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The vascular system maintains cellular homeostasis by transporting oxygen, nutrients, and metabolic waste products. The vascular system is involved in a variety of fundamental physiological phenomena and is closely associated with human vascular diseases. Additionally, the stability of drugs in the vasculature affects their efficacy. Therefore, researchers have used vascular models to study vascular diseases, assess drug stability, and screen drugs. However, there are many shortcomings in the animal models and in vitro two-dimensional vascular models that have been extensively developed. In this paper, we specifically review the construction methods of in vitro vascular models and classify the specific methods into photolithography, soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. The first two are microfluidics-based methods and the last three are non-microfluidics-based methods. The vascular model construction methods reviewed in this paper overcome the shortcomings of traditional models—which cannot accurately reproduce the human vascular microenvironment—and can assist in the construction of in vitro 3D vascular models and tissue engineering vascularization. These models can be reused by perfusion devices, and the cells within the channels reside on biocompatible materials that are used to simulate the microenvironment and 3D cellular organization of the vasculature in vivo. In addition, these models are reproducible in shape and length, allowing experiments to be repeated, which is difficult to do with natural vessels. In vitro vascular models are widely used in research and drug screening for diseases associated with endothelial dysfunction, cancer, and other vascular abnormalities. [ABSTRACT FROM AUTHOR]

The process of wound healing is complex and dynamic. Given the unique nature of the skin, wound healing requires dressings that meet a wide range of functional requirements. Due to their unique structure and properties, hydrogel dressings provide ideal conditions for supporting the process of wound healing and can be enhanced with additional functions to meet the specific requirements of different types of wounds. Compared to traditional wound dressings, the newly developed hydrogel wound dressing offers several advantages, including its soft texture, ability to retain moisture, oxygen permeability, and comfort. With the advancement of medical technology, higher demands are being placed on the functionality of hydrogel dressings. Therefore, this paper offers a comprehensive overview of hydrogel wound dressings with various functions. These functions primarily include hemostatic hydrogel dressings, antibacterial hydrogel dressings, angiogenesis-promoting hydrogel dressings, and other functional hydrogel dressings. The paper also reviews the research and application of these dressings in recent years. [ABSTRACT FROM AUTHOR]

