Process Of Angiogenesis Research Articles

Expression of Immunohistochemical Markers in the Walls of Pelvic Varicose Veins in Women.

The tissue preparations of the pelvic veins obtained during laparoscopy were examined. The expression of markers of proliferation (Ki-67), apoptosis (p53), and angiogenesis (CD31, CD34), as well as estrogen and progesterone receptors in women with pelvic varicose veins was assessed by the immunohistochemical method. A decrease in the median expression of the proliferation marker (Ki-67) and estrogen and progesterone receptors and simultaneous increase in the expression of apoptosis marker (p53) and activation of angiogenesis processes (markers CD31 and CD34) were observed with increasing the severity of the disease. These data extend our understanding of the pathogenetic mechanisms of pelvic varicose veins and contribute to the development of methods of pathogenetically based targeted therapy.

Blood Proteome Study to Assess the Regulation of Angiogenesis in Cosmonauts After the End of the Flight

A study of blood samples of 18 cosmonauts who had long flights as members of Russian crews of the International Space Station was performed using the method of quantitative proteomics based on mass spectrometry. The study was focused on elucidation of possible connection of proteome changes under the influence of space flight (SF) factors with the processes of angiogenesis. The analysis was performed with a targeted panel of 125 labeled 13C/15N peptides using chromatography-mass spectrometry with multiple reaction monitoring (LC/MRM-MS). A total of 125 different proteins were quantitatively characterized. Among them, a group of 61 proteins involved in the processes of angiogenesis and its regulation was found. Bioinformatic methods showed that the isolated angiogenesis proteins were participants of 13 biological processes, including lymphangiogenesis. Significant changes of protein level in blood after landing, in relation to preflight samples, were observed in 7 cases. The results have shown that the elimination of gravity (microgravity), space radiation and overloads of the final stage of flight have a combined effect on the processes of angiogenesis, which is manifested by changes in proteomic composition on 1 day after the completion of long-term CP.

Progress on angiogenic and antiangiogenic agents in the tumor microenvironment.

The development of tumors and their metastasis relies heavily on the process of angiogenesis. When the volume of a tumor expands, the resulting internal hypoxic conditions trigger the body to enhance the production of various angiogenic factors. These include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor-α (TGF-α), all of which work together to stimulate the activation of endothelial cells and catalyze angiogenesis. Antiangiogenic therapy (AAT) aims to normalize tumor blood vessels by inhibiting these angiogenic signals. In this review, we will explore the molecular mechanisms of angiogenesis within the tumor microenvironment, discuss traditional antiangiogenic drugs along with their limitations, examine new antiangiogenic drugs and the advantages of combination therapy, and consider future research directions in the field of antiangiogenic drugs. This comprehensive overview aims to provide insights that may aid in the development of more effective anti-tumor treatments.

Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy.

Avascular necrosis of the femoral head (ANFH) is a type of osteonecrosis due to the cessation of blood supply, characterized by persistent local pain and collapse of the joint. The etiology of ANFH is multifaceted, and while its precise pathogenesis remains elusive, it is currently widely believed that the femoral head is highly dependent on the vascular system. A large number of studies have shown that vascular injury is the initial factor in the onset of ANFH. In this review, we briefly introduced the process of angiogenesis and the blood supply to the femoral head, with a focus on summarizing the existing research on promoting angiogenesis for the treatment of ANFH. We conclude that providing alternative pathways through angiogenesis to resolve the problem of the obstructed free flow of the blood is an important means of treating ANFH. Moreover, we also looked forward to the mechanism of endothelial metabolism, which has not yet been studied in femoral head necrosis models, providing potential strategies for more effective use of angiogenesis for the treatment of femoral head necrosis.

Exploring the Current Potential of Snake Venom Disintegrins as Chemotherapeutic Agents: A Narrative Update on their Clinical Translational Potential

