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Angiogenesis is of high clinical relevance as it plays a crucial role in physiological (e.g., tissue regeneration) and pathological processes (e.g., tumor growth). Besides chemical signals, such as VEGF, the relationship between cells and the extracellular matrix (ECM) can influence endothelial cell behavior during angiogenesis. Previously, in terms of the connection between angiogenesis and mechanical factors, researchers have focused on shear forces due to blood flow. However, it is becoming increasingly important to include the direct influence of the ECM on biological processes, such as angiogenesis. In this context, we focus on the stiffness of the surrounding ECM and the adhesion of cells to the ECM. Furthermore, we highlight the mechanical cues during the main stages of angiogenesis: cell migration, tip and stalk cells, and vessel stabilization. It becomes clear that the different stages of angiogenesis require various chemical and mechanical cues to be modulated by/modulate the stiffness of the ECM. Thus, changes of the ECM during tumor growth represent additional potential dysregulations of angiogenesis in addition to erroneous biochemical signals. This awareness could be the basis of therapeutic approaches to counteract specific processes in tumor angiogenesis.

We report a comparative study of multipotent mesenchymal stromal cells (MSC) delivered by injection, MSC-based cell sheets (CS) or MSC secretome to induce healing of cutaneous pressure ulcer in C57Bl/6 mice. We found that transplantation of CS from adipose-derived MSC resulted in reduction of fibrosis and recovery of skin structure with its appendages (hair and cutaneous glands). Despite short retention of CS on ulcer surface (3–7 days) it induced profound changes in granulation tissue (GT) structure, increasing its thickness and altering vascularization pattern with reduced blood vessel density and increased maturation of blood vessels. Comparable effects on GT vascularization were induced by MSC secretome, yet this treatment has failed to induce repair of skin with its appendages we observed in the CS group. Study of secretome components produced by MSC in monolayer or sheets revealed that CS produce more factors involved in pericyte chemotaxis and blood vessel maturation (PDGF-BB, HGF, G-CSF) but not sprouting inducer (VEGF165). Analysis of transcriptome using RNA sequencing and Gene Ontology mapping found in CS upregulation of proteins responsible for collagen binding and GT maturation as well as fatty acid metabolism enzymes known to be negative regulators of blood vessel sprouting. At the same time, downregulated transcripts were enriched by factors activating capillary growth, suggesting that in MSC sheets paracrine activity may shift towards matrix remodeling and maturation of vasculature, but not activation of blood vessel sprouting. We proposed a putative paracrine trigger mechanism potentially rendering an impact on GT vascularization and remodeling. Our results suggest that within sheets, MSC may change their functional state and spectrum of soluble factors that influence tissue repair and induce more effective skin healing inclining towards regeneration and reduced scarring.

The vascular response following injury is pivotal for successful bone‐defect repair but constitutes a major hurdle in the field of regenerative medicine. Throughout this process, vessel stabilization is crucial to provide an adequate nutrient supply and facilitate efficient waste removal. Therefore, this study investigated whether promoting vascular stabilization improves bone defect repair outcomes. The findings show that insulin‐like growth factor‐binding protein (IGFBP) 7 exhibits a novel biological function in attenuating vascular permeability and enhancing vascular wall integrity. The potential underlying mechanism involves the up‐regulation of insulin‐like growth factor 1 receptor (IGF1R) expression by IGFBP7 on endothelial cell membrane, followed by activation of the downstream PI3K/AKT signaling pathway and upregulated expression of the tight junction protein zonula occludens‐1 (ZO‐1). IGFBP7 delayed administration in mice with cranial defects significantly improved bone defect healing by increasing ZO‐1 and CD31 co‐localization within vessel walls and optimizing the perfusion function of the final vascular network. Furthermore, the application of the typical tight junction regulator AT1001 effectively promoted ZO‐1‐dependent vascular stabilization and facilitated bone defect repair. This study presents a new approach to enhance bone defect healing via vascular stabilization‐targeted interventions and significantly advances the understanding of the complex interplay between osteogenesis and angiogenesis in bone defect healing. This research uncovers a new biological function of IGFBP7 in promoting vascular stability by upregulating ZO‐1 protein expression within endothelial tight junctions. The findings thus demonstrate the ability of IGFBP7 to expedite bone defect healing while concurrently enhancing blood vessel stabilization, providing continuous support for tissue repair. This work proposes vascular stabilization as an innovative intervention target for bone defect repair.

