closure. Other protocols had little to no impact on healing with some evidence that 0.6 g accelerations negatively affected wound closure. The 0.3 g, 45 Hz protocol also increased levels of insulin-like growth factor-1 and tended to increase levels of vascular endothelial growth factor in wounds, but had no effect on levels of basic fibroblast growth factor or platelet derived growth factor-bb, indicating that this LIV protocol induces specific growth factors during wound healing. Our findings demonstrate parameter-dependent effects of LIV for improving wound healing that can be exploited for future mechanistic and therapeutic studies.