Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.

Research progress on febrile non-hemolytic transfusion reaction: a narrative review.

Background and Objective: About 1% of patients who receive blood transfusions will develop transfusion reactions. Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. It not only leads to misdiagnosis and delayed treatment, but also incurs a huge economic burden. This article reviews FNHTR systematically, aiming to make clinicians have a more comprehensive understanding of FNHTR and reduce the occurrence of this side effect. Methods: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. Medical Subject Headings (MeSH) included Blood Transfusion, Transfusion Reaction, and Febrile Non-Hemolytic Transfusion Reaction. The searches and literature screening were performed by 2 researchers; any differences of opinion or results were resolved through negotiation. Key Content and Findings: The pathophysiological mechanisms of FNHTR mainly included immune and non-immune pathways. The former was associated with antibodies against human leukocyte antigen (HLA) produced in transfused patients, while the latter was associated with cytokines released from blood products during storage. Women with a reproductive history and those patients with multiple blood transfusions were more likely to experience FNHTR. Primary hematologic disease, malignant disease, and transfusion with over 6 units of leukocyte-depleted packed red blood cells were independent risk factors for the development of FNHTR. FNHTR could be diagnosed by accompaniment of the fever symptom (body temperature ≥38 ℃, maybe an increase of body temperature of more than 1 ℃ compared with that before blood transfusion) during or within 4 hours after transfusion, or the presence of chills, shakes, headache, and nausea, among other symptoms. FNHTR should be mainly differentiated from other types of transfusion reactions with similar symptoms. Prophylactic strategies for the routine use of antipyretic drugs before transfusion remain controversial. Removal of leukocyte components from blood could reduce the incidence of FNHTR significantly. Conclusions: The pathogenesis of FNHTR is mainly associated with anti-HLA antibodies and cytokines released from blood products during storage. Specific markers and effective detection methods for FNHTR are still lacking. Treatment for FNHTR is currently limited to antipyretic drugs, sedation, and other symptomatic treatment measures. More studies are warranted to focus on the pathological mechanism of FNHTR.

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.

N6-Methyladenosine (m6A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m6A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m6A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m6A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m6A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m6A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.