A potential source of multiple enzymatic and nonenzymatic molecules that protect the host is snake venom. In these venoms, several kinds of peptides that have significant beneficial effects were discovered and characterized. Disintegrins act by blocking integrins on transmembrane cell surfaces, inhibiting tumor cells from adhering, migrating, forming new blood vessels, and spreading. This has an important effect on delaying the development, neovascularization, and growth of tumors. These cells are ideal candidates for novel therapies for the management of malignancies due to their tumor selectivity and decreased size. As research findings in various <i>in vivo</i> & <i>in vitro</i>, disintegrin proteins are low-molecular-weight polypeptides that are found in the venom of vipers and rattle snakes. They act by blocking the β1 and β3 integrin receptors. Angiogenesis and metastatic processes in cancer are mediated through β1 and β3 integrins. Hence, blocking β1 and β3 integrin receptors plays a prominent role in blocking the progression of cancer, and disintegrins seem to be promising candidates for antineoplastic therapies. The disintegrins with anticancer properties include Crotatroxin 2, Alternagin-C, Rubistatin, Leucurogin, Mojastin- 1, Contortrostatin, Acostatin, Vicrostatin, Tzabcan, Eristostatin, Purpureomaculatus, Saxatilin, Lebein, Salmosin, and Rhodostomin. The above mentioned disintegrins were considered in this study. This review is based on the origins of these disintegrins, their modes of targeting, their categorization, and their inherent anticancer potential.

The Effect of Paracetamol on The Development of Chicken Embryos

Paracetamol (N-Acetylaminophenol) is the most widely used over-the-counter drug in the world. Although considered safe for pregnant mothers, there is a concern regarding the teratogenic effect of paracetamol. This study aims to observe the teratogenic effect of paracetamol developing embryos. Using chicken embryos, the embryos were incubated for 48 hours and then injected with paracetamol in 3 concentrations, namely 10 ppm, 15 ppm, and 20 ppm. The control group and treatment group consisted of 3 replicates of fertile embryos. Then, the embryos were incubated again for 48 hours in the incubator. Data analysis was carried out qualitatively by observing any developmental alterations. Results showed that paracetamol caused enlargement of the head and heart edema. Exposure to paracetamol at concentrations of 15 ppm and 20 ppm affects the morphology of chicken embryos, especially the formation of the head and disrupts the process of angiogenesis and normal heart formation, causing bleeding and edema at higher concentrations.

Carboxymethyl chitosan and sodium alginate oxide pH-sensitive dual-release hydrogel for diabetes wound healing: The combination of astilbin liposomes and diclofenac sodium

Difficulty in diabetic wound healing presents a significant challenge in clinical practice. This study developed a hydrogel utilizing oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) as the matrix. Astilbin (ASB), known for its antioxidant properties, was incorporated into Astilbin liposome (AL) using a thin film dispersion method. Diclofenac sodium (DS) and AL, both possessing anti-inflammatory properties, were then encapsulated in the hydrogel to create a pH-responsive dual-release system for topical application to expedite diabetic wound healing. Results from the research demonstrate that the composite hydrogel exhibits favorable biodegradability, stable rheology, and swelling capacity, facilitating the controlled release of AL and DS. In vivo and in vitro data demonstrated that the hydrogel was biocompatible and anti-inflammatory, antibacterial and homeostatic, and significantly promoted the process of inflammation suppression, angiogenesis and fibrotic repair of wounds. In conclusion, this novel hydrogel provides a simple and effective method for the repair of chronic diabetic wounds.

Characterization of the Cytotoxic Effect of Naphthalenacetamides Hydrochlorides on Cervical Cancer-Derived Cells

Introduction: Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but these are not always effective, which gives rise to the search for new compounds using cheminformatics tools. Method: Therapies directed at the σ1 receptor may be a treatment alternative since this receptor modulates the processes of cell proliferation and angiogenesis, producing cytoprotective or cytotoxic actions depending on the ligand with which it is coupled. Objective: The objective of this study was to design, synthesize, and biologically evaluate N-(2- morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)- N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) on the HeLa cell line in vitro. The referenced cell line from the American Type Culture Collection (ATCC®CCL-2™) was used, and the effect on cell viability was determined by MTT metabolic reduction-based assay at 24, 48, and 72 h. Results: The analysis showed that compounds 1 and 2 presented activity on HeLa cancer cells and viability at micromolar concentrations (1.923 μmol/mL and 0.374 μmol/mL, respectively). Moreover, the effect was maintained for less than 72 h. Conclusion: Naphthaleneacetamide derivatives exhibited an inhibitory effect on the HeLa cell line, and the OSIRIS program predicted less toxicity than cisplatin.