Background: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear., Methods: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels., Results: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group., Conclusions: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The present study probes into the complexities of wound management in obesity by proposing a novel biomaterial designed to reprogram the altered skin physiology prevalent in obese conditions. The strategy involves the development of a multifunctional biomaterial addressing issues such as excessive exudate, pressure ulcers, and reduced vascularity. The bio-matrix demonstrates the localized transformation of white adipocytes through trans-browning, coupled with the simultaneous induction of angiogenesis at obese wound sites, resulting in expedited wound closure. The collagen bio-matrices, stabilized with Resveratrol (Rsv), exhibit remarkable thermal, mechanical, and biological stability. The porous 3D microstructure of the Rsv-stabilized collagen bio-matrix closely resembled the natural extracellular matrix, facilitating effective cell adhesion. The bio-matrix exhibited the unique capability to induce localized thermogenesis in the subcutaneous fat layer while concurrently activating angiogenesis. In vivo wound healing studies conducted on DIO-C57BL6 mice demonstrated complete healing within 10 days, showcasing accelerated tissue regeneration, blood vessel formation, robust collagen deposition, and significant activation of browning in the subcutaneous adipose layer. This study introduces the concept of tailored regenerative biomaterials with the ability to reprogram the challenging wound environment associated with obesity. This innovative approach opens up new avenues for enhanced wound care strategies, particularly for bariatric patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. During the preparation of the manuscript, the authors used ChatGPT and Paperpal to correct typographical and grammatical errors. After using this tool, the authors reviewed and edited the content as needed and takes full responsibility for the content of the publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coumarin is a natural compound that is rich in plants. Coumarin and its derivates were reported to have many biological activities, such as anti-bacterial, anti-tumor, and anti-coagulation. In this study, we examined the angiogenic modulating activities of six previously synthesized coumarin derivatives (Compound #1-#6) in zebrafish embryos and further confirmed them in a chick model. According to the survival rate in a zebrafish model, Compound #1 (100 %), #2 (82.5-100 %), and #4 (100 %) showed much less toxicity than Compound #3 (19.2-100 %), #5 (0-100 %), and #6 (0-100 %). Using a green blood vessel fluorescent transgenic fish Tg(fli1:egfp) to record the angiogenesis-modulating effects of Compound #1, #2, and #4, we found that Compound #2 had the highest effects in interfering intersegmental vessel growth, subintestinal vein growth, and caudal vein plexus remodeling. Chick chorioallantoic membrane (CAM) assay also showed that Compound #2 exposure led to a reduction of blood vessel growth. Real-time PCR experiments revealed that Compound #2 significantly changed the expression of vascular growth-related genes flt1, cdh5, and nrp1a in zebrafish. Based on our data from zebrafish and chick models, a new coumarin-derivative (Compound #2) possesses anti-angiogenic activity with low toxicity, but further investigation in mammal models is asked to confirm our findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective(s): The material used for bone tissue repair needs to be simultaneously osteoconductive, osteoinductive, and osteogenic. To overcome this problem, researchers combine hydroxyapatite (HA) with natural materials to improve properties. This paper compares the effects of angiogenesis and osteogenesis with different composites through in vivo experiments and characterization analysis. Materials and Methods: Chitosan/nHA (CS/nHA) and sodium alginate/nHA (SA/nHA) microspheres were synthesized via reverse-phase emulsification crosslinking and analyzed using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), and X-ray diffraction (XRD). Implanted into mouse thigh muscles, their angiogenic and osteogenic potentials were assessed after 8 and 12 weeks through various staining methods and immunohistochemistry. Results: The mean vascular density (MVD) of CS/nHA, CaP/nHA, and SA/nHA groups was (134.92±35.30) n/mm², (159.09±22.14) n/mm², (160.31±42.23) n/mm² at 12 weeks, respectively. The MVD of the CaP/nHA and SA/nHA groups were significantly higher than that of the CS/nHA group. The collagen volume fractions (CVF) were 34.13%, 51.53%, and 54.96% in the CS/nHA, CaP/nHA, and SA/ nHA groups, respectively. In addition, the positive expression area ratios of OPN and CD31 in the CaP/ nHA and SA/nHA groups were also significantly higher than those in the CS/nHA group. Conclusion: The ability of SA/nHA composite microspheres in osteogenesis and angiogenesis is clearly superior to that of the CS/nHA group and is comparable to that of CaP/nHA, which has superior osteogenesis ability, indicating that SA/nHA composite microspheres have greater application prospects in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Cervical cancer accounts for most deaths due to cancer in women, majorly in developing nations. The culprit behind this disease is the human papillomavirus (HPV) which accounts for more than 90% of cervical cancer cases. The viral strains produce proteins that favor the knocking down of the apoptosis process and continuous growth of cells in the cervix leading to tumor growth. Proangiogenic growth factors, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), angiopoietins, and other endothelial growth factors (EGF), are secreted by tumor cells and the surrounding microenvironment, which further advances the development of cancer. The extracellular domain of receptor tyrosine kinases is employed by ligands (like VEGF and EGF) to engage and activate them by inducing receptor dimerization, which facilitates the cascade impact of these factors. The tyrosine kinase domains of each receptor autophosphorylate each other, activating the receptor and initiating signaling cascades that promote angiogenesis, migration, proliferation, and survival of endothelial cells. Cancer cells benefit from its modified signaling pathways, which cause oncogenic activation. Upon early cervical cancer detection, the second-line therapy strategy involves blocking the signaling pathways with VEGF and small molecule tyrosine kinase inhibitors (TKIs). This review paper highlights the genesis of cervical cancer and combating it using VEGF and tyrosine kinase inhibitors by delving into the details of the currently available inhibitors. Further, we have discussed the inhibitor molecules that are currently in various phases of clinical trials. This paper will surely enhance the understanding of cervical cancer and its treatment approaches and what further interventions can be done to alleviate the disease currently serving as a major health burden in the developing world. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The vascular system is a vital circulatory network in the human body that plays a critical role in almost all physiological processes. The production of blood vessels in the body is a significant area of interest for researchers seeking to improve their understanding of vascular function and maintain normal vascular operation. However, an excessive or insufficient vascular regeneration process may lead to the development of various ailments such as cancer, eye diseases, and ischemic diseases. Recent preclinical and clinical studies have revealed new molecular targets and principles that may enhance the therapeutic effect of anti-angiogenic strategies. A thorough comprehension of the mechanism responsible for the abnormal vascular growth in disease processes can enable researchers to better target and effectively suppress or treat the disease. N 6 -methyladenosine (m 6 A), a common RNA methylation modification method, has emerged as a crucial regulator of various diseases by modulating vascular development. In this review, we will cover how m 6 A regulates various vascular-related diseases, such as cancer, ocular diseases, neurological diseases, ischemic diseases, emphasizing the mechanism of m 6 A methylation regulators on angiogenesis during pathological process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diabetic wounds (DW) constitute a substantial burden on global healthcare owing to their widespread occurrence as a complication of diabetes. Angiogenesis, a crucial process, plays a pivotal role in tissue recovery by supplying essential oxygen and nutrients to the injury site. Unfortunately, in diabetes mellitus, various factors disrupt angiogenesis, hindering wound healing. While biomaterials designed to enhance angiogenesis hold promise for the treatment of DWs, there is an urgent need for more in-depth investigations to fully unlock their potential in clinical management. In this review, we explore the intricate mechanisms of angiogenesis that are crucial for DW recovery. We introduce a rational design for angiogenesis-enhancing drug delivery systems (DDS) and provide a comprehensive summary and discussion of diverse biomaterials that enhance angiogenesis for facilitating DW healing. Lastly, we address emerging challenges and prospects in angiogenesis-enhancing DDS for facilitating DW healing, aiming to offer a comprehensive understanding of this critical healthcare issue and potential solutions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Advanced stages of Age-related Macular Degeneration (AMD) are characterized by retinal neurodegeneration and aberrant angiogenesis, and mitochondrial dysfunction contributes to the pathogenesis of AMD. In this study, we tested the hypothesis that Humanin G (HNG), a cytoprotective mitochondrial-derived peptide, positively regulates cell proliferation, cell death, and the protein levels of angiogenesis and neurodegeneration markers, in normal (control) and AMD RPE transmitochondrial cybrid cell lines. These normal and AMD RPE transmitochondrial cybrid cell lines had identical nuclei derived from mitochondria-deficient ARPE-19 cell line, but differed in mitochondrial DNA (mtDNA) content that was derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrid cell lines, and the Luminex XMAP multiplex assay was used to examine the protein levels of angiogenesis and neurodegeneration markers. Humanin G reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cell lines, thereby suggesting Humanin G's positive regulatory role in AMD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this paper, a mathematical model for a solid spherically symmetric vascular tumor growth with nutrient periodic supply and time delays is studied. Compared to the apoptosis process of tumor cells, there is a time delay in the process of tumor cell division. The cells inside the tumor obtain nutrient σ(r,t) through blood vessels, and the tumor attracts blood vessels at a rate proportional to α(t). So, the boundary value condition ∂σ ∂r + α(t)(σ − ψ(t)) = 0,r = R(t),t > 0, holds on the boundary, where the function ψ(t) is the concentration of nutrient externally supplied to the tumor. Considering that the nutrients provided by the outside world are often periodic, the research in this paper assumes that ψ(t) is a periodic function. Sufficient conditions for the global stability of zero steady state are presented. Under certain conditions, we prove that there exists at least one periodic solution to the model. The results are illustrated by computer simulations. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment. Natural medicines has a long history of treating RA, and numerous reports have suggested that natural medicines have a strong inhibitory activity on synovial angiogenesis, thereby improving the progression of RA. Natural medicines could regulate the following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs pathway, NF-κB pathway, PPARγ pathway, JAK2/STAT3 pathway, etc., thereby inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, and total glucoside of Paeonia lactiflora Pall. Are currently the most representative of all natural products worthy of development and utilization. In this paper, the main factors affecting angiogenesis were discussed and different types of natural medicines that inhibit angiogenesis were systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming to provide new perspective and options for the management of RA by targeting angiogenesis. [ABSTRACT FROM AUTHOR]

Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti‐inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word "Cancer" depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard. [ABSTRACT FROM AUTHOR]

Acting as a cysteine protease, small ubiquitin-like modifier (SUMO)/sentrinspecific protease1 (SENP1) involved in multiple physiological and pathological processes through processing the precursor SUMO protein into mature form and deSUMOylating target protein. It has been reported that SENP1 is highly expressed and plays a carcinogenic role in various cancers. In this paper, we mainly explore the function and mechanism of SENP1 in tumor cell proliferation, apoptosis, invasion, metastasis, stemness, angiogenesis, metabolism and drug resistance. Furthermore, the research progress of SENP1 inhibitors for cancer treatment is introduced. This study aims to provide theoretical references for cancer therapy by targeting SENP1. [ABSTRACT FROM AUTHOR]

Alterations in angiogenic properties play a pivotal role in the manifestation and onset of various pathologies, including vascular diseases and cancer. Thrombospondin-1 (TSP1) protein is one of the master regulators of angiogenesis. This study unveils a novel aspect of TSP1 regulation through reversible phosphorylation. The silencing of the B55α regulatory subunit of protein phosphatase 2A (PP2A) in endothelial cells led to a significant decrease in TSP1 expression. Direct interaction between TSP1 and PP2A-B55α was confirmed via various methods. Truncated TSP1 constructs were employed to identify the phosphorylation site and the responsible kinase, ultimately pinpointing PKC as the enzyme phosphorylating TSP1 on Ser93. The biological effects of B55α–TSP1 interaction were also analyzed. B55α silencing not only counteracted the increase in TSP1 expression during wound closure but also prolonged wound closure time. Although B55α silenced cells initiated tube-like structures earlier than control cells, their spheroid formation was disrupted, leading to disintegration. Cells transfected with phosphomimic TSP1 S93D exhibited smaller spheroids and reduced effectiveness in tube formation, revealing insights into the effects of TSP1 phosphorylation on angiogenic properties. In this paper, we introduce a new regulatory mechanism of angiogenesis by reversible phosphorylation on TSP1 S93 by PKC and PP2A B55α. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20 years, many antiangiogenic drugs have been developed based on VEGF/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China. [ABSTRACT FROM AUTHOR]

Angiogenesis, or the development of blood vessels by growing from already-formed vessels, is observed in embryonic development, physiological cyclical processes such as wound healing, the encapsulation of foreign bodies, tumor growth, and some other situations. In this review, we analyze the cellular mechanisms of angiogenesis, namely, angiogenesis by sprouting, ansiform (by loop formation) angiogenesis, coalescent angiogenesis, and angiogenesis by intussusception (splitting the capillary into two channels). The analysis of data revealed a lot of unanswered questions and contradictions. Here, we propose several new models of angiogenesis explaining these contradictions. [ABSTRACT FROM AUTHOR]

In this paper, we study a free‐boundary problem modeling the growth of spherically symmetric tumors with angiogenesis and a necrotic core, where the Robin boundary condition is imposed for the nutrient concentration. The existence of a global solution is established by first reducing the free‐boundary problem into an equivalent initial boundary value problem for a nonlinear strongly singular parabolic equation on a fixed domain, then proving that an approximation problem admits a unique solution by the Schauder fixed point theorem combined with the Lp$$ {L}^p $$ estimates for parabolic equations, and finally taking the limit. Compared with the Dirichlet boundary value condition problem, the Robin condition causes some new difficulties in making rigorous analysis of the model, particularly on the uniqueness of solutions to the approximation problem. [ABSTRACT FROM AUTHOR]

Background: Elevated mortality rates in patients with metabolic syndrome (MetS) are partly due to adverse remodeling of multiple organs, which may lead to cardiovascular disease, nonalcoholic fatty liver disease, kidney failure, or other conditions. MetS symptoms, such as obesity, hypertension, hyperglycemia, dyslipidemia, associated with insulin and leptin resistance, are recognized as major cardiovascular risk factors that adversely affect the heart. Summary: Pathological cardiac remodeling is accompanied by endothelial cell dysfunction which may result in diminished coronary flow, dysregulated oxygen demand/supply balance, as well as vessel rarefaction. The reduced number of vessels and delayed or inhibited formation of collaterals after myocardial infarction in MetS heart may be due to unfavorable changes in endothelial cell metabolism but also to altered expression of vascular endothelial growth factor molecules, their receptors, and changes in signal transduction from the cell membrane, which severely affect angiogenesis. Key Messages: Given the established role of cardiac vessel endothelial cells in maintaining tissue homeostasis, defining the molecular background underlying vessel dysfunction associated with impaired angiogenesis is of great importance for future therapeutic purposes. Therefore, the aim of this paper was to present current information regarding vascular endothelial growth factor signaling in the myocardium of MetS individuals. [ABSTRACT FROM AUTHOR]

Myocardial infarction is myocardial necrosis caused by acute and persistent ischemia and hypoxia of coronary artery, with high incidence rate and mortality. Although the recovery of blood supply through coronary intervention or thrombolytic drugs can improve the survival rate of patients, it is difficult to rescue the lost cardiomyocytes in the infarcted area, and the limited self repair ability of the adult mammalian heart is the main factor that causes myocardial fibrosis and eventually progresses to heart failure. For a long time, the existing treatment methods are difficult to reverse the process of heart failure after myocardial infarction. Cell transplantation is a promising therapeutic method to promote the repair and regeneration of infarcts. Due to the ischemia and hypoxia microenvironment, the limited survival and retention of stem cells after transplantation are not ideal. And acellular biomaterials promoting angiogenesis and reducing fibrosis show the potential of preclinical treatment. This paper summarizes the advantages and disadvantages of various acellular biomaterials, epicardial infarct repair and intramyocardial injection in a minimally invasive manner to promote cardiac regeneration and improve cardiac function, and to promote myocardial regeneration by combining acellular biomaterials with optimized drugs in the future for reference. [ABSTRACT FROM AUTHOR]

