String-like micellar nanoparticles formed by complexation of PEG-b-PPA and plasmid DNA and their transfection efficiency.

Purpose: To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion.

Methods: PEG-b-PPA/DNA micellar nanoparticles were prepared in aqueous solution through spontaneous self-assembly between plasmid DNA and PEG(10K)-b-PPA(4K) or PEG(10K)-b-PP(13K) polymer. The stability of these micellar nanoparticles in different physiological media was evaluated by monitoring the particle size change of micellar nanoparticles with dynamic light scattering (DLS).

DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription.

Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L), have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e.

Hepatitis C virus core protein promotes the migration and invasion of hepatocyte via activating transcription of extracellular matrix metalloproteinase inducer.

The chronic infection of hepatitis C virus (HCV) becomes a main factor evoking hepatocellular carcinoma, where the HCV core protein plays a central role in hepatocarcinogenesis. Whether the core protein directly contributes to metastasis of hepatocytes still remains to be reported in literature. Transwell chamber migration assay, Boyden chamber invasion assays and scanning electron microscopy observations were performed to determine the prometastatic ability of HCV core protein when expressed in human hepatocyte L02 cells.

Comparative assessment of the effects of gender-specific heparan sulfates on mesenchymal stem cells.

We compare here the structural and functional properties of heparan sulfate (HS) chains from both male or female adult mouse liver through a combination of molecular sieving, enzymatic cleavage, and strong anion exchange-HPLC. The results demonstrated that male and female HS chains are significantly different by a number of parameters; size determination showed that HS chain lengths were ∼100 and ∼22 kDa, comprising 30-40 and 6-8 disaccharide repeats, respectively. Enzymatic depolymerization and disaccharide composition analyses also demonstrated significant differences in domain organization and fine structure.

BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo.

We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days.

Site-specific conjugation of monodispersed DOTA-PEGn to a thiolated diabody reveals the effect of increasing peg size on kidney clearance and tumor uptake with improved 64-copper PET imaging.

Optimal PET imaging of tumors with radiolabeled engineered antibodies requires, among other parameters, matching blood clearance and tumor uptake with the half-life of the engineered antibody. Although diabodies have favorable molecular sizes (50 kDa) for rapid blood clearance (t(1/2) = 30-60 min) and are bivalent, thereby increasing tumor uptake, they exhibit substantial kidney uptake as their major route of clearance, which is especially evident when they are labeled with the PET isotope (64)Cu (t(1/2) = 12 h). To overcome this drawback, diabodies may be conjugated to PEG, a modification that increases the apparent molecular size of the diabody and reduces kidney uptake without adversely affecting tumor uptake or the tumor to blood ratio.

Challenges in obtaining adequate genetic sample sets in clinical trials: the perspective of the industry pharmacogenomics working group.

Collection of DNA samples from subjects participating in clinical trials is vital to understanding variability in drug response. The purpose of this study was to assess pharmacogenetic sample-collection practices in the industry and to gather information on issues affecting collection. A survey questionnaire was developed and distributed to 20 pharmaceutical companies; 15 provided responses.

Coronary artery disease affecting the atrial branches is an independent determinant of atrial fibrillation after myocardial infarction.

Background: During acute myocardial infarction (MI), the incidence of atrial fibrillation (AF) is 6% to 22%, and its occurrence in this setting is associated with increased short- and long-term morbidity and mortality.

Objective: The purpose of this case control study was evaluate the characteristics associated with the development of new-onset AF.

Methods: Of 2,460 consecutive patients with acute MI, 149 (6%) were identified as having AF within 7 days of MI.

Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) are promising candidate cell sources for regenerative medicine. However, despite the common ability of hiPSCs and hESCs to differentiate into all 3 germ layers, their functional equivalence at the single cell level remains to be demonstrated. Moreover, single cell heterogeneity amongst stem cell populations may underlie important cell fate decisions.

The accuracy of identifying the greater palatine neurovascular bundle: a cadaver study.

Background: The palate is a common site for harvesting subepithelial connective tissue grafts (SCTG). The size of SCTG that can be harvested is dictated by the position of the greater palatine neurovascular bundle (GPB). The aims of this cadaver study are to assess the accuracy of predicting the location of the GPB on study models and to evaluate anatomic factors that might influence the predictability.