Morphological assessment of angiogenesis factor expression in tumor and microenvironment of breast fibroadenoma and ductal carcinoma: An observational cohort study

Background. Angiogenesis plays a crucial role in the progression of breast cancer. Identifying and investigating the key components of this process, focused on phenotype as well as microenvironment of the tumor, is considered highly relevant for understanding tumor biology. Studies into the expression of angiogenesis-related factors by means of immunohistochemical methods appear valuable for both assessing conventional chemotherapy options and identifying new targets in targeted therapy for breast cancer. Objectives. To investigate angiogenesis in breast ductal carcinoma by assessing the expression of vascular endothelial growth factor, angiopoietin-2, and hypoxia-inducible factor alpha in the context of various therapeutic strategies. Methods. An observational cohort study was conducted using biopsy samples from female patients with confirmed diagnoses of “fibroadenoma” and “ductal carcinoma of the breast,” residents of the Republic of Crimea, who applied to oncological hospitals in Simferopol from January 2021 to January 2023. Examination involved histological sections of breast tumor tissue from 68 patients with verified diagnoses of “ductal carcinoma” and “fibroadenoma” (the mean age of the patients was 65 ± 5). The following cohorts were formed in the study: control group, consisting of patients with breast fibroadenoma (n = 20); two subgroups of patients with ductal carcinoma of the breast (n = 48), including Group I — patients with ductal carcinoma of the breast who had not received chemotherapy (n = 23), Group II — patients with ductal carcinoma of the breast, who underwent surgery following one or more courses of chemotherapy (n = 25). The study involved examining the tumor tissue sections obtained from paraffin blocks, assessing the expression of angiogenesis markers via immunohistochemistry using primary antibodies against vascular endothelial growth factor, angiopoietin 2, and hypoxia-inducible factor alpha. Statistical analysis was carried out using Statistica 10.0 (StatSoft, USA). Differences were considered significant at error probability p ≤ 0.05. The value of p < 0.05 was deemed statistically significant for all types of analysis. Results. The expression of hypoxia-inducible and vascular growth factors differed significantly between both groups with breast ductal carcinoma as well as when compared to the control group. The hypoxia-inducible factor having cytoplasmic localization was detected in the control group with benign processes, whereas the nuclear expression was noted in the breast ductal carcinoma groups. Significant differences in the nuclear expression of hypoxia-inducible factor have been established among groups of patients with confirmed ductal carcinoma of the breast: in Group II, which underwent chemotherapy, expression was notably higher in both the tumor stroma and in the stroma of tumor-free areas. The hypoxia-inducible factor expression was significantly greater at the demarcation zone than that observed in samples from surgically treated women in Group I (p = 0.033; p = 0.034, p < 0.001, respectively). In the tumor epithelium of patients with breast ductal carcinoma, vascular endothelial growth factor was expressed significantly more intensively in the group who did not receive chemotherapy compared to the other group (p < 0.001). Conversely, in the tumor stroma, angiopoietin exhibited significantly higher expression levels among patients who underwent chemotherapy compared to those who received no treatment; this was observed in both the tumor areas due to endothelial cell involvement (p = 0.004) and in conditionally healthy regions of the breast (p < 0.001). In the control group represented by fibroadenoma patients, the expression of the studied factors is more pronounced than in the groups with ductal carcinoma of the breast. Conclusion. The obtained data indicate the activation of angiogenesis processes in the group of patients after chemotherapy, as evidenced by the increased expression of hypoxia-inducible factor, vascular endothelial growth factor, and angiopoietin. This result is associated with the high prevalence of resistant forms of breast ductal carcinoma in Group II. The study of the signaling pathways of angiogenesis and its components provides valuable insights into patterns of occurrence and strategies to overcome chemotherapy resistance in ductal carcinoma of the breast.

Potential role of G protein‑coupled receptor 124 in cardiovascular and cerebrovascular disease (Review).

G protein-coupled receptor 124 (GPR124) has a key role in regulating the proliferation and differentiation of endothelial cells, activating inflammatory bodies and promoting angiogenesis and other processes, thus affecting various pathological and physiological processes in the body. GPR124 is vital for promoting the development of the nervous system and maintaining the stability of the blood-brain barrier, and is also associated with cardiovascular and cerebrovascular diseases and cancer. This article will elaborate on the biological information regarding GPR124 published in recent years and its possible related signaling pathways in the field of diseases and provide a reference for further revealing the role of GPR124 in the occurrence and development of diseases.

