Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future

Identification of Target Genes Involved in the Antiproliferative Effect of Enzyme-Modified Ginseng Extract in HepG2 Hepatocarcinoma Cell

Ginsenosides are ginseng saponins, which are the major biologically active components of Panax ginseng, often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng increased after enzymatic processing of ginseng saponin (50% inhibitory concentration [IC50], >30 μg/mL), which may be the result of the accumulation of minor saponins, such as Rh1, Rg3, compound K, and PPT constituents in ginseng saponin. Using the Agilent PrimeView Human Gene Expression Array, we found that the expression of several genes involved in apoptosis (caspase-4, Annexin A2, HSPA9, AIFM1, UQCRC2, and caspase-7) were increased in HepG2 human hepatocarcinoma cells after their treatment with enzyme-modified ginseng extract (EMGE). Furthermore, several genes implicated in cell cycle progression (CDCA3, CDCA8, CABLES2, CDC25B, CNNM3, and CCNK) showed decreased expression in HepG2 cells treated with EMGE. Finally, from flow cytometric analysis, we found that EMGE-treated HepG2 cells showed increased apoptotic sub-G1 population (24%), compared with that observed in DMSO-treated control cells (1.6%). Taken together, our results suggest that EMGE induces anticancer activity through the induction of apoptosis-related genes and cell cycle arrest via decreased expression of cell cycle regulatory genes

An Ontology-Based Interpretable Fuzzy Decision Support System for Diabetes Diagnosis

Diabetes is a serious chronic disease. The importance of clinical decision support systems (CDSSs) to diagnose diabetes has led to extensive research efforts to improve the accuracy, applicability, interpretability, and interoperability of these systems. However, this problem continues to require optimization. Fuzzy rule-based systems are suitable for the medical domain, where interpretability is a main concern. The medical domain is data-intensive, and using electronic health record data to build the FRBS knowledge base and fuzzy sets is critical. Multiple variables are frequently required to determine a correct and personalized diagnosis, which usually makes it difficult to arrive at accurate and timely decisions. In this paper, we propose and implement a new semantically interpretable FRBS framework for diabetes diagnosis. The framework uses multiple aspects of knowledge-fuzzy inference, ontology reasoning, and a fuzzy analytical hierarchy process (FAHP) to provide a more intuitive and accurate design. First, we build a two-layered hierarchical and interpretable FRBS; then, we improve this by integrating an ontology reasoning process based on SNOMED CT standard ontology. We incorporate FAHP to determine the relative medical importance of each sub-FRBS. The proposed system offers numerous unique and critical improvements regarding the implementation of an accurate, dynamic, semantically intelligent, and interpretable CDSS. The designed system considers the ontology semantic similarity of diabetes complications and symptoms concepts in the fuzzy rules' evaluation process. The framework was tested using a real data set, and the results indicate how the proposed system helps physicians and patients to accurately diagnose diabetes mellitusThis work was supported by National Research Foundation of Korea-Grant funded by the Korean Government (Ministry of Science, ICT and Future Planning)-NRF-2017R1A2B2012337)S

KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells

The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α (IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation

Coronary-artery Calcium Scores Using Electron Beam CT in Patients with Chronic Renal Failure

We evaluated the risk of coronary-artery disease in patients with chronic renal failure (CRF) by measuring the coronary-artery calcium scores with electron beam CT (EBCT). A total of 81 CRF patients were divided into three groups; pre-dialysis (group I, n=35), hemodialysis (group II, n=31) and peritoneal dialysis (group III, n=15). The several serum biochemical markers and calcium score levels by EBCT were determined. The Ca×P products were significantly higher in groups II (p<0.05) and III (p<0.01) than in group I. The serum calcium levels were significantly higher in group III than in both group I (p<0.01) and II (p<0.05). The serum calcium level in 15 patients with a calcium score > 400 was significantly higher than the 66 patients with a score ≤400 (p<0.01). The calcium score was significantly higher in the 15 patients with cardiovascular complications than in the 66 patients without cardiovascular complications (628.9±904.8 vs. 150.4±350.9, p<0.01). EBCT seemed to be a good diagnostic tool for evaluating the risk of coronary-artery disease "non-invasively" in CRF patients who are at increased risk of cardiovascular morbidity and mortality

The effect of the surface modification of titanium using a recombinant fragment of fibronectin and vitronectin on cell behavior

The surface of titanium implants is in direct contact with host tissue and plays a critical role in determining biocompatibility. Fibronectin (FN) and vitronectin (VN) are major cell adhesive proteins found in the extracellular matrix (ECM) of various tissues, and in circulating blood. The aim of this study was to evaluate the engineered biomimetic surface of titanium by using recombinant fragment of FN8–10 and VNNTD that contains the binding site for integrins. MC3T3-E1 cells seeded upon the FN8−10-coated titanium showed a marked increase in cell adhesion, proliferation, and differentiation over VNNTD-coated titanium. In addition, we confirmed that the surface properties of titanium prefer for FN8–10 over VNNTD (p<0.05) in protein adhesion. These results suggest that the FN8–10-modified titanium surface can be used to improve the osseointegration of titanium implants by enhancing bone formation

The Osteogenic Differentiation Effect of the FN Type 10-Peptide Amphiphile on PCL Fiber

The fibronectin type 10-peptide amphiphile (FNIII10-PA) was previously genetically engineered and showed osteogenic differentiation activity on rat bone marrow stem cells (rBMSCs). In this study, we investigated whether FNIII10-PA demonstrated cellular activity on polycaprolactone (PCL) fibers. FNIII10-PA significantly increased protein production and cell adhesion activity on PCL fibers in a dose-dependent manner. In cell proliferation results, there was no effect on cell proliferation activity by FNIII10-PA; however, FNIII10-PA induced the osteogenic differentiation of MC3T3-E1 cells via upregulation of bone sialoprotein (BSP), collagen type I (Col I), osteocalcin (OC), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) mitochondrial RNA (mRNA) levels; it did not increase the alkaline phosphatase (ALP) mRNA level. These results indicate that FNIII10-PA has potential as a new biomaterial for bone tissue engineering applications

Evaluation of Sustained BMP-2 Release Profiles Using a Novel Fluorescence-Based Retention Assay.

The purpose of this study was to develop and characterize a novel fluorescence-based retention assay for the evaluation of the release profile of bone morphogenetic protein-2 (BMP-2) released from bone graft carrier. In this study, we evaluated the binding, release kinetics, and delivery efficacies of BMP-2 incorporated into hydroxyapatite (HA) bone grafts. The evaluation of the release profile of BMP-2 from HA bone grafts using a fluorescence-based retention assay revealed initial burst releases from the HA bone grafts followed by long sustained releases up to 14 weeks. The sustained biological activity of the released BMP-2 from HA bone grafts over the full 14-week period supports a long sustained mechanism via fluorescence-based retention assay. Thus, the results from this study show that BMP-2 could be incorporated into HA bone grafts for sustained release over a prolonged period of time with retention of bioactivity and our fluorescence-based retention assay, which is principally detecting the retention profile of BMP-2 in HA bone grafts, is more accurate than conventionally collecting the released BMP-2 for evaluation of BMP-2 release profiles

Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future