Overview of the Role for Calreticulin in the Enhancement of Wound Healing through Multiple Biological Effects

Calreticulin (CRT), an intracellular chaperone protein crucial for the proper folding and transport of proteins through the endoplasmic reticulum, has more recent acclaim as a critical regulator of extracellular functions, particularly in mediating cellular migration and as a requirement for phagocytosis of apoptotic cells. Consistent with these functions, we show that the topical application of CRT has profound effects on the process of wound healing by causing a dose-dependent increase in epithelial migration and granulation tissue formation in both murine and porcine normal and impaired animal models of skin injury. These effects of CRT are substantiated, in vitro, as we show that CRT strongly induces cell migration/wound closure of human keratinocytes and fibroblasts, using a wound/scratch plate assay, and stimulates cellular proliferation of human keratinocytes, fibroblasts, and vascular endothelial cells, providing mechanistic insight into how CRT functions in repair. Similarly, in both animal models, the histology of the wounds show marked proliferation of basal keratinocytes and dermal fibroblasts, dense cellularity of the dermis with notably increased numbers of macrophages and well-organized collagen fibril deposition. Thus, CRT profoundly affects the wound healing process by recruiting cells essential for repair into the wound, stimulating cell growth, and increasing extracellular matrix production

Imaging Mass Spectrometry for Assessing Cutaneous Wound Healing: Analysis of Pressure Ulcers

Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing

Diffusion Tensor Tractrography Visualizes Partial Nerve Laceration Severity as Early as 1 Week After Surgical Repair in a Rat Model Ex Vivo.

BACKGROUND: Previous studies in our laboratory have demonstrated that a magnetic resonance imaging method called diffusion tensor imaging (DTI) can differentiate between crush and complete transection peripheral nerve injuries in a rat model ex vivo. DTI measures the directionally dependent effect of tissue barriers on the random diffusion of water molecules. In ordered tissues such as nerves, this information can be used to reconstruct the primary direction of diffusion along fiber tracts, which may provide information on fiber tract continuity after nerve injury and surgical repair. METHODS: Sprague-Dawley rats were treated with different degrees of partial transection of the sciatic nerve followed by immediate repair and euthanized after 1 week of recovery. Nerves were then harvested, fixed, and scanned with a 7 Tesla magnetic resonance imaging to obtain DTIand fiber tractography in each sample. Additional behavioral (sciatic function index, foot fault asymmetry) and histological (Toluidine blue staining) assessments were performed for validation. RESULTS: Tractography yielded a visual representation of the degree of injury that correlated with behavioral and histological evaluations. CONCLUSIONS: DTI tractography is a noninvasive tool that can yield a visual representation of a partial nerve transection as early as 1 week after surgical repair

Abstract

The Pahlavan Mahmud Mausoleum is the shrine of Khiva's patron saint, Pahlavan Mahmud, and the dynastic burial complex of the Qungrat Khans. The ensemble lies south of Khiva's famed Allah ad-Din tomb, near the Islam Khwaja Complex in the Ichan-Kala (inner fortress). It was built in the fourteenth century around the tomb of Pahlavan Mahmud, who is believed to be a gifted poet, soldier, furrier, professional wrestler and healer of diseases. The complex today consists of a domed monastic hall (khanqah), yard and gate pavilion (darvaza khana) along north-south axis, with a summer mosque, Quran reading rooms (qori khana), kitchen and other ancillary structures arranged on either side. Source: Archnetexterior, side view of the khanagah with adjacent tombs in the foreground and bench set up for photo opportunity, 200