Evaluating the Effect of Argon and Helium Atmospheric Cold Plasma Jets on Wound Healing in Rats: A Comparative Histopathological and Biochemical Analysis

Background: Cold atmospheric plasma (CAP) has emerged as a promising therapy for wound healing to deliver controlled doses of reactive species to tissues. Argon and helium, as gases used in CAP, are noted for their unique properties and therapeutic potential. Objectives: This study compared the effects of argon and helium atmospheric cold plasma jets on wound healing in a rat model, assessing histopathological changes and biochemical parameters. Methods: This randomized, controlled experimental study involved 18 male Wistar rats randomly assigned to control, helium-treated, and argon-treated groups. Wounds were created between the shoulders under anesthesia, treated with respective plasmas, and monitored for healing progress through macroscopic and microscopic evaluations. Results: Hemoglobin (HGB) and hematocrit (HCT) levels were significantly higher in experimental groups compared to controls (P < 0.05), while mean corpuscular volume (MCV) was lower (P < 0.05). Tumor necrosis factor alpha (TNF-α) levels were highest in helium-treated and lowest in argon-treated rats (P < 0.05). Argon-treated rats showed enhanced IL-6, hyperemia, angiogenesis, and re-epithelialization, with lower TNF-α and necrotic layer thickness than other groups (P < 0.05). Conclusions: Both argon and helium atmospheric cold plasma jets enhanced wound healing in rat models, demonstrating superior efficacy in promoting angiogenesis and re-epithelialization processes.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

YAP/TAZ drives Notch and angiogenesis mechanoregulation in silico

Endothelial cells are key players in the cardiovascular system. Among other things, they are responsible for sprouting angiogenesis, the process of new blood vessel formation essential for both health and disease. Endothelial cells are strongly regulated by the juxtacrine signaling pathway Notch. Recent studies have shown that both Notch and angiogenesis are influenced by extracellular matrix stiffness; however, the underlying mechanisms are poorly understood. Here, we addressed this challenge by combining computational models of Notch signaling and YAP/TAZ, stiffness- and cytoskeleton-regulated mechanotransducers whose activity inhibits both Dll4 (Notch ligand) and LFng (Notch-Dll4 binding modulator). Our simulations successfully mimicked previous experiments, indicating that this YAP/TAZ-Notch crosstalk elucidates the Notch and angiogenesis mechanoresponse to stiffness. Additional simulations also identified possible strategies to control Notch activity and sprouting angiogenesis via cytoskeletal manipulations or spatial patterns of alternating stiffnesses. Our study thus inspires new experimental avenues and provides a promising modeling framework for further investigations into the role of Notch, YAP/TAZ, and mechanics in determining endothelial cell behavior during angiogenesis and similar processes.

RNA-Seq based selection signature analysis for identifying genomic footprints associated with the fat-tail phenotype in sheep.

Understanding the genetic background behind fat-tail development in sheep can be useful to develop breeding programs for genetic improvement, while the genetic basis of fat-tail formation is still not well understood. Here, to identify genomic regions influencing fat-tail size in sheep, a comprehensive selection signature identification analysis was performed through comparison of fat- and thin-tailed sheep breeds. Furthermore, to gain the first insights into the potential use of RNA-Seq for selection signature identification analysis, SNP calling was performed using RNA-Seq datasets. In total, 45 RNA-Seq samples from seven cohort studies were analyzed, and the FST method was used to detect selection signatures. Our findings indicated that RNA-Seq could be of potential utility for selection signature identification analysis. In total, 877 SNPs related to 103 genes were found to be under selection in 92 genomic regions. Functional annotation analysis reinforced the hypothesis that genes involved in fatty acid oxidation May modulate fat accumulation in the tail of sheep and highlighted the potential regulatory role of angiogenesis process in the fat deposition. In agreement with most previous studies, our results re-emphasize that the BMP2 gene is targeted by selection during sheep evolution. Further gene annotation analysis of the regions targeted by the sheep evolution process revealed that a large number of genes included in these regions are directly associated with fat metabolism, including those previously reported as candidates involved in sheep fat-tail morphology, such as NID2, IKBKG, RGMA, IGFBP7, UBR5, VEGFD and WLS. Moreover, a number of genes, including BDH2, ECHS1, AUH, ERBIN and CYP4V2 were of particular interest because they are well-known fat metabolism-associated genes and are considered novel candidates involved in fat-tail size. Consistent with the selection signature identification analysis, principal component analysis clustered the samples into two completely separate groups according to fat- and thin-tailed breeds. Our results provide novel insights into the genomic basis of phenotypic diversity related to the fat-tail of sheep breeds and can be used to determine directions for improving breeding strategies in the future.

New Insights into the Pathophysiology of Coronary Artery Aneurysms.

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms' pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes.

