Emerging Role of Non-collagenous Bone Proteins as Osteokines in Extraosseous Tissues.

Bone is a unique tissue, composed of various types of cells embedded in a calcified extracellular matrix (ECM), whose dynamic structure consists of organic and inorganic compounds produced by bone cells. The main inorganic component is represented by hydroxyapatite, whilst the organic ECM is primarily made up of type I collagen and non-collagenous proteins. These proteins play an important role in bone homeostasis, calcium regulation, and maintenance of the hematopoietic niche. Recent advances in bone biology have highlighted the importance of specific bone proteins, named "osteokines", possessing endocrine functions and exerting effects on nonosseous tissues. Accordingly, osteokines have been found to act as growth factors, cell receptors, and adhesion molecules, thus modifying the view of bone from a static tissue fulfilling mobility to an endocrine organ itself. Since bone is involved in a paracrine and endocrine cross-talk with other tissues, a better understanding of bone secretome and the systemic roles of osteokines is expected to provide benefits in multiple topics: such as identification of novel biomarkers and the development of new therapeutic strategies. The present review discusses in detail the known osseous and extraosseous effects of these proteins and the possible respective clinical and therapeutic significance.

EBV Plasma Epstein-Barr Virus (EBV) DNA as a Biomarker for Diagnosis of EBV-positive Hodgkin Lymphoma in Syria.

INTRODUCTION: Epstein Barr Virus - positive Hodgkin lymphoma is defined by the presence of Epstein-Barr virus (EBV) in tumor cells. EBV plays an important role in the development and prognosis of Hodgkin's lymphoma. The standard way to detect EBV in Hodgkin lymphoma is immunohistochemistry stains for latent membrane protein-1 (LMP1) in tumor cells. The present study aimed to evaluate plasma Epstein-Barr virus (EBV) DNA as a noninvasive biomarker for diagnosis of EBV-positive Hodgkin lymphoma. METHODOLOGY: The study included 60 newly diagnosed patients with Hodgkin lymphoma, ranging in age from 4 to 60 years, and 55 sex and age-matched controls. (60) Formalin-fixed paraffin embedded blocks of Hodgkin lymphoma tissue samples were used to investigate the EBV by in immunohistochemistry stains for (LMP1) in tumor cells. Plasma EBV DNA was quantified by real-time quantitative polymerase chain reaction (PCR) for all Hodgkin lymphoma patients prior to therapy and for control. RESULTS: The results showed that (25/60, 41.7%) of Hodgkin lymphoma were positive for histological LMP1, whereas plasma EBV DNA was detectable (range from 1.1×103 to 1.5×104 copies/mL, median: 1.1×104 copies/mL) in all EBV-positive Hodgkin lymphoma samples (25/25). EBV DNA was undetectable in all cases of EBV-negative Hodgkin lymphoma (35/35) and all healthy control (55/55). It is worth mentioning that our results demonstrated that the EBV DNA load was high in the EBV associated Hodgkin lymphoma patients suffering poor prognostic state. CONCLUSIONS: Plasma EBV-DNA can be used as a noninvasive biomarker for diagnosis of EBV- positive Hodgkin lymphoma.