Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis.

Epigenetic therapy has gained interest in treating cardiovascular diseases, but preclinical studies often encounter challenges with cell-type-specific effects or batch-to-batch variation, which have limited identification of novel drug candidates targeting angiogenesis. To address these limitations and improve the reproducibility of epigenetic drug screening, we redesigned a 3D in vitro fibrin bead assay to utilize immortalized human aortic endothelial cells (TeloHAECs) and screened a focused compound library with 105 agents. Compared to the established model using primary human umbilical vein endothelial cells, TeloHAECs needed a higher-density fibrin gel for optimal sprouting, successfully forming sprouts under both normoxic and hypoxic cell culture conditions.

Amino Acid-Based Boron Carriers in Boron Neutron Capture Therapy (BNCT).

Interest in the design of boronated amino acids has emerged, partly due to the utilization of boronophenylalanine (BPA), one of the two agents employed in clinical Boron Neutron Capture Therapy (BNCT). The boronated amino acids synthesized thus far for BNCT investigations can be classified into two categories based on the source of boron: boronic acids or carboranes. Amino acid-based boron carriers, employed in the context of BNCT treatment, demonstrate significant potential in the treatment of challenging tumors, such as those located in the brain.

BMP2 gene transfer induces pericardial effusion and inflammatory response in the ischemic porcine myocardium.

Pro-angiogenic gene therapy is being developed to treat coronary artery disease (CAD). We recently showed that bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor-A synergistically regulate endothelial cell sprouting . BMP2 was also shown to induce endocardial angiogenesis in neonatal mice post-myocardial infarction.

ErbB signaling is a potential therapeutic target for vascular lesions with fibrous component.

Background: Sporadic venous malformation (VM) and angiomatosis of soft tissue (AST) are benign, congenital vascular anomalies affecting venous vasculature. Depending on the size and location of the lesion, symptoms vary from motility disturbances to pain and disfigurement. Due to the high recurrence of the lesions, more effective therapies are needed.

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space.

Three-dimensional image analyses are required to improve the understanding of the regulation of blood vessel formation and heterogeneity. Currently, quantitation of 3D endothelial structures or vessel branches is often based on 2D projections of the images losing their volumetric information. Here, we developed SproutAngio, a Python-based open-source tool, for fully automated 3D segmentation and analysis of endothelial lumen space and sprout morphology.

Breed-typical front limb angular deformity is associated with clinical findings in three chondrodysplastic dog breeds.

Angular front limb deformity (ALD) refers to an excessively curved limb conformation, which is seen in some chondrodysplastic dog breeds. Common characteristics of ALD include carpal valgus (VALG), front limb rotation (ROT), elbow incongruity, and lateral radial head subluxation. These may cause lameness and discomfort in affected dogs.

Systematic design of cell membrane coating to improve tumor targeting of nanoparticles.

Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force.

Development of invasive pink salmon (Oncorhynchus gorbuscha Walbaum) eggs in a large Barents Sea river.

The spawning and egg development of invasive pink salmon Oncorhynchus gorbuscha were investigated in the large River Teno in the Barents Sea area where they spawned for the first time on a large scale in 2021. The spawning period started in early August and egg development was rapid. All eggs were eyed by mid-September and the first juveniles hatched in late September.

Profiling of Primary and Mature miRNA Expression in Atherosclerosis-Associated Cell Types.

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BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF.

The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway.

The intra- and intertester repeatability of radiographic elbow incongruity grading is high in chondrodystrophic dog breeds.

Elbow incongruity is a form of elbow dysplasia that causes osteoarthritis, pain, and lameness, and it is common in chondrodystrophic dog breeds. The objective of this retrospective secondary analysis study was to evaluate the intra- and interobserver repeatability of a novel radiographic incongruity grading system for assessing elbow incongruity in three chondrodystrophic dog breeds-the dachshund, Skye Terrier, and Glen of Imaal Terrier. We conducted an observer agreement study that included 220 mediolateral antebrachial radiographs from 110 dogs with the elbow in 90° flexion.

Cascade processing of softwood bark with hot water extraction, pyrolysis and anaerobic digestion.

A process model based on hot water extraction (HWE), slow pyrolysis and anaerobic digestion (AD) were used for pine and spruce bark utilisation. First tannins (32 mg/g and 11.8 mg/g, respectively) and polyphenols were recovered via HWE.

Critical-sized cartilage defects in the equine carpus.

Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options.

Material And Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.

Peptides for bone tissue engineering.

Molecular signals in the form of growth factors are the main modulators of cell behavior. However, the use of growth factors in tissue engineering has several drawbacks, including their costs, difficult production, immunogenicity and short half-life. Furthermore, many of them are pleiotropic and, since a single growth factor can have different active domains, their effect is not always fully controllable.

