Analysis of the vasculature by immunohistochemistry in paraffin-embedded brains.

The brain vasculature can be investigated in different ways ranging from in vivo to biochemical analysis. Immunohistochemistry is a simple and powerful technique that can also be applied to archival tissues. However, staining of brain vessels on paraffin sections has been challenging.

An aptamer-based biosensor for detection of doxorubicin by electrochemical impedance spectroscopy.

An aptamer-based biosensor was developed for the detection of doxorubicin using electrochemical impedance spectroscopy. Doxorubicin and its 14-dehydroxylated version daunorubicin are anthracyclines often used in cancer treatment. Due to their mutagenic and cardiotoxic effects, detection in groundwater is desirable.

Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells.

Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2.

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI.

In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 10 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice.

Effects of cryopreservation on adipose tissue-derived microvascular fragments.

Adipose tissue-derived microvascular fragments (ad-MVF) are effective vascularization units for tissue engineering. They rapidly reassemble into new microvascular networks after seeding on scaffolds and subsequent in vivo implantation. Herein, we analyzed whether the vascularization capacity of ad-MVF is affected by cryopreservation.

Notch signaling controls sprouting angiogenesis of endometriotic lesions.

Angiogenesis is essential for the engraftment and growth of endometriotic lesions. In this study, we analyzed whether this process is regulated by Notch signaling. Endometriotic lesions were induced by endometrial tissue transplantation into dorsal skinfold chambers of C57BL/6 mice, which were treated with the γ-secretase inhibitor DAPT or vehicle.

Nerve/glial antigen (NG) 2 is a crucial regulator of intercellular adhesion molecule (ICAM)-1 expression.

The proteoglycan nerve/glial antigen (NG) 2 is expressed on multiple cell types and mediates cell proliferation and migration. However, little is known about its function in gene regulation. In this study, we demonstrate that in pericytes and glioblastoma cells intercellular adhesion molecule (ICAM)-1, an essential protein for leukocyte adhesion and transmigration, underlies a NG2-dependent expression.

Seeding density is a crucial determinant for the in vivo vascularisation capacity of adipose tissue-derived microvascular fragments.

Adipose tissue-derived microvascular fragments (ad-MVF) represent effective vascularisation units for the seeding of dermal substitutes. However, particularly in case of extensive skin defects, the required amounts of donor fat tissue for the harvesting of ad-MVF may not always be available. Therefore, we herein determined the lowest ad-MVF density needed to induce a sufficient vascularisation and incorporation of seeded implants.

Excited-State Gradients in Polarizable QM/MM Models: An Induced Dipole Formulation.

Charge and structural relaxation of electronically excited states in embedded systems are strongly affected by the environment. It is known that the largest part of environment effects comes from electrostatics. However, polarization can also play a role by tuning the electronic and geometrical properties of the states, finally modifying the fluorescence.

Spheroids as vascularization units: From angiogenesis research to tissue engineering applications.

Multi-cellular spheroids mimic the complex three-dimensional environment of natural tissues. Accordingly, they are also used as vascularization units in angiogenesis research and regenerative medicine. Spheroid sprouting assays are versatile in vitro models for the analysis of molecular and cellular determinants of blood vessel development, including different endothelial cell phenotypes, pro- and anti-angiogenic factors as well as cell-matrix and cell-cell interactions.

Mechanical and biological characterization of alkaline substituted orthophosphate bone substitutes containing meta- and diphosphates.

Despite the growing knowledge on the mechanisms of fracture healing, bone defects often do not heal in a timely manner. Clinically, tricalcium phosphate (TCP) bone substitutes are used to fill bone defects and promote bone healing. However, the degradation rate of these implants is often too slow for sufficient bone replacement.

Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced inflammation.

Background: Ischemia-reperfusion (I/R) induces tissue inflammation, which is characterized by an increased leukocyte-endothelial cell interaction and leukocyte transmigration. These processes are mediated by the activation of the nuclear factor (NF)κB signaling pathway, resulting in an elevated expression of specific adhesion molecules. The phytochemical indole-3-carbinol (I3C) has been shown to exert anti-inflammatory effects by interfering with NFκB signal transduction.