ObjectiveThe vascular chip has emerged as a significant research tool, garnering increasing interest and exploration. We utilize bibliometric techniques to analyze literature from the Web of Science (WOS) database, focusing on core journal publications. The aim is to provide a systematic review and prospective outlook on research trends within the vascular chip field, delving into current dynamics and highlighting areas for further investigation.MethodsWe retrieved articles, proceedings papers, and early-access publications related to vascular chips published between January 2012 and December 2022 reported by Web of Science Core Collection (WoSCC) in 2023. Scientific bibliometric analysis was performed using R-bibliometrix, CiteSpace, VOSviewer, and Microsoft Excel software tools.ResultsA total of 456 publications were obtained, including 444 articles, 11 proceedings papers, and one early-access article. These originated from 167 academic journals and 751 research institutions across 44 countries/regions. The United States contributed the majority of publications (41%), with Harvard University leading in contributions (6.6%). Lab on a Chip was the top journal in terms of publications. Notably, authors Jeon NL and Huh D wielded significant influence, with the former being the most prolific author and the latter garnering the most citations. Recent research has predominantly focused on angiogenesis in relation to endothelial cells.ConclusionThis scientometric investigation comprehensively surveys literature on vascular chips over past decade, providing valuable insights for scholars in the field. Our study reveals global increases in publications, with endothelial cells and angiogenesis being primary research focuses. This trend will persist, drawing continued attention from researchers.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-B pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

The vascular system maintains cellular homeostasis by transporting oxygen, nutrients, and metabolic waste products. The vascular system is involved in a variety of fundamental physiological phenomena and is closely associated with human vascular diseases. Additionally, the stability of drugs in the vasculature affects their efficacy. Therefore, researchers have used vascular models to study vascular diseases, assess drug stability, and screen drugs. However, there are many shortcomings in the animal models and in vitro two-dimensional vascular models that have been extensively developed. In this paper, we specifically review the construction methods of in vitro vascular models and classify the specific methods into photolithography, soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. The first two are microfluidics-based methods and the last three are non-microfluidics-based methods. The vascular model construction methods reviewed in this paper overcome the shortcomings of traditional models—which cannot accurately reproduce the human vascular microenvironment—and can assist in the construction of in vitro 3D vascular models and tissue engineering vascularization. These models can be reused by perfusion devices, and the cells within the channels reside on biocompatible materials that are used to simulate the microenvironment and 3D cellular organization of the vasculature in vivo. In addition, these models are reproducible in shape and length, allowing experiments to be repeated, which is difficult to do with natural vessels. In vitro vascular models are widely used in research and drug screening for diseases associated with endothelial dysfunction, cancer, and other vascular abnormalities.