[...]a treatment to eliminate the fragile vessels by suppressing excess angiogenesis or enhancing vessel maturation would be useful for treating these clinical conditions. Recently, anti-VEGF antibodies have been approved to treat eye diseases such as age-related macular degeneration and cancer, and show steady efficacy [1, 10, 11]. [...]medicines which accomplish abnormal vessel elimination through mechanisms different from anti-VEGF therapy would be useful to provide other options for patients showing resistance or insufficient response to the anti-VEGF therapy. Power SYBR Green PCR Master Mix and Taqman Gene Expression Master Mix were purchased from Applied Biosystems. After being stirred for 15 min at that temperature, N-acetyl-L-cysteine (1.6 g, 9.67 mmol) was added to the reaction mixture and stirred for 1 h. The reaction mixture was warmed up to room temperature and stirred for 1 h. The reaction was quenched by addition of 1 N HCl (30 ml) at 0°C and extracted with ethyl acetate.

The stromal vascular fraction (SVF) of human adipose tissue is an attractive cell source for engineering grafts with intrinsic vascularization potential, as it is rich in vasculogenic progenitors. However, in order to maintain their functional perfusion it is important to promote the stabilization of newly assembled microvascular networks. We previously found that Semaphorin 3A (Sema3A) promotes the rapid stabilization of new blood vessels induced by VEGF overexpression in skeletal muscle. Here we investigated whether Sema3A could promote the assembly, connection to circulation and persistence of human SVF-derived microvascular networks in engineered grafts. Recombinant Sema3A was engineered with a transglutaminase substrate sequence (TG-Sema3A) to allow cross-linking into fibrin hydrogels. Grafts were prepared with freshly isolated human SVF cells in fibrin hydrogels decorated with 0, 0.1 or 100 μg/ml TG-Sema3A and implanted subcutaneously in immune-deficient mice. After 1 week in vivo, the assembly of human-derived networks was similar in all conditions. The outer part of the grafts was populated by blood vessels of both human and mouse origin, which formed abundant hybrid structures within a common basal lamina. About 90% of human-derived blood vessels were functionally connected to the host circulation in all conditions. However, in the control samples human vessels were unstable. In fact, they significantly regressed by 6 weeks and could no longer be found by 12 weeks. In contrast, a low Sema3A dose (0.1 μg/ml) promoted further human vascular expansion by about 2-fold at 6 weeks and protected them from regression until 12 weeks. From a mechanistic point of view, the stabilization of SVF-derived vessels by 0.1 μg/ml of Sema3A correlated with the recruitment of a specific population of monocytes expressing its receptor Neuropilin-1. In conclusion, Sema3A is a potent stimulator of long-term persistence of microvascular networks derived from human SVF. Therefore, decoration of matrices with Sema3a can be envisioned to promote the functional support of tissue engineered grafts.

The article performs the issues of positioning and ensuring the movement of a geophysical vessel along a routing line, applied aspects of marine geophysical technologies according to the technical characteristics of a vessel, allowing to carry out the operation complex on the shelf zone of the World Ocean. The points of balancing modes and stability region of the controlled object without stalling vessel in the circulation of the vertical plane relative to center-line plane are calculated for the realization of the parameters of the vessel motion. We determine a linearized model of a controlled device and a table of the numerical values of the coefficients determined in the vicinity of various balancing modes. In addition, the roots of a characteristic equation for the pair of towed objects directly from an underground garage and a vehicle have been established.

Angiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from within the cellular microenvironment, such as biochemical gradients and perfusion. However, many of these cues are missing in current in vitro models of angiogenic sprouting. We here describe an in vitro platform that integrates both perfusion and the generation of stable biomolecular gradients and demonstrate its potential to study more physiologically relevant angiogenic sprouting and microvascular stabilization. The platform consists of an array of 40 individually addressable microfluidic units that enable the culture of perfused microvessels against a three-dimensional collagen-1 matrix. Upon the introduction of a gradient of pro-angiogenic factors, the endothelial cells differentiated into tip cells that invaded the matrix. Continuous exposure resulted in continuous migration and the formation of lumen by stalk cells. A combination of vascular endothelial growth factor-165 (VEGF-165), phorbol 12-myristate 13-acetate (PMA), and sphingosine-1-phosphate (S1P) was the most optimal cocktail to trigger robust, directional angiogenesis with S1P being crucial for guidance and repetitive sprout formation. Prolonged exposure forces the angiogenic sprouts to anastomose through the collagen to the other channel. This resulted in remodeling of the angiogenic sprouts within the collagen: angiogenic sprouts that anastomosed with the other perfusion channel remained stable, while those who did not retracted and degraded. Furthermore, perfusion with 150 kDa FITC-Dextran revealed that while the angiogenic sprouts were initially leaky, once they fully crossed the collagen lane they became leak tight. This demonstrates that once anastomosis occurred, the sprouts matured and suggests that perfusion can act as an important survival and stabilization factor for the angiogenic microvessels. The robustness of this platform in combination with the possibility to include a more physiological relevant three-dimensional microenvironment makes our platform uniquely suited to study angiogenesis in vitro.