Cycle-dependent matrix remodeling gene expression response in fatigue-loaded rat patellar tendons.

Expression profiling of selected matrix remodeling genes was conducted to evaluate differences in molecular response to low-cycle (100) and high-cycle (7,200) sub-failure-fatigue loading of patellar tendons. Using our previously developed in vivo patellar tendon model, tendons were loaded for 100 or 7,200 cycles and expression of selected metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and collagens were quantified by real-time RT-PCR at 1- and 7-day post-loading. Expression profiles were also obtained from lacerated tendons as an acute injury model.

Physiological loading of joints prevents cartilage degradation through CITED2.

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation.

Novel therapeutic option for orbital atypical lymphoid hyperplasia.

Ocular lymphoid tumours represent a spectrum of lymphoproliferative disease and can be subdivided into benign or reactive lymphoid hyperplasia, indeterminate or atypical lymphoid proliferations and malignant lymphoma. Treatment options include a wait and watch approach, systemic steroids, local radiotherapy or systemic chemotherapy. We describe a case of bilateral atypical lymphoid hyperplasia treated successfully with combination immunotherapy and radiotherapy.

Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy.

Cardiac fibrosis plays an important prognostic role in nonischemic cardiomyopathy (NICM), making it a potential therapeutic target. Although electromechanical mapping has been used to identify myocardial scar and facilitate intramyocardial intervention in the setting of ischemic heart disease, its application has not been described in NICM. We assessed the detection of myocardial fibrosis by endoventricular electromechanical mapping in an experimental model of NICM.

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions.

Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate.

Aging is a major risk factor for tendon injury and impaired tendon healing, but the basis for these relationships remains poorly understood. Here we show that rat tendon- derived stem ⁄ progenitor cells (TSPCs) differ in both self-renewal and differentiation capability with age. The frequency of TSPCs in tendon tissues of aged animals is markedly reduced based on colony formation assays.

Monodispersed DOTA-PEG-conjugated anti-TAG-72 diabody has low kidney uptake and high tumor-to-blood ratios resulting in improved 64Cu PET.

Unlabelled: Diabodies are noncovalent dimers of single-chain antibody fragments that retain the avidity of intact IgG but have more favorable blood clearance than intact IgG. Radiometals offer a wide range of half-lives and emissions for matching imaging and therapy requirements and provide facile labeling of chelate-antibody conjugates. However, because of their high retention and metabolism in the kidney, the use of radiometal-labeled diabodies can be problematic for both imaging and therapy.

Long-term mechanical consequences of permanent right ventricular pacing: effect of pacing site.

Introduction: Long-term right ventricular apical (RVA) pacing has been associated with adverse effects on left ventricular systolic function; however, the comparative effects of right ventricular outflow tract (RVOT) pacing are unknown. Our aim was therefore to examine the long-term effects of septal RVOT versus RVA pacing on left ventricular and atrial structure and function.

Methods: Fifty-eight patients who were prospectively randomized to long-term pacing either from the right ventricular apex or RVOT septum were studied echocardiographically.

Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo.

Divisions of polarised blastomeres that allocate polar cells to outer and apolar cells to inner positions initiate the first cell fate decision in the mouse embryo. Subsequently, outer cells differentiate into trophectoderm while inner cells retain pluripotency to become inner cell mass (ICM) of the blastocyst. Elimination of zygotic expression of trophectoderm-specific transcription factor Cdx2 leads to defects in the maintenance of the blastocyst cavity, suggesting that it participates only in the late stage of trophectoderm formation.

Heart failure with normal ejection fraction: the complementary roles of echocardiography and CMR imaging.

Heart failure with normal ejection fraction (HFNEF), previously referred to as diastolic heart failure, has increased in prevalence as a cause of heart failure, now accounting for up to 50% of all cases. Contrary to initial evidence, the prognostic outlook in HFNEF may be similar to that of heart failure with reduced ejection fraction. According to current consensus statements, the diagnosis of HFNEF requires the demonstration of relatively preserved systolic left ventricular function and evidence of diastolic dysfunction.