Identifying chick's sex as early and as accurately as possible is a vital task in chicken farming. The prominent methods are feather, color, and vent sexing, in 1-day old chicks, but these tasks require a skilled examiner. Alternatively, gonad inspection is also adopted, but it is more invasive and usually involves anesthetic and surgical procedures. To resolve their shortcomings, in ovo sex determination was recently proposed. Some techniques relied on analyzing biochemical contents (hormone) or spectroscopic patterns (feather pigment) in a developing embryo. The others need to precisely make a small hole on an eggshell, while keeping the inner membrane intact. Furthermore, advanced and costly equipment involved has impeded wider adoption in most smaller farm settings. To address both issues, this paper proposes a noninvasive in ovo sexing technique that focuses on the phenotypic differences. Particularly, chorioallantoic maturation and vascular anastomosis at days 10 and 12 of incubation were characterized and hence discerned between sexes. The appearance of embryologic vasculature was represented by the entropy of its multiband visual features, extracted from a candled egg. These features were then used to identify their sexes by a supervised classifier. The experiments showed that, as early as day 12, the method could predict embryo's sex from its candled image with accuracy, precision, recall, and balanced accuracy of 83.33, 84.62, 73.33, and 81.90%, respectively. Moreover, false discovery and false omission rates, which reflect practical errors, were 15.38 and 17.39%, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Co-doping can, but not necessarily, further enhance silicates compared to mono-doping. • A summative, synergistic, or antagonistic interaction occurs between co-dopants in silicates. • The outcome of co-doping depends on the composition, crystallinity, and surface area of the host silicate. Silicate bioceramics have attracted significant attention in medical applications, particularly in hard tissue regeneration, because of their controllable chemical, physical, and biological functionalities, while ensuring biocompatibility. The coordination of silicate bioceramics with mono-dopants has been extensively studied to enhance their osteogenesis, angiogenesis, and antibacterial activity. However, the concept of employing dual or multiple co-doping to further enhance these biomaterials still demands more attention. This review paper originally focuses on the effect of chemical interactions among co-dopants and the principal constituents of the silicates, on the bio-behavior of these bioceramics. Additionally, future prospects of co-doped silicate bioceramics are outlined, including in vivo studies, clinical trials, and potential commercialization. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Epilepsy is characterized by abnormal synchronous electrical activity of neurons in the brain. The blood-brain barrier, which is mainly composed of endothelial cells, pericytes, astrocytes and other cell types and is formed by connections between a variety of cells, is the key physiological structure connecting the blood and brain tissue and is critical for maintaining the microenvironment in the brain. Physiologically, the blood-brain barrier controls the microenvironment in the brain mainly by regulating the passage of various substances. Disruption of the blood-brain barrier and increased leakage of specific substances, which ultimately leading to weakened cell junctions and abnormal regulation of ion concentrations, have been observed during the development and progression of epilepsy in both clinical studies and animal models. In addition, disruption of the blood-brain barrier increases drug resistance through interference with drug trafficking mechanisms. The changes in the blood-brain barrier in epilepsy mainly affect molecular pathways associated with angiogenesis, inflammation, and oxidative stress. Further research on biomarkers is a promising direction for the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: In the repair of massive tissue defects using expanded large skin flaps, the incidence of complications increases with the size of the expanded area. Currently, stem cell therapy has limitations to solve this problem. We hypothesized that conditioned medium of adipose-derived stem cells (ADSC-CM) collected following mechanical pretreatment can assist skin expansion. Methods: Rat aortic endothelial cells and fibroblasts were cultured with ADSC-CM collected under 0%, 10%, 12%, and 15% stretching force. Ten-milliliter cylindrical soft tissue expanders were subcutaneously implanted into the backs of 36 Sprague-Dawley rats. The 0% and 10% stretch groups were injected with ADSC-CM collected under 0% and 10% stretching force, respectively, while the control group was not injected. After 3, 7, 14, and 30 days of expansion, expanded skin tissue was harvested for staining and qPCR analyses. Results: Endothelial cells had the best lumen formation and highest migration rate, and fibroblasts secreted the most collagen upon culture with ADSC-CM collected under 10% stretching force. The skin expansion rate was significantly increased in the 10% stretch group. After 7 days of expansion, the number of blood vessels in the expanded area, expression of the angiogenesis-associated proteins vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, and collagen deposition were significantly increased in the 10% stretch group. Conclusions: The optimal mechanical force upregulates specific paracrine proteins in ADSCs to increase angiogenesis and collagen secretion, and thereby promote skin regeneration and expansion. This study provides a new auxiliary method to expand large skin flaps. [ABSTRACT FROM AUTHOR]

