The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows.

The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis.

Combined blockade of angiotensin II type 1 receptor and activation of peroxisome proliferator-activated receptor-γ by telmisartan effectively inhibits vascularization and growth of murine endometriosis-like lesions.

Study Question: Is telmisartan effective in the treatment of endometriosis?

Summary Answer: Combined blockade of angiotensin II type 1 receptor (AT1R) and activation of peroxisome proliferator-activated receptor (PPAR)-γ by telmisartan inhibits vascularization and growth of murine endometriosis-like lesions.

What Is Known Already: AT1R and PPAR-γ are involved in the regulation of inflammation, proliferation and angiogenesis. These processes are also crucial for the pathogenesis of endometriosis and both receptors are expressed in endometrial tissue.

Curcumin intake affects miRNA signature in murine melanoma with mmu-miR-205-5p most significantly altered.

Melanoma is the most aggressive form of skin cancer with estimated 48,000 deaths per year worldwide. The polyphenol curcumin derived from the plant Curcuma longa is well known for its anti-inflammatory and anti-cancerogenic properties. Accordingly, dietary intake of this compound may be suitable for melanoma prevention.

Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period.

Generation of co-culture spheroids as vascularisation units for bone tissue engineering.

Cell spheroids represent attractive building units for bone tissue engineering, because they provide a three-dimensional environment with intensive direct cell-cell contacts. Moreover, they allow for co-culture of both osteoblasts and vessel-forming cells, which may markedly increase their survival and vascularisation after transplantation. To test this hypothesis, we generated co-culture spheroids by aggregating different combinations of primary human osteoblasts (HOB), human dermal microvascular endothelial cells (HDMEC) and normal human dermal fibroblasts (NHDF) using the liquid overlay technique.

Glucose regulates protein kinase CK2 in pancreatic β-cells and its interaction with PDX-1.

The pancreatic duodenal homeodomain transcription factor PDX-1 plays a pivotal role in the development of the pancreas and the maintenance of glucose homeostasis by pancreatic β-cells. Recently, we found that the highly conserved, ubiquitously expressed tetrameric Ser/Thr protein kinase CK2, which is formed by two catalytic subunits (α and/or α') and two non-catalytic subunits (β), phosphorylates PDX-1. So far, only little is known about CK2 in pancreatic β-cells and how this enzyme is regulated in these cells.

Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice.

Background: Bronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia.

Objectives: We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD.

Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions.

Objective: To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.

Design: Intravital microscopic, histologic, and immunohistochemical study.

Setting: University institute.

Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3) cells.

Rodent animal models of delayed bone healing and non-union formation: a comprehensive review.

Despite the growing knowledge on the mechanisms of fracture healing, delayed healing and non-union formation remain a major clinical challenge. Animal models are needed to study the complex process of normal and impaired fracture healing and to develop new therapeutic strategies. Whereas in the past mainly large animals have been used to study normal and impaired fracture healing, nowadays rodent models are of increasing interest.

Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells.

Despite success with BRAFV600E inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. We identified a mechanism of intrinsic multidrug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly leads to enrichment of slow-cycling, long-term tumor-maintaining melanoma cells expressing the H3K4-demethylase JARID1B/KDM5B/PLU-1.

Mechanical thrombectomy of iliac vein thrombosis in a pig model using the Rotarex and Aspirex catheters.

Purpose: To investigate the efficacy and safety of mechanical thrombectomy for iliac vein thrombosis using Rotarex and Aspirex catheters in a pig model.

Materials And Methods: Iliac vein thrombosis was induced in six pigs by means of an occlusion-balloon catheter and thrombin injection. The presence of thrombi was verified by digital subtraction angiography (DSA) and computed tomography (CT).

Inhibition of angiogenesis: a novel antitumor mechanism of the herbal compound arctigenin.

Arctigenin, a functional ingredient of several traditional Chinese herbs, has been reported to have potential antitumor activity. However, its mechanisms of action are still not well elucidated. Because the establishment and metastatic spread of tumors is crucially dependent on angiogenesis, here we investigated whether arctigenin inhibits tumor growth by disturbing blood vessel formation.

4-hydroxybenzyl alcohol: a novel inhibitor of tumor angiogenesis and growth.

Aims: The herbal compound 4-hydroxybenzyl alcohol (HBA) is a pleiotropic agent, which has been shown to effectively inhibit the development of new blood vessels by targeting multiple mechanisms of the angiogenic process. Because angiogenesis is a major prerequisite for tumor growth, the aim of this study was to analyze for the first time, whether HBA may be used for anti-cancer therapy.