Mathematical modeling of 18F-Fluoromisonidazole (18F-FMISO) radiopharmaceutical transport in vascularized solid tumors

18F-Fluoromisonidazole (18F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of 18F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind 18F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes.

Angiogenesis in endometrial cancer: clinical and biological significance

Objective: to summarize the available data on the features of vascularization of endometrioid adenocarcinoma (EAC). Material and Methods. The search for relevant sources was performed in the “PubMed” database using the keywords “endometrium + cancer + angiogenesis”, “endometrium + cancer + angiogenesis + lymph”. Of the selected sources, 78 were included in this review. Results. Angiogenesis is an important and necessary stage in the pathogenesis of the appearance, progression and metastasis of EAC and, thus, the study of tumor vascularization provides an opportunity to improve diagnosis and personalized approach to treatment. Vascular density correlates with advanced stage of EAC, high grade of malignancy, myometrial invasion, cervical and adnexal lesions, vascular invasion, metastases to lymph nodes (LN), the presence of cancer cells in the peritoneal fluid, low overall survival and survival without tumor progression. There are publications that deny the connection of vascularization with the histological type of tumor, its grade, lymphovascular invasion, lymph node metastases, the depth of myometrial invasion, and these publications even prove that microvessel density is not an independent prognostic factor. So, there is still no consensus and final opinion, as evidenced by low or high vascularization of EAC. Recently, there are many drugs that affect both the processes of angiogenesis directly and the inducers and factors that control vascular growth. Unfortunately, all such drugs have a fairly high toxicity, and resistance to them very quickly develops. Conclusion. Despite numerous results of studies devoted to the study of the formation of blood vessels and isolated data on lymphangiogenesis in EAC, there is no data in the literature on studying changes in the vascularization of LN in gynecological cancer. However, proangiogenic and antiangiogenic factors are disseminated throughout the body and must exert their effects in distant organs and tissues. Based on changes in the vascularization of LN, it will apparently become possible to predict the activity of angiogenesis in the primary tumor, assess the prognosis of the disease, and the effectiveness of the treatment. In addition, significant expression of the vascular network in an enlarged lymph node biopsied for diagnosis may be a symptom of the development of a malignant tumor in the lymph collection region, even in the absence of metastases.

The Impact of Potent Addictive Substances on Angiogenic Behavior: A Comprehensive Review.

Angiogenesis, the formation of new vasculature from preexisting vasculature, is involved in the development of several diseases as well as various physiological processes. Strict cooperation of proangiogenic and antiangiogenic factors mediates the control of angiogenesis. The fundamental steps in angiogenesis include endothelial cell proliferation, migration, and invasion. Addictive substances, which are considered therapeutic candidates in research and medicine, are classified as natural substances, such as nicotine, or synthetic substances, such as synthetic cannabinoids. Addictive substances have been shown to either enhance or suppress angiogenesis. This review article provides an overview of recent studies concerning the effects of several addictive substances on the process of angiogenesis. Google Scholar and PubMed were used to collect the scientific literature used in this review. The addictive substances addressed in this review are nicotine, opioids such as morphine and heroin, alcohol, cocaine, methamphetamine, and cannabinoids. An accurate assessment of the influence of these substances on the angiogenic process may help to construct a potentially effective therapeutic protocol to control and treat several angiogenesis-related diseases.

Regulatory effect of N6-methyladenosine on tumor angiogenesis.

Previous studies have demonstrated that genetic alterations governing epigenetic processes frequently drive tumor development and that modifications in RNA may contribute to these alterations. In the 1970s, researchers discovered that N6-methyladenosine (m6A) is the most prevalent form of RNA modification in advanced eukaryotic messenger RNA (mRNA) and noncoding RNA (ncRNA). This modification is involved in nearly all stages of the RNA life cycle. M6A modification is regulated by enzymes known as m6A methyltransferases (writers) and demethylases (erasers). Numerous studies have indicated that m6A modification can impact cancer progression by regulating cancer-related biological functions. Tumor angiogenesis, an important and unregulated process, plays a pivotal role in tumor initiation, growth, and metastasis. The interaction between m6A and ncRNAs is widely recognized as a significant factor in proliferation and angiogenesis. Therefore, this article provides a comprehensive review of the regulatory mechanisms underlying m6A RNA modifications and ncRNAs in tumor angiogenesis, as well as the latest advancements in molecular targeted therapy. The aim of this study is to offer novel insights for clinical tumor therapy.

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.