This review explores the intricate roles of metal ions—iron, copper, zinc, and selenium—in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Corneal neovascularization (CNV) is a sight-threatening condition that necessitates epigenetic control. The role of lysine-specific demethylase 1 (LSD1) in CNV remains unclear, despite its established significance in tumor angiogenesis regulation. Methods: An alkali burn-induced CNV mouse model was used in vivo. The effects of LSD1 inhibitor tranylcypromine hydrochloride (TCP) were examined through slit lamp, histological staining, and immunofluorescence. The expression of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed in corneal tissues. Oxidative stress and ferrous ion expression during CNV were determined using 4-HNE, GPX4, and FerroOrange staining. In vitro, a hypoxia-reoxygenation (H/R) model was established using human umbilical vein endothelial cells (HUVECs) to study LSD1 or hypoxia-inducible factor (HIF-1α) knockdown and lentiviral overexpression of HIF-1α. The effects on HUVECs migration, invasion, and angiogenesis were evaluated through cell scratching assay, transwell migration assay and tube formation assay. The role of ferroptosis was investigated using ROS staining, FerroOrange staining, and key ferroptosis proteins. Further, The JAK2/STAT3 pathway's involvement in CNV regulation was explored through in vivo experiments with subconjunctival injection of AG490. Results: The results showed a substantial correlation between corneal damage and LSD1 levels. In addition, HIF-1α expression was also elevated after alkali burns, and subconjunctival injection of TCP reduced corneal inflammation and neovascularization. Corneal alkali burns increased ROS levels and reduced antioxidative stress indicators, accompanied by elevated ferrous ion levels, which were reversed by TCP injection. In vitro, TCP or siRNAs inhibited H/R-induced ferroptosis and angiogenesis in HUVECs by affecting specific protein expressions and MDA, SOD, and GSH levels. HIF-1α levels, associated with ROS production, ferroptosis, and angiogenesis, increased during H/R, but were reversed by TCP or siRNA administration. HIF-1α overexpression counteracted the effects of LSD1 inhibition. Additionally, AG490 injection effectively reduced HIF-1α and VEGFA expression in the CNV model. Discussion: These findings suggest that LSD1 inhibition via the HIF-1α-driven pathway prevents angiogenesis, oxidative stress, and ferroptosis in corneal alkali burn-induced CNV, highlighting LSD1 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is associated with a wide variety of signs and symptoms and can lead to infertility, embryo death, and even miscarriage. Although the exact pathogenesis and etiology of endometriosis is still unclear, it has been shown that it has a chronic inflammatory nature and angiogenesis is also involved in it. Objective: This review aims to explore the role of inflammation and angiogenesis in endometriosis and suggest a potential treatment targeting these pathways. Findings: Among the pro‐inflammatory cytokines, studies have shown solid roles for interleukin 1β (IL‐β), IL‐6, and tumor necrosis factor α (TNF‐α) in the pathogenesis of this condition. Other than inflammation, angiogenesis, the formation of new blood vessels from pre‐existing capillaries, is also involved in the pathogenesis of endometriosis. Among angiogenic factors, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor 1α (HIF‐1α), transforming growth factor β1 (TGF‐β1), and matrix metalloproteinases (MMPs) are more essential in the pathogenesis of endometriosis. Interestingly, it has been shown that inflammation and angiogenesis share some similar pathways with each other that could be potentially targeted for treatment of diseases caused by these two processes. Cannabidiol (CBD) is a non‐psychoactive member of cannabinoids which has well‐known and notable anti‐inflammatory and antiangiogenic properties. This agent has been shown to decrease IL‐1β, IL‐6, TNF‐α, VEGF, TGFβ, and MMPs in different animal models of diseases. Conclusion: It seems that CBD could be a possible treatment for endometriosis due to its anti‐inflammatory and antiangiogenic activity, however, further studies are needed. [ABSTRACT FROM AUTHOR]

Recently, therapies utilizing extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) have begun to show promise in clinical trials. However, EV therapeutic potential varies with MSC tissue source and in vitro expansion through passaging. To find the optimal MSC source for clinically translatable EV‐derived therapies, this study aims to compare the angiogenic and immunomodulatory potentials and the protein and miRNA cargo compositions of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, across different passage numbers. Primary bone marrow‐derived MSCs (BMSCs) and adipose‐derived MSCs (ASCs) were isolated from adult female Lewis rats and expanded in vitro to the indicated passage numbers (P2, P4, and P8). EVs were isolated from the culture medium of P2, P4, and P8 BMSCs and ASCs and characterized for EV size, number, surface markers, protein content, and morphology. EVs isolated from different tissue sources showed different EV yields per cell, EV sizes, and protein yield per EV. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of proteomics data and miRNA seq data identified key proteins and pathways associated with differences between BMSC‐EVs and ASC‐EVs, as well as differences due to passage number. In vitro tube formation assays employing human umbilical vein endothelial cells suggested that both tissue source and passage number had significant effects on the angiogenic capacity of EVs. With or without lipopolysaccharide (LPS) stimulation, EVs more significantly impacted expression of M2‐macrophage genes (IL‐10, Arg1, TGFβ) than M1‐macrophage genes (IL‐6, NOS2, TNFα). By correlating the proteomics analyses with the miRNA seq analysis and differences observed in our in vitro immunomodulatory, angiogenic, and proliferation assays, this study highlights the trade‐offs that may be necessary in selecting the optimal MSC source for development of clinical EV therapies. [ABSTRACT FROM AUTHOR]