Magnetic Resonance Lymphography at 9.4 T Using a Gadolinium-Based Nanoparticle in Rats: Investigations in Healthy Animals and in a Hindlimb Lymphedema Model.

Objectives: Magnetic resonance lymphography (MRL) in small animals is a promising but challenging tool in preclinical lymphatic research. In this study, we compared the gadolinium (Gd)-based nanoparticle AGuIX with Gd-DOTA for interstitial MRL in healthy rats and in a chronic rat hindlimb lymphedema model.

Materials And Methods: A comparative study with AGuIX and Gd-DOTA for interstitial MRL was performed in healthy Lewis rats (n = 6).

Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth.

The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown.

Helping prometheus: liver protection in acute hemorrhagic shock.

Acute hemorrhagic hypovolemic shock is caused by a significant high blood loss and leads to hemodynamic instability. The decrease in intravascular volume results in cellular hypoxia and finally in damage to organs such as the liver and the kidney. The liver plays a decisive role in the development or prevention of multiple organ failure after hemorrhagic shock.

Retrieval of Migrated Volume Coils Using Different Clot Retrievers in a Porcine Model.

Purpose: During endovascular treatment of intracranial aneurysms using coils, migration is a serious complication that increases neurological morbidity. The aim of this experimental study was to assess the effectiveness and complications of retrieving volume coils with different, currently available clot retrievers in a porcine model.

Methods: Volume coils of three-dimensional (3D) shape and different sizes were placed in the axillary artery of pigs.

Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease.

Cushing's disease, characterized by elevated plasma cortisol levels, can be controlled by inhibition of 11β-hydroxylase (CYP11B1). The previously identified selective and potent CYP11B1 inhibitor 5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine Ref 7 (IC= 2 nM) exhibited promutagenic potential as well as very low oral bioavailability in rats (F = 2%) and was therefore modified to overcome these drawbacks. Successful lead optimization resulted in similarly potent and selective 5-((5-methoxypyridin-3-yl)methyl)-3-phenylisoxazole 25 (IC = 2 nM, 14-fold selectivity over CYP11B2), exhibiting a superior pharmacological profile with no mutagenic potential.

Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions.

Background And Purpose: Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone.

The regulatory mechanisms of NG2/CSPG4 expression.

Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2.

Isolation of Murine Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Tissue Engineering.

A functional microvascular network is of pivotal importance for the survival and integration of engineered tissue constructs. For this purpose, several angiogenic and prevascularization strategies have been established. However, most cell-based approaches include time-consuming in vitro steps for the formation of a microvascular network.

Dual inhibition of PI3K and mTOR by VS-5584 suppresses thrombus formation.

VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin.

miR-191 suppresses angiogenesis by activation of NF-κB signaling.

MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development.

Pelvic ring fractures in the elderly now and then - a pelvic registry study.

Objectives: To analyze the changes in demographic data stratified for age, sex and type of injury of elderly patients suffering from pelvic ring fractures over a 22-year observation period.

Design/setting: Data has been collected prospectively, multi-centrically in hospitals participating in the German Pelvic Trauma Registry.

Patients: We analyzed the data of 5665 patients with an age ≥60years included in the German Pelvic Trauma Registry from 1991 to 2013.

Potentials and limitations of Integra® flowable wound matrix seeded with adipose tissue-derived microvascular fragments.

Adipose tissue-derived microvascular fragments (ad-MVF) represent promising vascularisation units for bioengineered Integra® matrix wound dressing (MWD). However, due to the sheet-like structure with small pore sizes, the seeding of this matrix with ad-MVF is mainly limited to its surface. Integra® flowable wound matrix (FWM) may be suitable to achieve a more homogeneous distribution and, thus, improved vascularisation, because this gel-like matrix allows for the direct admixture of ad-MVF during sample preparation.