Osteochondral repair: evaluation with sweep imaging with fourier transform in an equine model.

Purpose: To evaluate the status of articular cartilage and bone in an equine model of spontaneous repair by using the sweep imaging with Fourier transform (SWIFT) magnetic resonance (MR) imaging technique.

Materials And Methods: Experiments were approved by the Utrecht University Animal Ethics Committee. Six-millimeter-diameter chondral (n = 5) and osteochondral (n = 5, 3-4 mm deep into subchondral bone) defects were created in the intercarpal joints of seven 2-year-old horses and examined with SWIFT at 9.

Pathogenic bacteria in Finnish bulk tank milk.

While the quality of raw cow milk in Finland is known for its high hygienic standard, with the national average total bacterial count being below 10(4) CFU/mL annually, the prevalence of pathogenic bacteria in Finnish raw milk is underreported. The aim of this study was to determine the occurrence of Listeria monocytogenes, thermophilic Campylobacter spp., Salmonella spp.

Cluster analysis of infrared spectra can differentiate intact and repaired articular cartilage.

Objective: Successful repair of articular cartilage (AC) defects would be a major advantage due to the low ability of AC to heal spontaneously. Sensitive methods to determine changes in AC composition and structure are required to monitor the success of repair. This study evaluates the ability of unsupervised cluster analysis applied to Fourier transform infrared (FTIR) microspectroscopy to discriminate between healthy and repaired AC.

Repair of osteochondral defects with recombinant human type II collagen gel and autologous chondrocytes in rabbit.

Objective: Recombinant human type II collagen (rhCII) gels combined with autologous chondrocytes were tested as a scaffold for cartilage repair in rabbits in vivo.

Method: Autologous chondrocytes were harvested, expanded and combined with rhCII-gel and further pre-cultivated for 2 weeks prior to transplantation into a 4 mm diameter lesion created into the rabbit's femoral trochlea (n = 8). Rabbits with similar untreated lesions (n = 7) served as a control group.

Contrast-Enhanced Micro-Computed Tomography in Evaluation of Spontaneous Repair of Equine Cartilage.

Objective: Contrast-enhanced computed tomography (CECT) has been introduced for the evaluation of cartilage integrity. Furthermore, CECT enables imaging of the structure and density of subchondral bone. In this laboratory study, we investigate the potential of microCECT to simultaneously image cartilage and subchondral bone for the evaluation of tissue healing.

Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage.

The aim of this study was to compare sensitivity of ultrasound and optical coherence tomography (OCT) techniques for the evaluation of the integrity of spontaneously repaired horse cartilage. Articular surfaces of horse intercarpal joints, featuring both intact tissue and spontaneously healed chondral or osteochondral defects, were imaged ex vivo with arthroscopic ultrasound and laboratory OCT devices. Quantitative ultrasound (integrated reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI)) and optical parameters (optical reflection coefficient (ORC), optical roughness index (ORI) and optical backscattering (OBS)) were determined and compared with histological integrity and mechanical properties of the tissue.

Engineering of cartilage in recombinant human type II collagen gel in nude mouse model in vivo.

Objective: Our goal was to test the recombinant human type II collagen (rhCII) material as a gel-like scaffold for chondrocytes in a nude mouse model in vivo.

Design: Isolated bovine chondrocytes (6x10(6)) were seeded into rhCII gels (rhCII-cell) and injected subcutaneously into the backs of nude mice. For comparison, chondrocytes (6x10(6)) in culture medium (Med-cell) and cell-free rhCII gels (rhCII-gel) were similarly injected (n=24 animals, total of three injections/animal).

Quantitative evaluation of spontaneously and surgically repaired rabbit articular cartilage using intra-articular ultrasound method in situ.

During the last decade, a major effort has been devoted to developing surgical methods for repairing localized articular cartilage lesions. Despite some promising results no ultimate breakthrough in surgical cartilage repair has been achieved. Improvements in repair techniques would benefit from more sensitive and quantitative methods for long-term follow-up of cartilage healing.

Recombinant human type II collagen as a material for cartilage tissue engineering.

Purpose: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro.

Methods: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks.

Bioreactor improves the growth and viability of chondrocytes in the knitted poly-L,D-lactide scaffold.

In the present study bovine chondrocytes were cultured in two different environments (static flasks and bioreactor) in knitted poly-L,D-lactide (PLDLA) scaffolds up to 4 weeks. Chondrocyte viability was assessed by employing cell viability fluorescence markers. The cells were visualized using confocal laser scanning microscopy and scanning electron microscopy.