A fishing boat shaft generator is a kind of power supply device driven by the main diesel engine, which has the advantage of saving energy compared with a diesel generator and eliminating the need to be equipped with an additional diesel engine, witnessing wide applications in the use of power supply equipment for fishing boats. However, because the shaft generator is mounted on the main diesel engine, the fishing boat encounters bad sea conditions at sea, and the speed of the diesel engine fluctuates, resulting in the instability of the power frequency and voltage sent by the shaft generator, which will endanger the electrical equipment of the fishing vessel in serious cases. In this paper, a design of a voltage and frequency stabilization system for a fishing vessel shaft generator based on a UPS backup power supply was proposed. The system consists of a three-phase shaft generator, inverter, battery, and electrical equipment. The inverter control strategy is introduced, and the battery charge/discharge and DC boost are designed.

Purpose The definitive impacts of intensive lipid-lowering therapy (LLT) on plaque stabilization and the relationship between the key markers during LLT and plaque stability remain unquestioned. Thus, these meta-analysis and meta-regression intend to holistically evaluate the influence exerted by rigorous LLT on the minimum fibrous cap thickness (FCT) and maximum lipid arc as discerned through optical coherence tomography (OCT). This study further scrutinizes the correlation of this impact with variations in high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), or additional parameters within patients diagnosed with coronary artery disease (CAD). Methods Comprehensive searches were conducted on platforms including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published until June 1, 2023. The search was language agnostic and targeted RCTs elaborating on the correlation between high-intensity statin therapy or statins used concomitantly with other lipid-lowering medications and the minimum FCT and maximum lipid arc as assessed by OCT. The meta-analyses were executed employing a standard mean difference (SMD) algorithm with random-effects on continuous variables. These methodologies align with the Preferred Reporting Items for Systematic and Meta-analysis (PRISMA) guidelines. Results A spectrum of 12 RCTs engaging 972 patients were identified and mobilized for these analyses. Meta-analysis outcomes depicted a conspicuous correlation between intensive LLT and an enhanced minimum FCT (12 studies with 972 participants; SMD, 0.87; 95% CI, 0.54 to 1.21; P < 0.01), reduced maximum lipid arc (9 studies with 564 participants; SMD, −0.43; 95% CI, −0.58 to −0.29; P < 0.01). Meta-regression analysis has determined an association of elevated minimum FCT with decreased LDL-C (β, −0.0157; 95% CI, −0.0292 to −0.0023; P = 0.025), total cholesterol (TC) (β, −0.0154; 95% CI, −0.0303 to −0.0005; P = 0.044), and apolipoprotein B (ApoB) (β, −0.0209; 95% CI, −0.0361 to −0.0057; P = 0.022). However, no significant association was discerned relative to variations in hs-CRP/CRP (β, −0.1518; 95% CI, −1.3766 to −1.0730; P = 0.772), triglyceride (TG) (β, −0.0030; 95% CI, −0.0258 to −0.0318; P = 0.822), and high-density lipoprotein cholesterol (HDL-C) (β, 0.0313; 95% CI, −0.0965 to 0.1590; P = 0.608). Subsequent subgroup meta-analysis demonstrated that high-intensity statin therapy (5 studies with 204 participants; SMD, 1.03; 95% CI, 0.67 to 1.39; P < 0.01), as well as a combinative approach including PCSK9 antibodies and statins (3 studies with 522 participants; SMD, 1.17; 95% CI, 0.62 to 1.73; P < 0.01) contributed to an increase in minimum FCT. Parallelly, high-intensity statin therapy (4 studies with 183 participants; SMD, −0.42; 95% CI, −0.65 to −0.19; P < 0.01) or the combined application of PCSK9 antibodies and statins (2 studies with 222 participants; SMD, −0.98; 95% CI, −1.26 to −0.70; P < 0.01) was evidenced to decrease the maximum lipid arc. Conclusions Intensive LLT, mainly high-intensity statin therapy and combined PCSK9 antibody with statin, has a beneficial effect on coronary plaque stabilization derived from OCT in patients with CAD. Coronary plaque stabilization is primarily due to lipid-lowering effect, not anti-inflammatory effect. Moreover, the lipid-lowering effect has nothing to do with the changes in HDL-C and TG, but is mainly related to the reduction of LDL-C, TC, and ApoB.