Main Methods: CT26.

Ultralarge von Willebrand factor fibers mediate luminal Staphylococcus aureus adhesion to an intact endothelial cell layer under shear stress.

Background: During pathogenesis of infective endocarditis, Staphylococcus aureus adherence often occurs without identifiable preexisting heart disease. However, molecular mechanisms mediating initial bacterial adhesion to morphologically intact endocardium are largely unknown.

Methods And Results: Perfusion of activated human endothelial cells with fluorescent bacteria under high-shear-rate conditions revealed 95% attachment of the S aureus by ultralarge von Willebrand factor (ULVWF).

Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: closer to clinical features?

Despite increased survival of very preterm newborns, bronchopulmonary dysplasia (BPD) remains a major threat, as it affects long-term pulmonary function and neurodevelopmental outcome. Recent research focused on mechanisms of lung repair. Animal models of BPD in term rodents use postnatal hyperoxia in order to mimic features observed in very preterm human neonates: reduced alveolarization and impaired septal architecture without profound inflammatory changes.

Silver acetate coating promotes early vascularization of Dacron vascular grafts without inducing host tissue inflammation.

Background: Silver acetate is frequently used as an antimicrobial coating of prosthetic vascular grafts. However, the effects of this coating on the early inflammatory and angiogenic host tissue response still remain elusive. Therefore, the aim of the present in vivo study was to analyze the biocompatibility and vascularization of silver acetate-coated and uncoated vascular grafts during the initial phase after implantation.

Regional treatment with liquid barrier agents: a novel therapeutic option for intraperitoneal endometriosis?

Endometriosis is a frequent gynecological disease, which is characterized by the presence of endometriotic lesions, i.e. ectopic endometrial glands and stroma, outside the uterine cavity.

[The effects of tobacco smoke on alveolar macrophages - an in vivo mouse lung model for short-term smoking].

Background: The effect of cigarette smoke (CS) on the phagocytosis of alveolar macrophages is discussed controversially on the basis of in vitro experiments. In this short report we describe the in vivo observations that we have performed.

Methods: For this purpose mice were exposed to CS for three consecutive days.

Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis.

Study Question: Does the phytochemical compound resveratrol inhibit vascularization of endometriotic lesions?

Summary Answer: Resveratrol suppresses the development of new microvessels in endometriotic lesions by inhibiting endothelial cell proliferation.

What Is Known Already: Establishment and progression of endometriosis is crucially dependent on angiogenesis. Resveratrol is a pleiotropic agent, which dose-dependently suppresses the development of new blood vessels.

Three-dimensional spheroids of adipose-derived mesenchymal stem cells are potent initiators of blood vessel formation in porous polyurethane scaffolds.

Adipose-derived mesenchymal stem cells (adMSCs) exhibit a high angiogenic activity. Accordingly, their incorporation into tissue constructs represents a promising vascularization strategy in tissue engineering. In the present study, we analyzed whether the efficacy of this approach can be improved by seeding adMSCs as three-dimensional spheroids onto porous scaffolds.

Direct visualisation of microparticles in the living lung.

Microparticles (MP) and fibres can be inhaled and cause inflammatory lung diseases. So far MP and fibres have not observed directly in the lung of living animals. A direct visualisation of particles and fibres would be important to study interactions with local and immigration host cells.

External inosculation as a feature of revascularization occurs after free transplantation of murine liver grafts.

The induction of angiogenesis is essential for successful engraftment of freely transplanted cells or cellular composites. How to augment angiogenesis to ensure an appropriate viability of the grafts is still under investigation. This study evaluated the proangiogenic capability of different syngeneic free liver transplants and elucidated the origin of the newly formed vascular network via use of an eGFP(+) /eGFP(-) (enhanced green fluorescent protein) cross-over design.

Direct in vivo observations of P-selectin glycoprotein ligand-1-mediated leukocyte-endothelial cell interactions in the pulmonary microvasculature in abdominal sepsis in mice.

Objective: P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage.

Two-step labeling of Staphylococcus aureus with Lysostaphin-Azide and DIBO-Alexa using click chemistry.

Specific bacteria imaging is highly desirable in clinical diagnostics. Probes enabling rapid and specific diagnostics of bacteria are limited. Current clinical infection diagnostics is time consuming and invasive, relies on microbiological cultures.