Background: Incontinence‐associated dermatitis (IAD) is a tough problem in clinical settings, not only increasing the risk of complications like catheter‐related urinary tract infections and pressure ulcers in elderly and critically ill patients, but also prolonging hospital stays, raising hospital costs, and possibly leading to medical disputes. This study is aimed to evaluate the therapeutic effect of silicone dressing combined with topical oxygen therapy on IAD in a rat model. Methods: An IAD rat model induced by synthetic urine with trypsin was established. Hematoxylin & eosin staining was carried out to examine skin histology. Using immunofluorescence, the microvessel density in the affected skin tissues was determined. ELISA was performed to measure the concentrations of inflammatory cytokines and angiogenic factors in serum. The mRNA expression of EGF, PDGF, and VEGF was detected via qRT‐PCR. Western blotting was employed to determine NF‐κB p65/STAT1 pathway‐related protein levels. Results: Compared to single therapy, silicone dressing combined with topical oxygen therapy could significantly reduce the severity of IAD, improve skin histology, inhibit inflammation, and promote angiogenesis in IAD rat models. Additionally, the results showed that relatively speaking, the combined therapy suppressed the NF‐κB p65/STAT1 signaling pathway more effectively. Conclusion: These findings indicated that silicone dressing combined with topical oxygen therapy can alleviate IAD through promoting wound healing and inhibiting inflammation via NF‐κB p65/STAT1 signaling pathway in a rat model, which provided a theoretical basis for the prevention and treatment of IAD in clinic. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate acute wound healing with dynamic optical coherence tomography (D‐OCT). From 22 patients with 23 split skin graft donor sites, vessels at four wound edges, the wound bed, and adjacent and unaffected skin of the contralateral leg were measured by D‐OCT at six time points from surgery to 4 weeks of healing. Changes in vessel orientation, density, diameter, morphology and pattern in horizontal, vertical and 3D images were analysed for wound healing and re‐epithelialization. At 300 μm depth, there were significant differences of blobs and serpiginous vessels between normal and wounded skin. The wound had significantly more vertically oriented vessels, a higher degree of branching, vessel density and diameter compared with healthy skin. 3D images showed increased angiogenesis from healthy skin towards the wound centre, significantly higher vessel density at the wound than at normal skin and the highest at the interface. During wound healing blobs, coils and serpiginous vessels occurred significantly more frequently in lesional than healthy skin. Vessel density was greatest at the beginning, decreased and then increased by 4 weeks post‐surgery. D‐OCT helps to evaluate acute wound healing by visualizing and quantifying blood vessel growth in addition to re‐epithelialization. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is the most general malignancy of the primary central nervous system that is characterized by high aggressiveness and lethality. Transmembrane protein 159 (TMEM159) is an endoplasmic reticulum protein that can form oligomers with seipin. The TMEM159-seipin complex decides the site of lipid droplet (LD) formation, and the formation of LDs is a marker of GBM. However, the role of TMEM159 in the progression of GBM has not been investigated to date. Methods: In this study, we examined the genes that may be associated with patient prognosis in GBM by bioinformatics analyses, and identified the key genes that affect the development of GBM using single-cell RNA sequencing technology. The biological functions of TMEM159 in GBM cells were additionally assessed by clone formation and transwell assays as well as using a model of chick embryo chorioallantois membrane (CAM) and western blotting. The association between TMEM159 and epidermal growth factor receptor (EGFR) was finally analyzed in GBM cells. Results: A prognostic model was established and validated for predicting the prognosis. Survival curve analysis showed a critical difference in the prognosis of the high- and low-risk groups predicted by the prognostic model. The results demonstrated that TMEM159 affected the proliferation and invasion of GBM cells. The chick embryo CAM assays demonstrated that the inhibition of TMEM159 expression reduced angiogenesis in the CAM model. Conclusions: The prognostic model achieved good predictive potential for high-risk patients. The findings also revealed that TMEM159 might be an important prognostic factor for GBM, indicating that the protein may be a promising therapeutic target for suppressing the development of GBM. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) regulate physiological and pathological processes, including ischemia-induced angiogenesis and neovascularization. They can be transferred between cells by extracellular vesicles (EVs). However, the specific miRs that are packaged in EVs released from skeletal muscles, and how this process is modulated by ischemia, remain to be determined. We used a mouse model of hindlimb ischemia and next generation sequencing (NGS) to perform a complete profiling of miR expression and determine the effect of ischemia in skeletal muscles, and in EVs of different sizes (microvesicles (MVs) and exosomes) released from these muscles. Ischemia significantly modulated miR expression in whole muscles and EVs, increasing the levels of several miRs that can have pro-angiogenic effects (angiomiRs). We found that specific angiomiRs are selectively enriched in MVs and/or exosomes in response to ischemia. In silico approaches indicate that these miRs modulate pathways that play key roles in angiogenesis and neovascularization, including HIF1/VEGF signaling, regulation of actin cytoskeleton and focal adhesion, NOTCH, PI3K/AKT, RAS/MAPK, JAK/STAT, TGFb/SMAD signaling and the NO/cGMP/PKG pathway. Thus, we show for the first time that angiomiRs are selectively enriched in MVs and exosomes released from ischemic muscles. These angiomiRs could be targeted in order to improve the angiogenic function of EVs for potential novel therapeutic applications in patients with severe ischemic vascular diseases. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP's pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management. [ABSTRACT FROM AUTHOR]

Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments. [ABSTRACT FROM AUTHOR]