Activated leukocyte cell adhesion molecule/cluster of differentiation 166 rs10933819 (G>A) variant is associated with familial intracranial aneurysms.

Rupture of intracranial aneurysms (IAs) is the most common cause of subarachnoid hemorrhage (SAH). Currently, there is sufficient evidence to indicate that inflammatory responses contribute to aneurysm rupture. Moreover, the familial occurrence of SAH suggests that genetic factors may be involved in disease susceptibility. In the present study, a clinically proven case of IA in a patient who is a heterozygous mutation carrier of the activated leukocyte cell adhesion molecule (ALCAM)/cluster of differentiation 166 (CD166) gene, is reported. Genomic DNA was extracted from two siblings diagnosed with SAH and other available family members. A variant prioritization strategy that focused on functional prediction, frequency, predicted pathogenicity, and segregation within the family was employed. Sanger sequencing was also performed on the unaffected relatives to assess the segregation of variants within the phenotype. The verified mutations were sequenced in 145 ethnicity-matched healthy individuals. Based on whole exome sequencing data obtained from three individuals, two of whom were diagnosed with IAs, the single-nucleotide variant rs10933819 was prioritized in the family. Only one variant, rs10933819 (G>A), in ALCAM co-segregated with the phenotype, and this mutation was absent in ethnicity-matched healthy individuals. Collectively, ALCAM c1382 G>A p.Gly229Val was identified, for the first time, as a pathogenic mutation in this IA pedigree.

Immunology of Acute and Chronic Wound Healing.

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1ß, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

Progress and Prospects of Polymer-Based Drug Delivery Systems for Bone Tissue Regeneration.

Despite the high regenerative capacity of bone tissue, there are some cases where bone repair is insufficient for a complete functional and structural recovery after damage. Current surgical techniques utilize natural and synthetic bone grafts for bone healing, as well as collagen sponges loaded with drugs. However, there are certain disadvantages associated with these techniques in clinical usage. To improve the therapeutic efficacy of bone tissue regeneration, a number of drug delivery systems based on biodegradable natural and synthetic polymers were developed and examined in in vitro and in vivo studies. Recent studies have demonstrated that biodegradable polymers play a key role in the development of innovative drug delivery systems and tissue engineered constructs, which improve the treatment and regeneration of damaged bone tissue. In this review, we discuss the most recent advances in the field of polymer-based drug delivery systems for the promotion of bone tissue regeneration and the physical-chemical modifications of polymers for controlled and sustained release of one or more drugs. In addition, special attention is given to recent developments on polymer nano- and microparticle-based drug delivery systems for bone regeneration.